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Sample records for prolonged stress exposure

  1. Prolonged Exposure Therapy For Post Traumatic Stress Disorder

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    Levent SÜTÇİGİL

    2012-07-01

    Full Text Available Post-traumatic Stress Disorder (PTSD is a psychiatric illness that usually develops after an event that threatens one’s life and body integrity and it affects quality of life and impairs social functioning significantly. Many studies have shown therapeutic effect of cognitive behavioral therapies on posttraumatic stress disorder, so that these therapies take part in the first step of treatment guides. Exposure is a practice that is generally used to reduce pathological fear and related emotions common in posttraumatic stress disorder (PTSD and other anxiety disorders. During exposure, patients intentionally confront with feared objects, situations, thoughts and similar stimuli in order to reduce anxiety level. Exposure can be divided into two main techniques as in vivo exposure and imaginal exposure. Prolonged exposure therapy is a specialized treatment program configured for the treatment of posttraumatic stress disorder and it is based on emotional processing theory. Program is comprised of four main components: (a Psycho-education about trauma and posttraumatic disorders, (b Training for breathing exercises, (c repeated facing with objects, persons, situations and thoughts which causes re-experience about trauma, (d Patient are instructed for telling repeatedly and loudly about traumatic experiences . Prolonged exposure usually involves 9 to 12 sessions, each lasting about 60-90 minutes, administered once or twice a week. Prolonged exposure therapy was started to be implemented since the 1980s, during this period the effectiveness of the therapy has been shown in various empirical studies.

  2. Prolonged Exposure Therapy For Post Traumatic Stress Disorder

    Directory of Open Access Journals (Sweden)

    Levent SÜTÇÝGÝL

    2012-08-01

    Full Text Available Post-traumatic Stress Disorder (PTSD is a psychiatric illness that usually develops after an event that threatens one’s life and body integrity and it affects quality of life and impairs social functioning significantly. Many studies have shown therapeutic effect of cognitive behavioral therapies on posttraumatic stress disorder, so that these therapies take part in the first step of treatment guides. Exposure is a practice that is generally used to reduce pathological fear and related emotions common in posttraumatic stress disorder (PTSD and other anxiety disorders. During exposure, patients intentionally confront with feared objects, situations, thoughts and similar stimuli in order to reduce anxiety level. Exposure can be divided into two main techniques as in vivo exposure and imaginal exposure. Prolonged exposure therapy is a specialized treatment program configured for the treatment of posttraumatic stress disorder and it is based on emotional processing theory. Program is comprised of four main components: (a Psycho-education about trauma and posttraumatic disorders, (b Training for breathing exercises, (c repeated facing with objects, persons, situations and thoughts which causes re-experience about trauma, (d Patient are instructed for telling repeatedly and loudly about traumatic experiences . Prolonged exposure usually involves 9 to 12 sessions, each lasting about 60-90 minutes, administered once or twice a week. Prolonged exposure therapy was started to be implemented since the 1980s, during this period the effectiveness of the therapy has been shown in various empirical studies. [JCBPR 2012; 1(2.000: 98-104

  3. Neural Circuits via Which Single Prolonged Stress Exposure Leads to Fear Extinction Retention Deficits

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    Knox, Dayan; Stanfield, Briana R.; Staib, Jennifer M.; David, Nina P.; Keller, Samantha M.; DePietro, Thomas

    2016-01-01

    Single prolonged stress (SPS) has been used to examine mechanisms via which stress exposure leads to post-traumatic stress disorder symptoms. SPS induces fear extinction retention deficits, but neural circuits critical for mediating these deficits are unknown. To address this gap, we examined the effect of SPS on neural activity in brain regions…

  4. Severe, multimodal stress exposure induces PTSD-like characteristics in a mouse model of single prolonged stress.

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    Perrine, Shane A; Eagle, Andrew L; George, Sophie A; Mulo, Kostika; Kohler, Robert J; Gerard, Justin; Harutyunyan, Arman; Hool, Steven M; Susick, Laura L; Schneider, Brandy L; Ghoddoussi, Farhad; Galloway, Matthew P; Liberzon, Israel; Conti, Alana C

    2016-04-15

    Appropriate animal models of posttraumatic stress disorder (PTSD) are needed because human studies remain limited in their ability to probe the underlying neurobiology of PTSD. Although the single prolonged stress (SPS) model is an established rat model of PTSD, the development of a similarly-validated mouse model emphasizes the benefits and cross-species utility of rodent PTSD models and offers unique methodological advantages to that of the rat. Therefore, the aims of this study were to develop and describe a SPS model for mice and to provide data that support current mechanisms relevant to PTSD. The mouse single prolonged stress (mSPS) paradigm, involves exposing C57Bl/6 mice to a series of severe, multimodal stressors, including 2h restraint, 10 min group forced swim, exposure to soiled rat bedding scent, and exposure to ether until unconsciousness. Following a 7-day undisturbed period, mice were tested for cue-induced fear behavior, effects of paroxetine on cue-induced fear behavior, extinction retention of a previously extinguished fear memory, dexamethasone suppression of corticosterone (CORT) response, dorsal hippocampal glucocorticoid receptor protein and mRNA expression, and prefrontal cortex glutamate levels. Exposure to mSPS enhanced cue-induced fear, which was attenuated by oral paroxetine treatment. mSPS also disrupted extinction retention, enhanced suppression of stress-induced CORT response, increased mRNA expression of dorsal hippocampal glucocorticoid receptors and decreased prefrontal cortex glutamate levels. These data suggest that the mSPS model is a translationally-relevant model for future PTSD research with strong face, construct, and predictive validity. In summary, mSPS models characteristics relevant to PTSD and this severe, multimodal stress modifies fear learning in mice that coincides with changes in the hypothalamo-pituitary-adrenal (HPA) axis, brain glucocorticoid systems, and glutamatergic signaling in the prefrontal cortex

  5. Physiological Stress Responses to Prolonged Exposure to MS-222 and Surgical Implantation in Juvenile Chinook Salmon

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    Wagner, Katie A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Woodley, Christa M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Seaburg, Adam [Univ. of Washington, Seattle, WA (United States); Skalski, John R. [Univ. of Washington, Seattle, WA (United States); Eppard, Matthew B. [U.S. Army Corps of Engineers, Portland, OR (United States)

    2014-07-17

    While many studies have investigated the effects of transmitters on fish condition, behavior, and survival, to our knowledge, no studies have taken into account anesthetic exposure time in addition to tag and surgery effects. We investigated stress responses to prolonged MS-222 exposure after stage 4 induction in surgically implanted juvenile Chinook salmon (Oncorhynchus tshawytscha). Survival, tag loss, plasma cortisol concentration, and blood Na+, K+, Ca2+, and pH were measured immediately following anesthetic exposure and surgical implantation and 1, 7, and 14 days post-treatment. Despite the prolonged anesthetic exposure, 3-15 minutes post Stage 4 induction, there were no mortalities or tag loss in any treatment. MS-222 was effective at delaying immediate cortisol release during surgical implantation; however, osmotic disturbances resulted, which were more pronounced in longer anesthetic time exposures. From day 1 to day 14, Na+, Ca2+, and pH significantly decreased, while cortisol significantly increased. The cortisol increase was exacerbated by surgical implantation. There was a significant interaction between MS-222 time exposure and observation day for Na+, Ca2+, K+, and pH; variations were seen in the longer time exposures, although not consistently. In conclusion, stress response patterns suggest stress associated with surgical implantation is amplified with increased exposure to MS-222.

  6. Effectiveness of Cognitive Processing Therapy and Prolonged Exposure in the Department of Veterans Affairs.

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    Rutt, Benjamin T; Oehlert, Mary E; Krieshok, Thomas S; Lichtenberg, James W

    2018-04-01

    Objective This study evaluated the effectiveness of cognitive processing therapy and prolonged exposure in conditions reflective of current clinical practice within the Veterans Health Administration. Method This study involved a retrospective review of 2030 charts. A total of 750 veterans from 10 U.S. states who received cognitive processing therapy or prolonged exposure in individual psychotherapy were included in the study (participants in cognitive processing therapy, N = 376; participants in prolonged exposure, N = 374). The main dependent variable was self-reported posttraumatic stress disorder symptoms as measured by total scores on the Posttraumatic Stress Disorder Checklist. The study used multilevel modeling to evaluate the absolute and relative effectiveness of both treatments and determine the relationship between patient-level variables and total Posttraumatic Stress Disorder Checklist scores during treatment. Results Cognitive processing therapy and prolonged exposure were equally effective at reducing total Posttraumatic Stress Disorder Checklist scores. Veterans who completed therapy reported significantly larger reductions in the Posttraumatic Stress Disorder Checklist than patients who did not complete therapy. There were no significant differences in the improvement of posttraumatic stress disorder symptoms with respect to age and three racial/ethnic groups (Caucasian, African American, and Hispanic). Conclusions Cognitive processing therapy and prolonged exposure were shown to be effective in conditions highly reflective of clinical practice and with a highly diverse sample of veterans. Challenges related to dropout from trauma focused therapy should continue to be researched.

  7. Prolonged Exposure Therapy For Post Traumatic Stress Disorder

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    Levent SÜTÇÝGÝL; Selçuk ASLAN

    2012-01-01

    Post-traumatic Stress Disorder (PTSD) is a psychiatric illness that usually develops after an event that threatens one’s life and body integrity and it affects quality of life and impairs social functioning significantly. Many studies have shown therapeutic effect of cognitive behavioral therapies on posttraumatic stress disorder, so that these therapies take part in the first step of treatment guides. Exposure is a practice that is generally used to reduce pathological fear and related ...

  8. The Relationship between Posttraumatic and Depressive Symptoms during Prolonged Exposure with and without Cognitive Restructuring for the Treatment of Posttraumatic Stress Disorder

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    Aderka, Idan M.; Gillihan, Seth J.; McLean, Carmen P.; Foa, Edna B.

    2013-01-01

    Objective: In the present study, we examined the relationship between posttraumatic and depressive symptoms during prolonged exposure (PE) treatment with and without cognitive restructuring (CR) for the treatment of posttraumatic stress disorder (PTSD). Method: Female assault survivors (N = 153) with PTSD were randomized to either PE alone or PE…

  9. Paternal work stress and prolonged time to pregnancy.

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    Lee, Mi-Sun; Paek, Domyung; Eum, Ki-Do; Siegrist, Johannes; Li, Jian; Lee, Hye-Eun; Cho, Sung-Il

    2009-01-01

    The aim of this study was to explore an association between psychosocial stress at work in married men and their spouses' prolonged time to pregnancy (TTP). All married male workers of a large Korean petrochemical enterprise and their wives fulfilling the selection criteria were included. Main selection criteria were lack of use of contraceptives and experienced pregnancy in recent past. Data were available from 322 couples. Psychosocial stress at work was measured by the effort-reward imbalance questionnaire. Prolonged TTP was measured by the "TTP questionnaire". After adjustment for confounding effects of demographic and life-style characteristics and benzene exposure, delayed TTP, defined by frequency of first-cycle pregnancy, was associated with one standard deviation (SD) increase of the effort-reward ratio in the chronically stressed group of married men (OR = 0.47; 95% CI = 0.22-0.99) in logistic regression analysis. A similar, but somewhat weaker effect, was found for the overall group (OR = 0.67; 95% CI = 0.47-0.94). Paternal stress at work, as measured by effort-reward imbalance, seemed to be associated with a decreased number of conceptions in the first menstrual cycle.

  10. Glycyrrhizin Treatment Facilitates Extinction of Conditioned Fear Responses After a Single Prolonged Stress Exposure in Rats

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    Shuhua Lai

    2018-03-01

    Full Text Available Background/Aims: Impaired fear memory extinction is widely considered a key mechanism of post-traumatic stress disorder (PTSD. Recent studies have suggested that neuroinflammation after a single prolonged stress (SPS exposure may play a critical role in the impaired fear memory extinction. Studies have shown that high mobility group box chromosomal protein 1 (HMGB-1 is critically involved in neuroinflammation. However, the role of HMGB-1 underlying the development of impairment of fear memory extinction is still not known. Methods: Thus, we examined the levels of HMGB-1 in the basolateral amygdala (BLA following SPS using Western blot and evaluated the levels of microglia and astrocytes activation in the BLA after SPS using immunohistochemical staining. We then examined the effects of pre-SPS intra-BLA administration of glycyrrhizin, an HMGB1 inhibitor, or LPS-RS, a competitive TLR4 antagonist, on subsequent post-SPS fear extinction. Results: We found that SPS treatment prolonged the extinction of contextual fear memory after the SPS. The impairment of SPS-induced extinction of contextual fear memory was associated with increased HMGB1 and Toll-like receptor 4 (TLR4 levels in the BLA. Additionally, the impairment of SPS-induced extinction of contextual fear memory was associated with increased activation of microglia and astrocyte in the BLA. Intra-BLA administrations of glycyrrhizin (HMGB-1 inhibitor or LPS-RS (TLR4 antagonist can prevent the development of SPS-induced fear extinction impairment. Conclusion: Taken together, these results suggested that SPS treatment may not only produce short term effects on the HMGB1/TLR4-mediated pro-inflammation, but alter the response of microglia and astrocytes to the exposure to fear associated contextual stimuli.

  11. Glycyrrhizin Treatment Facilitates Extinction of Conditioned Fear Responses After a Single Prolonged Stress Exposure in Rats.

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    Lai, Shuhua; Wu, Gangwei; Jiang, Zhixian

    2018-01-01

    Impaired fear memory extinction is widely considered a key mechanism of post-traumatic stress disorder (PTSD). Recent studies have suggested that neuroinflammation after a single prolonged stress (SPS) exposure may play a critical role in the impaired fear memory extinction. Studies have shown that high mobility group box chromosomal protein 1 (HMGB-1) is critically involved in neuroinflammation. However, the role of HMGB-1 underlying the development of impairment of fear memory extinction is still not known. Thus, we examined the levels of HMGB-1 in the basolateral amygdala (BLA) following SPS using Western blot and evaluated the levels of microglia and astrocytes activation in the BLA after SPS using immunohistochemical staining. We then examined the effects of pre-SPS intra-BLA administration of glycyrrhizin, an HMGB1 inhibitor, or LPS-RS, a competitive TLR4 antagonist, on subsequent post-SPS fear extinction. We found that SPS treatment prolonged the extinction of contextual fear memory after the SPS. The impairment of SPS-induced extinction of contextual fear memory was associated with increased HMGB1 and Toll-like receptor 4 (TLR4) levels in the BLA. Additionally, the impairment of SPS-induced extinction of contextual fear memory was associated with increased activation of microglia and astrocyte in the BLA. Intra-BLA administrations of glycyrrhizin (HMGB-1 inhibitor) or LPS-RS (TLR4 antagonist) can prevent the development of SPS-induced fear extinction impairment. Taken together, these results suggested that SPS treatment may not only produce short term effects on the HMGB1/TLR4-mediated pro-inflammation, but alter the response of microglia and astrocytes to the exposure to fear associated contextual stimuli. © 2018 The Author(s). Published by S. Karger AG, Basel.

  12. Heart Rate Variability Frequency Domain Alterations among Healthy Nurses Exposed to Prolonged Work Stress.

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    Borchini, Rossana; Veronesi, Giovanni; Bonzini, Matteo; Gianfagna, Francesco; Dashi, Oriana; Ferrario, Marco Mario

    2018-01-11

    The deregulation of the autonomic nervous system assessed through the heart rate variability (HRV) analysis is a promising pathway linking work stress and cardiovascular diseases. We aim to investigate the associations between HRV High Frequency (HF) and Low Frequency (LF) powers and work stress in a sample of 36 healthy nurses. Perceived work stress was assessed twice one year apart, using the Job Content and Effort Reward Imbalance questionnaires. This allows to classify nurses in three exposure groups: "prolonged high stress" (PHS), "recent high stress" (RHS) and "stable low stress" (SLS). A 24-h ECG monitoring was later performed during a working day (WD) and a subsequent resting day (RD). Statistically significantly lower ( p working periods. In the subsequent resting periods, HF means showed increases over time in the RHS (beta = +0.41, p working and resting periods. Our study evidences that both prolonged and recent perceived high work stress were associated with a reduction of HF and LF powers during work. In addition, prolonged stress was associated with a lack of recovery during not-working and resting periods.

  13. Dynamics of immediate early gene and neuropeptide gene response to prolonged immobilization stress: evidence against a critical role of the termination of exposure to the stressor.

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    Trnecková, Lenka; Rotllant, David; Klenerová, Vera; Hynie, Sixtus; Armario, Antonio

    2007-02-01

    Stress-induced expression of immediate early genes (IEGs) appears to be transient even if the exposure to the stressor persists. However, there are some exceptions which suggest that particular characteristics of stressors can affect the dynamics of IEG expression. We studied in selected telencephalic, diencephalic and brainstem regions the mRNA levels of two clearly distinct IEGs (c-fos and arc) during prolonged exposure to a severe stressor such as immobilization (IMO) and after releasing the rats from the situation. Although regional differences were observed with the two IEGs, overall, c-fos mRNA levels progressively declined over the course of 4 h of continuous exposure to IMO, whereas arc mRNA levels were maintained at high levels in the brain regions that express this gene under stress (telencephalon). Levels of CRF hnRNA in the hypothalamus paraventricular nucleus only slightly declined during prolonged exposure to IMO. Surprisingly, termination of exposure to IMO did not modify CRF gene expression in the paraventricular nucleus or the pattern of IEGs expression, with the exception of c-fos in the lateral septum. Thus, putative signals associated to the termination of exposure to IMO were unable to modify either IEG expression in most brain areas or CRF gene expression in the paraventricular nucleus.

  14. Implementation of Prolonged Exposure in the Army: Is Consultation Necessary for Effective Dissemination

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    2015-10-01

    to hiring websites and local advertisements , and several candidates were identified. An initial part-time offer was made to Loreli Leos, LPC in July...2015). Prolonged exposure vs eye movement desensitization and reprocessing vs waiting list for posttraumatic stress disorder in patients with a

  15. Prolonged endoplasmic reticulum stress alters placental morphology and causes low birth weight

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    Kawakami, Takashige; Yoshimi, Masaki; Kadota, Yoshito; Inoue, Masahisa; Sato, Masao; Suzuki, Shinya

    2014-01-01

    The role of endoplasmic reticulum (ER) stress in pregnancy remains largely unknown. Pregnant mice were subcutaneously administered tunicamycin (Tun), an ER stressor, as a single dose [0, 50, and 100 μg Tun/kg/body weight (BW)] on gestation days (GDs) 8.5, 12.5, and 15.5. A high incidence (75%) of preterm delivery was observed only in the group treated with Tun 100 μg/kg BW at GD 15.5, indicating that pregnant mice during late gestation are more susceptible to ER stress on preterm delivery. We further examined whether prolonged in utero exposure to ER stress affects fetal development. Pregnant mice were subcutaneously administered a dose of 0, 20, 40, and 60 μg Tun/kg from GD 12.5 to 16.5. Tun treatment decreased the placental and fetal weights in a dose-dependent manner. Histological evaluation showed the formation of a cluster of spongiotrophoblast cells in the labyrinth zone of the placenta of Tun-treated mice. The glycogen content of the fetal liver and placenta from Tun-treated mice was lower than that from control mice. Tun treatment decreased mRNA expression of Slc2a1/glucose transporter 1 (GLUT1), which is a major transporter for glucose, but increased placental mRNA levels of Slc2a3/GLUT3. Moreover, maternal exposure to Tun resulted in a decrease in vascular endothelial growth factor receptor-1 (VEGFR-1), VEGFR-2, and placental growth factor. These results suggest that excessive and exogenous ER stress may induce functional abnormalities in the placenta, at least in part, with altered GLUT and vascular-related gene expression, resulting in low infant birth weight. - Highlights: • Maternal exposure to excessive ER stress induced preterm birth and IUGR. • Prolonged excessive ER stress altered the formation of the placental labyrinth. • ER stress decreased GLUT1 mRNA expression in the placenta, but increased GLUT3. • ER stress-induced IUGR causes decreased glycogen and altered glucose transport

  16. Prolonged endoplasmic reticulum stress alters placental morphology and causes low birth weight

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    Kawakami, Takashige, E-mail: tkawakami@ph.bunri-u.ac.jp; Yoshimi, Masaki; Kadota, Yoshito; Inoue, Masahisa; Sato, Masao; Suzuki, Shinya

    2014-03-01

    The role of endoplasmic reticulum (ER) stress in pregnancy remains largely unknown. Pregnant mice were subcutaneously administered tunicamycin (Tun), an ER stressor, as a single dose [0, 50, and 100 μg Tun/kg/body weight (BW)] on gestation days (GDs) 8.5, 12.5, and 15.5. A high incidence (75%) of preterm delivery was observed only in the group treated with Tun 100 μg/kg BW at GD 15.5, indicating that pregnant mice during late gestation are more susceptible to ER stress on preterm delivery. We further examined whether prolonged in utero exposure to ER stress affects fetal development. Pregnant mice were subcutaneously administered a dose of 0, 20, 40, and 60 μg Tun/kg from GD 12.5 to 16.5. Tun treatment decreased the placental and fetal weights in a dose-dependent manner. Histological evaluation showed the formation of a cluster of spongiotrophoblast cells in the labyrinth zone of the placenta of Tun-treated mice. The glycogen content of the fetal liver and placenta from Tun-treated mice was lower than that from control mice. Tun treatment decreased mRNA expression of Slc2a1/glucose transporter 1 (GLUT1), which is a major transporter for glucose, but increased placental mRNA levels of Slc2a3/GLUT3. Moreover, maternal exposure to Tun resulted in a decrease in vascular endothelial growth factor receptor-1 (VEGFR-1), VEGFR-2, and placental growth factor. These results suggest that excessive and exogenous ER stress may induce functional abnormalities in the placenta, at least in part, with altered GLUT and vascular-related gene expression, resulting in low infant birth weight. - Highlights: • Maternal exposure to excessive ER stress induced preterm birth and IUGR. • Prolonged excessive ER stress altered the formation of the placental labyrinth. • ER stress decreased GLUT1 mRNA expression in the placenta, but increased GLUT3. • ER stress-induced IUGR causes decreased glycogen and altered glucose transport.

  17. Does unconscious stress play a role in prolonged cardiovascular stress recovery?

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    Brosschot, J F; Geurts, S A E; Kruizinga, I; Radstaak, M; Verkuil, B; Quirin, M; Kompier, M A J

    2014-08-01

    According to recent insights, humans might not be aware of a substantial part of their cognitive stress representations while these still have prolonged physiological effects. 'Unconscious stress' can be measured by implicit affect (IA) tests. It was shown that IA predicts physiological stress responses, in fact better than explicit ('conscious') affect. It is not known yet whether IA is associated with concurrent prolonged stress responses. In two studies (n = 62 and 123), anger harassment was used to induce stress. Blood pressure (BP) and heart rate (HR) were measured continuously. During BP and HR recovery, IA was measured by an 'anger' version of the implicit association test (IAT) or the implicit positive and negative affect test (IPANAT). Blood pressure and HR increased during anger harassment and recovery afterwards. When using the IPANAT BP recovery levels were lower when positive IA was high and higher when negative IA was high, independent of explicit affect and rumination. These results were not found using the IAT. These results provide preliminary evidence that physiological stress recovery is associated with IA. This is in line with the theory that unconscious stress is responsible for a-possibly considerable-part of unhealthy prolonged stress-related physiological activity. Copyright © 2014 John Wiley & Sons, Ltd.

  18. Behavioral changes over time in post-traumatic stress disorder: Insights from a rat model of single prolonged stress.

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    Wu, Zhuoyun; Tian, Qing; Li, Feng; Gao, Junqiao; Liu, Yan; Mao, Meng; Liu, Jing; Wang, Shuyan; Li, Genmao; Ge, Dongyu; Mao, Yingqiu; Zhang, Wei; Liu, Zhaolan; Song, Yuehan

    2016-03-01

    Post-traumatic stress disorder (PTSD) is manifested as a persistent mental and emotional condition after potentially life-threatening events. Different animal models of PTSD have been developed for neuro-pathophysiology and pharmacological evaluations. A single prolonged stress (SPS) induced animal model has demonstrated to result in specific neuro-endocrinological dysregulation, and behavior abnormalities observed in PTSD. However, animal studies of PTSD have mostly been performed at one time point after SPS exposure. To better understand the development of PTSD-like behaviors in the SPS animal model, and to identify an optimal period of study, we examined depressive behavior, anxiety-like behavior, physical activity and body weight in SPS model rats for two weeks. Our results confirmed the SPS-induced PTSD-like behavior and physical activity observed in previous studies, and indicated that the most pronounced symptomatic behavior changes were observed on day 1 and 7 after SPS exposure, which may involve stress-induced acute hormone changes and unclear secondary neurobiological changes, respectively. These results provide a solid basis for further investigation into the neuro-pathophysiology of or neuropharmacology for PTSD using the SPS rat model. However, for chronic (pharmacological) studies longer than 7 days, a prolonged PTSD animal model should be developed, perhaps using enhanced stimulation. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Evidence of Complex Posttraumatic Stress Disorder (CPTSD) across populations with prolonged trauma of varying intensity and ages of exposure

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    Palic, Sabina; Zerach, G; Shevlin, Mark

    2016-01-01

    , with a "Dissociative PTSD-subtype" class. ICD-11's CPTSD was not exclusively associated with childhood abuse, but also with exposure to adulthood trauma of severe interpersonal intensity. Furthermore, all types of prolonged trauma were equally associated with the "Anxiety symptoms" class. Finally, of all the classes......The ICD-11 proposes different types of prolonged trauma as risk factors for complex PTSD (CPTSD). However, CPTSD's construct validity has only been examined in childhood abuse, and single trauma exposure samples. Thus, the extent to which CPTSD applies to other repeatedly traumatized populations...... is unknown. This study examined ICD-11's PTSD and CPTSD across populations with prolonged trauma of varying interpersonal intensity and ages of exposure, including: 1) childhood sexual abuse, 2) adulthood trauma of severe interpersonal intensity (refugees and ex-prisoners of war), and 3) adulthood trauma...

  20. Prolonged Pulmonary Exposure to Diesel Exhaust Particles Exacerbates Renal Oxidative Stress, Inflammation and DNA Damage in Mice with Adenine-Induced Chronic Renal Failure

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    Abderrahim Nemmar

    2016-05-01

    Full Text Available Background/Aims: Epidemiological evidence indicates that patients with chronic kidney diseases have increased susceptibility to adverse outcomes related to long-term exposure to particulate air pollution. However, mechanisms underlying these effects are not fully understood. Methods: Presently, we assessed the effect of prolonged exposure to diesel exhaust particles (DEP on chronic renal failure induced by adenine (0.25% w/w in feed for 4 weeks, which is known to involve inflammation and oxidative stress. DEP (0.5m/kg was intratracheally (i.t. instilled every 4th day for 4 weeks (7 i.t. instillation. Four days following the last exposure to either DEP or saline (control, various renal endpoints were measured. Results: While body weight was decreased, kidney weight increased in DEP+adenine versus saline+adenine or DEP. Water intake, urine volume, relative kidney weight were significantly increased in adenine+DEP versus DEP and adenine+saline versus saline. Plasma creatinine and urea increased and creatinine clearance decreased in adenine+DEP versus DEP and adenine+saline versus saline. Tumor necrosis factor α, lipid peroxidation and reactive oxygen species were significantly increased in adenine+DEP compared with either DEP or adenine+saline. The antioxidant calase was significantly decreased in adenine+DEP compared with either adenine+saline or DEP. Notably, renal DNA damage was significantly potentiated in adenine+DEP compared with either adenine+saline or DEP. Similarly, systolic blood pressure was increased in adenine+DEP versus adenine+saline or DEP, and in DEP versus saline. Histological evaluation revealed more collagen deposition, higher number of necrotic cell counts and dilated tubules, cast formation and collapsing glomeruli in adenine+DEP versus adenine+saline or DEP. Conclusion: Prolonged pulmonary exposure to diesel exhaust particles worsen renal oxidative stress, inflammation and DNA damage in mice with adenine-induced chronic

  1. Does Unconscious Stress Play a Role in Prolonged Cardiovascular Stress Recovery?

    NARCIS (Netherlands)

    Brosschot, J.F.; Geurts, S.A.E.; Kruizinga, I.; Radstaak, M.; Verkuil, B.; Quirin, M.R.; Kompier, M.A.J.

    2014-01-01

    According to recent insights, humans might not be aware of a substantial part of their cognitive stress representations while these still have prolonged physiological effects. Unconscious stress' can be measured by implicit affect (IA) tests. It was shown that IA predicts physiological stress

  2. Response of Escherichia coli to Prolonged Berberine Exposure.

    Science.gov (United States)

    Budeyri Gokgoz, Nilay; Avci, Fatma Gizem; Yoneten, Kubra Karaosmanoglu; Alaybeyoglu, Begum; Ozkirimli, Elif; Sayar, Nihat Alpagu; Kazan, Dilek; Sariyar Akbulut, Berna

    2017-07-01

    Berberine is a plant-derived alkaloid possessing antimicrobial activity; unfortunately, its efflux through multidrug resistance pumps reduces its efficacy. Cellular life span of Escherichia coli is generally shorter with prolonged berberine exposure; nevertheless, about 30% of the cells still remain robust following this treatment. To elucidate its mechanism of action and to identify proteins that could be involved in development of antimicrobial resistance, protein profiles of E. coli cells treated with berberine for 4.5 and 8 hours were compared with control cells. A total of 42 proteins were differentially expressed in cells treated with berberine for 8 hours when compared to control cells. In both 4.5 and 8 hours of berberine-treated cells, carbohydrate and peptide uptake regimens remained unchanged, although amino acid maintenance regimen switched from transport to synthesis. Defect in cell division persisted and this condition was confirmed by images obtained from scanning electron microscopy. Universal stress proteins were not involved in stress response. The significant increase in the abundance of elongation factors could suggest the involvement of these proteins in protection by exhibiting chaperone activities. Furthermore, the involvement of the outer membrane protein OmpW could receive special attention as a protein involved in response to antimicrobial agents, since the expression of only this porin protein was upregulated after 8 hours of exposure.

  3. Stress-altered synaptic plasticity and DAMP signaling in the hippocampus-PFC axis; elucidating the significance of IGF-1/IGF-1R/CaMKIIα expression in neural changes associated with a prolonged exposure therapy.

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    Ogundele, Olalekan M; Ebenezer, Philip J; Lee, Charles C; Francis, Joseph

    2017-06-14

    Traumatic stress patients showed significant improvement in behavior after a prolonged exposure to an unrelated stimulus. This treatment method attempts to promote extinction of the fear memory associated with the initial traumatic experience. However, the subsequent prolonged exposure to such stimulus creates an additional layer of neural stress. Although the mechanism remains unclear, prolonged exposure therapy (PET) likely involves changes in synaptic plasticity, neurotransmitter function and inflammation; especially in parts of the brain concerned with the formation and retrieval of fear memory (Hippocampus and Prefrontal Cortex: PFC). Since certain synaptic proteins are also involved in danger-associated molecular pattern signaling (DAMP), we identified the significance of IGF-1/IGF-1R/CaMKIIα expression as a potential link between the concurrent progression of synaptic and inflammatory changes in stress. Thus, a comparison between IGF-1/IGF-1R/CaMKIIα, synaptic and DAMP proteins in stress and PET may highlight the significance of PET on synaptic morphology and neuronal inflammatory response. In behaviorally characterized Sprague-Dawley rats, there was a significant decline in neural IGF-1 (pIGF-1R expression. These animals showed a significant loss of presynaptic markers (synaptophysin; pIGF-1 (pIGF-1R was recorded in the Stress-PET group (pIGF-1/IGF-1R, an increase in activated hippocampal and cortical microglia was seen in stress (pIGF1/IGF-1R/CaMKIIα. Firstly, we showed a direct relationship between IGF-1/IGF-1R expression, presynaptic function (synaptophysin) and neurotransmitter activity in stress and PET. Secondly, we identified the possible role of CaMKIIα in post-synaptic function and regulation of small ion conductance channels. Lastly, we highlighted some of the possible links between IGF1/IGF-1R/CaMKIIα, the expression of DAMP proteins, Microglia activation, and its implication on synaptic plasticity during stress and PET. Copyright © 2017

  4. Cultural Adaptations of Prolonged Exposure Therapy for Treatment and Prevention of Posttraumatic Stress Disorder in African Americans

    Directory of Open Access Journals (Sweden)

    Monnica T. Williams

    2014-05-01

    Full Text Available Posttraumatic stress disorder (PTSD is a highly disabling disorder, afflicting African Americans at disproportionately higher rates than the general population. When receiving treatment, African Americans may feel differently towards a European American clinician due to cultural mistrust. Furthermore, racism and discrimination experienced before or during the traumatic event may compound posttrauma reactions, impacting the severity of symptoms. Failure to adapt treatment approaches to encompass cultural differences and racism-related traumas may decrease treatment success for African American clients. Cognitive behavioral treatment approaches are highly effective, and Prolonged Exposure (PE in particular has the most empirical support for the treatment of PTSD. This article discusses culturally-informed adaptations of PE that incorporates race-related trauma themes specific to the Black experience. These include adding more sessions at the front end to better establish rapport, asking directly about race-related themes during the assessment process, and deliberately bringing to the forefront race-related experiences and discrimination during treatment when indicated. Guidelines for assessment and the development of appropriate exposures are provided. Case examples are presented demonstrating adaptation of PE for a survivor of race-related trauma and for a woman who developed internalized racism following a sexual assault. Both individuals experienced improvement in their posttrauma reactions using culturally-informed adaptations to PE.

  5. Heart Rate Variability Frequency Domain Alterations among Healthy Nurses Exposed to Prolonged Work Stress

    Directory of Open Access Journals (Sweden)

    Rossana Borchini

    2018-01-01

    Full Text Available The deregulation of the autonomic nervous system assessed through the heart rate variability (HRV analysis is a promising pathway linking work stress and cardiovascular diseases. We aim to investigate the associations between HRV High Frequency (HF and Low Frequency (LF powers and work stress in a sample of 36 healthy nurses. Perceived work stress was assessed twice one year apart, using the Job Content and Effort Reward Imbalance questionnaires. This allows to classify nurses in three exposure groups: “prolonged high stress” (PHS, “recent high stress” (RHS and “stable low stress” (SLS. A 24-h ECG monitoring was later performed during a working day (WD and a subsequent resting day (RD. Statistically significantly lower (p < 0.02 HF and LF means were found in PHS and RHS nurses during the working periods. In the subsequent resting periods, HF means showed increases over time in the RHS (beta = +0.41, p < 0.05, but not in PHS nurses. LF means did not show any substantial increases in the resting periods, in the PHS group with geometric means lower when compared to SLS, in the non-working and resting periods. Our study evidences that both prolonged and recent perceived high work stress were associated with a reduction of HF and LF powers during work. In addition, prolonged stress was associated with a lack of recovery during not-working and resting periods.

  6. Prolonged Pulmonary Exposure to Diesel Exhaust Particles Exacerbates Renal Oxidative Stress, Inflammation and DNA Damage in Mice with Adenine-Induced Chronic Renal Failure.

    Science.gov (United States)

    Nemmar, Abderrahim; Karaca, Turan; Beegam, Sumaya; Yuvaraju, Priya; Yasin, Javed; Hamadi, Naserddine Kamel; Ali, Badreldin H

    2016-01-01

    Epidemiological evidence indicates that patients with chronic kidney diseases have increased susceptibility to adverse outcomes related to long-term exposure to particulate air pollution. However, mechanisms underlying these effects are not fully understood. Presently, we assessed the effect of prolonged exposure to diesel exhaust particles (DEP) on chronic renal failure induced by adenine (0.25% w/w in feed for 4 weeks), which is known to involve inflammation and oxidative stress. DEP (0.5m/kg) was intratracheally (i.t.) instilled every 4th day for 4 weeks (7 i.t. instillation). Four days following the last exposure to either DEP or saline (control), various renal endpoints were measured. While body weight was decreased, kidney weight increased in DEP+adenine versus saline+adenine or DEP. Water intake, urine volume, relative kidney weight were significantly increased in adenine+DEP versus DEP and adenine+saline versus saline. Plasma creatinine and urea increased and creatinine clearance decreased in adenine+DEP versus DEP and adenine+saline versus saline. Tumor necrosis factor α, lipid peroxidation and reactive oxygen species were significantly increased in adenine+DEP compared with either DEP or adenine+saline. The antioxidant calase was significantly decreased in adenine+DEP compared with either adenine+saline or DEP. Notably, renal DNA damage was significantly potentiated in adenine+DEP compared with either adenine+saline or DEP. Similarly, systolic blood pressure was increased in adenine+DEP versus adenine+saline or DEP, and in DEP versus saline. Histological evaluation revealed more collagen deposition, higher number of necrotic cell counts and dilated tubules, cast formation and collapsing glomeruli in adenine+DEP versus adenine+saline or DEP. Prolonged pulmonary exposure to diesel exhaust particles worsen renal oxidative stress, inflammation and DNA damage in mice with adenine-induced chronic renal failure. Our data provide biological plausibility that air

  7. Short-term pre- and post-operative stress prolongs incision-induced pain hypersensitivity without changing basal pain perception.

    Science.gov (United States)

    Cao, Jing; Wang, Po-Kai; Tiwari, Vinod; Liang, Lingli; Lutz, Brianna Marie; Shieh, Kun-Ruey; Zang, Wei-Dong; Kaufman, Andrew G; Bekker, Alex; Gao, Xiao-Qun; Tao, Yuan-Xiang

    2015-12-02

    Chronic stress has been reported to increase basal pain sensitivity and/or exacerbate existing persistent pain. However, most surgical patients have normal physiological and psychological health status such as normal pain perception before surgery although they do experience short-term stress during pre- and post-operative periods. Whether or not this short-term stress affects persistent postsurgical pain is unclear. In this study, we showed that pre- or post-surgical exposure to immobilization 6 h daily for three consecutive days did not change basal responses to mechanical, thermal, or cold stimuli or peak levels of incision-induced hypersensitivity to these stimuli; however, immobilization did prolong the duration of incision-induced hypersensitivity in both male and female rats. These phenomena were also observed in post-surgical exposure to forced swimming 25 min daily for 3 consecutive days. Short-term stress induced by immobilization was demonstrated by an elevation in the level of serum corticosterone, an increase in swim immobility, and a decrease in sucrose consumption. Blocking this short-term stress via intrathecal administration of a selective glucocorticoid receptor antagonist, RU38486, or bilateral adrenalectomy significantly attenuated the prolongation of incision-induced hypersensitivity to mechanical, thermal, and cold stimuli. Our results indicate that short-term stress during the pre- or post-operative period delays postoperative pain recovery although it does not affect basal pain perception. Prevention of short-term stress may facilitate patients' recovery from postoperative pain.

  8. Structural and functional changes in the gastric intramural nervous plexus in emotionally stressed rats exposed to low doses of prolonged ionizing radiation and lead

    International Nuclear Information System (INIS)

    Lapsha, V.I.; Bocharova, V.N.; Utkina, L.N.; Rolevich, I.V.

    1999-01-01

    Changes in the catecholamine content in adrenergic fibres, acethylcholinesterase activity, and in the energy metabolism enzymes lactate dehydrogenase and succinate dehydrogenase in neurons of the gastric intramural plexus during emotional stress in rats a day after combined exposure to prolonged (30 days) ionizing radiation at a total dose 1.0 Gy and 0.6 mg/kg lead were studied. A decrease in catecholamines in adrenergic fibres and acethylcholinesterase and lactate dehydrogenase activity in neurons was observed. An enhanced sensitivity of the gastric intramural plexus after the prolonged exposure to small doses of ionizing radiation and lead in conditions of emotional stress was suggested [ru

  9. Identifying Molecular Targets For PTSD Treatment Using Single Prolonged Stress

    Science.gov (United States)

    2014-10-01

    Post - traumatic stress disorder ( PTSD ) is a chronic, debilitating psychiatric disorder that can...SPS animals. Post - traumatic stress disorder ( PTSD ) is associated with neurocognitive impairments that have been attributed to functional deficits...and resilience. 2. KEYWORDS Post - traumatic stress disorder , Single Prolonged Stress , Neurobiological Mechanisms 5 3. ACCOMPLISHMENTS

  10. Prolonged effect of fluid flow stress on the proliferative activity of mesothelial cells after abrupt discontinuation of fluid streaming

    International Nuclear Information System (INIS)

    Aoki, Shigehisa; Ikeda, Satoshi; Takezawa, Toshiaki; Kishi, Tomoya; Makino, Junichi; Uchihashi, Kazuyoshi; Matsunobu, Aki; Noguchi, Mitsuru; Sugihara, Hajime; Toda, Shuji

    2011-01-01

    Highlights: ► Late-onset peritoneal fibrosis leading to EPS remains to be elucidated. ► Fluid streaming is a potent factor for peritoneal fibrosis in PD. ► We focused on the prolonged effect of fluid streaming on mesothelial cell kinetics. ► A history of fluid streaming exposure promoted mesothelial proliferative activity. ► We have thus identified a potent new factor for late-onset peritoneal fibrosis. -- Abstract: Encapsulating peritoneal sclerosis (EPS) often develops after transfer to hemodialysis and transplantation. Both termination of peritoneal dialysis (PD) and transplantation-related factors are risks implicated in post-PD development of EPS, but the precise mechanism of this late-onset peritoneal fibrosis remains to be elucidated. We previously demonstrated that fluid flow stress induced mesothelial proliferation and epithelial–mesenchymal transition via mitogen-activated protein kinase (MAPK) signaling. Therefore, we speculated that the prolonged bioactive effect of fluid flow stress may affect mesothelial cell kinetics after cessation of fluid streaming. To investigate how long mesothelial cells stay under the bioactive effect brought on by fluid flow stress after removal of the stress, we initially cultured mesothelial cells under fluid flow stress and then cultured the cells under static conditions. Mesothelial cells exposed to fluid flow stress for a certain time showed significantly high proliferative activity compared with static conditions after stoppage of fluid streaming. The expression levels of protein phosphatase 2A, which dephosphorylates MAPK, in mesothelial cells changed with time and showed a biphasic pattern that was dependent on the duration of exposure to fluid flow stress. There were no differences in the fluid flow stress-related bioactive effects on mesothelial cells once a certain time had passed. The present findings show that fluid flow stress exerts a prolonged bioactive effect on mesothelial cells after termination

  11. Glucocorticoid receptors and extinction retention deficits in the single prolonged stress model.

    Science.gov (United States)

    Knox, D; Nault, T; Henderson, C; Liberzon, I

    2012-10-25

    Single prolonged stress (SPS) is a rodent model of post traumatic stress disorder that is comprised of serial application of restraint (r), forced swim (fs), and ether (eth) followed by a 7-day quiescent period. SPS induces extinction retention deficits and it is believed that these deficits are caused by the combined stressful effect of serial exposure to r, fs, and eth. However, this hypothesis remains untested. Neurobiological mechanisms by which SPS induces extinction retention deficits are unknown, but SPS enhances glucocorticoid receptor (GR) expression in the hippocampus, which is critical for contextual modulation of extinction retrieval. Upregulation of GRs in extinction circuits may be a mechanism by which SPS induces extinction retention deficits, but this hypothesis has not been examined. In this study, we systematically altered the stressors that constitute SPS (i.e. r, fs, eth), generating a number of partial SPS (p-SPS) groups, and observed the effects SPS and p-SPSs had on extinction retention and GR levels in the hippocampus and prefrontal cortex (PFC). PFC GRs were assayed, because regions of the PFC are critical for maintaining extinction. We predicted that only exposure to full SPS would result in extinction retention deficits and enhance hippocampal and PFC GR levels. Only exposure to full SPS induced extinction retention deficits. Hippocampal and PFC GR expression was enhanced by SPS and most p-SPSs, however hippocampal GR expression was significantly larger following the full SPS exposure than all other conditions. Our findings suggest that the combined stressful effect of serial exposure to r, fs, and eth results in extinction retention deficits. The results also suggest that simple enhancements in GR expression in the hippocampus and PFC are insufficient to result in extinction retention deficits, but raise the possibility that a threshold-enhancement in hippocampal GR expression contributes to SPS-induced extinction retention deficits

  12. Pre-treatment Predictors of Dropout from Prolonged Exposure Therapy in Patients with Chronic Posttraumatic Stress Disorder and Comorbid Substance Use Disorders

    Science.gov (United States)

    Belleau, Emily L.; Chin, Eu Gene; Wanklyn, Sonya G.; Zambrano-Vazquez, Laura; Schumacher, Julie A.; Coffey, Scott F.

    2017-01-01

    Posttraumatic stress disorder (PTSD) and substance use disorders (SUDs) are commonly co-occurring disorders associated with more adverse consequences than PTSD alone. Prolonged exposure therapy (PE) is one of the most efficacious treatments for PTSD. However, among individuals with PTSD-SUD, 35–62% of individuals drop out of trauma-focused exposure treatments. Thus, it is important to identify predictors of PTSD treatment dropout among substance abusers with PTSD in order to gain information about adapting treatment strategies to enhance retention and outcomes. The current study explored pre-treatment predictors of early termination from PE treatment in a sample of 85 individuals receiving concurrent treatment for PTSD and a SUD in a residential treatment facility as part of a randomized controlled trial. The results indicated that less education and more anxiety sensitivity uniquely predicted PE treatment dropout. Demographic variables, PTSD severity, SUD severity, mental health comorbidities, and emotion regulation difficulties did not predict treatment dropout. These results suggest that adding pre-treatment interventions that address anxiety sensitivity, and promote social adjustment and cognitive flexibility, could possibly improve PE retention rates in clients with high anxiety or low education. PMID:28147254

  13. Protection of the public in situations of prolonged radiation exposure. The application of the Commission's system of radiological protection to controllable radiation exposure due to natural sources and long-lived radioactive residues.

    Science.gov (United States)

    1999-01-01

    This report provides guidance on the application of the ICRP system of radiological protection to prolonged exposure situations affecting members of the public. It addresses the general application of the Commission's system to the control of prolonged exposures resulting from practices and to the undertaking of interventions in prolonged exposure situations. Additionally, it provides recommendations on generic reference levels for such interventions. The report also considers some specific situations and discusses a number of issues that have been of concern, namely: natural radiation sources that may give rise to high doses; the restoration and rehabilitation of sites where human activities involving radioactive substances have been carried out; the return to 'normality' following an accident that has released radioactive substances to the environment; and the global marketing of commodities for public consumption that contain radioactive substances. Annexes provide some examples of prolonged exposure situations and discuss the radiological protection quantities, radiation-induced health effects and aspects of the Commission's system of radiological protection relevant to prolonged exposure. Quantitative recommendations for prolonged exposures are provided in the report. They must be interpreted with extreme caution; Chapters 4 and 5 stress the upper bound nature of the following values: Generic reference levels for intervention, in terms of existing total annual doses, are given as < approximately 100 mSv, above which intervention is almost always justifiable (situations for which the annual dose threshold for deterministic effects in relevant organs is exceeded will almost always require intervention), and < approximately 10 mSv, below which intervention is not likely to be justifiable (and above which it may be necessary). Intervention exemption levels for commodities, especially building materials, are expressed as an additional annual dose of approximately 1

  14. Prolonged Exposure: a Rapid Treatment for Phobias

    Science.gov (United States)

    Watson, J. P.; Gaind, R.; Marks, I. M.

    1971-01-01

    Ten adult patients with long-standing specific phobias were treated by prolonged continuous exposure to their phobic objects in fantasy and reality without avoidance. All patients were greatly helped by four to five hours' treatment in two or three sessions, and all improved more after practice than after imaginal sessions. The treatment method is more economical and efficient than other methods described so far. PMID:5539135

  15. Stress response in rat brain after different durations of noise exposure.

    Science.gov (United States)

    Samson, James; Sheeladevi, Rathinasamy; Ravindran, Rajan; Senthilvelan, Manohar

    2007-01-01

    The alteration in the levels of plasma corticosterone, brain norepinephrine (NE), and expression of brain heat shock proteins (Hsp70) after different durations of noise exposure (acute, 1 day; sub-acute, 15 days; chronic, 30 days) has been studied to analyze their role in combating time-dependent stress effects of noise. Broadband white noise (100dB) exposure to male Wistar albino rats significantly increased the levels of plasma corticosterone and NE in all three durations of noise exposure. The sustained increase observed in their levels in the chronic group suggests that animals are not getting adapted to noise even after 30 days of exposure. The important role of Hsp70 in combating noise induced stress is evident from the significant increase in its expression after chronic exposure, while there was a reciprocal decrease in the NE and corticosterone when compared with their levels after acute and sub-acute noise exposure. This clearly indicates that the time-dependent stress response to noise exposure is a complex mechanism involving highly interconnected systems such as hypothalamo-pituitary-adrenal (HPA) axis, heat shock proteins and may have serious implications in vital organs, particularly in the brain when there is a prolonged noise exposure.

  16. Repeated exposure to conditioned fear stress increases anxiety and delays sleep recovery following exposure to an acute traumatic stressor

    Directory of Open Access Journals (Sweden)

    Benjamin N Greenwood

    2014-10-01

    Full Text Available Repeated stressor exposure can sensitize physiological responses to novel stressors and facilitate the development of stress-related psychiatric disorders including anxiety. Disruptions in diurnal rhythms of sleep-wake behavior accompany stress-related psychiatric disorders and could contribute to their development. Complex stressors that include fear-eliciting stimuli can be a component of repeated stress experienced by humans, but whether exposure to repeated fear can prime the development of anxiety and sleep disturbances is unknown. In the current study, adult male F344 rats were exposed to either control conditions or repeated contextual fear conditioning for 22 days followed by exposure to either no, mild (10, or severe (100 acute uncontrollable tail shock stress. Exposure to acute stress produced anxiety-like behavior as measured by a reduction in juvenile social exploration and exaggerated shock-elicited freezing in a novel context. Prior exposure to repeated fear enhanced anxiety-like behavior as measured by shock-elicited freezing, but did not alter social exploratory behavior. The potentiation of anxiety produced by prior repeated fear was temporary; exaggerated fear was present 1 day but not 4 days following acute stress. Interestingly, exposure to acute stress reduced REM and NREM sleep during the hours immediately following acute stress. This initial reduction in sleep was followed by robust REM rebound and diurnal rhythm flattening of sleep / wake behavior. Prior repeated fear extended the acute stress-induced REM and NREM sleep loss, impaired REM rebound, and prolonged the flattening of the diurnal rhythm of NREM sleep following acute stressor exposure. These data suggest that impaired recovery of sleep / wake behavior following acute stress could contribute to the mechanisms by which a history of prior repeated stress increases vulnerability to subsequent novel stressors and stress-related disorders.

  17. Virtual reality exposure versus prolonged exposure for PTSD: Which treatment for whom?

    Science.gov (United States)

    Norr, Aaron M; Smolenski, Derek J; Katz, Andrea C; Rizzo, Albert A; Rothbaum, Barbara O; Difede, JoAnn; Koenen-Woods, Patricia; Reger, Mark A; Reger, Greg M

    2018-06-01

    The majority of studies comparing active psychological treatments for posttraumatic stress disorder (PTSD) do not find significant differences at posttreatment. This was the case in a recent trial examining prolonged exposure (PE) and virtual reality exposure (VRE) among active-duty soldiers with combat-related PTSD. Matching individual patients to specific treatments provides a potential avenue to improve significantly the public health impact of effective treatments for PTSD. A composite moderator approach was used to identify profiles of patients who would see superior PTSD symptom reduction in VRE or PE to inform future treatment matching. Active duty U.S. army soldiers (N = 108) were enrolled in a randomized clinical trial comparing VRE and PE in the treatment of PTSD stemming from deployments to Iraq or Afghanistan. Eighteen baseline variables were examined to identify treatment response heterogeneity in two patient groups: those with a superior response to PE and those with a superior response to VRE. The final composite moderator comprised four of 18 baseline variables. Results revealed that patients who were predicted to see greater PTSD symptom reduction in VRE were likely to be younger, not taking antidepressant medication, had greater PTSD hyperarousal symptoms, and were more likely to have greater than minimal suicide risk. Results suggest that treatment matching based on patient profiles could meaningfully improve treatment efficacy for combat-related PTSD. Future research can build on these results to improve our understanding of how to improve treatment matching for PTSD. © 2018 Wiley Periodicals, Inc.

  18. Binge-pattern cocaine administration causes long-lasting behavioral hyperarousal but does not enhance vulnerability to single prolonged stress in rats.

    Science.gov (United States)

    Lisieski, Michael J; Perrine, Shane A

    2017-11-01

    Cocaine use disorder and post-traumatic stress disorder (PTSD) commonly co-occur. This could be due to vulnerability to post-traumatic symptoms conferred by previous exposure to cocaine. Therefore, we combined chronic binge-pattern cocaine with a model of psychological trauma (single prolonged stress) to determine whether the behavioral effects of psychological trauma are enhanced in cocaine-sensitized individuals. Adult male Sprague Dawley rats received 14 days of cocaine (15mg/kg/injection) or saline in a binge pattern (3 injections per day, 1h apart). Seven days after the last injection animals were exposed to traumatic stress or a control procedure. Seven days after stress, activity and anxiety-like behaviors were measured. Binge-pattern cocaine increased locomotor activity in the open field and elevated plus maze, and both cocaine and SPS exposure increased the rapidity with which rats moved through grooming sequences. Neither binge-pattern cocaine nor SPS increased anxiety-like behaviors, and no interactions were found between binge-pattern cocaine exposure and SPS exposure. A behavioral phenotype categorization approach demonstrated that cocaine-exposed groups expressed a high incidence of hyperactivity-like symptoms. These results suggest that binge-pattern cocaine exposure causes a long-lasting hyper-exploratory phenotype but does not make individuals more vulnerable to a later traumatic stress exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Effect of prolonged exposure to low antigen concentration for sensitization

    International Nuclear Information System (INIS)

    Och, Francois M.M. van; Vandebriel, Rob J.; Jong, Wim H. de; Loveren, Henk van

    2003-01-01

    The local lymph node assay (LLNA) is an assay in mice to identify potential allergens. Compounds that do not induce a stimulation index (SI)≥3 are not considered sensitizers. Of the chemicals that do, the SI of 3 is used as a benchmark, and indicates the sensitizing potency of a chemical. Compared to the exposure duration of the LLNA (3 days), real life exposure often lasts for months or years. We therefore investigated whether prolonged exposure to sensitizers at concentrations that do not induce a SI≥3 in the LLNA, were able to surpass this threshold. Mice were treated for 2 months at 7-day intervals with a range of concentrations of the known allergens ethyl-p-aminobenzoate (benzocaine, BENZ), 2,4-dinitrochlorobenzene (DNCB), and tetramethyl thiuram disulfide (TMTD). Both proliferative activity and cytokine production were established at day 60. Neither BENZ nor TMTD showed a significant increase in the proliferation rate compared to vehicle controls. Only DNCB at concentrations originally above the EC 3 a significant increase in proliferation was seen after prolonged exposure. No significant effect on IFN-γ and IL-4 production was observed for all three compounds compared. These findings indicate that for classification of sensitizers the shorter exposure period employed in the standard LLNA is sufficient, and longer periods of exposure have no bearing on this classification

  20. The effect of shorter exposure versus prolonged exposure on treatment outcome in Tourette syndrome and chronic tic disorders - an open trial.

    Science.gov (United States)

    van de Griendt, Jolande M T M; van Dijk, Maarten K; Verdellen, Cara W J; Verbraak, Marc J P M

    2018-01-11

    Exposure and response prevention has shown to be an effective strategy and is considered a first-line intervention in the behavioural treatment of tic disorders. Prior research demonstrated significant tic reduction after 12 two hour sessions. In this open trial, the question is addressed whether, relative to these prolonged sessions, exposure sessions of shorter duration yield differential outcome for patients with tic disorders. A total of 29 patients diagnosed with Tourette syndrome (TS) or chronic tic disorder were treated with shorter exposure sessions (1 h), and these data were compared to the data from a study about prolonged exposure (2 h, n = 21). Outcome was measured by the Yale Global Tic Severity Scale (YGTSS). Results suggest that after taking the difference in illness duration between the two groups into account, the effectiveness of shorter exposure sessions is not inferior to that of prolonged exposure. Results suggest that treatment with shorter exposure might be more efficient and more patients can be reached. Future research is needed to gain more insight into the mechanisms underlying the efficacy of behavioural treatments for tics.

  1. A Comparison of Cognitive-Processing Therapy With Prolonged Exposure and a Waiting Condition for the Treatment of Chronic Posttraumatic Stress Disorder in Female Rape Victims

    Science.gov (United States)

    Resick, Patricia A.; Nishith, Pallavi; Weaver, Terri L.; Astin, Millie C.; Feuer, Catherine A.

    2010-01-01

    The purpose of this study was to compare cognitive-processing therapy (CPT) with prolonged exposure and a minimal attention condition (MA) for the treatment of posttraumatic stress disorder (PTSD) and depression. One hundred seventy-one female rape victims were randomized into 1 of the 3 conditions, and 121 completed treatment. Participants were assessed with the Clinician-Administered PTSD Scale, the PTSD Symptom Scale, the Structured Clinical Interview for DSM–IV, the Beck Depression Inventory, and the Trauma-Related Guilt Inventory. Independent assessments were made at pretreatment, posttreatment, and 3 and 9 months posttreatment. Analyses indicated that both treatments were highly efficacious and superior to MA. The 2 therapies had similar results except that CPT produced better scores on 2 of 4 guilt subscales. PMID:12182270

  2. Single Prolonged Stress Disrupts Retention of Extinguished Fear in Rats

    Science.gov (United States)

    Knox, Dayan; George, Sophie A.; Fitzpatrick, Christopher J.; Rabinak, Christine A.; Maren, Stephen; Liberzon, Israel

    2012-01-01

    Clinical research has linked post-traumatic stress disorder (PTSD) with deficits in fear extinction. However, it is not clear whether these deficits result from stress-related changes in the acquisition or retention of extinction or in the regulation of extinction memories by context, for example. In this study, we used the single prolonged stress…

  3. Reaction of chickens to graduated length of exposure to stress

    Science.gov (United States)

    Nvota, J.; Grom, A.; Faberova, A.

    1980-01-01

    The reactions of 60 day old chickens Arbor Acres 60 X Vantress to immobilization stress lasting 1/2, 1, 2, 4 hours and to application of ACTH, manifested by activity changes in the systems hypophysis-adrenal gland and hypophysis-thyroid gland were studied. The highest activity increase in the two neuro-endocrine systems of the chickens was found to occur after 1/2 hour exposure to stress. With prolonged stress the responses weakened and after 4 hours most of the values gradually regressed to their initial level. The responses of both systems were synchronized. Reactions of the chickens differed from those of laboratory rats in which an increased activity of the hypophysis-adrenal gland system coincided with attenuation of the hypophysis-thyroid gland system.

  4. Prolonged Particulate Hexavalent Chromium Exposure Suppresses Homologous Recombination Repair in Human Lung Cells.

    Science.gov (United States)

    Browning, Cynthia L; Qin, Qin; Kelly, Deborah F; Prakash, Rohit; Vanoli, Fabio; Jasin, Maria; Wise, John Pierce

    2016-09-01

    Genomic instability is one of the primary models of carcinogenesis and a feature of almost all cancers. Homologous recombination (HR) repair protects against genomic instability by maintaining high genomic fidelity during the repair of DNA double strand breaks. The defining step of HR repair is the formation of the Rad51 nucleofilament, which facilitates the search for a homologous sequence and invasion of the template DNA strand. Particulate hexavalent chromium (Cr(VI)), a human lung carcinogen, induces DNA double strand breaks and chromosome instability. Since the loss of HR repair increases Cr(VI)-induced chromosome instability, we investigated the effect of extended Cr(VI) exposure on HR repair. We show acute (24 h) Cr(VI) exposure induces a normal HR repair response. In contrast, prolonged (120 h) exposure to particulate Cr(VI) inhibited HR repair and Rad51 nucleofilament formation. Prolonged Cr(VI) exposure had a profound effect on Rad51, evidenced by reduced protein levels and Rad51 mislocalization to the cytoplasm. The response of proteins involved in Rad51 nuclear import and nucleofilament formation displayed varying responses to prolonged Cr(VI) exposure. BRCA2 formed nuclear foci after prolonged Cr(VI) exposure, while Rad51C foci formation was suppressed. These results suggest that particulate Cr(VI), a major chemical carcinogen, inhibits HR repair by targeting Rad51, causing DNA double strand breaks to be repaired by a low fidelity, Rad51-independent repair pathway. These results further enhance our understanding of the underlying mechanism of Cr(VI)-induced chromosome instability and thus, carcinogenesis. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Single-Prolonged Stress: A Review of Two Decades of Progress in a Rodent Model of Post-traumatic Stress Disorder

    Science.gov (United States)

    Lisieski, Michael J.; Eagle, Andrew L.; Conti, Alana C.; Liberzon, Israel; Perrine, Shane A.

    2018-01-01

    Post-traumatic stress disorder (PTSD) is a common, costly, and often debilitating psychiatric condition. However, the biological mechanisms underlying this disease are still largely unknown or poorly understood. Considerable evidence indicates that PTSD results from dysfunction in highly-conserved brain systems involved in stress, anxiety, fear, and reward. Pre-clinical models of traumatic stress exposure are critical in defining the neurobiological mechanisms of PTSD, which will ultimately aid in the development of new treatments for PTSD. Single prolonged stress (SPS) is a pre-clinical model that displays behavioral, molecular, and physiological alterations that recapitulate many of the same alterations observed in PTSD, illustrating its validity and giving it utility as a model for investigating post-traumatic adaptations and pre-trauma risk and protective factors. In this manuscript, we review the present state of research using the SPS model, with the goals of (1) describing the utility of the SPS model as a tool for investigating post-trauma adaptations, (2) relating findings using the SPS model to findings in patients with PTSD, and (3) indicating research gaps and strategies to address them in order to improve our understanding of the pathophysiology of PTSD. PMID:29867615

  6. Glucocorticoid augmentation of prolonged exposure therapy: rationale and case report

    Directory of Open Access Journals (Sweden)

    Laura Pratchett

    2010-12-01

    Full Text Available Rationale: Prolonged exposure (PE therapy has been found to reduce symptoms of posttraumatic stress disorder (PTSD; however, it is difficult for many patients to engage fully in the obligatory retelling of their traumatic experiences. This problem is compounded by the fact that habituation and cognitive restructuring – the main mechanisms through which PE is hypothesized to work – are not instantaneous processes, and often require several weeks before the distress associated with imaginal exposure abates. Case reports: Two cases are described that respectively illustrate the use of hydrocortisone and placebo, in combination with PE, for the treatment of combat-related PTSD. Based on known effects of glucocorticoids on learning and memory performance, we hypothesized that augmentation with hydrocortisone would improve the therapeutic effects of PE by hastening “new” learning and facilitating decreases in the emotional impact of fear memories during the course of treatment. The veteran receiving hydrocortisone augmentation of PE displayed an accelerated and ultimately greater decline in PTSD symptoms than the veteran receiving placebo. Conclusions: While no general conclusion can be derived from comparison of two patients, the findings are consistent with the rationale for augmentation. These case reports support the potential for an appropriately designed and powered clinical trial to examine the efficacy of glucocorticoids in augmenting the effects of psychotherapy for PTSD.

  7. Single prolonged stress impairs social and object novelty recognition in rats.

    Science.gov (United States)

    Eagle, Andrew L; Fitzpatrick, Chris J; Perrine, Shane A

    2013-11-01

    Posttraumatic stress disorder (PTSD) results from exposure to a traumatic event and manifests as re-experiencing, arousal, avoidance, and negative cognition/mood symptoms. Avoidant symptoms, as well as the newly defined negative cognitions/mood, are a serious complication leading to diminished interest in once important or positive activities, such as social interaction; however, the basis of these symptoms remains poorly understood. PTSD patients also exhibit impaired object and social recognition, which may underlie the avoidance and symptoms of negative cognition, such as social estrangement or diminished interest in activities. Previous studies have demonstrated that single prolonged stress (SPS), models PTSD phenotypes, including impairments in learning and memory. Therefore, it was hypothesized that SPS would impair social and object recognition memory. Male Sprague Dawley rats were exposed to SPS then tested in the social choice test (SCT) or novel object recognition test (NOR). These tests measure recognition of novelty over familiarity, a natural preference of rodents. Results show that SPS impaired preference for both social and object novelty. In addition, SPS impairment in social recognition may be caused by impaired behavioral flexibility, or an inability to shift behavior during the SCT. These results demonstrate that traumatic stress can impair social and object recognition memory, which may underlie certain avoidant symptoms or negative cognition in PTSD and be related to impaired behavioral flexibility. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Using the Single Prolonged Stress Model to Examine the Pathophysiology of PTSD

    Directory of Open Access Journals (Sweden)

    Rimenez R. Souza

    2017-09-01

    Full Text Available The endurance of memories of emotionally arousing events serves the adaptive role of minimizing future exposure to danger and reinforcing rewarding behaviors. However, following a traumatic event, a subset of individuals suffers from persistent pathological symptoms such as those seen in posttraumatic stress disorder (PTSD. Despite the availability of pharmacological treatments and evidence-based cognitive behavioral therapy, a considerable number of PTSD patients do not respond to the treatment, or show partial remission and relapse of the symptoms. In controlled laboratory studies, PTSD patients show deficient ability to extinguish conditioned fear. Failure to extinguish learned fear could be responsible for the persistence of PTSD symptoms such as elevated anxiety, arousal, and avoidance. It may also explain the high non-response and dropout rates seen during treatment. Animal models are useful for understanding the pathophysiology of the disorder and the development of new treatments. This review examines studies in a rodent model of PTSD with the goal of identifying behavioral and physiological factors that predispose individuals to PTSD symptoms. Single prolonged stress (SPS is a frequently used rat model of PTSD that involves exposure to several successive stressors. SPS rats show PTSD-like symptoms, including impaired extinction of conditioned fear. Since its development by the Liberzon lab in 1997, the SPS model has been referred to by more than 200 published papers. Here we consider the findings of these studies and unresolved questions that may be investigated using the model.

  9. Post-traumatic stress disorder after weaning from prolonged mechanical ventilation.

    Science.gov (United States)

    Jubran, Amal; Lawm, Gerald; Duffner, Lisa A; Collins, Eileen G; Lanuza, Dorothy M; Hoffman, Leslie A; Tobin, Martin J

    2010-12-01

    Weaning from prolonged mechanical ventilation may be associated with mental discomfort. It is not known whether such discomfort is linked with the development of post-traumatic stress disorder (PTSD). Accordingly, we investigated whether PTSD occurs in patients after weaning from prolonged ventilation. We also determined whether administering a questionnaire would identify patients at risk for developing PTSD. A prospective longitudinal study of patients transferred to a long-term acute-care hospital for weaning from prolonged ventilation was undertaken: 72 patients were studied 1 week after weaning, and 41 patients were studied again 3 months later. An experienced psychologist conducted a structured clinical interview 3 months after weaning to establish a diagnosis of PTSD. To assess for the presence of PTSD-related symptoms, the post-traumatic stress syndrome (PTSS-10) questionnaire was administered 1 week after weaning and 3 months later. The psychologist diagnosed PTSD in 12% of patients 3 months after ventilator weaning. Patients who developed PTSD were more likely to have a previous history of psychiatric disorders (P 20 one week after weaning reliably identified patients who were diagnosed with PTSD 3 months later: sensitivity 1.0; specificity 0.76; area under the receiver-operating characteristic curve 0.91. PTSD was diagnosed in 12% of patients who were weaned from prolonged ventilation. A PTSS-10 score >20 one week after weaning identified patients diagnosed with PTSD 3 months later. This finding suggests that a simple questionnaire administered before hospital discharge can identify patients at risk for developing PTSD.

  10. Prolonged particulate chromate exposure does not inhibit homologous recombination repair in North Atlantic right whale (Eubalaena glacialis) lung cells.

    Science.gov (United States)

    Browning, Cynthia L; Wise, Catherine F; Wise, John Pierce

    2017-09-15

    Chromosome instability is a common feature of cancers that forms due to the misrepair of DNA double strand breaks. Homologous recombination (HR) repair is a high fidelity DNA repair pathway that utilizes a homologous DNA sequence to accurately repair such damage and protect the genome. Prolonged exposure (>72h) to the human lung carcinogen, particulate hexavalent chromium (Cr(VI)), inhibits HR repair, resulting in increased chromosome instability in human cells. Comparative studies have shown acute Cr(VI) exposure induces less chromosome damage in whale cells than human cells, suggesting investigating the effect of this carcinogen in other species may inform efforts to prevent Cr(VI)-induced chromosome instability. Thus, the goal of this study was to determine the effect of prolonged Cr(VI) exposure on HR repair and clastogenesis in North Atlantic right whale (Eubalaena glacialis) lung cells. We show particulate Cr(VI) induces HR repair activity after both acute (24h) and prolonged (120h) exposure in North Atlantic right whale cells. Although the RAD51 response was lower following prolonged Cr(VI) exposure compared to acute exposure, the response was sufficient for HR repair to occur. In accordance with active HR repair, no increase in Cr(VI)-induced clastogenesis was observed with increased exposure time. These results suggest prolonged Cr(VI) exposure affects HR repair and genomic stability differently in whale and human lung cells. Future investigation of the differences in how human and whale cells respond to chemical carcinogens may provide valuable insight into mechanisms of preventing chemical carcinogenesis. Copyright © 2017. Published by Elsevier Inc.

  11. Treating posttraumatic stress disorder with MDMA-assisted psychotherapy: A preliminary meta-analysis and comparison to prolonged exposure therapy.

    Science.gov (United States)

    Amoroso, Timothy; Workman, Michael

    2016-07-01

    Since the wars in Iraq and Afghanistan, posttraumatic stress disorder (PTSD) has become a major area of research and development. The most widely accepted treatment for PTSD is prolonged exposure (PE) therapy, but for many patients it is intolerable or ineffective. ±3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy (MDMA-AP) has recently re-emerged as a new treatment option, with two clinical trials having been published and both producing promising results. However, these results have yet to be compared to existing treatments. The present paper seeks to bridge this gap in the literature. Often the statistical significance of clinical trials is overemphasized, while the magnitude of the treatment effects is overlooked. The current meta-analysis aims to provide a comparison of the cumulative effect size of the MDMA-AP studies with those of PE. Effect sizes were calculated for primary and secondary outcome measures in the MDMA-AP clinical trials and compared to those of a meta-analysis including several PE clinical trials. It was found that MDMA-AP had larger effect sizes in both clinician-observed outcomes than PE did (Hedges' g=1.17 vs. g=1.08, respectively) and patient self-report outcomes (Hedges' g=0.87 vs. g=0.77, respectively). The dropout rates of PE and MDMA-AP were also compared, revealing that MDMA-AP had a considerably lower percentage of patients dropping out than PE did. These results suggest that MDMA-AP offers a promising treatment for PTSD. © The Author(s) 2016.

  12. Prolonged cardiac effects of momentary assessed stressful events and worry episodes.

    Science.gov (United States)

    Pieper, Suzanne; Brosschot, Jos F; van der Leeden, Rien; Thayer, Julian F

    2010-07-01

    To test the hypothesize that increased heart rate (HR) and decreased heart rate variability (HRV) are not only due to concurrent stressful events and worries but also to stressors and worries occurring in the preceding hours or stressors anticipated to occur in the next hour. Worry was expected to mediate at least part of the prolonged effects of stressors. Ambulatory HR and HRV of 73 teachers were recorded for 4 days, during which the participants reported occurrence and duration of worry episodes and stressful events on an hourly basis, using computerized diaries. Multilevel regression models were used, accounting for effects of several biobehavioral variables. Stressful events were not associated with changes in HR or HRV. However, worry episodes had effects on concurrent HR and HRV (2.55 beats/minute; -5.76 milliseconds) and HR and HRV in the succeeding hour (3.05 beats/minute; -5.80 milliseconds) and 2 hours later (1.52 beats/minute; -3.14 milliseconds). These findings were independent of emotions, physical activity, posture, and other biobehavioral factors. Worry has effects on cardiac activity, and these effects were still visible after 2 hours. The latter finding suggests that a considerable part of prolonged activation may be induced by unconscious stress-related cognition.

  13. Prolonged exposure to particulate chromate inhibits RAD51 nuclear import mediator proteins.

    Science.gov (United States)

    Browning, Cynthia L; Wise, John Pierce

    2017-09-15

    Particulate hexavalent chromium (Cr(VI)) is a human lung carcinogen and a human health concern. The induction of structural chromosome instability is considered to be a driving mechanism of Cr(VI)-induced carcinogenesis. Homologous recombination repair protects against Cr(VI)-induced chromosome damage, due to its highly accurate repair of Cr(VI)-induced DNA double strand breaks. However, recent studies demonstrate Cr(VI) inhibits homologous recombination repair through the misregulation of RAD51. RAD51 is an essential protein in HR repair that facilitates the search for a homologous sequence. Recent studies show prolonged Cr(VI) exposure prevents proper RAD51 subcellular localization, causing it to accumulate in the cytoplasm. Since nuclear import of RAD51 is crucial to its function, this study investigated the effect of Cr(VI) on the RAD51 nuclear import mediators, RAD51C and BRCA2. We show acute (24h) Cr(VI) exposure induces the proper localization of RAD51C and BRCA2. In contrast, prolonged (120h) exposure increased the cytoplasmic localization of both proteins, although RAD51C localization was more severely impaired. These results correlate temporally with the previously reported Cr(VI)-induced RAD51 cytoplasmic accumulation. In addition, we found Cr(VI) does not inhibit interaction between RAD51 and its nuclear import mediators. Altogether, our results suggest prolonged Cr(VI) exposure inhibits the nuclear import of RAD51C, and to a lesser extent, BRCA2, which results in the cytoplasmic accumulation of RAD51. Cr(VI)-induced inhibition of nuclear import may play a key role in its carcinogenic mechanism since the nuclear import of many tumor suppressor proteins and DNA repair proteins is crucial to their function. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Towards an exposure-dependent model of post-traumatic stress: longitudinal course of post-traumatic stress symptomatology and functional impairment after the 2011 Oslo bombing.

    Science.gov (United States)

    Solberg, Ø; Birkeland, M S; Blix, I; Hansen, M B; Heir, T

    2016-11-01

    Our understanding of the dynamics of post-traumatic stress symptomatology and its link to functional impairment over time is limited. Post-traumatic stress symptomatology (Post-traumatic Checklist, PCL) was assessed three times in 1-year increments (T1, T2, T3) following the Oslo bombing of 22 July, 2011, in directly (n = 257) and indirectly exposed (n = 2223) government employees, together with demographics, measures of exposure and work and social adjustment. The dynamics of post-traumatic stress disorder symptom cluster interplay were examined within a structural equation modelling framework using a cross-lagged autoregressive panel model. Intrusions at T1 played a prominent role in predicting all symptom clusters at T2 for the directly exposed group, exhibiting especially strong cross-lagged relationships with avoidance and anxious arousal. For the indirectly exposed group, dysphoric arousal at T1 played the most prominent role in predicting all symptom clusters at T2, exhibiting a strong relationship with emotional numbing. Emotional numbing seemed to be the main driver behind prolonged stress at T3 for both groups. Functional impairment was predominately associated with dysphoric arousal and emotional numbing in both groups. For directly exposed individuals, memories of the traumatic incident and the following intrusions seem to drive their post-traumatic stress symptomatology. However, as these memories lose their potency over time, a sequela of dysphoric arousal and emotional numbing similar to the one reported by the indirectly exposed individuals seems to be the main driver for prolonged post-traumatic stress and functional impairment. Findings are discussed using contemporary models within an exposure-dependent perspective of post-traumatic stress.

  15. Previous Repeated Exposure to Food Limitation Enables Rats to Spare Lipid Stores during Prolonged Starvation.

    Science.gov (United States)

    McCue, Marshall D; Albach, Audrey; Salazar, Giovanni

    The risk of food limitation and, ultimately, starvation dates back to the dawn of heterotrophy in animals, yet starvation remains a major factor in the regulation of modern animal populations. Researchers studying starvation more than a century ago suggested that animals subjected to sublethal periods of food limitation are somehow more tolerant of subsequent starvation events. This possibility has received little attention over the past decades, yet it is highly relevant to modern science for two reasons. First, animals in natural populations are likely to be exposed to bouts of food limitation once or more before they face prolonged starvation, during which the risk of mortality becomes imminent. Second, our current approach to studying starvation physiology in the laboratory focuses on nourished animals with no previous exposure to nutritional stress. We examined the relationship between previous exposure to food limitation and potentially adaptive physiological responses to starvation in adult rats and found several significant differences. On two occasions, rats were fasted until they lost 20% of their body mass maintained lower body temperatures, and had presumably lower energy requirements when subjected to prolonged starvation than their naive cohort that never experienced food limitation. These rats that were trained in starvation also had lower plasma glucose set -points and reduced their reliance on endogenous lipid oxidation. These findings underscore (1) the need for biologists to revisit the classic hypothesis that animals can become habituated to starvation, using a modern set of research tools; and (2) the need to design controlled experiments of starvation physiology that more closely resemble the dynamic nature of food availability.

  16. Hormone supply of the organism in prolonged emotional stress

    Science.gov (United States)

    Amiragova, M. G.; Stulnikov, B. V.; Svirskaya, R. I.

    1980-01-01

    The effect of prolonged emotional stress of varying genesis on the hormonal function of the pancreas, thyroid gland, and adrenal cortex was studied. The amount of the hormonal secretion was found to depend on the type of adaptation activity and its duration. High secretion of the hormones observed outside the adaptation activity was examined as an index of the phase transition of defense reactions to the phase of overstress.

  17. Media Impacts on Women's Fertility Desires: A Prolonged Exposure Experiment.

    Science.gov (United States)

    Knobloch-Westerwick, Silvia; Willis, Laura E; Kennard, Ashley R

    2016-06-01

    Media exposure may have implications for family planning, a public health issue of key importance. Drawing on social comparison theory and social identity theory, a prolonged exposure experiment examined whether media portrayals of women's social roles affect fertility desires among 166 American, nonstudent, never married, childless women ages 21-35 years old. After sign-up and baseline sessions, participants viewed magazine pages five days in a row. Stimuli presented women in either mother/homemaker roles, beauty ideal roles, or professional roles. Three days later, participants again indicated their number of desired children and time planned until first birth. Exposure to mother/homemaker and beauty ideal portrayals increased the number of desired children across time. Exposure to professional portrayals increased the time planned until 1st birth compared to beauty ideal portrayals-this impact was partially mediated by a shift toward more progressive gender norms (per social identity theory) and assimilation (per social comparison theory).

  18. Stress Biology and Aging Mechanisms: Toward Understanding the Deep Connection Between Adaptation to Stress and Longevity

    OpenAIRE

    Epel, Elissa S.; Lithgow, Gordon J.

    2014-01-01

    The rate of biological aging is modulated in part by genes interacting with stressor exposures. Basic research has shown that exposure to short-term stress can strengthen cellular responses to stress (“hormetic stress”). Hormetic stress promotes longevity in part through enhanced activity of molecular chaperones and other defense mechanisms. In contrast, prolonged exposure to stress can overwhelm compensatory responses (“toxic stress”) and shorten lifespan. One key question is whether the str...

  19. Psychotropic Pharmacotherapy Associated With QT Prolongation Among Veterans With Posttraumatic Stress Disorder.

    Science.gov (United States)

    Stock, Eileen M; Zeber, John E; McNeal, Catherine J; Banchs, Javier E; Copeland, Laurel A

    2018-04-01

    In 2012, the Food and Drug Administration issued Drug Safety Communications on several drugs associated with QT prolongation and fatal ventricular arrhythmias. Among these was citalopram, a selective serotonin reuptake inhibitor (SSRI) approved for depression and commonly used for posttraumatic stress disorder (PTSD). Evaluation of the risk for QT prolongation among other psychotropic drugs for individuals with PTSD remains limited. Explore psychotropic drugs associated with QT prolongation among veterans with PTSD. Patients in the Veterans Health Administration in 2006-2009 with PTSD and QT prolongation (176 cases) were matched 1:4 on age, gender, visit date and setting, and physical comorbidity. Classification trees assessed QT prolongation risk among prescribed medications (n=880). Receipt of any drug with known risk of QT prolongation varied by group (23% QT cases vs 15% control, prisks included ziprasidone (3% vs 1%, p=0.02) and buspirone (6% vs 2%, p=0.01). Increased risk was not observed for the SSRIs, citalopram and fluoxetine. Classification trees found that sotalol and amitriptyline carried greater risk among cardiac patients and methadone, especially if prescribed with quetiapine, among noncardiac patients. Per adjusted survival model, patients with QT prolongation were at increased risk for death (hazard ratio=1.60; 95% CI=1.04-2.44). Decision models are particularly advantageous when exploring nonlinear relationships or nonadditive interactions. These findings may potentially affect clinical decision-making concerning treatment for PTSD. For patients at higher risk of QT prolongation, antidepressants other than amitriptyline should be considered. Medications for comorbid conditions should also be closely monitored for heightened QT prolongation risk.

  20. Long-term neuroendocrine and behavioural effects of a single exposure to stress in adult animals.

    Science.gov (United States)

    Armario, Antonio; Escorihuela, Rosa M; Nadal, Roser

    2008-08-01

    There is now considerable evidence for long-lasting sequels of stress. A single exposure to high intensity predominantly emotional stressors such as immobilisation in wooden-boards (IMO) induces long-term (days to weeks) desensitization of the hypothalamic-pituitary-adrenal (HPA) response to the same (homotypic) stressor, whereas the response to novel (heterotypic) stressors was enhanced. In addition, long-lasting changes in behaviour have been described after a single exposure to brief or more prolonged sessions of shocks, predator, predator odour, underwater stress or a combination of three stressors on 1 day. The most consistent changes are reduced entries into the open arms of the elevated plus-maze and enhanced acoustic startle response, both reflecting enhanced anxiety. However, it is unclear whether there is any relationship between the intensity of the stressors, as evaluated by the main physiological indexes of stress (e.g. HPA axis), the putative traumatic experience they represent and their long-term behavioural consequences. This is particularly critical when trying to model post-traumatic stress disorders (PTSD), which demands a great effort to validate such putative models.

  1. Decreased MORF leads to prolonged endoplasmic reticulum stress in periodontitis-associated chronic inflammation.

    Science.gov (United States)

    Xue, Peng; Li, Bei; An, Ying; Sun, Jin; He, Xiaoning; Hou, Rui; Dong, Guangying; Fei, Dongdong; Jin, Fang; Wang, Qintao; Jin, Yan

    2016-11-01

    The association between inflammation and endoplasmic reticulum (ER) stress has been described in many diseases. However, if and how chronic inflammation governs the unfolded protein response (UPR) and promotes ER homeostasis of chronic inflammatory disease remains elusive. In this study, chronic inflammation resulted in ER stress in mesenchymal stem cells in the setting of periodontitis. Long-term proinflammatory cytokines induced prolonged ER stress and decreased the osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Interestingly, we showed that chronic inflammation decreases the expression of lysine acetyltransferase 6B (KAT6B, also called MORF), a histone acetyltransferase, and causes the upregulation of a key UPR sensor, PERK, which lead to the persistent activation of the UPR in PDLSCs. Furthermore, we found that the activation of UPR mediated by MORF in chronic inflammation contributes to the PERK-related deterioration of the osteogenic differentiation of PDLSCs both in vivo and in vitro. Taken together, our results suggest that chronic inflammation compromises UPR function through MORF-mediated-PERK transcription, which is a previously unrecognized mechanism that contributes to impaired ER function, prolonged ER stress and defective osteogenic differentiation of PDLSCs in periodontitis.

  2. Glucocorticoid receptor activation is involved in producing abnormal phenotypes of single-prolonged stress rats: a putative post-traumatic stress disorder model.

    Science.gov (United States)

    Kohda, K; Harada, K; Kato, K; Hoshino, A; Motohashi, J; Yamaji, T; Morinobu, S; Matsuoka, N; Kato, N

    2007-08-10

    Post-traumatic stress disorder (PTSD) is a stress-related mental disorder caused by traumatic experience, and presents with characteristic symptoms, such as intrusive memories, a state of hyperarousal, and avoidance, that endure for years. Single-prolonged stress (SPS) is one of the animal models proposed for PTSD. Rats exposed to SPS showed enhanced inhibition of the hypothalamo-pituitary-adrenal (HPA) axis, which has been reliably reproduced in patients with PTSD, and increased expression of glucocorticoid receptor (GR) in the hippocampus. In this study, we characterized further neuroendocrinologic, behavioral and electrophysiological alterations in SPS rats. Plasma corticosterone recovered from an initial increase within a week, and gross histological changes and neuronal cell death were not observed in the hippocampus of the SPS rats. Behavioral analyses revealed that the SPS rats presented enhanced acoustic startle and impaired spatial memory that paralleled the deficits in hippocampal long-term potentiation (LTP) and depression. Contextual fear memory was enhanced in the rats 1 week after SPS exposure, whereas LTP in the amygdala was blunted. Interestingly, blockade of GR activation by administering 17-beta-hydroxy-11-beta-/4-/[methyl]-[1-methylethyl]aminophenyl/-17-alpha-[prop-1-ynyl]estra-4-9-diene-3-one (RU40555), a GR antagonist, prior to SPS exposure prevented potentiation of fear conditioning and impairment of LTP in the CA1 region. Altogether, SPS caused a number of behavioral changes similar to those described in PTSD, which marks SPS as a putative PTSD model. The preventive effects of a GR antagonist suggested that GR activation might play a critical role in producing the altered behavior and neuronal function of SPS rats.

  3. Effect of prolonged stress on the adrenal hormones of individuals with irritable bowel syndrome.

    Science.gov (United States)

    Sugaya, Nagisa; Izawa, Shuhei; Saito, Keisuke; Shirotsuki, Kentaro; Nomura, Shinobu; Shimada, Hironori

    2015-01-01

    The purpose of this study was to investigate the effect of prolonged stress on the salivary adrenal hormones (cortisol, dehydroepiandrosterone [DHEA], DHEA-sulfate [DHEA-S]) of individuals with irritable bowel syndrome (IBS). The participants were female college students, including 10 with IBS and 16 without IBS (control group), who were scheduled for a 2-week teaching practice at a kindergarten. Participants were asked to collect saliva for determining adrenal hormones immediately and 30 min after awakening and before sleep, 2 weeks before the practice, the first week of the practice, the second week of the practice, and a few days after the practice. Regarding cortisol/DHEA ratio, significantly increased levels were found during the first week of the practice, and a significant interaction between group and time was found; the ratio at 30 min after awakening in the IBS group was higher than that in the control group. For the other adrenal hormone indexes, no significant differences due to the presence of IBS were found. Individuals with IBS showed an elevated cortisol/DHEA ratio after awakening compared with individuals without IBS, and the elevated ratio peaked under the prolonged stress. The present study suggests that the cortisol effect is dominant in individuals with IBS under prolonged stress.

  4. Dose formation and hematologic effects with prolonged internal exposure of rats by isotope 131I

    International Nuclear Information System (INIS)

    Sova, O.A.; Drozd, Yi.P.

    2013-01-01

    Processes in single dose formation and long-term domestic revenue 131 I in rats was investigated. Original method of estimating absorbed doses in hemacyte for macro-dosemeters indicators was proposed. Dose factors for hemacyte and the dynamics of the blood-forming organs doses for prolonged two cases of prolonged exposure was calculated. Hematologic effects were studied for two variants of entry of the isotope. Peculiarities of doses formation and identified hematological effects are discussed

  5. Prolonged non-metabolic heart rate variability reduction as a physiological marker of psychological stress in daily life

    NARCIS (Netherlands)

    Verkuil, B.; Brosschot, J.F.; Tollenaar, M.S.; Lane, R.D.; Thayer, J.F.

    2016-01-01

    BACKGROUND Prolonged cardiac activity that exceeds metabolic needs can be detrimental for somatic health. Psychological stress could result in such "additional cardiac activity." PURPOSE In this study, we examined whether prolonged additional reductions in heart rate variability (AddHRVr) can be

  6. Changes of the rats’ heart rate variability caused by chlorpromazine modulation of central noradrenergic neurotransmission during prolonged stress

    Directory of Open Access Journals (Sweden)

    O. Z. Мelnikova

    2012-03-01

    Full Text Available It’s established that under the prolonged stress there were changes of geometric and spectral indices of the rats’ heart rate variability (HRV, manifestations of which depended on duration of stressful factors acting and represented the stress reaction development from the stage of anxiety to the exhaustion phase. Application of chlorpromazine at the beginning and against the background of stress blocked the central alpha adrenoceptors and contributed to renewal of the most HRV indices into the limits of control values at the end of experiment. The results of research show that the modulation of functional state of central noradrenergic system plays a great role in the changes of HRV during prolonged stress.

  7. Antioxidative stress responses in the floating macrophyte Lemna minor L. with cylindrospermopsin exposure.

    Science.gov (United States)

    Flores-Rojas, Nelida Cecilia; Esterhuizen-Londt, Maranda; Pflugmacher, Stephan

    2015-12-01

    Cylindrospermopsin toxicity and oxidative stress have been examined in aquatic animals, however, only a few studies with aquatic plants have been conducted focusing on the potential for bioaccumulation of cylindrospermopsin. The oxidative stress effects caused by cylindrospermopsin on macrophytes have not yet been specifically studied. The oxidative stress response of Lemna minor L. with exposure to cylindrospermopsin, was therefore tested in this study. The hydrogen peroxide concentration together with the activities of the antioxidant enzymes (catalase, peroxidase, glutathione reductase and glutathione S-transferase) were determined after 24h (hours) of exposure to varying concentrations (0.025, 0.25, 2.5 and 25μg/L) of cylindrospermopsin. Responses with longer exposure periods (48, 96, 168h) were tested only with exposure to 2.5 and 25μg/L cylindrospermopsin. Additionally, the content of the carotenoids was determined as a possible non-enzymatic antioxidant defence mechanism against cylindrospermopsin. The levels of hydrogen peroxide increased after 24h even at the lowest cylindrospermopsin exposure concentrations. Catalase showed the most representative antioxidant response observed after 24h and maintained its activity throughout the experiment. Catalase activity corresponded with the contents of hydrogen peroxide at 2.5 and 25μg/L cylindrospermopsin. The data suggest that glutathione S-transferase, glutathione reductase and the carotenoid content act together with catalase but are more sensitive to higher concentrations of cylindrospermopsin and after a longer exposure period (168h). The results indicate that cylindrospermopsin promotes oxidative stress in L. minor at concentrations of 2.5 and 25μg/L. However, L. minor has sufficient defence mechanisms in place against this cyanobacterial toxin. Even though L. minor exhibits the potential to managing and control cylindrospermopsin contamination in aquatic systems, further studies in tolerance limits to

  8. Prolonged inorganic arsenite exposure suppresses insulin-stimulated AKT S473 phosphorylation and glucose uptake in 3T3-L1 adipocytes: involvement of the adaptive antioxidant response.

    Science.gov (United States)

    Xue, Peng; Hou, Yongyong; Zhang, Qiang; Woods, Courtney G; Yarborough, Kathy; Liu, Huiyu; Sun, Guifan; Andersen, Melvin E; Pi, Jingbo

    2011-04-08

    There is growing evidence that chronic exposure of humans to inorganic arsenic, a potent environmental oxidative stressor, is associated with the incidence of type 2 diabetes (T2D). One critical feature of T2D is insulin resistance in peripheral tissues, especially in mature adipocytes, the hallmark of which is decreased insulin-stimulated glucose uptake (ISGU). Despite the deleterious effects of reactive oxygen species (ROS), they have been recognized as a second messenger serving an intracellular signaling role for insulin action. Nuclear factor erythroid 2-related factor 2 (NRF2) is a central transcription factor regulating cellular adaptive response to oxidative stress. This study proposes that in response to arsenic exposure, the NRF2-mediated adaptive induction of endogenous antioxidant enzymes blunts insulin-stimulated ROS signaling and thus impairs ISGU. Exposure of differentiated 3T3-L1 cells to low-level (up to 2 μM) inorganic arsenite (iAs³(+)) led to decreased ISGU in a dose- and time-dependent manner. Concomitant to the impairment of ISGU, iAs³(+) exposure significantly attenuated insulin-stimulated intracellular ROS accumulation and AKT S473 phosphorylation, which could be attributed to the activation of NRF2 and induction of a battery of endogenous antioxidant enzymes. In addition, prolonged iAs³(+) exposure of 3T3-L1 adipocytes resulted in significant induction of inflammatory response genes and decreased expression of adipogenic genes and glucose transporter type 4 (GLUT4), suggesting chronic inflammation and reduction in GLUT4 expression may also be involved in arsenic-induced insulin resistance in adipocytes. Taken together our studies suggest that prolonged low-level iAs³(+) exposure activates the cellular adaptive oxidative stress response, which impairs insulin-stimulated ROS signaling that is involved in ISGU, and thus causes insulin resistance in adipocytes. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Short-term exposure to enriched environment rescues chronic stress-induced impaired hippocampal synaptic plasticity, anxiety, and memory deficits.

    Science.gov (United States)

    Bhagya, Venkanna Rao; Srikumar, Bettadapura N; Veena, Jayagopalan; Shankaranarayana Rao, Byrathnahalli S

    2017-08-01

    Exposure to prolonged stress results in structural and functional alterations in the hippocampus including reduced long-term potentiation (LTP), neurogenesis, spatial learning and working memory impairments, and enhanced anxiety-like behavior. On the other hand, enriched environment (EE) has beneficial effects on hippocampal structure and function, such as improved memory, increased hippocampal neurogenesis, and progressive synaptic plasticity. It is unclear whether exposure to short-term EE for 10 days can overcome restraint stress-induced cognitive deficits and impaired hippocampal plasticity. Consequently, the present study explored the beneficial effects of short-term EE on chronic stress-induced impaired LTP, working memory, and anxiety-like behavior. Male Wistar rats were subjected to chronic restraint stress (6 hr/day) over a period of 21 days, and then they were exposed to EE (6 hr/day) for 10 days. Restraint stress reduced hippocampal CA1-LTP, increased anxiety-like symptoms in elevated plus maze, and impaired working memory in T-maze task. Remarkably, EE facilitated hippocampal LTP, improved working memory performance, and completely overcame the effect of chronic stress on anxiety behavior. In conclusion, exposure to EE can bring out positive effects on synaptic plasticity in the hippocampus and thereby elicit its beneficial effects on cognitive functions. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Differential effects of controllable stress exposure on subsequent extinction learning in adult rats

    Directory of Open Access Journals (Sweden)

    Osnat eHadad-Ophir

    2016-01-01

    Full Text Available Deficits in fear extinction are thought to be related to various anxiety disorders. While failure to extinguish conditioned fear may result in pathological anxiety levels, the ability to quickly and efficiently attenuate learned fear through extinction processes can be extremely beneficial for the individual. One of the factors that may affect the efficiency of the extinction process is prior experience of stressful situations. In the current study, we examined whether exposure to controllable stress, which is suggested to induce stress resilience, can affect subsequent fear extinction. Here, following prolonged two-way shuttle (TWS avoidance training and a validation of acquired stress controllability, adult rats underwent either cued or contextual fear-conditioning (FC, followed by an extinction session. We further evaluated long lasting alterations of GABAergic targets in the medial pre-frontal cortex (mPFC, as these were implicated in FC and extinction and stress controllability. In cued, but not in contextual fear extinction, within-session extinction was enhanced following controllable stress compared to a control group. Interestingly, impaired extinction recall was detected in both extinction types following the stress procedure. Additionally, stress controllability-dependent alterations in GABAergic markers expression in infralimbic (IL, but not prelimbic (PL cortex, were detected. These alterations are proposed to be related to the within-session effect, but not the recall impairment. The results emphasize the contribution of prior experience on coping with subsequent stressful experiences. Moreover, the results emphasize that exposure to controllable stress does not generally facilitate future stress coping as previously claimed, but its effects are dependent on specific features of the events taking place.

  11. Subtleties in practical application of prolonged infusion of β-lactam antibiotics.

    Science.gov (United States)

    De Waele, Jan J; Lipman, Jeffrey; Carlier, Mieke; Roberts, Jason A

    2015-05-01

    Prolonged infusion (PI) of β-lactam antibiotics is increasingly used in order to optimise antibiotic exposure in critically ill patients. Physicians are often not aware of a number of subtleties that may jeopardise the treatment. In this clinically based paper, we stress pragmatic issues, such as the importance of a loading dose before PI, and discuss a number of important practicalities that are mandatory to benefit from the pharmacokinetic advantages of prolonged β-lactam antibiotic administration. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  12. Prolonged continuous exposure to high fine particulate matter associated with cardiovascular and respiratory disease mortality in Beijing, China

    Science.gov (United States)

    Wang, Jinfeng; Yin, Qian; Tong, Shilu; Ren, Zhoupeng; Hu, Maogui; Zhang, Hongrui

    2017-11-01

    Although many studies examined the effects of fine particulate matter (PM2.5) on the deaths of cardiovascular disease (CVD) and respiratory disease (RD), few research has paid attention to the effects of prolonged continuous exposure to high PM2.5 pollution. This study estimated the excess risks (ER) of CVD and RD mortalities associated with prolonged continuous exposure to high PM2.5 pollution for the whole population and specific subsociodemographic groups in Beijing, which is the capital city of China with over 20 million residents and having severe PM2.5 pollution problems. Our results suggested that when high PM2.5 pollution occurred continuously, at various thresholds and durations, the adverse effects on CVD and RD mortalities varied significantly. The CVD mortality risks in association with prolonged continuous high PM2.5 pollution exposure were more serious for single individuals (including unmarried, divorced, and widowed), illiterate and outdoor workers than for other specific subsociodemographic groups. When the daily PM2.5 concentration higher than 105 μg/m3 consecutively occurs, at the ninth day, the ERs of CVD death for single individuals, illiterate and outdoor workers groups reached to 45% (95% CI: 22, 71), 51% (95% CI: 28, 79) and 53% (95% CI: 29, 82) respectively. On the other hand, prolonged continuous high PM2.5 pollution level appeared to contribute a higher proportion of RD deaths among illiterate and outdoor workers, but less significant for the other specific subsociodemographic groups. When the duration with daily PM2.5 pollution higher than 115 μg/m3 reached to six days, the ERs for outdoor workers and illiterate attributed to prolonged continuous PM2.5 pollution exposure increased 36% (95% CI: 5, 76) and 49% (95% CI: 16, 91) respectively.

  13. Prolonged Exposure Therapy for a Vietnam Veteran with PTSD and Early-Stage Dementia

    Science.gov (United States)

    Duax, Jeanne M.; Waldron-Perrine, Brigid; Rauch, Sheila A. M.; Adams, Kenneth M.

    2013-01-01

    Although prolonged exposure therapy (PE) is considered an evidence-based treatment for PTSD, there has been little published about the use of this treatment for older adults with comorbid early-stage dementia. As the number of older adults in the United States continues to grow, so will their unique mental health needs. The present article…

  14. Effects of prolonged exposure to perchlorate on thyroid and reproductive function in zebrafish

    Science.gov (United States)

    Mukhi, S.; Patino, R.

    2007-01-01

    The objectives of this study were to determine the effects of prolonged exposure to perchlorate on (1) thyroid status and reproductive performance of adult zebrafish (Danio rerio) and (2) F1 embryo survival and early larval development. Using a static-renewal procedure, mixed sex populations of adult zebrafish were exposed to 0, 10, and 100 mg/l nominal concentrations of waterborne perchlorate for 10 weeks. Thyroid histology was qualitatively assessed, and females and males were separated and further exposed to their respective treatments for six additional weeks. Eight females in each tank replicate (n = 3) were paired weekly with four males from the same respective treatment, and packed-egg (spawn) volume (PEV) was measured each of the last five weeks. At least once during weeks 14-16 of exposure, other end points measured included fertilization rate, fertilized egg diameter, hatching rate, standard length, and craniofacial development of 4-day-postfertilization larvae and thyroid hormone content of 3.5-h embryos and of exposed mothers. At 10 weeks of exposure, perchlorate at both concentrations caused thyroidal hypertrophy and colloid depletion. A marked reduction in PEV was observed toward the end of the 6-week spawning period, but fertilization and embryo hatching rates were unaffected. Fertilized egg diameter and larval length were increased by parental exposure to perchlorate. Larval head depth was unaffected but the forward protrusion of the lower jaw-associated cartilage complexes, Meckel's and ceratohyal, was decreased. Exposure to both concentrations of perchlorate inhibited whole-body thyroxine content in mothers and embryos, but triiodothyronine content was unchanged. In conclusion, prolonged exposure of adult zebrafish to perchlorate not only disrupts their thyroid endocrine system but also impairs reproduction and influences early F1 development. ?? 2007 Oxford University Press.

  15. Separate and combined effects of exposure to heat stress and mental fatigue on endurance exercise capacity in the heat.

    Science.gov (United States)

    Otani, Hidenori; Kaya, Mitsuharu; Tamaki, Akira; Watson, Phillip

    2017-01-01

    This study investigated the effects of exposure to pre-exercise heat stress and mental fatigue on endurance exercise capacity in a hot environment. Eight volunteers completed four cycle exercise trials at 80% maximum oxygen uptake until exhaustion in an environmental chamber maintained at 30 °C and 50% relative humidity. The four trials required them to complete a 90 min pre-exercise routine of either a seated rest (CON), a prolonged demanding cognitive task to induce mental fatigue (MF), warm water immersion at 40 °C during the last 30 min to induce increasing core temperature (WI), or a prolonged demanding cognitive task and warm water immersion at 40 °C during the last 30 min (MF + WI). Core temperature when starting exercise was higher following warm water immersion (~38 °C; WI and MF + WI) than with no water immersion (~36.8 °C; CON and MF, P fatigue when commencing exercise was higher following cognitive task (MF and MF + WI) than with no cognitive task (CON and WI; P stress or mental fatigue, and this response is synergistically increased during combined exposure to them.

  16. Prolonged inorganic arsenite exposure suppresses insulin-stimulated AKT S473 phosphorylation and glucose uptake in 3T3-L1 adipocytes: Involvement of the adaptive antioxidant response

    International Nuclear Information System (INIS)

    Xue, Peng; Hou, Yongyong; Zhang, Qiang; Woods, Courtney G.; Yarborough, Kathy; Liu, Huiyu; Sun, Guifan; Andersen, Melvin E.; Pi, Jingbo

    2011-01-01

    Highlights: → In 3T3-L1 adipocytes iAs 3+ decreases insulin-stimulated glucose uptake. → iAs 3+ attenuates insulin-induced phosphorylation of AKT S473. → iAs 3+ activates the cellular adaptive oxidative stress response. → iAs 3+ impairs insulin-stimulated ROS signaling. → iAs 3+ decreases expression of adipogenic genes and GLUT4. -- Abstract: There is growing evidence that chronic exposure of humans to inorganic arsenic, a potent environmental oxidative stressor, is associated with the incidence of type 2 diabetes (T2D). One critical feature of T2D is insulin resistance in peripheral tissues, especially in mature adipocytes, the hallmark of which is decreased insulin-stimulated glucose uptake (ISGU). Despite the deleterious effects of reactive oxygen species (ROS), they have been recognized as a second messenger serving an intracellular signaling role for insulin action. Nuclear factor erythroid 2-related factor 2 (NRF2) is a central transcription factor regulating cellular adaptive response to oxidative stress. This study proposes that in response to arsenic exposure, the NRF2-mediated adaptive induction of endogenous antioxidant enzymes blunts insulin-stimulated ROS signaling and thus impairs ISGU. Exposure of differentiated 3T3-L1 cells to low-level (up to 2 μM) inorganic arsenite (iAs 3+ ) led to decreased ISGU in a dose- and time-dependent manner. Concomitant to the impairment of ISGU, iAs 3+ exposure significantly attenuated insulin-stimulated intracellular ROS accumulation and AKT S473 phosphorylation, which could be attributed to the activation of NRF2 and induction of a battery of endogenous antioxidant enzymes. In addition, prolonged iAs 3+ exposure of 3T3-L1 adipocytes resulted in significant induction of inflammatory response genes and decreased expression of adipogenic genes and glucose transporter type 4 (GLUT4), suggesting chronic inflammation and reduction in GLUT4 expression may also be involved in arsenic-induced insulin resistance in

  17. Prolonged inorganic arsenite exposure suppresses insulin-stimulated AKT S473 phosphorylation and glucose uptake in 3T3-L1 adipocytes: Involvement of the adaptive antioxidant response

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Peng [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); School of Public Health, China Medical University, Shenyang 110001 (China); Hou, Yongyong; Zhang, Qiang; Woods, Courtney G.; Yarborough, Kathy; Liu, Huiyu [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Sun, Guifan [School of Public Health, China Medical University, Shenyang 110001 (China); Andersen, Melvin E. [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Pi, Jingbo, E-mail: jpi@thehamner.org [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States)

    2011-04-08

    Highlights: {yields} In 3T3-L1 adipocytes iAs{sup 3+} decreases insulin-stimulated glucose uptake. {yields} iAs{sup 3+} attenuates insulin-induced phosphorylation of AKT S473. {yields} iAs{sup 3+} activates the cellular adaptive oxidative stress response. {yields} iAs{sup 3+} impairs insulin-stimulated ROS signaling. {yields} iAs{sup 3+} decreases expression of adipogenic genes and GLUT4. -- Abstract: There is growing evidence that chronic exposure of humans to inorganic arsenic, a potent environmental oxidative stressor, is associated with the incidence of type 2 diabetes (T2D). One critical feature of T2D is insulin resistance in peripheral tissues, especially in mature adipocytes, the hallmark of which is decreased insulin-stimulated glucose uptake (ISGU). Despite the deleterious effects of reactive oxygen species (ROS), they have been recognized as a second messenger serving an intracellular signaling role for insulin action. Nuclear factor erythroid 2-related factor 2 (NRF2) is a central transcription factor regulating cellular adaptive response to oxidative stress. This study proposes that in response to arsenic exposure, the NRF2-mediated adaptive induction of endogenous antioxidant enzymes blunts insulin-stimulated ROS signaling and thus impairs ISGU. Exposure of differentiated 3T3-L1 cells to low-level (up to 2 {mu}M) inorganic arsenite (iAs{sup 3+}) led to decreased ISGU in a dose- and time-dependent manner. Concomitant to the impairment of ISGU, iAs{sup 3+} exposure significantly attenuated insulin-stimulated intracellular ROS accumulation and AKT S473 phosphorylation, which could be attributed to the activation of NRF2 and induction of a battery of endogenous antioxidant enzymes. In addition, prolonged iAs{sup 3+} exposure of 3T3-L1 adipocytes resulted in significant induction of inflammatory response genes and decreased expression of adipogenic genes and glucose transporter type 4 (GLUT4), suggesting chronic inflammation and reduction in GLUT4

  18. Prolonged exposure therapy for the treatment of patients diagnosed with psychogenic non-epileptic seizures (PNES) and post-traumatic stress disorder (PTSD).

    Science.gov (United States)

    Myers, Lorna; Vaidya-Mathur, Urmi; Lancman, Marcelo

    2017-01-01

    Although there is general consensus that psychogenic non-epileptic seizures (PNES) are treated with psychotherapy, the effectiveness of most psychotherapeutic modalities remains understudied. In this treatment series of 16 patients dually diagnosed with PNES and post-traumatic stress disorder (PTSD), we evaluated the effect of prolonged exposure therapy (PE) on reduction of PNES. Secondary measures included Beck Depression Inventory (BDI-II) and Post-Traumatic Disorder Diagnostic Scale (PDS). Subjects diagnosed with video EEG-confirmed PNES and PTSD confirmed through neuropsychological testing and clinical interview were treated with traditional PE psychotherapy with certain modifications for the PNES. Treatment was conducted over the course of 12-15 weekly sessions. Seizure frequency was noted in each session by examining the patients' seizure logs, and mood and PTSD symptomatology was assessed at baseline and on the final session. Eighteen subjects enrolled, and 16 (88.8%) completed the course of treatment. Thirteen of the 16 (81.25%) therapy completers reported no seizures by their final PE session, and the other three reported a decline in seizure frequency (Z=-3.233, p=0.001). Mean scores on scales of depression (M=-13.56, SD=12.27; t (15)=-4.420, pPTSD symptoms (M=-17.1875, SD=13.01; t (15)=-5.281, pPTSD reduced the number of PNES and improved mood and post traumatic symptomatology. Follow-up revealed that gains made in seizure control on the last day of treatment were maintained over time. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Stress-related endocrinological and psychopathological effects of short- and long-term 50Hz electromagnetic field exposure in rats.

    Science.gov (United States)

    Szemerszky, Renáta; Zelena, Dóra; Barna, István; Bárdos, György

    2010-01-15

    It is believed that different electromagnetic fields do have beneficial and harmful biological effects. The aim of the present work was to study the long-term consequences of 50 Hz electromagnetic field (ELF-EMF) exposure with special focus on the development of chronic stress and stress-induced psychopathology. Adult male Sprague-Dawley rats were exposed to ELF-EMF (50 Hz, 0.5 mT) for 5 days, 8h daily (short) or for 4-6 weeks, 24h daily (long). Anxiety was studied in elevated plus maze test, whereas depression-like behavior of the long-treated group was examined in the forced swim test. Some days after behavioral examination, the animals were decapitated among resting conditions and organ weights, blood hormone levels as well as proopiomelanocortin mRNA level from the anterior lobe of the pituitary gland were measured. Both treatments were ineffective on somatic parameters, namely none of the changes characteristic to chronic stress (body weight reduction, thymus involution and adrenal gland hypertrophy) were present. An enhanced blood glucose level was found after prolonged ELF-EMF exposure (p=0.013). The hormonal stress reaction was similar in control and short-term exposed rats, but significant proopiomelanocortin elevation (pfloating time; p=0.006) were found following long-term ELF-EMF exposure. Taken together, long and continuous exposure to relatively high intensity electromagnetic field may count as a mild stress situation and could be a factor in the development of depressive state or metabolic disturbances. Although we should stress that the average intensity of the human exposure is normally much smaller than in the present experiment.

  20. In utero exposure to heat stress during late gestation has prolonged effects on the activity patterns and growth of dairy calves.

    Science.gov (United States)

    Laporta, J; Fabris, T F; Skibiel, A L; Powell, J L; Hayen, M J; Horvath, K; Miller-Cushon, E K; Dahl, G E

    2017-04-01

    Exposure to heat stress during late gestation exerts negative carryover effects on the postnatal performance of the calf. In this study, we evaluated the health, growth, and activity patterns of calves born to cows exposed to heat stress (HT, provided only shade, n = 31) or cooling (CL, fans, soakers, and shade, n = 29) during late gestation (∼46 d, maternal dry period). Calves' body weight, rectal temperature, suckling reflex, and movement scores were recorded at birth, and calves were fed 6.6 L of maternal colostrum in 2 meals. Blood samples were collected at birth (before feeding), 24 h after birth, and at d 10 and 28 of age. Calves were housed in individual pens, fed pasteurized milk (6 L/d), and had ad libitum access to grain and water until weaning (49 d). Activity was assessed during the first week of life (wk 1), at weaning (wk 7), and in the first week postweaning (wk 8) using electronic data loggers. Health and body weight were monitored weekly. At birth, calves born to CL cows were heavier (41.9 vs. 39.1 ± 0.8 kg), their temperature was lower (38.9 vs. 39.3 ± 0.08°C), and they were more efficient at absorbing IgG than HT calves. Suckling reflex and movement score at birth were not different between groups, but calves born to CL cows spent more time (50 min/d) standing in the first week of life as a result of longer standing bouts. In wk 7 and 8, calves born to CL cows had less frequent standing bouts than HT heifers, but CL heifers maintained greater total daily standing time (36 min/d) due to longer (7 min/bout) standing bouts. All calves were healthy, but HT heifers tended to have higher (looser) fecal scores on d 10. Heifers born from CL cows gained 0.2 kg/d more from birth to weaning, weighed 4 kg more at weaning, and had greater concentrations of IGF-1 than HT calves, particularly on d 28. In utero heat stress during late gestation had immediate and prolonged effects on passive immunity, growth, and activity patterns in dairy calves. Copyright

  1. Prolonged neuroinflammation after lipopolysaccharide exposure in aged rats.

    Directory of Open Access Journals (Sweden)

    Hui Qun Fu

    Full Text Available Inflammation is a hallmark of several disease states ranging from neurodegeneration to sepsis but is also implicated in physiological processes like ageing. Non-resolving inflammation and prolonged neuroinflammation are unclear processes implicated in several conditions, including ageing. In this study we studied the long-term effects of endotoxemia, as systemic lipopolysaccharide (LPS injection, focusing on the role of astrocyte activation and cytokine release in the brain of aged rats. A single dose of LPS (2 mg/kg or 0.9% saline was injected intraperitoneally in aged rats. Levels of pro-inflammatory cytokines (TNFα and IL-1β and NF-κB p65 activation were measured systemically and in hippocampal tissue. Astrocytes and cytokines release in the CNS were detected via double immunofluorescence staining at different time-points up to day 30. Serum levels of TNFα and IL-1β were significantly increased acutely after 30 minutes (p<0.001 and up to 6 hours (p<0.001 following LPS-injection. Centrally, LPS-treated rats showed up-regulated mRNA expression and protein levels of pro-inflammatory cytokines in the hippocampus. These changes associated with astrogliosis in the hippocampus dentate gyrus (DG, IL-1β immunoreactivity and elevated NF-κB p65 expression up to day 30 post LPS exposure. Overall, these data demonstrate that LPS induces prolonged neuroinflammation and astrocyte activation in the hippocampus of aged rats. Hippocampal NF-κB p65 and excessive astrocytes-derived IL-1β release may play a pivotal role in regulating long-lasting neuroinflammation.

  2. [Secondary traumatization/trauma among employees in palliative care units--the products of prolonged repeated exposure to suffering and death].

    Science.gov (United States)

    Samson, Tali; Shvartzman, Pesach

    2012-11-01

    The palliative care philosophy accepts the dying process as a natural phase in the life cycle and provides quality end of life care for terminal patients and their family members. Prolonged exposure to the physical symptoms and pain, as well as the psychological, spiritual, and existential suffering of the dying patient, may be fertile ground for the development of post-traumatic stress symptoms among palliative care teams. Work-related positive outcomes (such as compassion, satisfaction and meaning) and work-related negative outcomes (such as compassion fatigue, secondary traumatization and burnout) can exist side by side, and the unique balance between them will determine the quality of life of the worker. This review presents the current knowledge about the prevalence and causes of work-related stress outcomes among palliative care teams and measurement tools that are available. The literature review discusses secondary traumatization in palliative care teams and relevant messages for the development of treatment options, burnout prevention programs and support interventions for professionals who lead the care for terminal patients in Israel.

  3. Is Exposure Necessary? A Randomized Clinical Trial of Interpersonal Psychotherapy for PTSD

    Science.gov (United States)

    Markowitz, John C.; Petkova, Eva; Neria, Yuval; Van Meter, Page E.; Zhao, Yihong; Hembree, Elizabeth; Lovell, Karina; Biyanova, Tatyana; Marshall, Randall D.

    2015-01-01

    Background Exposure to trauma reminders has been considered imperative in psychotherapy for posttraumatic stress disorder (PTSD). No treatment benefits all patients, however. We tested Interpersonal Psychotherapy, which has demonstrated antidepressant efficacy and showed promise in pilot PTSD research, as a non-exposure-based, non-cognitive behavioral PTSD treatment. Methods A randomized, fourteen-week trial compared Interpersonal Psychotherapy; Prolonged Exposure, an exposure-based exemplar; and Relaxation Therapy, an active control psychotherapy. Subjects were 110 unmedicated patients having DSM-IV chronic PTSD and Clinician-Administered PTSD Scale (CAPS) score >50. Randomization stratified for comorbid major depression. We hypothesized Interpersonal Psychotherapy would be no more than minimally inferior (CAPS difference 30% CAPS improvement) were: Interpersonal Psychotherapy 63%, Prolonged Exposure 47%, Relaxation Therapy 38% (n.s.). Interpersonal psychotherapy and Prolonged Exposure CAPS outcome differed by 5.5 points (n.s.); the null hypothesis of more than minimal Interpersonal Psychotherapy inferiority was rejected (p=0.035). Patients with comorbid major depression dropped out from Prolonged Exposure nine times more than non-depressed Prolonged Exposure patients. Interpersonal Psychotherapy and Prolonged Exposure improved quality of life and social functioning more than Relaxation Therapy. Conclusions This first controlled study of individual Interpersonal Psychotherapy for PTSD demonstrated non-inferiority to the “gold standard” PTSD treatment. Interpersonal Psychotherapy had (non-significantly) lower attrition and higher response rates than Prolonged Exposure. Contradicting a widespread clinical belief, PTSD treatment may not require cognitive behavioral exposure to trauma reminders. Moreover, as differential therapeutics, patients with comorbid major depression may fare better in Interpersonal Psychotherapy than Prolonged Exposure. PMID:25677355

  4. Sequential Proximal Tibial Stress Fractures associated with Prolonged usage of Methotrexate and Corticosteroids: A Case Report

    Directory of Open Access Journals (Sweden)

    Tan TJL

    2015-11-01

    Full Text Available Stress fractures of the proximal tibia metaphysis are rare in the elderly. We present a case of a 65-year old male who developed sequential proximal tibia stress fractures associated with prolonged usage of methotrexate and prednisolone within a span of 18 months. Magnetic Resonance Imaging revealed an incomplete stress fracture involving the medial proximal tibial region. The patient was treated with stemmed total knee arthroplasty (TKA bilaterally. Stress fractures should be considered in patients with atypical knee pain who have a history of methotrexate and prednisolone usage. TKA is an effective treatment in stress fractures of the proximal tibia.

  5. Neural changes in extinction recall following prolonged exposure treatment for PTSD: A longitudinal fMRI study

    Directory of Open Access Journals (Sweden)

    Liat Helpman, PhD

    2016-01-01

    Conclusions: Prolonged exposure treatment appears to alter neural activation in PTSD patients during recall of fear extinction, and change in extinction recall (measured by SCR is associated with symptom reduction. We discuss results in the context of neural systems involved in response to affective stimuli.

  6. Effects of prolonged stress on salivary cortisol and dehydroepiandrosterone: a study of a two-week teaching practice.

    Science.gov (United States)

    Izawa, Shuhei; Saito, Keisuke; Shirotsuki, Kentaro; Sugaya, Nagisa; Nomura, Shinobu

    2012-06-01

    This study investigated variations in salivary levels of cortisol and dehydroepiandrosterone (DHEA) in a prolonged stressful situation (a two-week teaching practice). Thirty-three women for whom a two-week teaching practice at a kindergarten was scheduled were asked to collect saliva samples at awakening, 30 min after awakening, and bedtime at four time points: two weeks before the practice, the first week of the practice, the second week of the practice, and a few days after the practice. In addition, they completed questionnaires for assessing perceived stress and subjective moods on each day. A linear mixed model indicated that cortisol levels significantly increased during the first and second week of the practice compared with those before and after the practice period, and that DHEA levels significantly decreased after the practice period compared with those at the other time points. Further, cortisol awakening response after the practice period significantly reduced compared with that at the other time points. Scores of perceived stress and negative moods were also higher during the practice period. This study showed that prolonged stress affected cortisol and DHEA secretion during as well as after the stress period. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Chronic bronchiolitis in non-human primates after prolonged ozone exposure

    International Nuclear Information System (INIS)

    Eustis, S.L.

    1979-01-01

    Bonnet monkeys (Macaca radiata) were exposed to 0.0, 0.5, and 0.8 ppM ozone for 7, 28, or 90 consecutive d, eight h per d. Changes in the lung evoked by prolonged oxidant exposure were evaluated by light microscopy, scanning electron microscopy, transmission electron microscopy, autoradiography, and morphometry. Morphological changes were principally characterized as a low-grade chronic respiratory bronchiolitis. Proximal generations of respiratory bronchioles were the most consistently affected region of the pulmonary acinus. Major features of the bronchiolitis were intraluminal accumulations of macrophages and hypertrophy and hyperplasia of cuboidal bronchiolar epithelial cells. The degree of inflammation was greatest at the 0.8 ppM ozone concentration at each exposure period. The number of inflammatory cells observed at 90 d, however, was about one-half that observed at 7 d. Tritiated thymidine labeling and differential cell counts of respiratory bronchiolar epithelium demonstrated a proliferative response and an increase in the proportion of cubiodal bronchiolar cells which presumably function as the progenitor cell during cell renewal and repair of the epithelium. The labeling index remained elevated above control values through 90 d of ozone exposure despite a reduction below 7 d values at both 28 and 90 d. The epithelial hyperplasia persisted through 90 d at a level similar to but slightly above that present at 7 d. Since cell differentials remained shifted at 28 and 90 d, it appears that persistent ozone exposure delayed maturation and transformation of cubiodal bronchiolar cells to their mature phenotype

  8. Branched-chain amino acid supplementation reduces oxidative stress and prolongs survival in rats with advanced liver cirrhosis.

    Directory of Open Access Journals (Sweden)

    Motoh Iwasa

    Full Text Available Long-term supplementation with branched-chain amino acids (BCAA is associated with prolonged survival and decreased frequency of development of hepatocellular carcinoma (HCC in patients with liver cirrhosis. However, the pharmaceutical mechanism underlying this association is still unclear. We investigated whether continuous BCAA supplementation increases survival rate of rats exposed to a fibrogenic agent and influences the iron accumulation, oxidative stress, fibrosis, and gluconeogenesis in the liver. Further, the effects of BCAA on gluconeogenesis in cultured cells were also investigated. A significant improvement in cumulative survival was observed in BCAA-supplemented rats with advanced cirrhosis compared to untreated rats with cirrhosis (P<0.05. The prolonged survival due to BCAA supplementation was associated with reduction of iron contents, reactive oxygen species production and attenuated fibrosis in the liver. In addition, BCAA ameliorated glucose metabolism by forkhead box protein O1 pathway in the liver. BCAA prolongs survival in cirrhotic rats and this was likely the consequences of reduced iron accumulation, oxidative stress and fibrosis and improved glucose metabolism in the liver.

  9. Low lifetime stress exposure is associated with reduced stimulus–response memory

    Science.gov (United States)

    Goldfarb, Elizabeth V.; Shields, Grant S.; Daw, Nathaniel D.; Slavich, George M.; Phelps, Elizabeth A.

    2017-01-01

    Exposure to stress throughout life can cumulatively influence later health, even among young adults. The negative effects of high cumulative stress exposure are well-known, and a shift from episodic to stimulus–response memory has been proposed to underlie forms of psychopathology that are related to high lifetime stress. At the other extreme, effects of very low stress exposure are mixed, with some studies reporting that low stress leads to better outcomes, while others demonstrate that low stress is associated with diminished resilience and negative outcomes. However, the influence of very low lifetime stress exposure on episodic and stimulus–response memory is unknown. Here we use a lifetime stress assessment system (STRAIN) to assess cumulative lifetime stress exposure and measure memory performance in young adults reporting very low and moderate levels of lifetime stress exposure. Relative to moderate levels of stress, very low levels of lifetime stress were associated with reduced use and retention (24 h later) of stimulus–response (SR) associations, and a higher likelihood of using context memory. Further, computational modeling revealed that participants with low levels of stress exhibited worse expression of memory for SR associations than those with moderate stress. These results demonstrate that very low levels of stress exposure can have negative effects on cognition. PMID:28298555

  10. Prolonged Exposure Treatment of Chronic PTSD in Juvenile Sex Offenders: Promising Results from Two Case Studies

    Science.gov (United States)

    Hunter, John A.

    2010-01-01

    Prolonged exposure (PE) was used to treat chronic PTSD secondary to severe developmental trauma in two adolescent male sex offenders referred for residential sex offender treatment. Both youth were treatment resistant prior to initiation of PE and showed evidence of long-standing irritability and depression/anxiety. Clinical observation and…

  11. Potential Adverse Effects of Prolonged Sevoflurane Exposure on Developing Monkey Brain: From Abnormal Lipid Metabolism to Neuronal Damage.

    Science.gov (United States)

    Liu, Fang; Rainosek, Shuo W; Frisch-Daiello, Jessica L; Patterson, Tucker A; Paule, Merle G; Slikker, William; Wang, Cheng; Han, Xianlin

    2015-10-01

    Sevoflurane is a volatile anesthetic that has been widely used in general anesthesia, yet its safety in pediatric use is a public concern. This study sought to evaluate whether prolonged exposure of infant monkeys to a clinically relevant concentration of sevoflurane is associated with any adverse effects on the developing brain. Infant monkeys were exposed to 2.5% sevoflurane for 9 h, and frontal cortical tissues were harvested for DNA microarray, lipidomics, Luminex protein, and histological assays. DNA microarray analysis showed that sevoflurane exposure resulted in a broad identification of differentially expressed genes (DEGs) in the monkey brain. In general, these genes were associated with nervous system development, function, and neural cell viability. Notably, a number of DEGs were closely related to lipid metabolism. Lipidomic analysis demonstrated that critical lipid components, (eg, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol) were significantly downregulated by prolonged exposure of sevoflurane. Luminex protein analysis indicated abnormal levels of cytokines in sevoflurane-exposed brains. Consistently, Fluoro-Jade C staining revealed more degenerating neurons after sevoflurane exposure. These data demonstrate that a clinically relevant concentration of sevoflurane (2.5%) is capable of inducing and maintaining an effective surgical plane of anesthesia in the developing nonhuman primate and that a prolonged exposure of 9 h resulted in profound changes in gene expression, cytokine levels, lipid metabolism, and subsequently, neuronal damage. Generally, sevoflurane-induced neuronal damage was also associated with changes in lipid content, composition, or both; and specific lipid changes could provide insights into the molecular mechanism(s) underlying anesthetic-induced neurotoxicity and may be sensitive biomarkers for the early detection of anesthetic-induced neuronal damage. Published by Oxford University Press on behalf of the

  12. Suppression of endothelial t-PA expression by prolonged high laminar shear stress

    International Nuclear Information System (INIS)

    Ulfhammer, Erik; Carlstroem, Maria; Bergh, Niklas; Larsson, Pia; Karlsson, Lena; Jern, Sverker

    2009-01-01

    Primary hypertension is associated with an impaired capacity for acute release of endothelial tissue-type plasminogen activator (t-PA), which is an important local protective response to prevent thrombus extension. As hypertensive vascular remodeling potentially results in increased vascular wall shear stress, we investigated the impact of shear on regulation of t-PA. Cultured human endothelial cells were exposed to low (≤1.5 dyn/cm 2 ) or high (25 dyn/cm 2 ) laminar shear stress for up to 48 h in two different experimental models. Using real-time RT-PCR and ELISA, shear stress was observed to time and magnitude-dependently suppress t-PA transcript and protein secretion to approximately 30% of basal levels. Mechanistic experiments revealed reduced nuclear protein binding to the t-PA specific CRE element (EMSA) and an almost completely abrogated shear response with pharmacologic JNK inhibition. We conclude that prolonged high laminar shear stress suppresses endothelial t-PA expression and may therefore contribute to the enhanced risk of arterial thrombosis in hypertensive disease.

  13. Music exposure induced prolongation of cardiac allograft survival and generated regulatory CD4⁺ cells in mice.

    Science.gov (United States)

    Uchiyama, M; Jin, X; Zhang, Q; Amano, A; Watanabe, T; Niimi, M

    2012-05-01

    In clinical practice, music has been used to decrease stress, heart rate, and blood pressure and to provide a distraction from disease symptoms. We investigated sound effects on alloimmune responses in murine heart transplantation. Naïve and eardrum-ruptured CBA/N (CBA, H2(K)) underwent transplantation of a C57BL/6 (B6, H2(b)) heart and were exposed to 1 of 3 types of music-opera (La Traviata), classical (Mozart), and New Age (Enya)-or 1 of 6 different single sound frequencies for 7 days. An adoptive transfer study was performed to determine whether regulatory cells were generated in allograft recipients. Cell-proliferation, cytokine, and flow cytometry assessments were also performed. CBA recipients of a B6 graft exposed to opera and classical music had significantly prolonged allograft survival (median survival times [MSTs], 26.5 and 20 days, respectively), whereas those exposed to 6 single sound frequencies and New Age did not (MSTs, 7, 8, 9, 8, 8, 8, and 11 days, respectively). Untreated and eardrum-ruptured CBA rejected B6 grafts acutely (MSTs, 7 and 8.5 days, respectively). Adoptive transfer of whole splenocytes, CD4(+) cells, and CD4(+)CD25(+) cells from opera-exposed primary recipients resulted in significantly prolonged allograft survival in naive secondary recipients (MSTs, 36, 68, and >50 days, respectively). Cell-proliferation, interleukin (IL)-2 and interferon-γ were suppressed in opera-exposed mice, whereas IL-4 and IL-10 from opera-exposed recipients were up-regulated. Flow cytometry studies showed an increased CD4(+)CD25(+)Foxp3(+) cell population in splenocytes from opera-exposed mice. In conclusion, exposure to some types of music may induce prolonged survival of fully allogeneic cardiac allografts and generate CD4(+)CD25(+)Foxp3(+) regulatory cells. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Associations between Prolonged Grief Disorder, Depression, Posttraumatic Stress Disorder, and Anxiety in Rwandan Genocide Survivors

    Science.gov (United States)

    Schaal, Susanne; Dusingizemungu, Jean-Pierre; Jacob, Nadja; Neuner, Frank; Elbert, Thomas

    2012-01-01

    A number of studies have demonstrated that symptoms of prolonged grief disorder (PGD) represent a symptom cluster distinct from bereavement-related depression, anxiety, and posttraumatic stress disorder (PTSD). The aim of the present study was to confirm and extend these findings using the most recent criteria defining PGD. The authors interviewed…

  15. The Use of Dialectical Behavior Therapy and Prolonged Exposure to Treat Comorbid Dissociation and Self-Harm: The Case of a Client With Borderline Personality Disorder and Posttraumatic Stress Disorder.

    Science.gov (United States)

    Granato, Hollie F; Wilks, Chelsey R; Miga, Erin M; Korslund, Kathryn E; Linehan, Marsha M

    2015-08-01

    There is a high rate of comorbidity between borderline personality disorder (BPD) and posttraumatic stress disorder (PTSD; Pagura et al., 2010). Preliminary studies have evaluated the treatment of PTSD in a BPD population and found positive outcomes for the integration of dialectical behavior therapy (DBT) and prolonged exposure (PE). This case study illustrates the implementation of a PE protocol into standard DBT treatment, specifically focusing on the management of self-harm and severe dissociation for a client with co-occurring PTSD and BPD. The client entered into treatment with severe and persistent dissociation and a recent history of self-harm, and the case includes consideration of two separate pauses in PTSD treatment related to elevated dissociation and self-harm behaviors. The client successfully completed the DBT PE protocol and results indicate significant improvements in PTSD symptoms as well as outcomes related to self-harm and dissociation. These findings demonstrate the efficacy of combining DBT with PE for clients with comorbid BPD and PTSD and exemplify how complex clients with BPD who present with severe dissociation and self-harm behavior can safely and successfully receive treatment for PTSD. © 2015 Wiley Periodicals, Inc.

  16. Dynamic adaptation of cardiac baroreflex sensitivity to prolonged exposure to microgravity: data from a 16-day spaceflight

    NARCIS (Netherlands)

    Di Rienzo, Marco; Castiglioni, Paolo; Iellamo, Ferdinando; Volterrani, Maurizio; Pagani, Massimo; Mancia, Giuseppe; Karemaker, John M.; Parati, Gianfranco

    2008-01-01

    Di Rienzo M, Castiglioni P, Iellamo F, Volterrani M, Pagani M, Mancia G, Karemaker JM, Parati G. Dynamic adaptation of cardiac baroreflex sensitivity to prolonged exposure to microgravity: data from a 16-day spaceflight. J Appl Physiol 105: 1569-1575, 2008. First published August 28, 2008;

  17. Changes in negative cognitions mediate PTSD symptom reductions during client-centered therapy and prolonged exposure for adolescents.

    Science.gov (United States)

    McLean, Carmen P; Yeh, Rebecca; Rosenfield, David; Foa, Edna B

    2015-05-01

    To assess whether changes in negative trauma-related cognitions play an important role in reducing symptoms of posttraumatic stress disorder (PTSD) and depression during prolonged exposure therapy for adolescents (PE-A). Secondary analysis of data from a randomized controlled trial comparing PE-A with client-centered therapy (CCT) for PTSD. Participants were 61 adolescent female sexual assault survivors ages 13-18 who received 8-14 weekly sessions of PE-A or CCT at a community rape crisis center. PTSD severity was assessed at baseline, mid-treatment, post-treatment, and 3-months post-treatment. Participants also completed self-report measures of negative posttraumatic cognitions and depressive symptoms at the same assessment points. Cross lag panel mediation analyses showed that change in negative trauma-related cognitions mediated change in PTSD symptoms and depressive symptoms whereas change in PTSD and depressive symptoms did not mediate change in negative cognitions. Our findings support EPT and suggest that change in negative trauma-related cognitions is a mechanism of both PE-A and CCT. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Inhibiting corticosterone synthesis during fear memory formation exacerbates cued fear extinction memory deficits within the single prolonged stress model.

    Science.gov (United States)

    Keller, Samantha M; Schreiber, William B; Stanfield, Briana R; Knox, Dayan

    2015-01-01

    Using the single prolonged stress (SPS) animal model of post-traumatic stress disorder (PTSD), previous studies suggest that enhanced glucocorticoid receptor (GR) expression leads to cued fear extinction retention deficits. However, it is unknown how the endogenous ligand of GRs, corticosterone (CORT), may contribute to extinction retention deficits in the SPS model. Given that CORT synthesis during fear learning is critical for fear memory consolidation and SPS enhances GR expression, CORT synthesis during fear memory formation could strengthen fear memory in SPS rats by enhancing GR activation during fear learning. In turn, this could lead to cued fear extinction retention deficits. We tested the hypothesis that CORT synthesis during fear learning leads to cued fear extinction retention deficits in SPS rats by administering the CORT synthesis inhibitor metyrapone to SPS and control rats prior to fear conditioning, and observed the effect this had on extinction memory. Inhibiting CORT synthesis during fear memory formation in control rats tended to decrease cued freezing, though this effect never reached statistical significance. Contrary to our hypothesis, inhibiting CORT synthesis during fear memory formation disrupted extinction retention in SPS rats. This finding suggests that even though SPS exposure leads to cued fear extinction memory deficits, CORT synthesis during fear memory formation enhances extinction retention in SPS rats. This suggests that stress-induced CORT synthesis in previously stressed rats can be beneficial. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Biodiesel versus diesel exposure: Enhanced pulmonary inflammation, oxidative stress, and differential morphological changes in the mouse lung

    International Nuclear Information System (INIS)

    Yanamala, Naveena; Hatfield, Meghan K.; Farcas, Mariana T.; Schwegler-Berry, Diane; Hummer, Jon A.; Shurin, Michael R.; Birch, M. Eileen; Gutkin, Dmitriy W.; Kisin, Elena; Kagan, Valerian E.; Bugarski, Aleksandar D.; Shvedova, Anna A.

    2013-01-01

    The use of biodiesel (BD) or its blends with petroleum diesel (D) is considered to be a viable approach to reduce occupational and environmental exposures to particulate matter (PM). Due to its lower particulate mass emissions compared to D, use of BD is thought to alleviate adverse health effects. Considering BD fuel is mainly composed of unsaturated fatty acids, we hypothesize that BD exhaust particles could induce pronounced adverse outcomes, due to their ability to readily oxidize. The main objective of this study was to compare the effects of particles generated by engine fueled with neat BD and neat petroleum-based D. Biomarkers of tissue damage and inflammation were significantly elevated in lungs of mice exposed to BD particulates. Additionally, BD particulates caused a significant accumulation of oxidatively modified proteins and an increase in 4-hydroxynonenal. The up-regulation of inflammatory cytokines/chemokines/growth factors was higher in lungs upon BD particulate exposure. Histological evaluation of lung sections indicated presence of lymphocytic infiltrate and impaired clearance with prolonged retention of BD particulate in pigment laden macrophages. Taken together, these results clearly indicate that BD exhaust particles could exert more toxic effects compared to D. - Highlights: • Exposure of mice to BDPM caused higher pulmonary toxicity compared to DPM. • Oxidative stress and inflammation were higher in BD vs to D exposed mice. • Inflammatory lymphocyte infiltrates were seen only in lungs of mice exposed to BD. • Ineffective clearance, prolonged PM retention was present only after BD exposure

  20. Biodiesel versus diesel exposure: Enhanced pulmonary inflammation, oxidative stress, and differential morphological changes in the mouse lung

    Energy Technology Data Exchange (ETDEWEB)

    Yanamala, Naveena, E-mail: wqu1@cdc.gov [Pathology and Physiology Research Branch/NIOSH/CDC, Morgantown, WV 26505 (United States); Hatfield, Meghan K., E-mail: wla4@cdc.gov [Pathology and Physiology Research Branch/NIOSH/CDC, Morgantown, WV 26505 (United States); Farcas, Mariana T., E-mail: woe7@cdc.gov [Pathology and Physiology Research Branch/NIOSH/CDC, Morgantown, WV 26505 (United States); Schwegler-Berry, Diane [Pathology and Physiology Research Branch/NIOSH/CDC, Morgantown, WV 26505 (United States); Hummer, Jon A., E-mail: qzh3@cdc.gov [Office of Mine Safety and Health Research/NIOSH/CDC, Pittsburgh, PA 15236 (United States); Shurin, Michael R., E-mail: shurinmr@upmc.edu [Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Birch, M. Eileen, E-mail: mib2@cdc.gov [NIOSH/CDC, 4676 Columbia Parkway, Cincinnati, OH 45226 (United States); Gutkin, Dmitriy W., E-mail: dwgutkin@hotmail.com [Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Kisin, Elena, E-mail: edk8@cdc.gov [Pathology and Physiology Research Branch/NIOSH/CDC, Morgantown, WV 26505 (United States); Kagan, Valerian E., E-mail: kagan@pitt.edu [Department of Environmental and Occupational Health, University of Pittsburgh, PA (United States); Bugarski, Aleksandar D., E-mail: zjl1@cdc.gov [Office of Mine Safety and Health Research/NIOSH/CDC, Pittsburgh, PA 15236 (United States); Shvedova, Anna A., E-mail: ats1@cdc.gov [Pathology and Physiology Research Branch/NIOSH/CDC, Morgantown, WV 26505 (United States); Department Physiology and Pharmacology, WVU, Morgantown, WV 26505 (United States)

    2013-10-15

    The use of biodiesel (BD) or its blends with petroleum diesel (D) is considered to be a viable approach to reduce occupational and environmental exposures to particulate matter (PM). Due to its lower particulate mass emissions compared to D, use of BD is thought to alleviate adverse health effects. Considering BD fuel is mainly composed of unsaturated fatty acids, we hypothesize that BD exhaust particles could induce pronounced adverse outcomes, due to their ability to readily oxidize. The main objective of this study was to compare the effects of particles generated by engine fueled with neat BD and neat petroleum-based D. Biomarkers of tissue damage and inflammation were significantly elevated in lungs of mice exposed to BD particulates. Additionally, BD particulates caused a significant accumulation of oxidatively modified proteins and an increase in 4-hydroxynonenal. The up-regulation of inflammatory cytokines/chemokines/growth factors was higher in lungs upon BD particulate exposure. Histological evaluation of lung sections indicated presence of lymphocytic infiltrate and impaired clearance with prolonged retention of BD particulate in pigment laden macrophages. Taken together, these results clearly indicate that BD exhaust particles could exert more toxic effects compared to D. - Highlights: • Exposure of mice to BDPM caused higher pulmonary toxicity compared to DPM. • Oxidative stress and inflammation were higher in BD vs to D exposed mice. • Inflammatory lymphocyte infiltrates were seen only in lungs of mice exposed to BD. • Ineffective clearance, prolonged PM retention was present only after BD exposure.

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

    Science.gov (United States)

    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. Analysis of Oxidative Stress in Chronic Exposure to Petroleum Hydrocarbons in Karnataka, India

    Directory of Open Access Journals (Sweden)

    Suttur Malini

    2017-03-01

    Full Text Available Background:Several studies have reported the toxicological implications of inhalation of petroleum hydrocarbon fumes in animal models. But, there is certainly little or no documentation of the exposure to petroleum hydrocarbon fuel on oxidative stress levels in humans, unlike the pulmonary physiology. The present study was carried out to evaluate the effects of constituents of the hydrocarbon fuels on oxidative stress levels of the petrol fillers and tanker drivers. Methods: The study involved 165 males divided into three groups were the petrol fillers, tanker drivers and the controls. Case control data set was established wherein the control subjects are not exposed to hydrocarbon fuels with similar age. Serum samples of the subjects were collected and subjected for various biochemical assays. The enzymatic antioxidants such as superoxide dismutase, malondialdehyde a byproduct of lipid peroxidation and total antioxidant capacity of the individuals along with non-enzymatic antioxidant Vitamin A was estimated. Results: The results showed a no significant differences for age, body mass index, superoxide dismutase and levels of Malondialdehyde and total antioxidant capacity. But on the other hand, there is significant changes observed for total antioxidant capacity and vitamin A when exposed group is compared with control subject. Conclusion: It is evidential from the present study that prolonged exposure to petroleum hydrocarbon fumes leads to an increase in their oxidative stress in turn resulting broad spectrum of diseases. Hence, there is a raised need for public awareness about the health hazards in order to enable petrol attendants.

  3. Juvenile social defeat stress exposure persistently impairs social behaviors and neurogenesis.

    Science.gov (United States)

    Mouri, Akihiro; Ukai, Mayu; Uchida, Mizuki; Hasegawa, Sho; Taniguchi, Masayuki; Ito, Takahiro; Hida, Hirotake; Yoshimi, Akira; Yamada, Kiyofumi; Kunimoto, Shohko; Ozaki, Norio; Nabeshima, Toshitaka; Noda, Yukihiro

    2018-05-01

    Adverse juvenile experiences, including physical abuse, often have negative health consequences later in life. We investigated the influence of social defeat stress exposure as juveniles on neuropsychological behaviors, and the causal role of glucocorticoids in abnormal behaviors and impairment of neurogenesis in mice exposed to the stress. The juvenile (24-day-old) and adult (70-day-old) male C57BL/6J mice were exposed to social defeat stress induced by an aggressive ICR mouse. Social defeat stress exposure as juveniles, even for 1 day, induced persistent social avoidance to the unfamiliar ICR mouse in the social interaction test, but that was not observed in mice exposed to the stress as adults. Social avoidance by the stress exposure as juveniles for 10 consecutive days was observed, when the target mouse was not only unfamiliar ICR but also another C57BL/J mouse, but not an absent or an anesthetized ICR mouse. The stress exposure did not induce anxiety- and depression-like behaviors in spontaneous locomotor activity, elevated plus-maze test, marble-burying test, forced swimming test, or sucrose preference test. Serum corticosterone levels increased immediately after the stress exposure. The hippocampal neurogenesis was suppressed 1 day and 4 weeks after the stress exposure. Administration of mifepristone, a glucocorticoid receptor antagonist, prior to each stress exposure, blocked the persistent social avoidance and suppression of neurogenesis. In conclusion, social avoidance induced by social defeat stress exposure as juveniles are more persistent than that as adults. These social avoidances are associated with suppression of hippocampal neurogenesis via glucocorticoid receptors. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Effects of prolonged exposure to space flight factors for 175 days on lettuce seeds

    International Nuclear Information System (INIS)

    Nevzgodina, L.V.; Maximova, E.N.; Akatov, Yu.A.

    1981-01-01

    The effects of prolonged (up to 175 days) exposure of Lactuca sativa seeds to space flight factors, including primary cosmic radiation heavy ions have been studied. The data obtained evidence a significant fourfold increase of spontaneous mutagenesis in seeds both with regard to the total number of aberrant cells as well as the formation of single cells with multiple aberrations. Comparison of the present experiment with earlier works shows that the frequency of such aberrations increases with the duration of the flight

  5. Chronic restraint stress after injury and shock is associated with persistent anemia despite prolonged elevation in erythropoietin levels.

    Science.gov (United States)

    Bible, Letitia E; Pasupuleti, Latha V; Gore, Amy V; Sifri, Ziad C; Kannan, Kolenkode B; Mohr, Alicia M

    2015-07-01

    Following severe traumatic injury, critically ill patients have a prolonged hypercatacholamine state that is associated with bone marrow (BM) dysfunction and persistent anemia. However, current animal models of injury and shock result in a transient anemia. Daily restraint stress (chronic stress [CS]) has been shown to increase catecholamines. We hypothesize that adding CS following injury or injury and shock in rats will prolong the hypercatecholaminemia and prolong the initial anemia, despite elevated erythropoietin (EPO) levels. Male Sprague-Dawley rats (n = 6-8 per group) underwent lung contusion (LC) or combined LC/hemorrhagic shock (LCHS) followed by 6 days of CS. CS consisted of a 2-hour restraint period interrupted with repositioning and alarms every 30 minutes. At 7 days, urine was assessed for norepinephrine (NE) levels, blood for EPO and hemoglobin (Hgb), and BM for erythroid progenitor growth. Animals undergoing LC or combined LCHS predictably recovered by Day 7; urine NE, EPO, and Hgb levels were normal. The addition of CS to LC and LCHS models was associated with a significant elevation in NE on Day 6. The addition of CS to LC led to a persistent 20% to 25% decrease in the growth of BM hematopoietic progenitor cells. These findings were further exaggerated when CS was added following LCHS, resulting in a 20%q to 40% reduction in BM erythroid progenitor colony growth and a 20% decrease in Hgb when compared with LCHS alone. Exposing injured animals to CS results in prolonged elevation of NE and EPO, which is associated with worsening BM erythroid function and persistent anemia. Chronic restraint stress following injury and shock provides a clinically relevant model to further evaluate persistent injury-associated anemia seen in critically ill trauma patients. Furthermore, alleviating CS after severe injury is a potential therapeutic target to improve BM dysfunction and anemia.

  6. Endoplasmic reticulum stress-mediated neuronal apoptosis by acrylamide exposure

    Energy Technology Data Exchange (ETDEWEB)

    Komoike, Yuta, E-mail: komoike@research.twmu.ac.jp; Matsuoka, Masato, E-mail: matsuoka@research.twmu.ac.jp

    2016-11-01

    Acrylamide (AA) is a well-known neurotoxic compound in humans and experimental animals. However, intracellular stress signaling pathways responsible for the neurotoxicity of AA are still not clear. In this study, we explored the involvement of the endoplasmic reticulum (ER) stress response in AA-induced neuronal damage in vitro and in vivo. Exposure of SH-SY5Y human neuroblastoma cells to AA increased the levels of phosphorylated form of eukaryotic translation initiation factor 2α (eIF2α) and its downstream effector, activating transcription factor 4 (ATF4), indicating the induction of the unfolded protein response (UPR) by AA exposure. Furthermore, AA exposure increased the mRNA level of c/EBP homologous protein (CHOP), the ER stress-dependent apoptotic factor, and caused the accumulation of reactive oxygen species (ROS) in SH-SY5Y cells. Treatments of SH-SY5Y cells with the chemical chaperone, 4-phenylbutyric acid and the ROS scavenger, N-acetyl-cysteine reduced the AA-induced expression of ATF4 protein and CHOP mRNA, and resulted in the suppression of apoptosis. In addition, AA-induced eIF2α phosphorylation was also suppressed by NAC treatment. In consistent with in vitro study, exposure of zebrafish larvae at 6-day post fertilization to AA induced the expression of chop mRNA and apoptotic cell death in the brain, and also caused the disruption of brain structure. These findings suggest that AA exposure induces apoptotic neuronal cell death through the ER stress and subsequent eIF2α–ATF4–CHOP signaling cascade. The accumulation of ROS by AA exposure appears to be responsible for this ER stress-mediated apoptotic pathway. - Highlights: • Exposure of SH-SY5Y cells to AA activates the eIF2α–ATF4 pathway of the UPR. • Exposure of SH-SY5Y cells to AA induces the CHOP expression and apoptosis. • Exposure of zebrafish to AA induces the chop expression and apoptosis in the brain. • AA possibly induces apoptotic neuronal cell death through the ER

  7. Single prolonged stress effects on sensitization to cocaine and cocaine self-administration in rats.

    Science.gov (United States)

    Eagle, Andrew L; Singh, Robby; Kohler, Robert J; Friedman, Amy L; Liebowitz, Chelsea P; Galloway, Matthew P; Enman, Nicole M; Jutkiewicz, Emily M; Perrine, Shane A

    2015-05-01

    Posttraumatic stress disorder (PTSD) is often comorbid with substance use disorders (SUD). Single prolonged stress (SPS) is a well-validated rat model of PTSD that provides a framework to investigate drug-induced behaviors as a preclinical model of the comorbidity. We hypothesized that cocaine sensitization and self-administration would be increased following exposure to SPS. Male Sprague-Dawley rats were exposed to SPS or control treatment. After SPS, cocaine (0, 10 or 20 mg/kg, i.p.) was administered for 5 consecutive days and locomotor activity was measured. Another cohort was assessed for cocaine self-administration (0.1 or 0.32 mg/kg/i.v.) after SPS. Rats were tested for acquisition, extinction and cue-induced reinstatement behaviors. Control animals showed a dose-dependent increase in cocaine-induced locomotor activity after acute cocaine whereas SPS rats did not. Using a sub-threshold sensitization paradigm, control rats did not exhibit enhanced locomotor activity at Day 5 and therefore did not develop behavioral sensitization, as expected. However, compared to control rats on Day 5 the locomotor response to 20mg/kg repeated cocaine was greatly enhanced in SPS-treated rats, which exhibited enhanced cocaine locomotor sensitization. The effect of SPS on locomotor activity was unique in that SPS did not modify cocaine self-administration behaviors under a simple schedule of reinforcement. These data show that SPS differentially affects cocaine-mediated behaviors causing no effect to cocaine self-administration, under a simple schedule of reinforcement, but significantly augmenting cocaine locomotor sensitization. These results suggest that SPS shares common neurocircuitry with stimulant-induced plasticity, but dissociable from that underlying psychostimulant-induced reinforcement. Copyright © 2015. Published by Elsevier B.V.

  8. Contribution of Hippocampal 5-HT3 Receptors in Hippocampal Autophagy and Extinction of Conditioned Fear Responses after a Single Prolonged Stress Exposure in Rats.

    Science.gov (United States)

    Wu, Zhong-Min; Yang, Li-Hua; Cui, Rong; Ni, Gui-Lian; Wu, Feng-Tian; Liang, Yong

    2017-05-01

    One of the hypotheses about the pathogenesis of posttraumatic stress disorder (PTSD) is the dysfunction of serotonin (5-HT) neurotransmission. While certain 5-HT receptor subtypes are likely critical for the symptoms of PTSD, few studies have examined the role of 5-HT 3 receptor in the development of PTSD, even though 5-HT 3 receptor is critical for contextual fear extinction and anxiety-like behavior. Therefore, we hypothesized that stimulation of 5-HT 3 receptor in the dorsal hippocampus (DH) could prevent hippocampal autophagy and the development of PTSD-like behavior in animals. To this end, we infused SR57227, selective 5-HT 3 agonist, into the DH after a single prolonged stress (SPS) treatment in rats. Three weeks later, we evaluated the effects of this pharmacological treatment on anxiety-related behaviors and extinction of contextual fear memory. We also accessed hippocampal autophagy and the expression of 5-HT 3A subunit, Beclin-1, LC3-I, and LC3-II in the DH. We found that SPS treatment did not alter anxiety-related behaviors but prolonged the extinction of contextual fear memory, and such a behavioral phenomenon was correlated with increased hippocampal autophagy, decreased 5-HT 3A expression, and increased expression of Beclin-1 and LC3-II/LC3-I ratio in the DH. Furthermore, intraDH infusions of SR57227 dose-dependently promoted the extinction of contextual fear memory, prevented hippocampal autophagy, and decreased expression of Beclin-1 and LC3-II/LC3-I ratio in the DH. These results indicated that 5-HT 3 receptor in the hippocampus may play a critical role in the pathogenesis of hippocampal autophagy, and is likely involved in the pathophysiology of PTSD.

  9. Single-prolonged stress induces apoptosis in dorsal raphe nucleus in the rat model of posttraumatic stress disorder

    Directory of Open Access Journals (Sweden)

    Liu Dongjuan

    2012-11-01

    Full Text Available Abstract Introduction Post-traumatic stress disorder (PTSD is an anxiety disorder that develops after exposure to a life-threatening traumatic experience. Meta-analyses of the brainstem showed that midsagittal area of the pons was significantly reduced in patients with PTSD, suggesting a potential apoptosis in dorsal raphe nucleus after single-prolonged stress (SPS. The aim of this study is to investigate whether SPS induces apoptosis in dorsal raphe nucleus in PTSD rats, which may be a possible mechanism of reduced volume of pons and density of gray matter. Methods In this study, rats were randomly divided into 1d, 7d and 14d groups after SPS along with the control group. The apoptosis rate was determined using annexin V-FITC/PI double-labeled flow cytometry (FCM. Levels of Cytochrome c (Cyt-C was examined by Western blotting. Expression of Cyt-C on mitochondria in the dorsal raphe nucleus neuron was determined by enzymohistochemistry under transmission electron microscopy (TEM. The change of thiamine monophosphatase (TMP levels was assessed by enzymohistochemistry under light microscope and TEM. Morphological changes of the ultrastructure of the dorsal raphe nucleus neuron were determined by TEM. Results Apoptotic morphological alterations were observed in dorsal raphe nucleus neuron for all SPS-stimulate groups of rats. The apoptosis rates were significantly increased in dorsal raphe nucleus neuron of SPS rats, along with increased release of cytochrome c from the mitochondria into the cytoplasm, increased expression of Cyt-C and TMP levels in the cytoplasm, which reached to the peak of increase 7 days of SPS. Conclusions The results indicate that SPS induced Cyt-C released from mitochondria into cytosol and apoptosis in dorsal raphe nucleus neuron of rats. Increased TMP in cytoplasm facilitated the clearance of apoptotic cells. We propose that this presents one of the mechanisms that lead to reduced volume of pons and gray matter associated

  10. Pankiller effect of prolonged exposure to menadione on glioma cells: potentiation by vitamin C.

    Science.gov (United States)

    Vita, Marina F; Nagachar, Nivedita; Avramidis, Dimitrios; Delwar, Zahid M; Cruz, Mabel H; Siden, Åke; Paulsson, Kajsa M; Yakisich, Juan Sebastian

    2011-12-01

    Menadione (Vitamin K3) has anti-tumoral effects against a wide range of cancer cells. Its potential toxicity to normal cells and narrow therapeutic range limit its use as single agent but in combination with radiation or other anti-neoplastic agents can be of therapeutic use. In this paper, we first evaluated the early (within 3 h) effect of menadione on ongoing DNA replication. In normal rat cerebral cortex mini-units menadione showed an age dependent anti-proliferative effect. In tissue mini-units prepared from newborn rats, menadione inhibited ongoing DNA replication with an IC (50) of approximately 10 μM but 50 μM had no effect on mini-units from prepared adult rat tissue. The effect of short (72 h) and prolonged exposure (1-2 weeks) to menadione alone in the DBTRG.05MG human glioma cells line and in combination with vitamin C was studied. After short period of exposure data show that menadione alone or in combination with vitamin C provided similar concentration-response curves (and IC(50) values). Prolonged exposure to these drugs was evaluated by their ability to kill 100% of glioma cells and prevent regrowth when cells are re-incubated in drug-free media. In this long-term assay, menadione:vitamin C at a ratio 1:100 showed higher anti-proliferative activity when compared to each drug alone and allowed to reduce each drug concentration between 2.5 to 5-fold. Similar anti-proliferative effect was demonstrated in 8 patient derived glioblastoma cell cultures. Our data should be able to encourage further advanced studies on animal models to evaluate the potential use of this combination therapy for glioma treatment.

  11. ACTH, corticosterone, and beta-endorphin in rat blood plasma after prolonged immobilization stress

    Energy Technology Data Exchange (ETDEWEB)

    Kiyatkin, E.A.; Amiragova, M.G.; Kushlinskii, N.E.; Polyntsev, Yu. V.

    1986-01-01

    To assess functional relations between changes in ACTH, beta-endorphin (BE), and corticosterone (CS) levels, plasma concentrations of these hormones were studied in rats during the development of prolonged immobilization stress. Plasma hormone concentrations were determined by radioimmunoassay. The results were analyzed by standard statistical methods on a microcomputer. A particular feature about the kit used to determine BE was the presence of 50% cross-reactivity of the antiserum against beta-lipotrophin. To determine CS a highly specific antiserum produced by a laboratory was used.

  12. Branched-Chain Amino Acid Supplementation Reduces Oxidative Stress and Prolongs Survival in Rats with Advanced Liver Cirrhosis

    Science.gov (United States)

    Mifuji-Moroka, Rumi; Hara, Nagisa; Miyachi, Hirohide; Sugimoto, Ryosuke; Tanaka, Hideaki; Fujita, Naoki; Gabazza, Esteban C.; Takei, Yoshiyuki

    2013-01-01

    Long-term supplementation with branched-chain amino acids (BCAA) is associated with prolonged survival and decreased frequency of development of hepatocellular carcinoma (HCC) in patients with liver cirrhosis. However, the pharmaceutical mechanism underlying this association is still unclear. We investigated whether continuous BCAA supplementation increases survival rate of rats exposed to a fibrogenic agent and influences the iron accumulation, oxidative stress, fibrosis, and gluconeogenesis in the liver. Further, the effects of BCAA on gluconeogenesis in cultured cells were also investigated. A significant improvement in cumulative survival was observed in BCAA-supplemented rats with advanced cirrhosis compared to untreated rats with cirrhosis (PBCAA supplementation was associated with reduction of iron contents, reactive oxygen species production and attenuated fibrosis in the liver. In addition, BCAA ameliorated glucose metabolism by forkhead box protein O1 pathway in the liver. BCAA prolongs survival in cirrhotic rats and this was likely the consequences of reduced iron accumulation, oxidative stress and fibrosis and improved glucose metabolism in the liver. PMID:23936183

  13. Developmental Exposure to Mild Variable Stress: Adult ...

    Science.gov (United States)

    In utero exposure to mild variable stress has been reported to influence learning and memory formation in offspring. Our research aims to examine whether nonchemical environmental stressors will exacerbate effects to chemical exposure. This study utilized a varying stress paradigm to simulate human psychosocial stress incurred during and after pregnancy to identify phenotypic learning changes in adult offspring that are potential stress markers. We additionally wanted to compare these behavioral outcomes to rat performance induced by perinatal exposure to manganese (Mn), a neurotoxic environmental element, at 2 or 5 g/l in drinking water throughout gestation and lactation. Pregnant Long Evans rats were exposed to an unpredictable series of mild stressful events which had previously been shown to increase maternal corticosterone levels. Nonchemical stressors were presented from GD 13 through GD 21 and included varying noise, light, housing, and confinement during both sleep and wake cycles. A subgroup of offspring was also exposed to periods of maternal separation. Starting at PND 97 offspring were trained with a trace fear conditioning protocol whereby rats were exposed to a compound cue (light and tone) followed by 30 seconds (trace period) and a mild foot shock (1mA, 0.5 seconds). Five paired training sessions occurred on the first day. The following day, context and cue learning were assessed by measuring motor activity. Preliminary data suggests adu

  14. Daily propranolol prevents prolonged mobilization of hematopoietic progenitor cells in a rat model of lung contusion, hemorrhagic shock, and chronic stress.

    Science.gov (United States)

    Bible, Letitia E; Pasupuleti, Latha V; Gore, Amy V; Sifri, Ziad C; Kannan, Kolenkode B; Mohr, Alicia M

    2015-09-01

    Propranolol has been shown previously to decrease the mobilization of hematopoietic progenitor cells (HPCs) after acute injury in rodent models; however, this acute injury model does not reflect the prolonged period of critical illness after severe trauma. Using our novel lung contusion/hemorrhagic shock/chronic restraint stress model, we hypothesize that daily administration of propranolol will decrease prolonged mobilization of HPCs without worsening lung healing. Male Sprague-Dawley rats underwent 6 days of restraint stress after undergoing lung contusion or lung contusion/hemorrhagic shock. Restraint stress consisted of a daily 2-hour period of restraint interrupted every 30 minutes by alarms and repositioning. Each day after the period of restraint stress, the rats received intraperitoneal propranolol (10 mg/kg). On day 7, peripheral blood was analyzed for granulocyte-colony stimulating factor (G-CSF) and stromal cell-derived factor 1 via enzyme-linked immunosorbent assay and for mobilization of HPCs using c-kit and CD71 flow cytometry. The lungs were examined histologically to grade injury. Seven days after lung contusion and lung contusion/hemorrhagic shock, the addition of chronic restraint stress significantly increased the mobilization of HPC, which was associated with persistently increased levels of G-CSF and increased lung injury scores. The addition of propranolol to lung contusion/chronic restraint stress and lung contusion/hemorrhagic shock/chronic restraint stress models greatly decreased HPC mobilization and restored G-CSF levels to that of naïve animals without worsening lung injury scores. The daily administration of propranolol after both lung contusion and lung contusion/hemorrhagic shock subjected to chronic restraint stress decreased the prolonged mobilization of HPC from the bone marrow and decreased plasma G-CSF levels. Despite the decrease in mobilization of HPC, lung healing did not worsen. Alleviating chronic stress with propranolol

  15. Ability to Discriminate Between Sustainable and Unsustainable Heat Stress Exposures-Part 1: WBGT Exposure Limits.

    Science.gov (United States)

    Garzón-Villalba, Ximena P; Wu, Yougui; Ashley, Candi D; Bernard, Thomas E

    2017-07-01

    Heat stress exposure limits based on wet-bulb globe temperature (WBGT) were designed to limit exposures to those that could be sustained for an 8-h day using limited data from Lind in the 1960s. In general, Sustainable exposures are heat stress levels at which thermal equilibrium can be achieved, and Unsustainable exposures occur when there is a steady increase in core temperature. This paper addresses the ability of the ACGIH® Threshold Limit Value (TLV®) to differentiate between Sustainable and Unsustainable heat exposures, to propose alternative occupational exposure limits, and ask whether an adjustment for body surface area improves the exposure decision. Two progressive heat stress studies provided data on 176 trials with 352 pairs of Sustainable and Unsustainable exposures over a range of relative humidities and metabolic rates using 29 participants wearing woven cotton clothing. To assess the discrimination ability of the TLV, the exposure metric was the difference between the observed WBGT and the TLV adjusted for metabolic rate. Conditional logistic regression models and receiver operating characteristic curves (ROC) along with ROC's area under the curve (AUC) were used. Four alternative models for an occupational exposure limit were also developed and compared to the TLV. For the TLV, the odds ratio (OR) for Unsustainable was 2.5 per 1°C-WBGT [confidence interval (CI) 2.12-2.88]. The AUC for the TLV was 0.85 (CI 0.81-0.89). For the alternative models, the ORs were also about 2.5/°C-WBGT, with AUCs between 0.84 and 0.88, which were significantly different from the TLV's AUC but have little practical difference. This study (1) confirmed that the TLV is appropriate for heat stress screening; (2) demonstrated the TLV's discrimination accuracy with an ROC AUC of 0.85; and (3) established the OR of 2.5/°C-WBGT for unsustainable exposures. The TLV has high sensitivity, but its specificity is very low, which is protective. There were no important

  16. Effects of combined exposure to pyridostigmine bromide and shaker stress on acoustic startle response, pre-pulse inhibition and open field behavior in mice.

    Science.gov (United States)

    Dubovicky, M; Paton, S; Morris, M; Mach, M; Lucot, J B

    2007-01-01

    The present study investigated the effect of combined exposure of pyridostigmine bromide (PB) and chronic shaker stress on acoustic startle responses (ASR), pre-pulse inhibition (PPI) and open field behavior of adult C57BL/6J mice. PB (10 mg kg(-1) day(-1) for 7 days) or saline was administered subcutaneously using osmotic Alzet minipumps implanted under the skin on the back of the mice. At the same time, the mice were exposed to 7 days of intermittent shaker stress. They were tested for ASR (100 dB and 120 dB stimuli) and PPI (70 dB + 100 dB and 70 dB + 120 dB) in the acoustic startle monitor system. The mice were assessed during the shaker stress on days 2 and 7 and 7, 14, 21 and 28 days after discontinuation of treatment. Separate groups of mice were tested in the open field in 15 min sessions on days 1, 3 and 6 during shaker stress and PB treatment. Exposure of mice to PB resulted in an exaggerated ASR, reduced PPI and non-significant decrease in locomotor activity. These behavioral changes were apparent only during exposure to PB. Repeated shaker stress did not have any effect on sensorimotor functions or open field behavior of mice. There was no prolonged or delayed effect of PB and/or stress on individual behavioral variables. The study found C57BL/6J mice to be behaviorally sensitive to PB treatment. (c) 2007 John Wiley & Sons, Ltd.

  17. The effects of prolonged oral administration of the disinfectant calcium hypochlorite in Nigerian commercial cockerels

    Directory of Open Access Journals (Sweden)

    Temitayo O. Iji

    2013-11-01

    Full Text Available This study was designed to investigate the effects of prolonged oral administration of calcium hypochlorite in the drinking water of commercial cockerels. It was carried out in order to ascertain probable toxicity associated with prolonged exposure to calcium hypochlorite. Thirty-two healthy birds were used; they were grouped into four groups of eight. Group 1, which served as the control, received 10 mL/kg body weight of physiological saline. Groups 2, 3 and 4 received 0.0375 g, 0.375 g and 0.75 g of calcium hypochlorite per 10 litres of drinking water for six weeks respectively. Six weeks after the administration of calcium hypochlorite, blood was collected from the jugular vein to assess liver function, lipid profiles and for markers of oxidative stress. The results revealed a significant (p < 0.05 increase in alanine aminotransferase activity in a dose-dependent manner when compared with the control. Also, there was a significant (p < 0.05 increase in aspartate aminotransferase and alkaline phosphatase activity. Similarly, there was a significant (p < 0.05 increase in total cholesterol, triglycerides, high-density lipoprotein and low-density lipoprotein levels compared with the control. There was a significant increase in malondialdehyde and hydrogen peroxide generation with a concomitant significant (p < 0.05 decrease in serum glutathione level in a dose-dependent manner when compared with the control. In this study, calcium hypochloriteinduced hepatic damage via oxidative stress and decrease in antioxidant defense system was found. Therefore, prolonged exposure of chickens to calcium hypochlorite is potentially harmful.

  18. Exhaustion from prolonged gambling

    Directory of Open Access Journals (Sweden)

    Fatimah Lateef

    2013-01-01

    Full Text Available Complaints of fatigue and physical exhaustion are frequently seen in the acute medical setting, especially amongst athletes, army recruits and persons involved in strenuous and exertional physical activities. Stress-induced exhaustion, on the other hand, is less often seen, but can present with very similar symptoms to physical exhaustion. Recently, three patients were seen at the Department of Emergency Medicine, presenting with exhaustion from prolonged involvement in gambling activities. The cases serve to highlight some of the physical consequences of prolonged gambling.

  19. Chronic Stress and Glucocorticoids: From Neuronal Plasticity to Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Sheela Vyas

    2016-01-01

    Full Text Available Stress and stress hormones, glucocorticoids (GCs, exert widespread actions in central nervous system, ranging from the regulation of gene transcription, cellular signaling, modulation of synaptic structure, and transmission and glial function to behavior. Their actions are mediated by glucocorticoid and mineralocorticoid receptors which are nuclear receptors/transcription factors. While GCs primarily act to maintain homeostasis by inducing physiological and behavioral adaptation, prolonged exposure to stress and elevated GC levels may result in neuro- and psychopathology. There is now ample evidence for cause-effect relationships between prolonged stress, elevated GC levels, and cognitive and mood disorders while the evidence for a link between chronic stress/GC and neurodegenerative disorders such as Alzheimer’s (AD and Parkinson’s (PD diseases is growing. This brief review considers some of the cellular mechanisms through which stress and GC may contribute to the pathogenesis of AD and PD.

  20. Heterotrophic compensation: a possible mechanism for resilience of coral reefs to global warming or a sign of prolonged stress?

    Directory of Open Access Journals (Sweden)

    Adam D Hughes

    Full Text Available Thermally induced bleaching has caused a global decline in corals and the frequency of such bleaching events will increase. Thermal bleaching severely disrupts the trophic behaviour of the coral holobiont, reducing the photosynthetically derived energy available to the coral host. In the short term this reduction in energy transfer from endosymbiotic algae results in an energy deficit for the coral host. If the bleaching event is short-lived then the coral may survive this energy deficit by depleting its lipid reserves, or by increasing heterotrophic energy acquisition. We show for the first time that the coral animal is capable of increasing the amount of heterotrophic carbon incorporated into its tissues for almost a year following bleaching. This prolonged heterotrophic compensation could be a sign of resilience or prolonged stress. If the heterotrophic compensation is in fact an acclimatization response, then this physiological response could act as a buffer from future bleaching by providing sufficient heterotrophic energy to compensate for photoautotrophic energy losses during bleaching, and potentially minimizing the effect of subsequent elevated temperature stresses. However, if the elevated incorporation of zooplankton is a sign that the effects of bleaching continue to be stressful on the holobiont, even after 11 months of recovery, then this physiological response would indicate that complete coral recovery requires more than 11 months to achieve. If coral bleaching becomes an annual global phenomenon by mid-century, then present temporal refugia will not be sufficient to allow coral colonies to recover between bleaching events and coral reefs will become increasingly less resilient to future climate change. If, however, increasing their sequestration of zooplankton-derived nutrition into their tissues over prolonged periods of time is a compensating mechanism, the impacts of annual bleaching may be reduced. Thus, some coral species

  1. Better executive function under stress mitigates the effects of recent life stress exposure on health in young adults.

    Science.gov (United States)

    Shields, Grant S; Moons, Wesley G; Slavich, George M

    2017-01-01

    Executive function is a neuropsychological construct that enables controlled cognitive processing, which has been hypothesized to enhance individuals' resilience to stress. However, little empirical work has directly examined how executive function under different conditions mitigates the negative effects of stress exposure on health. To address this issue, we recruited 110 healthy young adults and assessed their recent life stress exposure, executive function in either a stressful or non-stressful context, and current health complaints. Based on existing research, we hypothesized that individuals exhibiting better executive function following a laboratory-based stressor (but not a control task) would demonstrate weaker associations between recent stress exposure and health because they perceived recent life stressors as being less severe. Consistent with this hypothesis, better executive function during acute stress, but not in the absence of stress, was associated with an attenuated link between participants' recent life stress exposure and their current health complaints. Moreover, this attenuating effect was mediated by lesser perceptions of stressor severity. Based on these data, we conclude that better executive function under stress is associated with fewer health complaints and that these effects may occur by reducing individuals' perceptions of stressor severity. The data thus suggest the possibility of reducing stress-related health problems by enhancing executive function.

  2. Monocyte Trafficking to the Brain with Stress and Inflammation: A Novel Axis of Immune-to-Brain Communication that Influences Mood and Behavior

    Directory of Open Access Journals (Sweden)

    Eric S Wohleb

    2015-01-01

    Full Text Available Psychological stressors cause physiological, immunological, and behavioral alterations in humans and rodents that can be maladaptive and negatively affect quality of life. Several lines of evidence indicate that psychological stress disrupts key functional interactions between the immune system and brain that ultimately affects mood and behavior. For example, activation of microglia, the resident innate immune cells of the brain, has been implicated as a key regulator of mood and behavior in the context of prolonged exposure to psychological stress. Emerging evidence implicates a novel neuroimmune circuit involving microglia activation and sympathetic outflow to the peripheral immune system that further reinforces stress-related behaviors by facilitating the recruitment of inflammatory monocytes to the brain. Evidence from various rodent models, including repeated social defeat (RSD, revealed that trafficking of monocytes to the brain promoted the establishment of anxiety-like behaviors following prolonged stress exposure. In addition, new evidence implicates monocyte trafficking from the spleen to the brain as key regulator of recurring anxiety following exposure to prolonged stress. The purpose of this review is to discuss mechanisms that cause stress-induced monocyte re-distribution in the brain and how dynamic interactions between microglia, endothelial cells, and brain macrophages lead to maladaptive behavioral responses.

  3. Integrating Dialectical Behavior Therapy and Prolonged Exposure to Treat Co-Occurring Borderline Personality Disorder and PTSD: Two Case Studies

    Science.gov (United States)

    Harned, Melanie S.; Linehan, Marsha M.

    2008-01-01

    Despite the high rate of trauma and PTSD among individuals with borderline personality disorder (BPD), no studies have specifically evaluated the treatment of PTSD in a BPD population. These case studies illustrate the use of a protocol based on prolonged exposure therapy that can be integrated into standard dialectical behavior therapy to treat…

  4. Stress biology and aging mechanisms: toward understanding the deep connection between adaptation to stress and longevity.

    Science.gov (United States)

    Epel, Elissa S; Lithgow, Gordon J

    2014-06-01

    The rate of biological aging is modulated in part by genes interacting with stressor exposures. Basic research has shown that exposure to short-term stress can strengthen cellular responses to stress ("hormetic stress"). Hormetic stress promotes longevity in part through enhanced activity of molecular chaperones and other defense mechanisms. In contrast, prolonged exposure to stress can overwhelm compensatory responses ("toxic stress") and shorten lifespan. One key question is whether the stressors that are well understood in basic models of aging can help us understand psychological stressors and human health. The psychological stress response promotes regulatory changes important in aging (e.g., increases in stress hormones, inflammation, oxidative stress, insulin). The negative effects of severe stress are well documented in humans. Potential positive effects of acute stress (stress resistance) are less studied, especially at the cellular level. Can stress resistance slow the rate of aging in humans, as it does in model organisms? If so, how can we promote stress resistance in humans? We urge a new research agenda embracing the continuum from cellular stress to psychological stress, using basic and human research in tandem. This will require interdisciplinary novel approaches that hold much promise for understanding and intervening in human chronic disease. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Low Lifetime Stress Exposure Is Associated with Reduced Stimulus-Response Memory

    Science.gov (United States)

    Goldfarb, Elizabeth V.; Shields, Grant S.; Daw, Nathaniel D.; Slavich, George M.; Phelps, Elizabeth A.

    2017-01-01

    Exposure to stress throughout life can cumulatively influence later health, even among young adults. The negative effects of high cumulative stress exposure are well-known, and a shift from episodic to stimulus-response memory has been proposed to underlie forms of psychopathology that are related to high lifetime stress. At the other extreme,…

  6. The effect of predator exposure and reproduction on oxidative stress parameters in the Catarina scallop Argopecten ventricosus.

    Science.gov (United States)

    Guerra, C; Zenteno-Savín, T; Maeda-Martínez, A N; Abele, D; Philipp, E E R

    2013-05-01

    Predation is known to impact growth and reproduction, and the physiological state of the prey, including its susceptibility to oxidative stress. In this study, we investigated how prolonged exposure to predators modulates tissue specific antioxidant defense and oxidative damage in the short-lived epibenthic scallop Argopecten ventricosus (2years maximum lifespan). Scallops that were experimentally exposed to predators had not only lower antioxidant capacities (superoxide dismutase and catalase), but also lower oxidative damage (protein carbonyls and TBARS=thiobarbituric acid reactive substances including lipid peroxides) in gills and mantle compared to individuals not exposed to predators. In contrast, oxidative damage in the swimming muscle was higher in predator-exposed scallops. When predator-exposed scallops were on the verge of spawning, levels of oxidative damage increased in gills and mantle in spite of a parallel increase in antioxidant defense in both tissues. Levels of oxidative damage increased also in the swimming muscle whereas muscle antioxidant capacities decreased. Interestingly, post-spawned scallops restored antioxidant capacities and oxidative damage to immature levels, suggesting they can recover from spawning-related oxidative stress. Our results show that predator exposure and gametogenesis modulate oxidative damage in a tissue specific manner and that high antioxidant capacities do not necessarily coincide with low oxidative damage. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Openness to experience and adapting to change: Cardiovascular stress habituation to change in acute stress exposure.

    Science.gov (United States)

    Ó Súilleabháin, Páraic S; Howard, Siobhán; Hughes, Brian M

    2018-05-01

    Underlying psychophysiological mechanisms of effect linking openness to experience to health outcomes, and particularly cardiovascular well-being, are unknown. This study examined the role of openness in the context of cardiovascular responsivity to acute psychological stress. Continuous cardiovascular response data were collected for 74 healthy young female adults across an experimental protocol, including differing counterbalanced acute stressors. Openness was measured via self-report questionnaire. Analysis of covariance revealed openness was associated with systolic blood pressure (SBP; p = .016), and diastolic blood pressure (DBP; p = .036) responsivity across the protocol. Openness was also associated with heart rate (HR) responding to the initial stress exposure (p = .044). Examination of cardiovascular adaptation revealed that higher openness was associated with significant SBP (p = .001), DBP (p = .009), and HR (p = .002) habituation in response to the second differing acute stress exposure. Taken together, the findings suggest persons higher in openness are characterized by an adaptive cardiovascular stress response profile within the context of changing acute stress exposures. This study is also the first to demonstrate individual differences in cardiovascular adaptation across a protocol consisting of differing stress exposures. More broadly, this research also suggests that future research may benefit from conceptualizing an adaptive fitness of openness within the context of change. In summary, the present study provides evidence that higher openness stimulates short-term stress responsivity, while ensuring cardiovascular habituation to change in stress across time. © 2017 Society for Psychophysiological Research.

  8. Different regional gray matter loss in recent onset PTSD and non PTSD after a single prolonged trauma exposure.

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    Yunchun Chen

    Full Text Available OBJECTIVE: Gray matter loss in the limbic structures was found in recent onset post traumatic stress disorder (PTSD patients. In the present study, we measured regional gray matter volume in trauma survivors to verify the hypothesis that stress may cause different regional gray matter loss in trauma survivors with and without recent onset PTSD. METHOD: High resolution T1-weighted magnetic resonance imaging (MRI were obtained from coal mine flood disaster survivors with (n = 10 and without (n = 10 recent onset PTSD and 20 no trauma exposed normal controls. The voxel-based morphometry (VBM method was used to measure the regional gray matter volume in three groups, the correlations of PTSD symptom severities with the gray matter volume in trauma survivors were also analyzed by multiple regression. RESULTS: Compared with normal controls, recent onset PTSD patients had smaller gray matter volume in left dorsal anterior cingulate cortex (ACC, and non PTSD subjects had smaller gray matter volume in the right pulvinar and left pallidum. The gray matter volume of the trauma survivors correlated negatively with CAPS scores in the right frontal lobe, left anterior and middle cingulate cortex, bilateral cuneus cortex, right middle occipital lobe, while in the recent onset PTSD, the gray matter volume correlated negatively with CAPS scores in bilateral superior medial frontal lobe and right ACC. CONCLUSION: The present study identified gray matter loss in different regions in recent onset PTSD and non PTSD after a single prolonged trauma exposure. The gray matter volume of left dorsal ACC associated with the development of PTSD, while the gray matter volume of right pulvinar and left pallidum associated with the response to the severe stress. The atrophy of the frontal and limbic cortices predicts the symptom severities of the PTSD.

  9. Mutant HFE H63D Protein Is Associated with Prolonged Endoplasmic Reticulum Stress and Increased Neuronal Vulnerability*

    Science.gov (United States)

    Liu, Yiting; Lee, Sang Y.; Neely, Elizabeth; Nandar, Wint; Moyo, Mthabisi; Simmons, Zachary; Connor, James R.

    2011-01-01

    A specific polymorphism in the hemochromatosis (HFE) gene, H63D, is over-represented in neurodegenerative disorders such as amyotrophic lateral sclerosis and Alzheimer disease. Mutations of HFE are best known as being associated with cellular iron overload, but the mechanism by which HFE H63D might increase the risk of neuron degeneration is unclear. Here, using an inducible expression cell model developed from a human neuronal cell line SH-SY5Y, we reported that the presence of the HFE H63D protein activated the unfolded protein response (UPR). This response was followed by a persistent endoplasmic reticulum (ER) stress, as the signals of UPR sensors attenuated and followed by up-regulation of caspase-3 cleavage and activity. Our in vitro findings were recapitulated in a transgenic mouse model carrying Hfe H67D, the mouse equivalent of the human H63D mutation. In this model, UPR activation was detected in the lumbar spinal cord at 6 months then declined at 12 months in association with increased caspase-3 cleavage. Moreover, upon the prolonged ER stress, the number of cells expressing HFE H63D in early apoptosis was increased moderately. Cell proliferation was decreased without increased cell death. Additionally, despite increased iron level in cells carrying HFE H63D, it appeared that ER stress was not responsive to the change of cellular iron status. Overall, our studies indicate that the HFE H63D mutant protein is associated with prolonged ER stress and chronically increased neuronal vulnerability. PMID:21349849

  10. Mixed chemical-induced oxidative stress in occupational exposure ...

    African Journals Online (AJOL)

    Mixed chemical-induced oxidative stress in occupational exposure in Nigerians. JI Anetor, SA Yaqub, GO Anetor, AC Nsonwu, FAA Adeniyi, S Fukushima. Abstract. Exposure to single chemicals and associated disorders in occupational environments has received significant attention. Understanding these events holds ...

  11. Oxidative stress in patients with type 1 diabetes mellitus: is it affected by a single bout of prolonged exercise?

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    Maria Pia Francescato

    Full Text Available Presently, no clear-cut guidelines are available to suggest the more appropriate physical activity for patients with type 1 diabetes mellitus due to paucity of experimental data obtained under patients' usual life conditions. Accordingly, we explored the oxidative stress levels associated with a prolonged moderate intensity, but fatiguing, exercise performed under usual therapy in patients with type 1 diabetes mellitus and matched healthy controls. Eight patients (4 men, 4 women; 49±11 years; Body Mass Index 25.0±3.2 kg·m(-2; HbA1c 57±10 mmol·mol(-1 and 14 controls (8 men, 6 women; 47±11 years; Body Mass Index 24.3±3.3 kg·m(-2 performed a 3-h walk at 30% of their heart rate reserve. Venous blood samples were obtained before and at the end of the exercise for clinical chemistry analysis and antioxidant capacity. Capillary blood samples were taken at the start and thereafter every 30 min to determine lipid peroxidation. Patients showed higher oxidative stress values as compared to controls (95.9±9.7 vs. 74.1±12.2 mg·L(-1 H2O2; p<0.001. In both groups, oxidative stress remained constant throughout the exercise (p = NS, while oxidative defence increased significantly at the end of exercise (p<0.02 from 1.16±0.13 to 1.19±0.10 mmol·L(-1 Trolox in patients and from 1.09±0.21 to 1.22±0.14 mmol·L(-1 Trolox in controls, without any significant difference between the two groups. Oxidative stress was positively correlated to HbA1c (p<0.005 and negatively related with uric acid (p<0.005. In conclusion, we were the first to evaluate the oxidative stress in patients with type 1 diabetes exercising under their usual life conditions (i.e. usual therapy and diet. Specifically, we found that the oxidative stress was not exacerbated due to a single bout of prolonged moderate intensity aerobic exercise, a condition simulating several outdoor leisure time physical activities. Oxidative defence increased in both patients and controls, suggesting

  12. Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury

    Science.gov (United States)

    Azzam, Edouard I.; Jay-Gerin, Jean-Paul; Pain, Debkumar

    2013-01-01

    Cellular exposure to ionizing radiation leads to oxidizing events that alter atomic structure through direct interactions of radiation with target macromolecules or via products of water radiolysis. Further, the oxidative damage may spread from the targeted to neighboring, non-targeted bystander cells through redox-modulated intercellular communication mechanisms. To cope with the induced stress and the changes in the redox environment, organisms elicit transient responses at the molecular, cellular and tissue levels to counteract toxic effects of radiation. Metabolic pathways are induced during and shortly after the exposure. Depending on radiation dose, dose-rate and quality, these protective mechanisms may or may not be sufficient to cope with the stress. When the harmful effects exceed those of homeostatic biochemical processes, induced biological changes persist and may be propagated to progeny cells. Physiological levels of reactive oxygen and nitrogen species play critical roles in many cellular functions. In irradiated cells, levels of these reactive species may be increased due to perturbations in oxidative metabolism and chronic inflammatory responses, thereby contributing to the long-term effects of exposure to ionizing radiation on genomic stability. Here, in addition to immediate biological effects of water radiolysis on DNA damage, we also discuss the role of mitochondria in the delayed outcomes of ionization radiation. Defects in mitochondrial functions lead to accelerated aging and numerous pathological conditions. Different types of radiation vary in their linear energy transfer (LET) properties, and we discuss their effects on various aspects of mitochondrial physiology. These include short and long-term in vitro and in vivo effects on mitochondrial DNA, mitochondrial protein import and metabolic and antioxidant enzymes. PMID:22182453

  13. Heat shock and prolonged heat stress attenuate neurotoxin and sporulation gene expression in group I Clostridium botulinum strain ATCC 3502.

    Science.gov (United States)

    Selby, Katja; Mascher, Gerald; Somervuo, Panu; Lindström, Miia; Korkeala, Hannu

    2017-01-01

    Foodborne pathogenic bacteria are exposed to a number of environmental stresses during food processing, storage, and preparation, and in the human body. In order to improve the safety of food, the understanding of molecular stress response mechanisms foodborne pathogens employ is essential. Many response mechanisms that are activated during heat shock may cross-protect bacteria against other environmental stresses. To better understand the molecular mechanisms Clostridium botulinum, the causative agent of botulism, utilizes during acute heat stress and during adaptation to stressfully high temperature, the C. botulinum Group I strain ATCC 3502 was grown in continuous culture at 39°C and exposed to heat shock at 45°C, followed by prolonged heat stress at 45°C to allow adaptation of the culture to the high temperature. Growth in continuous culture was performed to exclude secondary growth phase effects or other environmental impacts on bacterial gene transcription. Changes in global gene expression profiles were studied using DNA microarray hybridization. During acute heat stress, Class I and III heat shock genes as well as members of the SOS regulon were activated. The neurotoxin gene botA and genes encoding the neurotoxin-associated proteins were suppressed throughout the study. Prolonged heat stress led to suppression of the sporulation machinery whereas genes related to chemotaxis and motility were activated. Induced expression of a large proportion of prophage genes was detected, suggesting an important role of acquired genes in the stress resistance of C. botulinum. Finally, changes in the expression of a large number of genes related to carbohydrate and amino acid metabolism indicated remodeling of the cellular metabolism.

  14. Perceived stress at work is associated with attenuated DHEA-S response during acute psychosocial stress.

    Science.gov (United States)

    Lennartsson, Anna-Karin; Theorell, Töres; Kushnir, Mark M; Bergquist, Jonas; Jonsdottir, Ingibjörg H

    2013-09-01

    Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) have been suggested to play a protective role during acute psychosocial stress, because they act as antagonists to the effects of the stress hormone cortisol. This study aims to investigate whether prolonged psychosocial stress, measured as perceived stress at work during the past week, is related to the capacity to produce DHEA and DHEA-S during acute psychosocial stress. It also aims to investigate whether prolonged perceived stress affects the balance between production of cortisol and DHEA-S during acute psychosocial stress. Thirty-six healthy subjects (19 men and 17 women, mean age 37 years, SD 5 years), were included. Perceived stress at work during the past week was measured by using the Stress-Energy (SE) Questionnaire. The participants were divided into three groups based on their mean scores; Low stress, Medium stress and High stress. The participants underwent the Trier Social Stress Test (TSST) and blood samples were collected before, directly after the stress test, and after 30 min of recovery. General Linear Models were used to investigate if the Medium stress group and the High stress group differ regarding stress response compared to the Low stress group. Higher perceived stress at work was associated with attenuated DHEA-S response during acute psychosocial stress. Furthermore, the ratio between the cortisol production and the DHEA-S production during the acute stress test were higher in individuals reporting higher perceived stress at work compared to individuals reporting low perceived stress at work. There was no statistical difference in DHEA response between the groups. This study shows that prolonged stress, measured as perceived stress at work during the past week, seems to negatively affect the capacity to produce DHEA-S during acute stress. Given the protective functions of DHEA-S, attenuated DHEA-S production during acute stress may lead to higher risk for adverse

  15. Exposure to stressors and trajectories of perceived stress among older adults.

    Science.gov (United States)

    Vasunilashorn, Sarinnapha; Lynch, Scott M; Glei, Dana A; Weinstein, Maxine; Goldman, Noreen

    2015-03-01

    Models of stress incorporate both the environmental demands experienced by individuals (stressors) and the appraisal of these life events (perceptions). Because little is known about the extent to which experience and perceptions are related, we examine this relationship in a nationally representative population of older Taiwanese adults. Using growth models applied to data from 3 waves (1999, 2003, and 2007) of the Taiwan Longitudinal Study of Aging, we (a) investigate patterns of change in perceived stress in later adulthood and (b) examine how experienced stressors influence perceived stress. Participants were asked to report the presence of, and in some cases the degree of, exposure to stressors including total number of medical conditions, difficulty with activities of daily living, difficulty with mobility functions, being financially worse off compared with the prior wave, experiencing the death of a child, and experiencing a marital disruption. Items reflecting perceived stress included concerns about various domains pertaining to the respondent and his/her family member. Our results indicate that exposure to stressors increases, whereas perceived stress decreases, over time. Change in exposure to stressors is not generally associated with change in perceptions of stress, with the exception of a summary measure of health-related exposure to stressors. An increase in poor health over time is related to an increase in perceived stress in all domains. The results underscore the importance of distinguishing between perceptions of stress and exposure to stressors when studying the links between stress and health among older adults. Furthermore, the diminishing linkage between experienced stressors and perceptions of stress suggests that older adults' appraisal may be an adaptive coping strategy that emerges to buffer some of the difficulties that are inevitable in later life. © The Author 2014. Published by Oxford University Press on behalf of The

  16. Global gradients of coral exposure to environmental stresses and implications for local management.

    Directory of Open Access Journals (Sweden)

    Joseph Maina

    Full Text Available BACKGROUND: The decline of coral reefs globally underscores the need for a spatial assessment of their exposure to multiple environmental stressors to estimate vulnerability and evaluate potential counter-measures. METHODOLOGY/PRINCIPAL FINDINGS: This study combined global spatial gradients of coral exposure to radiation stress factors (temperature, UV light and doldrums, stress-reinforcing factors (sedimentation and eutrophication, and stress-reducing factors (temperature variability and tidal amplitude to produce a global map of coral exposure and identify areas where exposure depends on factors that can be locally managed. A systems analytical approach was used to define interactions between radiation stress variables, stress reinforcing variables and stress reducing variables. Fuzzy logic and spatial ordinations were employed to quantify coral exposure to these stressors. Globally, corals are exposed to radiation and reinforcing stress, albeit with high spatial variability within regions. Based on ordination of exposure grades, regions group into two clusters. The first cluster was composed of severely exposed regions with high radiation and low reducing stress scores (South East Asia, Micronesia, Eastern Pacific and the central Indian Ocean or alternatively high reinforcing stress scores (the Middle East and the Western Australia. The second cluster was composed of moderately to highly exposed regions with moderate to high scores in both radiation and reducing factors (Caribbean, Great Barrier Reef (GBR, Central Pacific, Polynesia and the western Indian Ocean where the GBR was strongly associated with reinforcing stress. CONCLUSIONS/SIGNIFICANCE: Despite radiation stress being the most dominant stressor, the exposure of coral reefs could be reduced by locally managing chronic human impacts that act to reinforce radiation stress. Future research and management efforts should focus on incorporating the factors that mitigate the effect of

  17. Molecular basis for arsenic-Induced alteration in nitric oxide production and oxidative stress: implication of endothelial dysfunction

    International Nuclear Information System (INIS)

    Kumagai, Yoshito; Pi Jingbo

    2004-01-01

    Accumulated epidemiological studies have suggested that prolonged exposure of humans to arsenic in drinking water is associated with vascular diseases. The exact mechanism of how this occurs currently unknown. Nitric oxide (NO), formed by endothelial NO synthase (eNOS), plays a crucial role in the vascular system. Decreased availability of biologically active NO in the endothelium is implicated in the pathophysiology of several vascular diseases and inhibition of eNOS by arsenic is one of the proposed mechanism s for arsenic-induced vascular diseases. In addition, during exposure to arsenic, overproduction of reactive oxygen species (ROS) can occur, resulting in oxidative stress, which is another major risk factor for vascular dysfunction. The molecular basis for decreased NO levels and increased oxidative stress during arsenic exposure is poorly understood. In this article, evidence for arsenic-mediated alteration in NO production and oxidative stress is reviewed. The results of a cross-sectional study in an endemic area of chronic arsenic poisoning and experimental animal studies to elucidate a potential mechanism for the impairment of NO formation and oxidative stress caused by prolonged exposure to arsenate in the drinking water are also reviewed

  18. [Complex posttraumatic stress disorder].

    Science.gov (United States)

    Green, Tamar; Kotler, Moshe

    2007-11-01

    The characteristic symptoms resulting from exposure to an extreme trauma include three clusters of symptoms: persistent experience of the traumatic event, persistent avoidance of stimuli associated with the trauma and persistent symptoms of increased arousal. Beyond the accepted clusters of symptoms for posttraumatic stress disorder exists a formation of symptoms related to exposure to extreme or prolonged stress e.g. childhood abuse, physical violence, rape, and confinement within a concentration camp. With accumulated evidence of the existence of these symptoms began a trail to classify a more complex syndrome, which included, but was not confined to the symptoms of posttraumatic stress disorder. This review addresses several subjects for study in complex posttraumatic stress disorder, which is a complicated and controversial topic. Firstly, the concept of complex posttraumatic stress disorder is presented. Secondly, the professional literature relevant to this disturbance is reviewed and finally, the authors present the polemic being conducted between the researchers of posttraumatic disturbances regarding validity, reliability and the need for separate diagnosis for these symptoms.

  19. Oxidative stress in patients with type 1 diabetes mellitus: is it affected by a single bout of prolonged exercise?

    Science.gov (United States)

    Francescato, Maria Pia; Stel, Giuliana; Geat, Mario; Cauci, Sabina

    2014-01-01

    Presently, no clear-cut guidelines are available to suggest the more appropriate physical activity for patients with type 1 diabetes mellitus due to paucity of experimental data obtained under patients' usual life conditions. Accordingly, we explored the oxidative stress levels associated with a prolonged moderate intensity, but fatiguing, exercise performed under usual therapy in patients with type 1 diabetes mellitus and matched healthy controls. Eight patients (4 men, 4 women; 49±11 years; Body Mass Index 25.0±3.2 kg·m(-2); HbA1c 57±10 mmol·mol(-1)) and 14 controls (8 men, 6 women; 47±11 years; Body Mass Index 24.3±3.3 kg·m(-2)) performed a 3-h walk at 30% of their heart rate reserve. Venous blood samples were obtained before and at the end of the exercise for clinical chemistry analysis and antioxidant capacity. Capillary blood samples were taken at the start and thereafter every 30 min to determine lipid peroxidation. Patients showed higher oxidative stress values as compared to controls (95.9±9.7 vs. 74.1±12.2 mg·L(-1) H2O2; pexercise (p = NS), while oxidative defence increased significantly at the end of exercise (pdiabetes exercising under their usual life conditions (i.e. usual therapy and diet). Specifically, we found that the oxidative stress was not exacerbated due to a single bout of prolonged moderate intensity aerobic exercise, a condition simulating several outdoor leisure time physical activities. Oxidative defence increased in both patients and controls, suggesting beneficial effects of prolonged aerobic fatiguing exercise.

  20. Developmental Exposure to Mild Variable Stress: Adult Offspring Performance in Trace Fear Conditioning after Prenatal and Postnatal Stress

    Science.gov (United States)

    In utero exposure to mild variable stress has been reported to influence learning and memory formation in offspring. Our research aims to examine whether nonchemical environmental stressors will exacerbate effects to chemical exposure. This study utilized a varying stress parad...

  1. Physiologic response of rats to cold stress after exposure to 60-Hz electric fields

    International Nuclear Information System (INIS)

    Hilton, D.I.; Phillips, R.D.; Free, M.J.; Lang, L.L.; Chandon, J.H.; Kaune, W.T.

    1978-01-01

    In two experiments, the responses of the hypothalamo-pituitary-adrenal, thermoregulatory and cardiovascular systems were assessed in rats subjected to cold stress after exposure to uniform 60-Hz electric fields of 100 kV/m for one month. In the first experiment, plasma corticosterone levels were measured following exposure or sham exposure with the animals maintained at room temperature (∼23 deg). Corticosterone levels were also measured in rats subjected to cold stress (-13 deg. for one hour) immediately after the exposure period. Plasma corticosterone levels in the cold-stressed animals were significantly higher than in those kept at room temperature; however, there were no significant differences between exposed and sham-exposed animals for either the ambient or cold-stress situations. The second experiment followed the same field exposure and cold-stress protocol, only measurements of heart rate, deep colonic temperature and skin temperature were made before, during and after cold-stressing. The results for exposed and sham-exposed animals were essentially identical, failing to demonstrate any effect of electric field exposure on thermoregulatory and cardiovascular response to cold stress. (author)

  2. Feasibility and Efficacy of Prolonged Exposure for PTSD among Individuals with a Psychotic Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Anouk L. Grubaugh

    2017-06-01

    Full Text Available Objective: Few empirical studies have examined the feasibility of trauma-focused treatment among individuals with schizophrenia. This lack of research is important given the substantial overlap of trauma exposure and subsequent PTSD with psychotic spectrum disorders, and the potential for PTSD to complicate the course and prognosis of schizophrenia and other variants of severe mental illness.Method: As part of a larger study, 14 veterans with a psychotic spectrum disorder were enrolled to receive prolonged exposure (PE for PTSD within a single arm open trial study design. Patient reactions and responses to PE were examined using feasibility indices such as attrition, survey reactions, and treatment expectancy; pre and post-changes in PTSD severity and diagnostic status; and thematic interviews conducted post-intervention.Results: Quantitative and qualitative data indicate that implementation of PE is feasible, subjectively well-tolerated, and may result in clinically significant reductions in PTSD symptoms in patients with psychotic spectrum disorders.Conclusion: Consistent with treatment outcome data in clinical populations with a broader range of severe mental illnesses, the current results support the use of PTSD exposure-based interventions, such as PE, for individuals with psychotic spectrum disorders.

  3. Treatment of Posttraumatic Stress Disorder in Rape Victims: A Comparison between Cognitive-Behavioral Procedures and Counseling.

    Science.gov (United States)

    Foa, Edna B.; And Others

    1991-01-01

    Assigned 45 rape victims with posttraumatic stress disorder (PTSD) to stress inoculation training (SIT), prolonged exposure (PE), supportive counseling, or wait-list. All conditions produced improvements on PTSD symptoms, rape-related distress, general anxiety, and depression. SIT produced significantly more improvement on PTSD symptoms than did…

  4. Psychobiology of cumulative trauma: hair cortisol as a risk marker for stress exposure in women.

    Science.gov (United States)

    Morris, Matthew C; Abelson, James L; Mielock, Alyssa S; Rao, Uma

    2017-07-01

    Childhood trauma (CT) is associated with long-lasting alterations of the hypothalamic-pituitary-adrenal (HPA) axis and elevated risk for stress exposure in adulthood. Although HPA alterations are present in the early aftermath of trauma, it remains unclear how initial HPA activity is associated with subsequent stress exposure and whether CT exposure influences the strength and direction of this association. The present study examined prospective associations between hair cortisol content (HCC) and stress exposure from baseline to 3-month follow-up in young adult women with recent (i.e. past 3 months) exposure to interpersonal violence (IPV; i.e. physical or sexual assault) and non-traumatized controls. History of significant CT abuse or neglect was determined based on clinical cutoffs for a self-report CT measure: 12 women had abuse or neglect and recent IPV exposure (CT + IPV); 7 women had abuse or neglect but no IPV exposure (CT); 15 women had no history of trauma (NTC). HCC was computed for 3 cm sections reflecting cortisol secretion during the 3 months preceding the baseline assessment. The interaction of cumulative trauma and HCC predicted stress exposure over 3-month follow-up, controlling for baseline stress exposure and depressive symptoms. Simple slopes analyses revealed that lower baseline HCC predicted greater stress exposure in the CT + IPV group compared to the CT group; HCC was not associated with stress exposure in the NTC group. The present findings highlight the potential utility of HCC as a predictor of stress exposure for women with a history of childhood abuse or neglect, particularly in the context of recent IPV. Lay summary Adults with a history of CT show long-lasting alterations in major stress response systems, including the HPA axis. They are also more likely to experience stressful life events in adulthood. However, it is not clear how altered HPA activity influences risk for stress exposure and whether CT affects their

  5. Carbon monoxide exposure enhances arrhythmia after cardiac stress: involvement of oxidative stress.

    Science.gov (United States)

    André, Lucas; Gouzi, Fares; Thireau, Jérôme; Meyer, Gregory; Boissiere, Julien; Delage, Martine; Abdellaoui, Aldja; Feillet-Coudray, Christine; Fouret, Gilles; Cristol, Jean-Paul; Lacampagne, Alain; Obert, Philippe; Reboul, Cyril; Fauconnier, Jérémy; Hayot, Maurice; Richard, Sylvain; Cazorla, Olivier

    2011-11-01

    Arrhythmias following cardiac stress are a key predictor of death in healthy population. Carbon monoxide (CO) is a ubiquitous pollutant promoting oxidative stress and associated with hospitalization for cardiovascular disease and cardiac mortality. We investigated the effect of chronic CO exposure on the occurrence of arrhythmic events after a cardiac stress test and the possible involvement of related oxidative stress. Wistar rats exposed chronically (4 weeks) to sustained urban CO pollution presented more arrhythmic events than controls during recovery after cardiac challenge with isoprenaline in vivo. Sudden death occurred in 22% of CO-exposed rats versus 0% for controls. Malondialdehyde (MDA), an end-product of lipid peroxidation, was increased in left ventricular tissue of CO-exposed rats. Cardiomyocytes isolated from CO-exposed rats showed higher reactive oxygen species (ROS) production (measured with MitoSox Red dye), higher diastolic Ca(2+) resulting from SR calcium leak and an higher occurrence of irregular Ca(2+) transients (measured with Indo-1) in comparison to control cells after a high pacing sequence. Acute treatment with a ROS scavenger (N-acetylcysteine, 20 mmol/L, 1 h) prevented this sequence of alterations and decreased the number of arrhythmic cells following high pacing. Chronic CO exposure promotes oxidative stress that alters Ca(2+) homeostasis (through RYR2 and SERCA defects) and thereby mediates the triggering of ventricular arrhythmia after cardiac stress that can lead to sudden death.

  6. school survey of exposure to violence and posttraumatic stress ...

    African Journals Online (AJOL)

    Epidemiological data specifically documenting PTSD prevalence following violence exposure in children and adolescents in South Africa is lacking. In this preliminary survey, a positive association was found between exposure to violent and multiple traumas and posttraumatic stress disorder symptoms in adolescents.

  7. "Dwelling in the Past": The Role of Rumination in the Treatment of Posttraumatic Stress Disorder

    Science.gov (United States)

    Echiverri, Aileen M.; Jaeger, Jeff J.; Chen, Jessica A.; Moore, Sally A.; Zoellner, Lori A.

    2011-01-01

    Prolonged exposure, a cognitive behavioral therapy including both in vivo and imaginal exposure to the traumatic memory, is one of several empirically supported treatments for chronic posttraumatic stress disorder (PTSD). In this article, we provide a case illustration in which this well-validated treatment did not yield expected clinical gains…

  8. Elastic stockings effect on leg volume variability in healthy workers under prolonged gravitational gradient exposure

    Directory of Open Access Journals (Sweden)

    Mirko Tessari

    2015-06-01

    Full Text Available The aim of this study was to determine the elastic stockings effect on healthy workers (HW who are exposed to a prolonged hydrostatic pressure overload for professional reasons. The cohort was composed by 20 HW who voluntarily underwent a water plethysmography test before and after eight hour of standing up in an operating room, wearing elastic stockings. After 8 h of gravity exposure, we demonstrated the absence of leg volume increase in case of elastic stockings use. In the morning measurement we found that the lower limb volume was 1967.5 mL±224, while in the evening it was 1962.5 mL±227 (P<0.0828. The decreased volume is significantly correlated with the time that was spent under gravity forces for working purpose wearing elastic stockings (R2=0.99, P<0.0001. Our experiment demonstrates that elastic stockings may effectively counteract the increased leg volume over time in workers who are exposed to prolonged gravitational gradient. Further longitudinal studies are needed to determine if the above effect could correct one of the major risk factors for the development of chronic venous insufficiency.

  9. Changes in ventricular function during emotional stress and cold exposure

    International Nuclear Information System (INIS)

    Kiess, M.C.; Moore, R.A.; Dimsdale, J.; Alpert, N.M.; Boucher, C.A.; Strauss, H.W.

    1984-01-01

    Patients with cardiac disease frequently develop symptoms with emotional stress or cold exposure. To investigate the effects of these stresses in normal subjects, an ambulatory ventricular function monitor (VEST) (previously reported to measure EFs which correlate well with gamma camera measurements) was employed to record sequential 2 minute time activity curves from the left ventricles of 6 healthy men (ages 19-24) during a control period and during a 30 minute stress interview with a psychiatrist. Four of the subjects were also monitored in a cold room (1 0 C) for 20 min. In addition to the left ventricular time-activity curve, heart rate (HR), and BP (cuff) were recorded. All subjects had increases in HR, BP and EF during the stress interview. Cold, however, produced decreases in HR and EF and an increase in BP. The results (mean +- SD) are tabulated. End-systolic and end-diastolic counts and hence volume decreased during the interview and increased during cold exposure. The results suggest that (1) ambulatory changes in ventricular function can be measured with the VEST, and (2) significant changes in cardiovascular physiology are seen in normal subjects during a stress interview and exposure to cold

  10. Repeated exposure of adult rats to transient oxidative stress induces various long-lasting alterations in cognitive and behavioral functions.

    Directory of Open Access Journals (Sweden)

    Yoshio Iguchi

    Full Text Available Exposure of neonates to oxidative stress may increase the risk of psychiatric disorders such as schizophrenia in adulthood. However, the effects of moderate oxidative stress on the adult brain are not completely understood. To address this issue, we systemically administrated 2-cyclohexen-1-one (CHX to adult rats to transiently reduce glutathione levels. Repeated administration of CHX did not affect the acquisition or motivation of an appetitive instrumental behavior (lever pressing rewarded by a food outcome under a progressive ratio schedule. In addition, response discrimination and reversal learning were not affected. However, acute CHX administration blunted the sensitivity of the instrumental performance to outcome devaluation, and this effect was prolonged in rats with a history of repeated CHX exposure, representing pro-depression-like phenotypes. On the other hand, repeated CHX administration reduced immobility in forced swimming tests and blunted acute cocaine-induced behaviors, implicating antidepressant-like effects. Multivariate analyses segregated a characteristic group of behavioral variables influenced by repeated CHX administration. Taken together, these findings suggest that repeated administration of CHX to adult rats did not cause a specific mental disorder, but it induced long-term alterations in behavioral and cognitive functions, possibly related to specific neural correlates.

  11. Strength through adversity: Moderate lifetime stress exposure is associated with psychological resilience in breast cancer survivors.

    Science.gov (United States)

    Dooley, Larissa N; Slavich, George M; Moreno, Patricia I; Bower, Julienne E

    2017-12-01

    Stress research typically emphasizes the toxic effects of stress, but recent evidence has suggested that stress exposure, in moderation, can facilitate resilience. To test whether moderate stress exposure promotes psychological resilience to cancer, we examined the relationship between lifetime stress exposure prior to cancer diagnosis and postdiagnosis psychological functioning among 122 breast cancer survivors. Lifetime acute and chronic stress was assessed using an interview-based measure, and psychological functioning was assessed using measures of cancer-related intrusive thoughts and positive and negative affect. Results indicated that acute stress exposure was associated with cancer-related intrusive thoughts in a quadratic fashion (p = .016), such that participants with moderate acute stress reported fewer intrusive thoughts compared to those with low or high acute stress. Similarly, a quadratic relationship emerged between acute stress exposure and positive affect (p = .009), such that individuals with moderate acute stress reported the highest levels of positive affect. In contrast, acute and chronic stress were related to negative affect in a positive, linear fashion (ps < .05). In conclusion, moderate stress exposure was associated with indicators of psychological resilience among breast cancer survivors, supporting stress exposure as a key factor influencing adjustment to breast cancer and providing evidence for stress-induced resilience in a novel population. Copyright © 2017 John Wiley & Sons, Ltd.

  12. Prenatal flavor exposure affects flavor recognition and stress-related behavior of piglets.

    Science.gov (United States)

    Oostindjer, Marije; Bolhuis, J Elizabeth; van den Brand, Henry; Kemp, Bas

    2009-11-01

    Exposure to flavors in the amniotic fluid and mother's milk derived from the maternal diet has been shown to modulate food preferences and neophobia of young animals of several species. Aim of the experiment was to study the effects of pre- and postnatal flavor exposure on behavior of piglets during (re)exposure to this flavor. Furthermore, we investigated whether varying stress levels, caused by different test settings, affected behavior of animals during (re)exposure. Piglets were exposed to anisic flavor through the maternal diet during late gestation and/or during lactation or never. Piglets that were prenatally exposed to the flavor through the maternal diet behaved differently compared with unexposed pigs during reexposure to the flavor in several tests, suggesting recognition of the flavor. The differences between groups were more pronounced in tests with relatively high stress levels. This suggests that stress levels, caused by the design of the test, can affect the behavior shown in the presence of the flavor. We conclude that prenatal flavor exposure affects behaviors of piglets that are indicative of recognition and that these behaviors are influenced by stress levels during (re)exposure.

  13. [Impact of Socioeconomic Risk Exposure on Maternal Sensitivity, Stress and Family Functionality].

    Science.gov (United States)

    Sidor, Anna; Köhler, Hubert; Cierpka, Manfred

    2018-03-01

    Impact of Socioeconomic Risk Exposure on Maternal Sensitivity, Stress and Family Functionality Parental stress exposure can influence the parent-child relationship, child development and child wellbeing in negative ways. The aim of this study was to investigate the impact of socio-economic risk exposure on the quality of the mother-child-interaction and family functionality. A sample of 294 mother-infant dyads at psychosocial risk was compared with a lower-risk, middle-class sample of 125 mother-infant-dyads in regard to maternal sensitivity/child's cooperation (CARE-Index), maternal stress (PSI-SF) and family functionality (FB-K). Lower levels of maternal sensitivity/child's cooperation and by trend also of the family functionality were found among the mothers from the at-risk sample in comparison to the low-risk sample. The level of maternal stress was similar in both samples. The results underpin the negative effects of a socio-economic risk exposure on the mother-child relationship. An early, sensitivity-focused family support could be encouraged to counteract the negative effects of early socioeconomic stress.

  14. The Buffer Effect of Therapy Dog Exposure on Stress Reactivity in Undergraduate Students

    Directory of Open Access Journals (Sweden)

    Alexandra J. Fiocco

    2017-06-01

    Full Text Available Stress is an insidious health risk that is commonly reported among university students. While research suggests that dog exposure may facilitate recovery from a stress response, little is known about the buffer effect of dog exposure on the stress response to a future stressor. This study examined whether interaction with a therapy dog could reduce the strength of the physiological stress response when exposed to a subsequent stressor. Sixty-one university students were randomly assigned to either a therapy dog (TD, n = 31 or a no-dog control (C, n = 30 group. The stress response was measured by electrodermal activity (EDA in response to the Paced Auditory Serial Addition Test (PASAT. Participants also completed questionnaires that assessed pet attitude, general stress levels, and affect. Analyses of covariance (ANCOVAs showed that increase in EDA was significantly more pronounced in the C group than in the TD group (p < 0.01. Pet attitudes did not modulate the buffer effect of therapy dog exposure. Results suggest that therapy dog exposure may buffer the stress response in university students, which has implications for the promotion of a viable stress management program on university campuses.

  15. Repeated Exposure to Conditioned Fear Stress Increases Anxiety and Delays Sleep Recovery Following Exposure to an Acute Traumatic Stressor

    OpenAIRE

    Greenwood, Benjamin N.; Thompson, Robert S.; Opp, Mark R.; Fleshner, Monika

    2014-01-01

    Repeated stressor exposure can sensitize physiological responses to novel stressors and facilitate the development of stress-related psychiatric disorders including anxiety. Disruptions in diurnal rhythms of sleep–wake behavior accompany stress-related psychiatric disorders and could contribute to their development. Complex stressors that include fear-eliciting stimuli can be a component of repeated stress experienced by human beings, but whether exposure to repeated fear can prime the develo...

  16. Heart Rate, Stress, and Occupational Noise Exposure among Electronic Waste Recycling Workers.

    Science.gov (United States)

    Burns, Katrina N; Sun, Kan; Fobil, Julius N; Neitzel, Richard L

    2016-01-19

    Electronic waste (e-waste) is a growing occupational and environmental health issue around the globe. E-waste recycling is a green industry of emerging importance, especially in low-and middle-income countries where much of this recycling work is performed, and where many people's livelihoods depend on this work. The occupational health hazards of e-waste recycling have not been adequately explored. We performed a cross-sectional study of noise exposures, heart rate, and perceived stress among e-waste recycling workers at a large e-waste site in Accra, Ghana. We interviewed 57 workers and continuously monitored their individual noise exposures and heart rates for up to 24 h. More than 40% of workers had noise exposures that exceeded recommended occupational (85 dBA) and community (70 dBA) noise exposure limits, and self-reported hearing difficulties were common. Workers also had moderate to high levels of perceived stress as measured via Cohen's Perceived Stress Scale, and reported a variety of symptoms that could indicate cardiovascular disease. Noise exposures were moderately and significantly correlated with heart rate (Spearman's ρ 0.46, p stress, and unfavorable physical working conditions. These findings suggest that occupational and non-occupational noise exposure is associated with elevations in average heart rate, which may in turn predict potential cardiovascular damage.

  17. Early life trauma exposure and stress sensitivity in young children.

    Science.gov (United States)

    Grasso, Damion J; Ford, Julian D; Briggs-Gowan, Margaret J

    2013-01-01

    The current study replicates and extends work with adults that highlights the relationship between trauma exposure and distress in response to subsequent, nontraumatic life stressors. The sample included 213 2-4-year-old children in which 64.3% had a history of potential trauma exposure. Children were categorized into 4 groups based on trauma history and current life stress. In a multivariate analysis of variance, trauma-exposed children with current life stressors had elevated internalizing and externalizing problems compared with trauma-exposed children without current stress and nontrauma-exposed children with and without current stressors. The trauma-exposed groups with or without current stressors did not differ on posttraumatic stress disorder symptom severity. Accounting for number of traumatic events did not change these results. These findings suggest that early life trauma exposure may sensitize young children and place them at risk for internalizing or externalizing problems when exposed to subsequent, nontraumatic life stressors.

  18. Secondhand smoke exposure induces acutely airway acidification and oxidative stress.

    Science.gov (United States)

    Kostikas, Konstantinos; Minas, Markos; Nikolaou, Eftychia; Papaioannou, Andriana I; Liakos, Panagiotis; Gougoura, Sofia; Gourgoulianis, Konstantinos I; Dinas, Petros C; Metsios, Giorgos S; Jamurtas, Athanasios Z; Flouris, Andreas D; Koutedakis, Yiannis

    2013-02-01

    Previous studies have shown that secondhand smoke induces lung function impairment and increases proinflammatory cytokines. The aim of the present study was to evaluate the acute effects of secondhand smoke on airway acidification and airway oxidative stress in never-smokers. In a randomized controlled cross-over trial, 18 young healthy never-smokers were assessed at baseline and 0, 30, 60, 120, 180 and 240 min after one-hour secondhand smoke exposure at bar/restaurant levels. Exhaled NO and CO measurements, exhaled breath condensate collection (for pH, H(2)O(2) and NO(2)(-)/NO(3)(-) measurements) and spirometry were performed at all time-points. Secondhand smoke exposure induced increases in serum cotinine and exhaled CO that persisted until 240 min. Exhaled breath condensate pH decreased immediately after exposure (p secondhand smoke induced airway acidification and increased airway oxidative stress, accompanied by significant impairment of lung function. Despite the reversal in EBC pH and lung function, airway oxidative stress remained increased 4 h after the exposure. Clinical trial registration number (EudraCT): 2009-013545-28. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Harm expectancy violation during exposure therapy for posttraumatic stress disorder.

    Science.gov (United States)

    de Kleine, Rianne A; Hendriks, Lotte; Becker, Eni S; Broekman, Theo G; van Minnen, Agnes

    2017-06-01

    Exposure therapy has proven efficacy in the treatment of posttraumatic stress disorder (PTSD). Emotional processing theory proposes that fear habituation is a central mechanism in symptom reduction, but the empirical evidence supporting this is mixed. Recently it has been proposed that violation of harm expectancies is a crucial mechanism of action in exposure therapy. But to date, changes in harm expectancies have not been examined during exposure therapy in PTSD. The goal of the current study was to examine harm expectancy violation as mechanism of change in exposure therapy for posttraumatic stress disorder (PTSD). Patients (N=50, 44 female) with a primary diagnosis of chronic PTSD received intensive exposure therapy. Harm expectancies, harm experiences and subjective units of distress (SUDs) were assessed at each imaginal exposure session, and PTSD symptoms were assessed pre- and posttreatment with the Clinician Administered PTSD Scale (CAPS). Results showed that harm expectancies were violated within and strongly declined in-between exposure therapy sessions. However, expectancy violation was not related to PTSD symptom change. Fear habituation measures were moderately related to PTSD symptom reductions. In line with theory, exposure therapy promotes expectancy violation in PTSD patients, but this is not related to exposure therapy outcome. More work is warranted to investigate mechanisms of change during exposure therapy in PTSD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Perseverative Cognitions and Stress Exposure: Comparing Relationships With Psychological Health Across a Diverse Adult Sample.

    Science.gov (United States)

    Zawadzki, Matthew J; Sliwinski, Martin J; Smyth, Joshua M

    2018-03-29

    Both exposure to stress and perseverative cognitions (PCs)-repetitive cognitive representations of real or imagined stressors-are linked with poor psychological health. Yet, stress exposure and PCs are correlated, thus potentially obscuring any unique effects. The purpose of this paper is to concurrently test associations between stress exposure and PCs and psychological health to examine the independent relationship of each with psychological health. Moreover, we examined whether these relationships are similar across sex, age, and race. An adult community sample (n = 302) completed a measure of stress exposure, three PCs scales, and questionnaires assessing self-reported psychological health, including emotional well-being, vitality, social functioning, role limitations due to personal problems, subjective well-being, depressive symptoms, and poor sleep quality. Structural equation modeling was used to test a model in which both stress exposure and PCs predict psychological health. PCs consistently predicted all the psychological health outcomes, but stress was largely unrelated to the outcomes despite bivariate correlations suggesting a relationship. A follow-up model identified indirect effects of stress exposure on psychological health via PCs. Results were fairly consistent regardless of one's sex, age, or race. PCs robustly predicted all of the psychological health outcomes, intimating PCs as a common pathway to poor psychological health. Results have implications for stress interventions, including the need to address PCs after experiencing stress.

  1. Hsp27, Hsp70, and metallothionein in MDCK and LLC-PK1 renal epithelial cells: effects of prolonged exposure to cadmium

    International Nuclear Information System (INIS)

    Bonham, Rita T.; Fine, Michael R.; Pollock, Fiona M.; Shelden, Eric A.

    2003-01-01

    Cadmium is a widely distributed industrial and environmental toxin. The principal target organ of chronic sublethal cadmium exposure is the kidney. In renal epithelial cells, acute high-dose cadmium exposure induces differential expression of proteins, including heat shock proteins. However, few studies have examined heat shock protein expression in cells after prolonged exposure to cadmium at sublethal concentrations. Here, we assayed total cell protein, neutral red uptake, cell death, and levels of metallothionein and heat shock proteins Hsp27 and inducible Hsp70 in cultures of MDCK and LLC-PK1 renal epithelial cells treated with cadmium for 3 days. Treatment with cadmium at concentrations equal to or greater than 10 μM (LLC-PK1) or 25 μM (MDCK) reduced measures of cell vitality and induced cell death. However, a concentration-dependent increase in Hsp27 was detected in both cell types treated with as little as 5 μM cadmium. Accumulation of Hsp70 was correlated only with cadmium treatment at concentrations also causing cell death. Metallothionein was maximally detected in cells treated with cadmium at concentrations that did not reduce cell vitality, and further increases were not detected at greater concentrations. These results reveal that heat shock proteins accumulate in renal epithelial cells during prolonged cadmium exposure, that cadmium induces differential expression of heat shock protein in epithelial cells, and that protein expression patterns in epithelial cells are specific to the cadmium concentration and degree of cellular injury. A potential role for Hsp27 in the cellular response to sublethal cadmium-induced injury is also implicated by our results

  2. Secondhand smoke exposure and endothelial stress in children and adolescents.

    Science.gov (United States)

    Groner, Judith A; Huang, Hong; Nagaraja, Haikady; Kuck, Jennifer; Bauer, John Anthony

    2015-01-01

    Links between secondhand smoke exposure and cardiovascular disease in adults are well established. Little is known about the impact of this exposure on cardiovascular status during childhood. The purpose of this study was to investigate relationships between secondhand smoke exposure in children and adolescents and cardiovascular disease risk--systemic inflammation, endothelial stress, and endothelial repair. A total of 145 subjects, aged 9 to 18 years, were studied. Tobacco smoke exposure was determined by hair nicotine level. Cardiovascular risk was assessed by markers of systemic inflammation (C-reactive protein [CRP] and adiponectin); by soluble intercellular adhesion molecule 1 (s-ICAM1), which measures endothelial activation after surface vascular injury; and by endothelial repair. This was measured by prevalence of endothelial progenitor cells (EPCs), which are bone marrow-derived cells that home preferentially to sites of vascular damage. Hair nicotine was directly correlated with s-ICAM1 (r = 0.4090, P Secondhand smoke exposure during childhood and adolescence is detrimental to vascular health because s-ICAM1 is a marker for endothelial activation and stress after vascular surface injury, and EPCs contribute to vascular repair. The fact that body mass index is also a factor in the model predicting s-ICAM1 is concerning, in that 2 risk factors may both contribute to endothelial stress. Copyright © 2015 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

  3. Modeling Exposure to Heat Stress with a Simple Urban Model

    Directory of Open Access Journals (Sweden)

    Peter Hoffmann

    2018-01-01

    Full Text Available As a first step in modeling health-related urban well-being (UrbWellth, a mathematical model is constructed that dynamically simulates heat stress exposure of commuters in an idealized city. This is done by coupling the Simple Urban Radiation Model (SURM, which computes the mean radiant temperature ( T m r t , with a newly developed multi-class multi-mode traffic model. Simulation results with parameters chosen for the city of Hamburg for a hot summer day show that commuters are potentially most exposed to heat stress in the early afternoon when T m r t has its maximum. Varying the morphology with respect to street width and building height shows that a more compact city configuration reduces T m r t and therefore the exposure to heat stress. The impact resulting from changes in the city structure on traffic is simulated to determine the time spent outside during the commute. While the time in traffic jams increases for compact cities, the total commuting time decreases due to shorter distances between home and work place. Concerning adaptation measures, it is shown that increases in the albedo of the urban surfaces lead to an increase in daytime heat stress. Dramatic increases in heat stress exposure are found when both, wall and street albedo, are increased.

  4. Changes in CR-39 proton sensitivity due to prolonged exposure to high vacuums relevant to the National Ignition Facility and OMEGA.

    Science.gov (United States)

    Manuel, M J-E; Rosenberg, M J; Sinenian, N; Rinderknecht, H; Zylstra, A B; Séguin, F H; Frenje, J; Li, C K; Petrasso, R D

    2011-09-01

    When used at facilities like OMEGA and the NIF, CR-39 is exposed to high vacuum environments before and after irradiation by charged particles and neutrons. Using an electrostatic linear accelerator at MIT, studies have been conducted to investigate the effects of high vacuum exposure on the sensitivity of CR-39 to fusion protons in the ~1-9 MeV energy range. High vacuum conditions, of order 10(-5) Torr, experienced by CR-39 samples at these facilities were emulated. It is shown that vacuum exposure times longer than ~16 h before proton irradiation result in a decrease in proton sensitivity, whereas no effect was observed for up to 67 h of vacuum exposure after proton irradiation. CR-39 sensitivity curves are presented for samples with prolonged exposure to high vacuum before and after proton irradiation. © 2011 American Institute of Physics

  5. Cortisol Reactivity to Stress and Its Association With White Matter Integrity in Adults With Schizophrenia.

    Science.gov (United States)

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

    2015-09-01

    Although acute hypothalamic-pituitary-adrenal axis response to stress is often adaptive, prolonged responses may have detrimental effects. Many components of white matter structures are sensitive to prolonged cortisol exposure. We aimed to identify a behavioral laboratory assay for cortisol response related to brain pathophysiology in schizophrenia. We hypothesized that an abnormally prolonged cortisol response to stress may be linked to abnormal white matter integrity in patients with schizophrenia. Acute and prolonged salivary cortisol response was measured outside the scanner at pretest and then at 0, 20, and 40 minutes after a psychological stress task in patients with schizophrenia (n = 45) and controls (n = 53). Tract-averaged white matter was measured by 64-direction diffusion tensor imaging in a subset of patients (n = 30) and controls (n = 33). Patients who did not tolerate the psychological stress task and quit had greater acute (t = 2.52 [p = .016] and t = 3.51 [p = .001] at 0 and 20 minutes) and prolonged (t = 3.62 [p = .001] at 40 minutes) cortisol reactivity compared with patients who finished the task. Abnormally prolonged cortisol reactivity in patients was significantly associated with reduced white matter integrity (r = -0.468, p = .009). Regardless of task completion status, acute cortisol response was not related to the white matter measures in patients or controls. This paradigm was successful at identifying a subset of patients whose cortisol response was associated with brain pathophysiology. Abnormal cortisol response may adversely affect white matter integrity, partly explaining this pathology observed in schizophrenia. Prolonged stress responses may be targeted for intervention to test for protective effects against white matter damages.

  6. Prenatal Exposure to Maternal Obesity Alters Anxiety and Stress Coping Behaviors in Aged Mice.

    Science.gov (United States)

    Balsevich, Georgia; Baumann, Valentin; Uribe, Andres; Chen, Alon; Schmidt, Mathias V

    2016-01-01

    There is growing evidence that maternal obesity and prenatal exposure to a high-fat diet program fetal development to regulate the physiology and behavior of the offspring in adulthood. Yet the extent to which the maternal dietary environment contributes to adult disease vulnerability remains unclear. In the current study we tested whether prenatal exposure to maternal obesity increases the offspring's vulnerability to stress-related psychiatric disorders. We used a mouse model of maternal diet-induced obesity to investigate whether maternal obesity affects the response to adult chronic stress exposure in young adult (3-month-old) and aged adult (12-month-old) offspring. Long-lasting, delayed impairments to anxiety-like behaviors and stress coping strategies resulted on account of prenatal exposure to maternal obesity. Although maternal obesity did not change the offspring's behavioral response to chronic stress per se, we demonstrate that the behavioral outcomes induced by prenatal exposure to maternal obesity parallel the deleterious effects of adult chronic stress exposure in aged male mice. We found that the glucocorticoid receptor (GR, Nr3c1) is upregulated in various hypothalamic nuclei on account of maternal obesity. In addition, gene expression of a known regulator of the GR, FKBP51, is increased specifically within the paraventricular nucleus. These findings indicate that maternal obesity parallels the deleterious effects of adult chronic stress exposure, and furthermore identifies GR/FKBP51 signaling as a novel candidate pathway regulated by maternal obesity. © 2015 S. Karger AG, Basel.

  7. Modified single prolonged stress reduces cocaine self-administration during acquisition regardless of rearing environment.

    Science.gov (United States)

    Hofford, Rebecca S; Prendergast, Mark A; Bardo, Michael T

    2018-02-15

    Until recently, there were few rodent models available to study the interaction of post-traumatic stress disorder (PTSD) and drug taking. Like PTSD, single prolonged stress (SPS) produces hypothalamic-pituitary-adrenal (HPA) axis dysfunction and alters psychostimulant self-administration. Other stressors, such as isolation stress, also alter psychostimulant self-administration. However, it is currently unknown if isolation housing combined with SPS can alter the acquisition or maintenance of cocaine self-administration. The current study applied modified SPS (modSPS; two hours restraint immediately followed by cold swim stress) to rats raised in an isolation condition (Iso), enrichment condition (Enr), or standard condition (Std) to measure changes in cocaine self-administration and HPA markers. Regardless of rearing condition, rats exposed to modSPS had greater corticosterone (CORT) release and reduced cocaine self-administration during initial acquisition compared to non-stressed controls. In addition, during initial acquisition, rats that received both Iso rearing and modSPS showed a more rapid increase in cocaine self-administration across sessions compared to Enr and Std rats exposed to modSPS. Following initial acquisition, a dose response analysis showed that Iso rats were overall most sensitive to changes in cocaine unit dose; however, modSPS had no effect on the cocaine dose response curve. Further, there was no effect of either modSPS or differential rearing on expression of glucocorticoid receptor (GR) in hypothalamus, medial prefrontal cortex, amygdala, or nucleus accumbens. By using modSPS in combination with Iso housing, this study identified unique contributions of each stressor to acquisition of cocaine self-administration. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Effects of a relaxation training programme on immediate and prolonged stress responses in women with preterm labour.

    Science.gov (United States)

    Chuang, Li-Lan; Lin, Li-Chan; Cheng, Po-Jen; Chen, Chung-Hey; Wu, Shiao-Chi; Chang, Chuan-Lin

    2012-01-01

    This paper is a report of an experimental study of the effects of relaxation-training programme on immediate and prolonged stress responses in women with preterm labour. Hospitalized pregnant women with preterm labour experience developmental and situational stress. However, few studies have been performed on stress management in such women. An experimental pretest and repeated post-test design was used to compare the outcomes for two groups in northern Taiwan from December 2008, to May 2010. A total of 129 women were randomly assigned to an experimental (n = 68) or control (n = 61) group. The experimental group participants were instructed to listen daily to a 13-minute relaxation programme. Measurements involved the stress visual analogue scale, finger temperatures, State Trait Anxiety Inventory, Perceived Stress Scale and Pregnancy-related Anxiety. Two-way analysis of variance and hierarchical linear modelling were used to analyse the group differences. Compared with those in the control group, participants in the experimental group showed immediate improvements in the stress visual analogue scale scores and finger temperatures. The State Trait Anxiety Inventory-State subscale score for the experimental group was significantly lower than that for the control group (P = 0·03). However, no statistically significant differences for the Perceived Stress Scale and Pregnancy-related Anxiety scores were found between the experimental group and the control group. The relaxation-training programme could improve the stress responses of women with preterm labour. © 2011 The Authors. Journal of Advanced Nursing © 2011 Blackwell Publishing Ltd.

  9. Exposure to radiofrequency radiation induces oxidative stress in duckweed Lemna minor L

    Energy Technology Data Exchange (ETDEWEB)

    Tkalec, Mirta [Department of Botany, Division of Biology, Faculty of Science, University of Zagreb, Rooseveltov trg 6, HR-10000 Zagreb (Croatia)], E-mail: mtkalec@zg.biol.pmf.hr; Malaric, Kresimir [Faculty of Electrical Engineering and Computing, University of Zagreb, Unska 3, HR-10000 Zagreb (Croatia); Pevalek-Kozlina, Branka [Department of Botany, Division of Biology, Faculty of Science, University of Zagreb, Rooseveltov trg 6, HR-10000 Zagreb (Croatia)

    2007-12-15

    Widespread use of radiofrequency radiation emitting devices increased the exposure to electromagnetic fields (EMFs) from 300 MHz to 300 GHz. Various biological effects of exposure to these fields have been documented so far, but very little work has been carried out on plants. The aim of the present work was to investigate the physiological responses of the plant Lemna minor after exposure to radiofrequency EMFs, and in particular, to clarify the possible role of oxidative stress in the observed effects. Duckweed was exposed for 2 h to EMFs of 400 and 900 MHz at field strengths of 10, 23, 41 and 120 V m{sup -1}. The effect of a longer exposure time (4 h) and modulation was also investigated. After exposure, parameters of oxidative stress, such as lipid peroxidation, H{sub 2}O{sub 2} content, activities and isoenzyme pattern of antioxidative enzymes as well as HSP70 expression were evaluated. At 400 MHz, lipid peroxidation and H{sub 2}O{sub 2} content were significantly enhanced in duckweed exposed to EMFs of 23 and 120 V m{sup -1} while other exposure treatments did not have an effect. Compared to the controls, the activities of antioxidative enzymes showed different behaviour: catalase (CAT) activity increased after most exposure treatments while pyrogallol (PPX) and ascorbate peroxidase (APX) activities were not changed. Exceptions were reduced PPX and APX activity after longer exposure at 23 V m{sup -1} and increased PPX activity after exposures at 10 and 120 V m{sup -1}. By contrast, at 900 MHz almost all exposure treatments significantly increased level of lipid peroxidation and H{sub 2}O{sub 2} content but mostly decreased PPX activity and did not affect CAT activity. Exceptions were exposures to a modulated field and to the field of 120 V m{sup -1} which increased PPX and CAT activity. At this frequency APX activity was significantly decreased after exposure at 10 V m{sup -1} and longer exposure at 23 V m{sup -1} but it increased after a shorter exposure at

  10. Exposure to radiofrequency radiation induces oxidative stress in duckweed Lemna minor L

    International Nuclear Information System (INIS)

    Tkalec, Mirta; Malaric, Kresimir; Pevalek-Kozlina, Branka

    2007-01-01

    Widespread use of radiofrequency radiation emitting devices increased the exposure to electromagnetic fields (EMFs) from 300 MHz to 300 GHz. Various biological effects of exposure to these fields have been documented so far, but very little work has been carried out on plants. The aim of the present work was to investigate the physiological responses of the plant Lemna minor after exposure to radiofrequency EMFs, and in particular, to clarify the possible role of oxidative stress in the observed effects. Duckweed was exposed for 2 h to EMFs of 400 and 900 MHz at field strengths of 10, 23, 41 and 120 V m -1 . The effect of a longer exposure time (4 h) and modulation was also investigated. After exposure, parameters of oxidative stress, such as lipid peroxidation, H 2 O 2 content, activities and isoenzyme pattern of antioxidative enzymes as well as HSP70 expression were evaluated. At 400 MHz, lipid peroxidation and H 2 O 2 content were significantly enhanced in duckweed exposed to EMFs of 23 and 120 V m -1 while other exposure treatments did not have an effect. Compared to the controls, the activities of antioxidative enzymes showed different behaviour: catalase (CAT) activity increased after most exposure treatments while pyrogallol (PPX) and ascorbate peroxidase (APX) activities were not changed. Exceptions were reduced PPX and APX activity after longer exposure at 23 V m -1 and increased PPX activity after exposures at 10 and 120 V m -1 . By contrast, at 900 MHz almost all exposure treatments significantly increased level of lipid peroxidation and H 2 O 2 content but mostly decreased PPX activity and did not affect CAT activity. Exceptions were exposures to a modulated field and to the field of 120 V m -1 which increased PPX and CAT activity. At this frequency APX activity was significantly decreased after exposure at 10 V m -1 and longer exposure at 23 V m -1 but it increased after a shorter exposure at 23 V m -1 . At both frequencies no differences in isoenzyme

  11. Media's role in broadcasting acute stress following the Boston Marathon bombings.

    Science.gov (United States)

    Holman, E Alison; Garfin, Dana Rose; Silver, Roxane Cohen

    2014-01-07

    We compared the impact of media vs. direct exposure on acute stress response to collective trauma. We conducted an Internet-based survey following the Boston Marathon bombings between April 29 and May 13, 2013, with representative samples of residents from Boston (n = 846), New York City (n = 941), and the remainder of the United States (n = 2,888). Acute stress symptom scores were comparable in Boston and New York [regression coefficient (b) = 0.43; SE = 1.42; 95% confidence interval (CI), -2.36, 3.23], but lower nationwide when compared with Boston (b = -2.21; SE = 1.07; 95% CI, -4.31, -0.12). Adjusting for prebombing mental health (collected prospectively), demographics, and prior collective stress exposure, six or more daily hours of bombing-related media exposure in the week after the bombings was associated with higher acute stress than direct exposure to the bombings (continuous acute stress symptom total: media exposure b = 15.61 vs. direct exposure b = 5.69). Controlling for prospectively collected prebombing television-watching habits did not change the findings. In adjusted models, direct exposure to the 9/11 terrorist attacks and the Sandy Hook School shootings were both significantly associated with bombing-related acute stress; Superstorm Sandy exposure wasn't. Prior exposure to similar and/or violent events may render some individuals vulnerable to the negative effects of collective traumas. Repeatedly engaging with trauma-related media content for several hours daily shortly after collective trauma may prolong acute stress experiences and promote substantial stress-related symptomatology. Mass media may become a conduit that spreads negative consequences of community trauma beyond directly affected communities.

  12. Heart Rate, Stress, and Occupational Noise Exposure among Electronic Waste Recycling Workers

    Directory of Open Access Journals (Sweden)

    Katrina N. Burns

    2016-01-01

    Full Text Available Electronic waste (e-waste is a growing occupational and environmental health issue around the globe. E-waste recycling is a green industry of emerging importance, especially in low-and middle-income countries where much of this recycling work is performed, and where many people’s livelihoods depend on this work. The occupational health hazards of e-waste recycling have not been adequately explored. We performed a cross-sectional study of noise exposures, heart rate, and perceived stress among e-waste recycling workers at a large e-waste site in Accra, Ghana. We interviewed 57 workers and continuously monitored their individual noise exposures and heart rates for up to 24 h. More than 40% of workers had noise exposures that exceeded recommended occupational (85 dBA and community (70 dBA noise exposure limits, and self-reported hearing difficulties were common. Workers also had moderate to high levels of perceived stress as measured via Cohen’s Perceived Stress Scale, and reported a variety of symptoms that could indicate cardiovascular disease. Noise exposures were moderately and significantly correlated with heart rate (Spearman’s ρ 0.46, p < 0.001. A mixed effects linear regression model indicated that a 1 dB increase in noise exposure was associated with a 0.17 increase in heart rate (p-value = 0.01 even after controlling for work activities, age, smoking, perceived stress, and unfavorable physical working conditions. These findings suggest that occupational and non-occupational noise exposure is associated with elevations in average heart rate, which may in turn predict potential cardiovascular damage.

  13. Violence Exposure in Home and Community: Influence on Posttraumatic Stress Symptoms in Army Recruits

    Science.gov (United States)

    Chapin, Mark G.

    2004-01-01

    This study assessed the levels and types of violence exposure, levels of posttraumatic stress symptoms, and the relationship among exposure to violence, posttraumatic stress symptoms, and early discharge in U.S. Army recruits at Basic Combat Training (BCT). The study applied a modified ABCX model of family stress adaptation developed by McCubbin,…

  14. The peculiarity of aerobic energy supply of rat tissues of different age upon prolonged ionizing and thermal exposure

    International Nuclear Information System (INIS)

    Tsyhun, G.F.

    1998-01-01

    Energy-producing functions of brain, myocardium, and hepatic mitochondria in mature and immature rats in remote period after prolonged ionizing X-ray at total dose 12,9 m C/kg and thermal exposure (4 hours, 37 degrees centigrade, 25 times) were studied. Dehydrogenase activities (pyruvate-, isocitrate-, 2-oxy glutarate-, succinate- and malate dehydrogenases) were reduced in mitochondria of different tissues of adult rats and it was especially considerable after combined influence. A higher resistance of young rats, as compared to adult ones, to combined radiation-thermal treatments was established

  15. The Role of Stress Exposure and Family Functioning in Internalizing Outcomes of Urban Families.

    Science.gov (United States)

    Sheidow, Ashli J; Henry, David B; Tolan, Patrick H; Strachan, Martha K

    2014-11-01

    Although research suggests that stress exposure and family functioning are associated with internalizing problems in adolescents and caregivers, surprisingly few studies have investigated the mechanisms that underlie this association. To determine whether family functioning buffers the development of internalizing problems in stress-exposed families, we assessed the relation between stress exposure, family functioning, and internalizing symptoms among a large sample of inner-city male youth and their caregivers living in poverty across five waves of data collection. We hypothesized that stress exposure and family functioning would predict development of subsequent youth and caregiver internalizing problems and that family functioning would moderate this relation, with higher functioning families demonstrating greater resiliency to stress exposure. We used a longitudinal, prospective design to evaluate whether family functioning (assessed at waves one through four) activated or buffered the effects of stress exposure (assessed at wave one) on subsequent internalizing symptoms (assessed at waves four and five). Stress from Developmental Transitions and family functioning were significant predictors of depressive symptoms and anxiety in youth; however, family functioning did not moderate the relation. Family functioning mediated the relation between stress from Daily Hassles and internalizing outcomes suggesting that poor parenting practices, low structure, and low emotional cohesion activate depression and anxiety in youth exposed to chronic and frequent everyday stressors. Surprisingly, only family functioning predicted depressive symptoms in caregivers. Results validate the use of a comprehensive, multi-informant assessment of stress when investigating internalizing outcomes in youth and support using family-based interventions in the treatment and prevention of internalizing.

  16. Developmental differences in stress responding after repeated underwater trauma exposures in rats.

    Science.gov (United States)

    Altman, Daniel E; Simmons, Laurence P; Vuong, Chau T; Taylor, Rachel M; Sousa, Jason C; Marcsisin, Sean R; Zottig, Victor E; Moore, Nicole L T

    2018-05-01

    Adolescence is a distinct developmental period characterized by behavioral and physiological maturation. Rapid ongoing changes during neurodevelopment in particular present potential opportunities for stress to have lasting effects on longitudinal outcomes of behavioral and neuroendocrine function. While adult stress effects on outcomes during adulthood have been characterized, little is known about the lasting effects of adolescent repeated stressor exposure on outcomes during adolescence. We have previously reported different stress responses in adolescent rats relative to adult rats, including a blunted fear response outcome in adulthood in rats stressed during adolescence. The present study characterized the ontogeny of behavioral and neuroendocrine responses to eight underwater trauma (UWT) exposures in rats over a two week poststress time period during adolescence (P34) or adulthood (P83) relative to age-matched control groups that underwent eight swimming episodes without UWT. Repeated UWT exposures starting in adolescence, but not adulthood, resulted in adverse behavioral responses on the elevated plus maze 1 day post-stress. Corticosterone responses did not differ between UWT-exposed and controls for either age group at 1 day or at 7 days poststress, although there was an effect of age on corticosterone levels. We conclude that repeated UWT stress events have a lasting, negative behavioral effect on adolescent rats that is not observed in adult rats after the two-week exposure window. These results suggest that neurophysiological mechanisms underlying recovery from a repeated stressor are immature in adolescence relative to adulthood in rats.

  17. Alantolactone Improves Prolonged Exposure of Interleukin-6-Induced Skeletal Muscle Inflammation Associated Glucose Intolerance and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Minjee Kim

    2017-06-01

    Full Text Available The pro-inflammatory cytokine, Interleukin-6 (IL-6, has been proposed to be one of the mediators that link chronic inflammation to glucose intolerance and insulin resistance. Many studies have demonstrated the effects of IL-6 on insulin action in the skeletal muscle. However, few studies have investigated the effect of long-term treatment of IL-6, leading to glucose intolerance and insulin resistance. In the present study, we observed protective effects of alantolactone, a sesquiterpene lactone isolated from Inula helenium against glucose intolerance and insulin resistance induced by prolonged exposure of IL-6. Alantolactone has been reported to have anti-inflammatory and anti-cancer effects through IL-6-induced signal transducer and activator of transcription 3 (STAT3 signaling pathway. The relationship between IL-6 exposure and expression of toll-like receptor 4 (TLR4, involved in inflammation in the skeletal muscle, and the underlying mechanisms were investigated. We observed maximum dysregulation of glucose uptake after 40 ng/ml IL-6 induction for 24 h in L6 myotubes. Prolonged IL-6 exposure suppressed glucose uptake regulating alpha serine/threonine-protein kinase (AKT phosphorylation; however, pretreatment with alantolactone activated AKT phosphorylation and improved glucose uptake. Alantolactone also attenuated IL-6-stimulated STAT3 phosphorylation, followed by an increase in expression of negative regulator suppressor of cytokine signaling 3 (SOCS3. Furthermore, IL-6-induced expression of pathogen recognition receptor, TLR4, was also suppressed by alantolactone pretreatment. Post-silencing of STAT3 using siRNA approach, IL-6-stimulated siRNA-STAT3 improved glucose uptake and suppressed TLR4 gene expression. Taken together, we propose that, as a STAT3 inhibitor, alantolactone, improves glucose regulation in the skeletal muscle by inhibiting IL-6-induced STAT3-SOCS3 signaling followed by inhibition of the TLR4 gene expression. Therefore

  18. Exposure to Violence during Adolescence as a Predictor of Perceived Stress Trajectories in Emerging Adulthood.

    Science.gov (United States)

    Heinze, Justin E; Stoddard, Sarah A; Aiyer, Sophie M; Eisman, Andria B; Zimmerman, Marc A

    2017-01-01

    Early exposure to violence during adolescence is related to negative psycho-social outcomes later in life. In the present study, we examined the influence of cumulative exposure to violence during adolescence and trajectories of perceived stress in emerging adulthood in a sample of at-risk urban youth ( N = 850; 80.1% African American; 50% female). Growth curve modeling indicated an overall decrease in reported stress as individuals aged. Baseline levels of violence exposure ( M age = 14.9) were associated with higher perceived stress levels in emerging adulthood ( M age = 20.1), but also slightly more negative perceived stress slopes from adolescence into emerging adulthood ( M age = 15.9-22.1). Individuals reporting increased violence exposure over time during adolescence also reported higher perceived stress levels in emerging adulthood ( M age = 20.1). Associations held after controlling for demographics and baseline functioning variables. The results suggest that violence exposure may disrupt normative adaptation to daily stressors in emerging adulthood.

  19. Gender/Sex Differences in the Relationship between Psychosocial Work Exposures and Work and Life Stress.

    Science.gov (United States)

    Padkapayeva, Kathy; Gilbert-Ouimet, Mahée; Bielecky, Amber; Ibrahim, Selahadin; Mustard, Cameron; Brisson, Chantal; Smith, Peter

    2018-04-18

    Stress is an important factor affecting the health of working population. While work exposures are determinants of levels of work and life stress, we do not know whether similar or different exposures are related to stress levels for men and women. This study aimed to formally examine male/female differences in the relationships between psychosocial work exposures and work and life stress in a representative sample of Canadian labour market participants. We used data from 2012 cycle of the Canadian Community Health Survey (CCHS), a representative population-based survey conducted by Statistics Canada. The sample was restricted to employed labour force participants working 15+ hours per week (N = 8328, 48% female). To examine the relationship between work exposures and work and life stress, we conducted path analyses. Psychosocial work exposures included social support, job insecurity, job control, and job strain. Differences between estimates for men and women were explored using multigroup analyses, constraining paths between male and female models to be equivalent and examining the impact on change in model fit. Male/female differences were observed in the relationships between supervisor support and work stress levels as well as between job control, job insecurity, job strain, and life stress levels. Higher levels of supervisor support at work were associated with lower work stress among women, but not among men. Low job control had a direct protective effect on life stress for men but not for women, while high job strain had a direct adverse effect on life stress among women but not among men. Higher job insecurity was more strongly associated with higher life stress among men compared with women. The relationship between work stress and life stress was similar among men and women. The findings of this study suggest that the relationships between psychosocial exposures and work and life stress differ for men and women. Our study also raised important questions

  20. Perceived life stress exposure modulates reward-related medial prefrontal cortex responses to acute stress in depression.

    Science.gov (United States)

    Kumar, Poornima; Slavich, George M; Berghorst, Lisa H; Treadway, Michael T; Brooks, Nancy H; Dutra, Sunny J; Greve, Douglas N; O'Donovan, Aoife; Bleil, Maria E; Maninger, Nicole; Pizzagalli, Diego A

    2015-07-15

    Major depressive disorder (MDD) is often precipitated by life stress and growing evidence suggests that stress-induced alterations in reward processing may contribute to such risk. However, no human imaging studies have examined how recent life stress exposure modulates the neural systems that underlie reward processing in depressed and healthy individuals. In this proof-of-concept study, 12 MDD and 10 psychiatrically healthy individuals were interviewed using the Life Events and Difficulties Schedule (LEDS) to assess their perceived levels of recent acute and chronic life stress exposure. Additionally, each participant performed a monetary incentive delay task under baseline (no-stress) and stress (social-evaluative) conditions during functional MRI. Across groups, medial prefrontal cortex (mPFC) activation to reward feedback was greater during acute stress versus no-stress conditions in individuals with greater perceived stressor severity. Under acute stress, depressed individuals showed a positive correlation between perceived stressor severity levels and reward-related mPFC activation (r=0.79, p=0.004), whereas no effect was found in healthy controls. Moreover, for depressed (but not healthy) individuals, the correlations between the stress (r=0.79) and no-stress (r=-0.48) conditions were significantly different. Finally, relative to controls, depressed participants showed significantly reduced mPFC gray matter, but functional findings remained robust while accounting for structural differences. Small sample size, which warrants replication. Depressed individuals experiencing greater recent life stress recruited the mPFC more under stress when processing rewards. Our results represent an initial step toward elucidating mechanisms underlying stress sensitization and recurrence in depression. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Bryostatin and its synthetic analog, picolog rescue dermal fibroblasts from prolonged stress and contribute to survival and rejuvenation of human skin equivalents.

    Science.gov (United States)

    Khan, Tapan K; Wender, Paul A; Alkon, Daniel L

    2018-02-01

    Skin health is associated with the day-to-day activity of fibroblasts. The primary function of fibroblasts is to synthesize structural proteins, such as collagen, extracellular matrix proteins, and other proteins that support the structural integrity of the skin and are associated with younger, firmer, and more elastic skin that is better able to resist and recover from injury. At sub-nanomolar concentrations (0.03-0.3 nM), bryostatin-1 and its synthetic analog, picolog (0.1-10 nM) sustained the survival and activation of human dermal fibroblasts cultured under the stressful condition of prolonged serum deprivation. Bryostatin-1 treatment stabilized human skin equivalents (HSEs), a bioengineered combination of primary human skin cells (keratinocytes and dermal fibroblasts) on an extracellular matrix composed of mainly collagen. Fibroblasts activated by bryostatin-1 protected the structural integrity of HSEs. Bryostatin-1 and picolog prolonged activation of Erk in fibroblasts to promote cell survival. Chronic stress promotes the progression of apoptosis. Dermal fibroblasts constitutively express all components of Fas associated apoptosis, including caspase-8, an initiator enzyme of apoptosis. Prolong bryostatin-1 treatment reduced apoptosis by decreasing caspase-8 and protected dermal fibroblasts. Our data suggest that bryostatin-1 and picolog could be useful in anti-aging skincare, and could have applications in tissue engineering and regenerative medicine. © 2017 Wiley Periodicals, Inc.

  2. [Pathophysiology of prolonged hypokinesia].

    Science.gov (United States)

    Kovalenko, E A

    1976-01-01

    Hypokinesia is an important problem in modern medicine. In the pathogenetic effect of prolonged hypokinesia the main etiological factor is diminished motor activity; of major importance are disorders in the energy and plastic metabolism which affect the muscle system; the contributing factors are cardiovascular deconditioning and orthostatic intolerance. This is attributed to a decreased oxygen supply and eliminated hydrostatic influences during a prolonged recumbency. Blood redistribution in the vascular bed is related to the Gauer-Henry reflex and subsequent changes in the fluid-electrolyte balance. Decreased load on the bone system induces changes in the protein-phosphate-calcium metabolism, diminished bone density and increased calcium content in the blood and urine. Changes in the calcium metabolism are systemic. The activity of the higher nervous system and reflex functions is lowered. Changes in the function of the autonomic nervous system which include a noticeable decline of its adaptive-trophic role as a result of the decrease of afferent and efferent impulsation are of great importance. Changes in the hormonal function involve a peculiar stress-reaction which develops at an early stage of hypokinesia as a response to an unusual situation. Prolonged hypokinesia may result in a disturbed function of the pituitary-adrenal system. It is assumed that prolonged hypokinesia may induce a specific disease of hypokinesia during which man cannot lead a normal mode of life and work.

  3. Risky choice and brain CRF after adolescent ethanol vapor exposure and social stress in adulthood.

    Science.gov (United States)

    Boutros, Nathalie; Der-Avakian, Andre; Semenova, Svetlana; Lee, Soon; Markou, Athina

    2016-09-15

    Adolescent ethanol exposure increases risky choice and alters corticotropin releasing factor (CRF) systems in adulthood. The impact of stress on risky choice after adolescent intermittent ethanol (AIE) exposure is not known. We investigated time-specific effects of AIE vapor exposure during early adolescence on risky choice after stress or no stress in adulthood. Male Wistar rats were exposed to air or AIE vapor on postnatal days 28-42 (adolescence) and were exposed to 10days of social defeat or no stress on postnatal days 172-181 (adulthood). Risky choice was assessed in the probability discounting task under baseline conditions and after days 1 and 10 of social defeat. CRF and CRF receptor 1 (CRFR1) mRNA levels were assessed in the prefrontal cortex (PFC) and the central nucleus of the amygdala (CeA) 24h post-stress to evaluate persistent effects of stress on the brain. AIE exposure had no effect on risky choice either at baseline or after social defeat. Additionally, neither acute nor chronic social defeat affected risky choice in air-exposed rats. In the PFC, chronic social defeat selectively decreased CRF mRNA levels in air-exposed rats and increased CRFR1 mRNA levels in all rats. AIE exposure increased CRF mRNA levels in the CeA with no effect of social stress. Our results indicate no effect of ethanol exposure via vapor during early adolescence on risky choice, while our previous findings indicated that AIE exposure via gavage affected risky choice. Both AIE exposure and social defeat altered CRF and CRFR1 mRNA levels in the brain. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Hair and stress: A pilot study of hair and cytokine balance alteration in healthy young women under major exam stress.

    Directory of Open Access Journals (Sweden)

    Eva M J Peters

    Full Text Available Mouse models show that experimental stress mimicking prolonged life-stress exposure enhances neurogenic inflammation, induces adaptive immunity cytokine-imbalance characterized by a shift to Type 1 T-helper cell cytokines and increases apoptosis of epithelial cells. This affects hair growth in otherwise healthy animals. In this study, we investigate whether a prolonged naturalistic life-stress exposure affects cytokine balance and hair parameters in healthy humans. 33 (18 exam, 15 comparison female medical students with comparable sociobiological status were analyzed during a stressful final examination period, at three points in time (T 12 weeks apart. T1 was before start of the learning period, T2 between the three-day written exam and an oral examination, and T3 after a 12 week rest and recovery from the stress of the examination period. Assessments included: self-reported distress and coping strategies (Perceived Stress Questionnaire [PSQ], Trier Inventory for the Assessment of Chronic Stress [TICS], COPE, cytokines in supernatants of stimulated peripheral blood mononucleocytes (PBMCs, and trichogram (hair cycle and pigmentation analysis. Comparison between students participating in the final medical exam at T2 and non-exam students, revealed significantly higher stress perception in exam students. Time-wise comparison revealed that stress level, TH1/TH2 cytokine balance and hair parameters changed significantly from T1 to T2 in the exam group, but not the control. However, no group differences were found for cytokine balance or hair parameters at T2. The study concludes that in humans, naturalistic stress, as perceived during participation in a major medical exam, has the potential to shift the immune response to TH1 and transiently hamper hair growth, but these changes stay within a physiological range. Findings are instructive for patients suffering from hair loss in times of high stress. Replication in larger and more diverse sample

  5. ER stress responses in the absence of apoptosome: a comparative study in CASP9 proficient vs deficient mouse embryonic fibroblasts.

    Science.gov (United States)

    Deegan, Shane; Saveljeva, Svetlana; Gupta, Sanjeev; MacDonald, David C; Samali, Afshin

    2014-08-29

    Cells respond to endoplasmic reticulum (ER) stress through the unfolded protein response (UPR), autophagy and cell death. In this study we utilized casp9(+/+) and casp9(-/-) MEFs to determine the effect of inhibition of mitochondrial apoptosis pathway on ER stress-induced-cell death, UPR and autophagy. We observed prolonged activation of UPR and autophagy in casp9(-/-) cells as compared with casp9(+/+) MEFs, which displayed transient activation of both pathways. Furthermore we showed that while casp9(-/-) MEFs were resistant to ER stress, prolonged exposure led to the activation of a non-canonical, caspase-mediated mode of cell death. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Virtual reality exposure-based therapy for the treatment of post-traumatic stress disorder: a review of its efficacy, the adequacy of the treatment protocol, and its acceptability

    Directory of Open Access Journals (Sweden)

    Botella C

    2015-10-01

    Full Text Available Cristina Botella,1 Berenice Serrano,1 Rosa M Baños,2 Azucena Garcia-Palacios1 1Universitat Jaume I, Castellón de la Plana, Spain; 2Universitat de Valencia, Valencia, Spain Introduction: The essential feature of post-traumatic stress disorder (PTSD is the development of characteristic symptoms following exposure to one or more traumatic events. According to evidence-based intervention guidelines and empirical evidence, one of the most extensively researched and validated treatments for PTSD is prolonged exposure to traumatic events; however, exposure therapy can present some limitations. Virtual reality (VR can help to improve prolonged exposure because it creates fictitious, safe, and controllable situations that can enhance emotional engagement and acceptance. Objective: In addition to carrying out a review to evaluate the efficacy of VR exposure-based therapy (VR-EBT for the treatment of PTSD, the aim of this study was to contribute to analyzing the use of VR-EBT by: first, evaluating the adequacy of psychological treatment protocols that use VR-EBT to treat PTSD; and second, analyzing the acceptability of VR-EBT. Method: We performed a replica search with descriptors and databases used in two previous reviews and updated to April 2015. Next, we carried out an evaluation of the efficacy, adequacy, and acceptability of VR-EBT protocols. Results: Results showed that VR-EBT was effective in the treatment of PTSD. The findings related to adequacy showed that not all studies using VR-EBT reported having followed the clinical guidelines for evidence-based interventions in the treatment of PTSD. Regarding acceptability, few studies evaluated this subject. However, the findings are very promising, and patients reported high acceptability and satisfaction with the inclusion of VR in the treatment of PTSD. Conclusion: The main weaknesses identified in this review focus on the need for more controlled studies, the need to standardize treatment

  7. Media’s role in broadcasting acute stress following the Boston Marathon bombings

    Science.gov (United States)

    Holman, E. Alison; Garfin, Dana Rose; Silver, Roxane Cohen

    2014-01-01

    We compared the impact of media vs. direct exposure on acute stress response to collective trauma. We conducted an Internet-based survey following the Boston Marathon bombings between April 29 and May 13, 2013, with representative samples of residents from Boston (n = 846), New York City (n = 941), and the remainder of the United States (n = 2,888). Acute stress symptom scores were comparable in Boston and New York [regression coefficient (b) = 0.43; SE = 1.42; 95% confidence interval (CI), −2.36, 3.23], but lower nationwide when compared with Boston (b = −2.21; SE = 1.07; 95% CI, −4.31, −0.12). Adjusting for prebombing mental health (collected prospectively), demographics, and prior collective stress exposure, six or more daily hours of bombing-related media exposure in the week after the bombings was associated with higher acute stress than direct exposure to the bombings (continuous acute stress symptom total: media exposure b = 15.61 vs. direct exposure b = 5.69). Controlling for prospectively collected prebombing television-watching habits did not change the findings. In adjusted models, direct exposure to the 9/11 terrorist attacks and the Sandy Hook School shootings were both significantly associated with bombing-related acute stress; Superstorm Sandy exposure wasn't. Prior exposure to similar and/or violent events may render some individuals vulnerable to the negative effects of collective traumas. Repeatedly engaging with trauma-related media content for several hours daily shortly after collective trauma may prolong acute stress experiences and promote substantial stress-related symptomatology. Mass media may become a conduit that spreads negative consequences of community trauma beyond directly affected communities. PMID:24324161

  8. Coexistence of Ureaplasma and chorioamnionitis is associated with prolonged mechanical ventilation.

    Science.gov (United States)

    Jung, Euiseok; Choi, Chang Won; Kim, Su Yeong; Sung, Tae-Jung; Kim, Haeryoung; Park, Kyoung Un; Kim, Han-Suk; Kim, Beyong Il; Choi, Jung-Hwan

    2017-01-01

    Both histologic chorioamnionitis (HCAM) and Ureaplasma infection are considered important contributors to perinatal lung injury. We tested the hypothesis that coexistence of maternal HCAM and perinatal Ureaplasma exposure increases the risk of prolonged mechanical ventilation in extremely low-birthweight (ELBW) infants. A retrospective cohort study was carried out of all ELBW infants born between January 2008 and December 2013 at a single academic center. Placental pathology and gastric fluid Ureaplasma data were available for all infants. Culture and polymerase chain reaction were used to detect Ureaplasma in gastric fluid. Prolonged mechanical ventilation was defined as mechanical ventilation that began within 28 days after birth and continued. Of 111 ELBW infants enrolled, 84 survived beyond 36 weeks of postmenstrual age (PMA) and were included in the analysis. Eighteen infants (21.4%) had both HCAM and Ureaplasma exposure. Seven infants (8.3%) required mechanical ventilation beyond 36 weeks of PMA. Coexistence of HCAM and Ureaplasma in gastric fluid was significantly associated with prolonged mechanical ventilation after adjustment for gestational age, sex, mode of delivery, and use of macrolide antibiotics (OR, 8.7; 95%CI: 1.1-67.2). Coexistence of maternal HCAM and perinatal Ureaplasma exposure significantly increases the risk of prolonged mechanical ventilation in ELBW infants. © 2016 Japan Pediatric Society.

  9. Differential effect of exposure-based therapy and cognitive therapy on post-traumatic stress disorder symptom clusters: A randomized controlled trial.

    Science.gov (United States)

    Horesh, Danny; Qian, Meng; Freedman, Sara; Shalev, Arieh

    2017-06-01

    A question remains regarding differential effects of exposure-based versus non-exposure-based therapies on specific post-traumatic stress disorder (PTSD) symptom clusters. Traumatized emergency room patients were randomized to receive prolonged exposure (PE) or cognitive therapy (CT) without exposure. PE/CT had no differential effect on individual symptom clusters, and change in total PTSD score remained significant even after controlling for the reductions in all three symptom clusters. In addition, baseline levels of PTSD avoidance/intrusion/hyperarousal did not moderate the effects of PE and CT on total PTSD symptom scores. Taken together, these findings challenge the notion that PE and CT are specifically, and differentially, useful in treating one particular PTSD symptom cluster. Despite their different theoretical backgrounds and techniques, the notion that PE and CT (without exposure) target different PTSD symptoms was not confirmed in this study. Thus, both interventions may in fact be equally effective for treating intrusion, avoidance and hyperarousal symptoms. Baseline levels of avoidance, intrusion and hyperarousal may not be good a priori indicators for PTSD treatment selection. The effect of PE and CT on PTSD as a whole does not seem to depend on a reduction in any specific symptom cluster. These findings indicate that exposure and non-exposure interventions may lead to similar results in terms of reductions in specific PTSD symptoms. It is quite possible that individual PTSD clusters may respond to therapy in an inter-related fashion, with one cluster affecting the other. © 2016 The British Psychological Society.

  10. Avoidant Coping and Treatment Outcome in Rape-Related Posttraumatic Stress Disorder

    Science.gov (United States)

    Leiner, Amy S.; Kearns, Megan C.; Jackson, Joan L.; Astin, Millie C.; Rothbaum, Barbara O.

    2012-01-01

    Objective: This study investigated the impact of avoidant coping on treatment outcome in rape-related posttraumatic stress disorder (PTSD). Method: Adult women with rape-related PTSD (N = 62) received 9 sessions of prolonged exposure (PE) or eye movement desensitization and reprocessing (EMDR). The mean age for the sample was 34.7 years, and race…

  11. Long-Term Outcomes of Cognitive-Behavioral Treatments for Posttraumatic Stress Disorder among Female Rape Survivors

    Science.gov (United States)

    Resick, Patricia A.; Williams, Lauren F.; Suvak, Michael K.; Monson, Candice M.; Gradus, Jaimie L.

    2012-01-01

    Objective: We conducted a long-term follow-up (LTFU) assessment of participants from a randomized controlled trial comparing cognitive processing therapy (CPT) with prolonged exposure (PE) for posttraumatic stress disorder (PTSD). Competing hypotheses for positive outcomes (i.e., additional therapy, medication) were examined. Method:…

  12. How Do Stress Exposure and Stress Regulation Relate to Borderline Personality Disorder?

    Directory of Open Access Journals (Sweden)

    Nadège Bourvis

    2017-11-01

    Full Text Available Borderline personality disorder (BPD is a severe and frequent disorder characterized by a pervasive pattern of instability affecting impulse control, emotional regulation, cognitive processing, self-image and interpersonal relationships. Patients’ personal histories are often marked by stressful or traumatic experiences, either unique or repeated. Moreover, while clinical signs of the disorder include both chronic and acute features, acute features are mostly triggered by acute stressful situations. Such features include transient cognitive distortion, intense anger, uncontrollable impulsivity, and self-harm behavior – including suicide – and contribute to the burden of the disease. In this paper, we review the various aspects (epidemiological, clinical, and physiological contributing to the relationship between BDP and stress. In particular, we explore the statistical association between stress exposure and the emergence of BPD while taking into account other psychopathologies, such as post-traumatic stress disorder. Then, the different aspects of stress responses (namely, the phenomenological, behavioral, hormonal, neuro-vegetative and neural responses are reviewed in BPD patients. Pathophysiological hypotheses are formulated to explain the differences in responses between BPD patients and healthy subjects and their relation to BPD symptoms. Although the pathogenesis remains uncertain, our conclusions seem to reflect a specific biological and neural pattern of altered stress perception and regulation in BPD.

  13. How Do Stress Exposure and Stress Regulation Relate to Borderline Personality Disorder?

    Science.gov (United States)

    Bourvis, Nadège; Aouidad, Aveline; Cabelguen, Clémence; Cohen, David; Xavier, Jean

    2017-01-01

    Borderline personality disorder (BPD) is a severe and frequent disorder characterized by a pervasive pattern of instability affecting impulse control, emotional regulation, cognitive processing, self-image and interpersonal relationships. Patients' personal histories are often marked by stressful or traumatic experiences, either unique or repeated. Moreover, while clinical signs of the disorder include both chronic and acute features, acute features are mostly triggered by acute stressful situations. Such features include transient cognitive distortion, intense anger, uncontrollable impulsivity, and self-harm behavior - including suicide - and contribute to the burden of the disease. In this paper, we review the various aspects (epidemiological, clinical, and physiological) contributing to the relationship between BDP and stress. In particular, we explore the statistical association between stress exposure and the emergence of BPD while taking into account other psychopathologies, such as post-traumatic stress disorder. Then, the different aspects of stress responses (namely, the phenomenological, behavioral, hormonal, neuro-vegetative and neural responses) are reviewed in BPD patients. Pathophysiological hypotheses are formulated to explain the differences in responses between BPD patients and healthy subjects and their relation to BPD symptoms. Although the pathogenesis remains uncertain, our conclusions seem to reflect a specific biological and neural pattern of altered stress perception and regulation in BPD.

  14. How Do Stress Exposure and Stress Regulation Relate to Borderline Personality Disorder?

    Science.gov (United States)

    Bourvis, Nadège; Aouidad, Aveline; Cabelguen, Clémence; Cohen, David; Xavier, Jean

    2017-01-01

    Borderline personality disorder (BPD) is a severe and frequent disorder characterized by a pervasive pattern of instability affecting impulse control, emotional regulation, cognitive processing, self-image and interpersonal relationships. Patients’ personal histories are often marked by stressful or traumatic experiences, either unique or repeated. Moreover, while clinical signs of the disorder include both chronic and acute features, acute features are mostly triggered by acute stressful situations. Such features include transient cognitive distortion, intense anger, uncontrollable impulsivity, and self-harm behavior – including suicide – and contribute to the burden of the disease. In this paper, we review the various aspects (epidemiological, clinical, and physiological) contributing to the relationship between BDP and stress. In particular, we explore the statistical association between stress exposure and the emergence of BPD while taking into account other psychopathologies, such as post-traumatic stress disorder. Then, the different aspects of stress responses (namely, the phenomenological, behavioral, hormonal, neuro-vegetative and neural responses) are reviewed in BPD patients. Pathophysiological hypotheses are formulated to explain the differences in responses between BPD patients and healthy subjects and their relation to BPD symptoms. Although the pathogenesis remains uncertain, our conclusions seem to reflect a specific biological and neural pattern of altered stress perception and regulation in BPD. PMID:29250007

  15. The stress response in gametes and embryos after paternal chemical exposures

    International Nuclear Information System (INIS)

    Hales, Barbara F.; Aguilar-Mahecha, Adriana; Robaire, Bernard

    2005-01-01

    There is increasing concern that paternal exposure to toxic chemicals impacts negatively on progeny outcome. Exposure of male rats to a model male-mediated developmental toxicant and anticancer alkylating agent, cyclophosphamide, resulted in increased pre- and post-implantation loss, as well as in malformations. We hypothesize that the stage specificity of the effects of paternal cyclophosphamide exposure on progeny depends on the ability of germ cells to respond to stress, repair DNA or undergo apoptosis. Acute high dose exposure of male rats to cyclophosphamide increased the expression of heat shock proteins and DNA repair genes, predominantly in round spermatids. In contrast, chronic low dose treatment dramatically decreased the expression of stress response genes in pachytene spermatocytes and round spermatids, but not in elongated spermatids; this reduced ability to respond to stress may allow damage to accumulate, resulting in altered sperm function. Increased DNA damage was maximal 3 weeks after drug exposure, during spermiogenesis, a key point in sperm chromatin remodelling. Drug exposure for 9 weeks increased the frequency of spermatozoa with chromosome 4 disomy and nullisomy. DNA damage found in cyclophosphamide-exposed spermatozoa was imparted to the newly fertilized zygote. Drug-exposed spermatozoa decondensed more rapidly than control spermatozoa and male pronuclear formation was earlier. RNA synthesis was higher in 1-cell embryos sired by drug-treated fathers than in controls. Significantly, the profile of gene expression was altered in embryos sired by drug-treated males as early as the 1-cell stage. Thus, exposure of male rats to cyclophosphamide altered male germ cell quality with a consequent temporal and spatial disruption of the zygotic genome activation

  16. Trait anxiety mediates the effect of stress exposure on post-traumatic stress disorder and depression risk in cardiac surgery patients.

    Science.gov (United States)

    Kok, Lotte; Sep, Milou S; Veldhuijzen, Dieuwke S; Cornelisse, Sandra; Nierich, Arno P; van der Maaten, Joost; Rosseel, Peter M; Hofland, Jan; Dieleman, Jan M; Vinkers, Christiaan H; Joëls, Marian; van Dijk, Diederik; Hillegers, Manon H

    2016-12-01

    Post-traumatic stress disorder (PTSD) and depression are common after cardiac surgery. Lifetime stress exposure and personality traits may influence the development of these psychiatric conditions. Self-reported rates of PTSD and depression and potential determinants (i.e., trait anxiety and stress exposure) were established 1.5 to 4 years after cardiac surgery. Data was available for 1125 out of 1244 (90.4%) participants. Multivariable linear regressions were conducted to investigate mediating and/or moderating effects of trait anxiety on the relationship between stress exposure, and PTSD and depression. Pre-planned subgroup analyses were performed for both sexes. PTSD and depression symptoms were present in 10.2% and 13.1% of the participants, respectively. Trait anxiety was a full mediator of the association between stress exposure and depression in both the total cohort and female and male subgroups. Moreover, trait anxiety partially mediated the relationship between stress exposure and PTSD in the full cohort and the male subgroup, whereas trait anxiety fully mediated this relationship in female patients. Trait anxiety did not play a moderating role in the total patient sample, nor after stratification on gender. The unequal distribution of male (78%) and female patients (22%) might limit the generalizability of our findings. Furthermore, risk factors were investigated retrospectively and with variable follow-up time. In cardiac surgery patients, trait anxiety was found to be an important mediator of postoperative PTSD and depression. Prospective research is necessary to verify whether these factors are reliable screening measures of individuals' vulnerability for psychopathology development after cardiac surgery. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. The impact of life stress on adult depression and anxiety is dependent on gender and timing of exposure.

    Science.gov (United States)

    Herbison, Carly E; Allen, Karina; Robinson, Monique; Newnham, John; Pennell, Craig

    2017-10-01

    There is debate about the relative importance of timing of stressful events prenatally and over the life course and risk for subsequent depressive/anxious illness. The aim of this study was to examine the relative roles of prenatal stress and postnatal stress trajectories in predicting depression and anxiety in early adulthood in males and females. Exposure to life stress events was examined in the Western Australian Pregnancy Cohort (Raine) Study during pregnancy and ages 1, 2, 3, 5, 8, 10, 14, and 17 years. At age 20, offspring completed the Depression Anxiety Stress Scale. Prenatal stress and trajectories of stress events from age 1 to 17 were analyzed in linear regression analyses. Five postnatal stress trajectories were identified. In females, medium to high chronic stress exposure or exposure during puberty/adolescence predicted depression and anxiety symptoms while low or reduced stress exposure over the life course did not, after adjustment for relevant confounders. High stress early in pregnancy contributed to male depression/anxiety symptoms independent of postnatal stress trajectory. In females, postnatal stress trajectory was more important than prenatal stress in predicting depression/anxiety symptoms. Interventions focused on reducing and managing stress events around conception/pregnancy and exposure to chronic stress are likely to have beneficial outcomes on rates of depression and anxiety in adults.

  18. Critical disease windows shaped by stress exposure alter allocation trade-offs between development and immunity.

    Science.gov (United States)

    Kirschman, Lucas J; Crespi, Erica J; Warne, Robin W

    2018-01-01

    Ubiquitous environmental stressors are often thought to alter animal susceptibility to pathogens and contribute to disease emergence. However, duration of exposure to a stressor is likely critical, because while chronic stress is often immunosuppressive, acute stress can temporarily enhance immune function. Furthermore, host susceptibility to stress and disease often varies with ontogeny; increasing during critical developmental windows. How the duration and timing of exposure to stressors interact to shape critical windows and influence disease processes is not well tested. We used ranavirus and larval amphibians as a model system to investigate how physiological stress and pathogenic infection shape development and disease dynamics in vertebrates. Based on a resource allocation model, we designed experiments to test how exposure to stressors may induce resource trade-offs that shape critical windows and disease processes because the neuroendocrine stress axis coordinates developmental remodelling, immune function and energy allocation in larval amphibians. We used wood frog larvae (Lithobates sylvaticus) to investigate how chronic and acute exposure to corticosterone, the dominant amphibian glucocorticoid hormone, mediates development and immune function via splenocyte immunohistochemistry analysis in association with ranavirus infection. Corticosterone treatments affected immune function, as both chronic and acute exposure suppressed splenocyte proliferation, although viral replication rate increased only in the chronic corticosterone treatment. Time to metamorphosis and survival depended on both corticosterone treatment and infection status. In the control and chronic corticosterone treatments, ranavirus infection decreased survival and delayed metamorphosis, although chronic corticosterone exposure accelerated rate of metamorphosis in uninfected larvae. Acute corticosterone exposure accelerated metamorphosis increased survival in infected larvae. Interactions

  19. Social identity influences stress appraisals and cardiovascular reactions to acute stress exposure.

    Science.gov (United States)

    Gallagher, Stephen; Meaney, Sarah; Muldoon, Orla T

    2014-09-01

    This study tested a recent theoretical development in stress research to see whether group membership influenced cardiovascular reactions following exposure to acute stress. Participants (N = 104) were exposed to a message in which a maths test was described as stressful or challenging by an ingroup member (a student) or outgroup member (a stress disorder sufferer). Systolic blood pressure and diastolic blood pressure(DBP) and heart rate (HR) were monitored throughout a standard reactivity study. As expected, a significant interaction was found; relative to those who were told that the task was challenging, ingroup members reported more stress and had higher DBP and HR reactivity when told by an ingroup member that the maths task was stressful; task information did not have the same effect for outgroup members. These results indicate that informational support is not constant but varies as a function of group membership. Finally, this recent development in stress research may prove useful for those interested in investigating the interactions between social, psychological and physiological processes underlying health disparities. What is already known on this subject? Stress is a common risk factor for hypertension and coronary heart disease. Social support has been found to reduce cardiovascular reactions to acute psychological stress. The influence of social support on stress varies as a consequence of social identity. What does this study add? The social group that one belongs to influences how one appraises and responds to stress. Social identity provides a useful framework for understanding how social processes are associated with health disparities. © 2013 The British Psychological Society.

  20. The Buffer Effect of Therapy Dog Exposure on Stress Reactivity in Undergraduate Students.

    Science.gov (United States)

    Fiocco, Alexandra J; Hunse, Anastasia M

    2017-06-30

    Stress is an insidious health risk that is commonly reported among university students. While research suggests that dog exposure may facilitate recovery from a stress response, little is known about the buffer effect of dog exposure on the stress response to a future stressor. This study examined whether interaction with a therapy dog could reduce the strength of the physiological stress response when exposed to a subsequent stressor. Sixty-one university students were randomly assigned to either a therapy dog (TD, n = 31) or a no-dog control (C, n = 30) group. The stress response was measured by electrodermal activity (EDA) in response to the Paced Auditory Serial Addition Test (PASAT). Participants also completed questionnaires that assessed pet attitude, general stress levels, and affect. Analyses of covariance (ANCOVAs) showed that increase in EDA was significantly more pronounced in the C group than in the TD group ( p stress response in university students, which has implications for the promotion of a viable stress management program on university campuses.

  1. Traumatic exposure and posttraumatic stress disorder among flood victims: Testing a multiple mediating model.

    Science.gov (United States)

    Quan, Lijuan; Zhen, Rui; Yao, Benxian; Zhou, Xiao

    2017-05-01

    A total of 187 flood victims from Wuhu, a Chinese city affected most severely by a flood during July 2016, were selected to complete self-report measures of traumatic exposure, feelings of safety, fear, posttraumatic negative cognition, and posttraumatic stress disorder. The results found that traumatic exposure could directly predict posttraumatic stress disorder. Besides, traumatic exposure had indirect prediction on posttraumatic stress disorder through three ways, including a one-step path of negative self-cognition, a two-step path from feelings of safety to fear, and a three-step path from feelings of safety to negative self-cognition via fear. Implications and future directions are correspondingly discussed.

  2. Generalized Unsafety Theory of Stress: Unsafe Environments and Conditions, and the Default Stress Response.

    Science.gov (United States)

    Brosschot, Jos F; Verkuil, Bart; Thayer, Julian F

    2018-03-07

    Prolonged physiological stress responses form an important risk factor for disease. According to neurobiological and evolution-theoretical insights the stress response is a default response that is always "on" but inhibited by the prefrontal cortex when safety is perceived. Based on these insights the Generalized Unsafety Theory of Stress (GUTS) states that prolonged stress responses are due to generalized and largely unconsciously perceived unsafety rather than stressors. This novel perspective necessitates a reconstruction of current stress theory, which we address in this paper. We discuss a variety of very common situations without stressors but with prolonged stress responses, that are not, or not likely to be caused by stressors, including loneliness, low social status, adult life after prenatal or early life adversity, lack of a natural environment, and less fit bodily states such as obesity or fatigue. We argue that in these situations the default stress response may be chronically disinhibited due to unconsciously perceived generalized unsafety. Also, in chronic stress situations such as work stress, the prolonged stress response may be mainly caused by perceived unsafety in stressor-free contexts. Thus, GUTS identifies and explains far more stress-related physiological activity that is responsible for disease and mortality than current stress theories.

  3. Generalized Unsafety Theory of Stress: Unsafe Environments and Conditions, and the Default Stress Response

    Directory of Open Access Journals (Sweden)

    Jos F. Brosschot

    2018-03-01

    Full Text Available Prolonged physiological stress responses form an important risk factor for disease. According to neurobiological and evolution-theoretical insights the stress response is a default response that is always “on” but inhibited by the prefrontal cortex when safety is perceived. Based on these insights the Generalized Unsafety Theory of Stress (GUTS states that prolonged stress responses are due to generalized and largely unconsciously perceived unsafety rather than stressors. This novel perspective necessitates a reconstruction of current stress theory, which we address in this paper. We discuss a variety of very common situations without stressors but with prolonged stress responses, that are not, or not likely to be caused by stressors, including loneliness, low social status, adult life after prenatal or early life adversity, lack of a natural environment, and less fit bodily states such as obesity or fatigue. We argue that in these situations the default stress response may be chronically disinhibited due to unconsciously perceived generalized unsafety. Also, in chronic stress situations such as work stress, the prolonged stress response may be mainly caused by perceived unsafety in stressor-free contexts. Thus, GUTS identifies and explains far more stress-related physiological activity that is responsible for disease and mortality than current stress theories.

  4. Effects of maternal stress and perinatal fluoxetine exposure on behavioral outcomes of adult male offspring.

    Science.gov (United States)

    Kiryanova, V; Meunier, S J; Vecchiarelli, H A; Hill, M N; Dyck, R H

    2016-04-21

    Women of child-bearing age are the population group at highest risk for depression. In pregnant women, fluoxetine (Flx) is the most widely prescribed selective serotonin reuptake inhibitor (SSRI) used for the treatment of depression. While maternal stress, depression, and Flx exposure have been shown to effect neurodevelopment of the offspring, separately, combined effects of maternal stress and Flx exposure have not been extensively examined. The present study investigated the effects of prenatal maternal stress and perinatal exposure to the SSRI Flx on the behavior of male mice as adults. C57BL/6 dams exposed to chronic unpredictable stress from embryonic (E) day 4 to E18 and non-stressed dams were administered Flx (25 mg/kg/d) in the drinking water from E15 to postnatal day 12. A separate control group consisted of animals that were not exposed to stress or Flx. At 12 days of age, brain levels of serotonin were assessed in the male offspring. At two months of age, the male offspring of mothers exposed to prenatal stress (PS), perinatal Flx, PS and Flx, or neither PS or Flx, went through a comprehensive behavioral test battery. At the end of testing brain-derived neurotropic factor (BDNF) levels were assessed in the frontal cortex of the offspring. Maternal behavior was not altered by either stress or Flx treatment. Treatment of the mother with Flx led to detectible Flx and NorFlx levels and lead to a decrease in serotonin levels in pup brains. In the adult male offspring, while perinatal exposure to Flx increased aggressive behavior, prenatal maternal stress decreased aggressive behavior. Interestingly, the combined effects of stress and Flx normalized aggressive behavior. Furthermore, perinatal Flx treatment led to a decrease in anxiety-like behavior in male offspring. PS led to hyperactivity and a decrease in BDNF levels in the frontal cortex regardless of Flx exposure. Neither maternal stress or Flx altered offspring performance in tests of cognitive

  5. Increased albumin excretion in industrial workers due to shift work rather than to prolonged exposure to low concentrations of chlorinated hydrocarbons.

    OpenAIRE

    Boogaard, P J; Caubo, M E

    1994-01-01

    OBJECTIVES--It has been reported that groups of workers in petrochemical industries who have been exposed to low concentrations of chemicals for prolonged periods have an increased urinary albumin excretion compared with unexposed controls. This increase, however, seemed to be unrelated to the extent, duration, and type of exposure. The aim of the present study was to investigate the suggestion that the small increase in albumin excretion might be due to differences in physical workload betwe...

  6. Effects of Electromagnetic Radiation Exposure on Stress-Related Behaviors and Stress Hormones in Male Wistar Rats

    Science.gov (United States)

    Mahdavi, Seyed Mohammad; Sahraei, Hedayat; Yaghmaei, Parichehreh; Tavakoli, Hassan

    2014-01-01

    Studies have demonstrated that electromagnetic waves, as the one of the most important physical factors, may alter cognitive and non-cognitive behaviors, depending on the frequency and energy. Moreover, non-ionizing radiation of low energy waves e.g. very low frequency waves could alter this phenomenon via alterations in neurotransmitters and neurohormones. In this study, short, medium, and long-term exposure to the extremely low frequency electromagnetic field (ELF-EMF) (1 and 5 Hz radiation) on behavioral, hormonal, and metabolic changes in male Wistar rats (250 g) were studied. In addition, changes in plasma concentrations for two main stress hormones, noradrenaline and adrenocorticotropic hormone (ACTH) were evaluated. ELF-EMF exposure did not alter body weight, and food and water intake. Plasma glucose level was increased and decreased in the groups which exposed to the 5 and 1Hz wave, respectively. Plasma ACTH concentration increased in both using frequencies, whereas nor-adrenaline concentration showed overall reduction. At last, numbers of rearing, sniffing, locomotor activity was increased in group receiving 5 Hz wave over the time. In conclusions, these data showed that the effects of 1 and 5 Hz on the hormonal, metabolic and stress-like behaviors may be different. Moreover, the influence of waves on stress system is depending on time of exposure. PMID:25489427

  7. Effects of electromagnetic radiation exposure on stress-related behaviors and stress hormones in male wistar rats.

    Science.gov (United States)

    Mahdavi, Seyed Mohammad; Sahraei, Hedayat; Yaghmaei, Parichehreh; Tavakoli, Hassan

    2014-11-01

    Studies have demonstrated that electromagnetic waves, as the one of the most important physical factors, may alter cognitive and non-cognitive behaviors, depending on the frequency and energy. Moreover, non-ionizing radiation of low energy waves e.g. very low frequency waves could alter this phenomenon via alterations in neurotransmitters and neurohormones. In this study, short, medium, and long-term exposure to the extremely low frequency electromagnetic field (ELF-EMF) (1 and 5 Hz radiation) on behavioral, hormonal, and metabolic changes in male Wistar rats (250 g) were studied. In addition, changes in plasma concentrations for two main stress hormones, noradrenaline and adrenocorticotropic hormone (ACTH) were evaluated. ELF-EMF exposure did not alter body weight, and food and water intake. Plasma glucose level was increased and decreased in the groups which exposed to the 5 and 1Hz wave, respectively. Plasma ACTH concentration increased in both using frequencies, whereas nor-adrenaline concentration showed overall reduction. At last, numbers of rearing, sniffing, locomotor activity was increased in group receiving 5 Hz wave over the time. In conclusions, these data showed that the effects of 1 and 5 Hz on the hormonal, metabolic and stress-like behaviors may be different. Moreover, the influence of waves on stress system is depending on time of exposure.

  8. Adapting to warmer climate through prolonged maize grain filling period in the US Midwest

    Science.gov (United States)

    Zhu, P.; Zhuang, Q.; Jin, Z.

    2017-12-01

    Climate warming is expected to negatively impact the US food productivity. How to adapt to the future warmer environment and meet the rising food requirement becomes unprecedented urgent. Continuous satellite observational data provides an opportunity to examine the historic responses of crop plants to climate variation. Here 16 years crop growing phases information across US Midwest is generated based on satellite observations. We found a prolonged grain-filling period during 2000-2015, which could partly explain the increasing trend in Midwest maize yield. This longer grain-filling period might be resulted from the adoption of longer maturity group varieties or more resistant varieties to temperature variation. Other management practice changes like advance in planting date could be also an effective way of adapting future warmer climate through lowering the possibility of exposure to heat and drought stresses. If the progress in breeding technology enables the maize grain-filling period to prolong with the current rate, the maize grain filling length could be longer and maize yield in Midwest could adapt to future climate despite of the warming.

  9. Restoration of hippocampal growth hormone reverses stress-induced hippocampal impairment

    Directory of Open Access Journals (Sweden)

    Caitlin M. Vander Weele

    2013-06-01

    Full Text Available Though growth hormone (GH is synthesized by hippocampal neurons, where its expression is influenced by stress exposure, its function is poorly characterized. Here, we show that a regimen of chronic stress that impairs hippocampal function in rats also leads to a profound decrease in hippocampal GH levels. Restoration of hippocampal GH in the dorsal hippocampus via viral-mediated gene transfer completely reversed stress-related impairment of two hippocampus-dependent behavioral tasks, auditory trace fear conditioning and contextual fear conditioning, without affecting hippocampal function in unstressed control rats. GH overexpression reversed stress-induced decrements in both fear acquisition and long-term fear memory. These results suggest that loss of hippocampal GH contributes to hippocampal dysfunction following prolonged stress and demonstrate that restoring hippocampal GH levels following stress can promote stress resilience.

  10. Cumulative exposure to prior collective trauma and acute stress responses to the Boston marathon bombings.

    Science.gov (United States)

    Garfin, Dana Rose; Holman, E Alison; Silver, Roxane Cohen

    2015-06-01

    The role of repeated exposure to collective trauma in explaining response to subsequent community-wide trauma is poorly understood. We examined the relationship between acute stress response to the 2013 Boston Marathon bombings and prior direct and indirect media-based exposure to three collective traumatic events: the September 11, 2001 (9/11) terrorist attacks, Superstorm Sandy, and the Sandy Hook Elementary School shooting. Representative samples of residents of metropolitan Boston (n = 846) and New York City (n = 941) completed Internet-based surveys shortly after the Boston Marathon bombings. Cumulative direct exposure and indirect exposure to prior community trauma and acute stress symptoms were assessed. Acute stress levels did not differ between Boston and New York metropolitan residents. Cumulative direct and indirect, live-media-based exposure to 9/11, Superstorm Sandy, and the Sandy Hook shooting were positively associated with acute stress responses in the covariate-adjusted model. People who experience multiple community-based traumas may be sensitized to the negative impact of subsequent events, especially in communities previously exposed to similar disasters. © The Author(s) 2015.

  11. Effects of prenatal exposure to chronic mild stress and toluene in rats

    DEFF Research Database (Denmark)

    Hougaard, Karin; Andersen, Maibritt B; Hansen, Ase M

    2005-01-01

    The aim of the present study was to elucidate whether prenatal chronic stress, in combination with exposure to a developmental neurotoxicant, would increase effects in the offspring compared with the effects of either exposure alone. Development and neurobehavioral effects were investigated...... in female offspring of pregnant rats (Mol:WIST) exposed to chronic mild stress (CMS) during gestational days (GD) 9-20, or 1500 ppm toluene, 6 h/day during gestational days 7-20, or a combination of the two. Prenatal CMS was associated with decreased thymic weight and increased auditory startle response....... The corticosterone response to restraint seemed modified by prenatal exposure to toluene. Lactational body weight was decreased in offsprings subjected to CMS, primarily due to effects in the combined exposure group. Cognitive function was investigated in the Morris water maze, and some indications of improved...

  12. Stress responding in cannabis smokers as a function of trauma exposure, sex, and relapse in the human laboratory.

    Science.gov (United States)

    Chao, Thomas; Radoncic, Vanya; Hien, Denise; Bedi, Gillinder; Haney, Margaret

    2018-04-01

    Stress responding is linked to drug use, but little is known about stress responses in cannabis smokers. We investigated acute stress responding in cannabis smokers as a function of trauma exposure and sex, and relationships between stress responses and cannabis relapse. 125 healthy, non-treatment-seeking daily cannabis smokers (23F, 102 M) completed the Trier Social Stress Task (TSST), a standardized laboratory stressor; subsets also completed a trauma questionnaire (n = 106) and a laboratory cannabis relapse measure (n = 54). Stress responding was assessed with heart rate (HR), salivary cortisol (CORT), and self-rated mood. Cannabis smokers reporting at least one trauma exposure had higher CORT and anxiety overall compared to those reporting no trauma. Stress responding did not differ as a function of binary trauma exposure, although total number of exposures correlated positively with CORT and anxiety during stress. Females reported increased nervousness after stress relative to males matched to the females for cannabis and cigarette use. An interactive effect of sex and trauma on HR suggested that females with trauma exposure have increased cardiovascular stress responding relative to those without such exposure, with no differential effect in males. Stress responding did not predict laboratory cannabis relapse. We report differences in acute stress responding as a function of trauma, sex, and their interaction in a large sample of relatively homogenous cannabis smokers. Further investigation of how trauma impacts stress responding in male and female cannabis smokers, and how this relates to different aspects of cannabis use, is warranted. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Effects of prenatal exposure to chronic mild stress and toluene in rats

    DEFF Research Database (Denmark)

    Hougaard, K. S.; Andersen, Maud Bering; Hansen, A. M.

    2005-01-01

    The aim of the present study was to elucidate whether prenatal chronic stress, in combination with exposure to a developmental neurotoxicant, would increase effects in the offspring compared with the effects of either exposure alone. Development and neurobehavioral effects were investigated in fe...

  14. Exposure to Childhood Poverty and Mental Health Symptomatology in Adolescence: A Role of Coping Strategies.

    Science.gov (United States)

    Kim, Pilyoung; Neuendorf, Cynthia; Bianco, Hannah; Evans, Gary W

    2016-12-01

    Childhood poverty is associated with stress dysregulation which contributes to psychological illness in later ages. The adverse effects of childhood poverty on stress regulation may be mediated in part by the use of disengaging strategies to cope with stress. However, the relations among childhood poverty, coping strategies and psychopathology throughout childhood to adolescence have not been explored. This prospective, longitudinal study included 185 low- and middle-income adolescents at age 17. Chronic exposure to poverty from birth to early adolescence (age 13) was prospectively associated with increases in the use of disengagement versus engagement coping four years later. Increased use of disengagement coping between the ages of 13 and 17 explained the indirect link between poverty exposure since birth and both externalizing and internalizing symptoms at age 17. The findings provide evidence for a coping pathway underlying the link between prolonged exposure to childhood poverty and mental health sequelae. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  15. Competing for Consciousness: Prolonged Mask Exposure Reduces Object Substitution Masking

    Science.gov (United States)

    Goodhew, Stephanie C.; Visser, Troy A. W.; Lipp, Ottmar V.; Dux, Paul E.

    2011-01-01

    In object substitution masking (OSM) a sparse, temporally trailing 4-dot mask impairs target identification, even though it has different contours from, and does not spatially overlap with the target. Here, we demonstrate a previously unknown characteristic of OSM: Observers show reduced masking at prolonged (e.g., 640 ms) relative to intermediate…

  16. Measuring lifetime stress exposure and protective factors in life course research on racial inequality and birth outcomes.

    Science.gov (United States)

    Malat, Jennifer; Jacquez, Farrah; Slavich, George M

    2017-07-01

    There has been a long-standing interest in better understanding how social factors contribute to racial disparities in health, including birth outcomes. A recent emphasis in this context has been on identifying the effects of stress exposure and protective factors experienced over the entire lifetime. Yet despite repeated calls for a life course approach to research on this topic, very few studies have actually assessed how stressors and protective factors occurring over women's lives relate to birth outcomes. We discuss this issue here by describing how challenges in the measurement of lifetime stress exposure and protective factors have prevented researchers from developing an empirically-based life course perspective on health. First, we summarize prevailing views on racial inequality and birth outcomes; second, we discuss measurement challenges that exist in this context; and finally, we describe both new tools and needed tools for assessing lifetime stress exposure and suggest opportunities for integrating information on stress exposure and psychosocial protective factors. We conclude that more studies are needed that integrate information about lifetime stress exposures and the protective factors that promote resilience against such exposures to inform policy and practice recommendations to reduce racial disparities in birth outcomes.

  17. Single-Prolonged-Stress-Induced Changes in Autophagy-Related Proteins Beclin-1, LC3, and p62 in the Medial Prefrontal Cortex of Rats with Post-traumatic Stress Disorder.

    Science.gov (United States)

    Zheng, Shilei; Han, Fang; Shi, Yuxiu; Wen, Lili; Han, Dan

    2017-05-01

    Autophagy, or type II programmed cell death, plays a crucial role in many nervous system diseases. However, few studies have examined the role of autophagy in post-traumatic stress disorder (PTSD), and the mechanisms underlying PTSD are poorly understood. The objective of this research was to explore the expression of three important autophagy-related proteins, Beclin-1, microtubule-associated protein 1 light chain 3 (LC3), and p62/SQSTM1 (p62), in the medial prefrontal cortex (mPFC) of an animal model of PTSD to identify changes in autophagic activity during PTSD pathogenesis. PTSD was induced in rats by exposure to a single-prolonged stress (SPS). The Morris water maze was used to assess cognitive changes in rats from the SPS and control groups. Transmission electron microscopy (TEM) was employed to observe mPFC morphological changes. Immunohistochemistry, immunofluorescence, and Western blotting techniques were used to detect expression of Beclin-1, LC3, and p62 in the mPFC. The Morris water maze test results showed that the escape latency time was increased and that the percent time in the target quadrant was decreased in the SPS group compared with that in the control group. Numerous visible autolysosomes in mPFC neurons were observed using TEM after SPS stimulation. Compared with that in the control group, the expression of Beclin-1 and the LC3-II/I ratio significantly decreased at 1 day, then increased and peaked at 7 days, and slightly decreased at 14 days after SPS stimulation, whereas the converse was found for p62 expression. In conclusion, dysregulation of autophagic activity in the mPFC may play a crucial role in PTSD pathogenesis.

  18. Gene Expression Dynamics Accompanying the Sponge Thermal Stress Response.

    Science.gov (United States)

    Guzman, Christine; Conaco, Cecilia

    2016-01-01

    Marine sponges are important members of coral reef ecosystems. Thus, their responses to changes in ocean chemistry and environmental conditions, particularly to higher seawater temperatures, will have potential impacts on the future of these reefs. To better understand the sponge thermal stress response, we investigated gene expression dynamics in the shallow water sponge, Haliclona tubifera (order Haplosclerida, class Demospongiae), subjected to elevated temperature. Using high-throughput transcriptome sequencing, we show that these conditions result in the activation of various processes that interact to maintain cellular homeostasis. Short-term thermal stress resulted in the induction of heat shock proteins, antioxidants, and genes involved in signal transduction and innate immunity pathways. Prolonged exposure to thermal stress affected the expression of genes involved in cellular damage repair, apoptosis, signaling and transcription. Interestingly, exposure to sublethal temperatures may improve the ability of the sponge to mitigate cellular damage under more extreme stress conditions. These insights into the potential mechanisms of adaptation and resilience of sponges contribute to a better understanding of sponge conservation status and the prediction of ecosystem trajectories under future climate conditions.

  19. Expressions of Hippocampal Mineralocorticoid Receptor (MR) and Glucocorticoid Receptor (GR) in the Single-Prolonged Stress-Rats

    International Nuclear Information System (INIS)

    Zhe, Du; Fang, Han; Yuxiu, Shi

    2008-01-01

    Post-traumatic stress disorder (PTSD) is a stress-related mental disorder caused by traumatic experience. Single-prolonged stress (SPS) is one of the animal models proposed for PTSD. Rats exposed to SPS showed enhanced inhibition of the hypothalamo-pituitary-adrenal (HPA) axis, which has been reliably reproduced in patients with PTSD. Mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hippocampus regulate HPA axis by glucocorticoid negative feedback. Abnormalities in negative feedback are found in PTSD, suggesting that GR and MR might be involved in the pathophysiology of these disorders. In the present study, we performed immunohistochemistry and western blotting to examine the changes in hippocampal MR- and GR-expression after SPS. Immunohistochemistry revealed decreased MR- and GR-immunoreactivity (ir) in the CA1 of hippocampus in SPS animals. Change in GR sub-distribution was also observed, where GR-ir was shifted from nucleus to cytoplasm in SPS rats. Western blotting showed that SPS induced significantly decreased MR- and GR-protein in the whole hippocampus, although the degree of decreased expression of both receptors was different. Meanwhile, we also found the MR/GR ratio decreased in SPS rats. In general, SPS induced down-regulation of MR- and GR-expression. These findings suggest that MR and GR play critical roles in affecting hippocampal function. Changes in MR/GR ratio may be relevant for behavioral syndrome in PTSD

  20. Transgenerational effects of stress exposure on offspring phenotypes in apomictic dandelion.

    Directory of Open Access Journals (Sweden)

    Koen J F Verhoeven

    Full Text Available Heritable epigenetic modulation of gene expression is a candidate mechanism to explain parental environmental effects on offspring phenotypes, but current evidence for environment-induced epigenetic changes that persist in offspring generations is scarce. In apomictic dandelions, exposure to various stresses was previously shown to heritably alter DNA methylation patterns. In this study we explore whether these induced changes are accompanied by heritable effects on offspring phenotypes. We observed effects of parental jasmonic acid treatment on offspring specific leaf area and on offspring interaction with a generalist herbivore; and of parental nutrient stress on offspring root-shoot biomass ratio, tissue P-content and leaf morphology. Some of the effects appeared to enhance offspring ability to cope with the same stresses that their parents experienced. Effects differed between apomictic genotypes and were not always consistently observed between different experiments, especially in the case of parental nutrient stress. While this context-dependency of the effects remains to be further clarified, the total set of results provides evidence for the existence of transgenerational effects in apomictic dandelions. Zebularine treatment affected the within-generation response to nutrient stress, pointing at a role of DNA methylation in phenotypic plasticity to nutrient environments. This study shows that stress exposure in apomictic dandelions can cause transgenerational phenotypic effects, in addition to previously demonstrated transgenerational DNA methylation effects.

  1. Transgenerational effects of stress exposure on offspring phenotypes in apomictic dandelion.

    Science.gov (United States)

    Verhoeven, Koen J F; van Gurp, Thomas P

    2012-01-01

    Heritable epigenetic modulation of gene expression is a candidate mechanism to explain parental environmental effects on offspring phenotypes, but current evidence for environment-induced epigenetic changes that persist in offspring generations is scarce. In apomictic dandelions, exposure to various stresses was previously shown to heritably alter DNA methylation patterns. In this study we explore whether these induced changes are accompanied by heritable effects on offspring phenotypes. We observed effects of parental jasmonic acid treatment on offspring specific leaf area and on offspring interaction with a generalist herbivore; and of parental nutrient stress on offspring root-shoot biomass ratio, tissue P-content and leaf morphology. Some of the effects appeared to enhance offspring ability to cope with the same stresses that their parents experienced. Effects differed between apomictic genotypes and were not always consistently observed between different experiments, especially in the case of parental nutrient stress. While this context-dependency of the effects remains to be further clarified, the total set of results provides evidence for the existence of transgenerational effects in apomictic dandelions. Zebularine treatment affected the within-generation response to nutrient stress, pointing at a role of DNA methylation in phenotypic plasticity to nutrient environments. This study shows that stress exposure in apomictic dandelions can cause transgenerational phenotypic effects, in addition to previously demonstrated transgenerational DNA methylation effects.

  2. The Adverse Effects of Environmental Noise Exposure on Oxidative Stress and Cardiovascular Risk

    Science.gov (United States)

    Sørensen, Mette; Schmidt, Frank; Schmidt, Erwin; Steven, Sebastian; Kröller-Schön, Swenja; Daiber, Andreas

    2018-01-01

    Abstract Epidemiological studies have provided evidence that traffic noise exposure is linked to cardiovascular diseases such as arterial hypertension, myocardial infarction, and stroke. Noise is a nonspecific stressor that activates the autonomous nervous system and endocrine signaling. According to the noise reaction model introduced by Babisch and colleagues, chronic low levels of noise can cause so-called nonauditory effects, such as disturbances of activity, sleep, and communication, which can trigger a number of emotional responses, including annoyance and subsequent stress. Chronic stress in turn is associated with cardiovascular risk factors, comprising increased blood pressure and dyslipidemia, increased blood viscosity and blood glucose, and activation of blood clotting factors, in animal models and humans. Persistent chronic noise exposure increases the risk of cardiometabolic diseases, including arterial hypertension, coronary artery disease, diabetes mellitus type 2, and stroke. Recently, we demonstrated that aircraft noise exposure during nighttime can induce endothelial dysfunction in healthy subjects and is even more pronounced in coronary artery disease patients. Importantly, impaired endothelial function was ameliorated by acute oral treatment with the antioxidant vitamin C, suggesting that excessive production of reactive oxygen species contributes to this phenomenon. More recently, we introduced a novel animal model of aircraft noise exposure characterizing the underlying molecular mechanisms leading to noise-dependent adverse oxidative stress-related effects on the vasculature. With the present review, we want to provide an overview of epidemiological, translational clinical, and preclinical noise research addressing the nonauditory, adverse effects of noise exposure with focus on oxidative stress. Antioxid. Redox Signal. 28, 873–908. PMID:29350061

  3. Effect of thermal exposure on the residual stress relaxation in a hardened cylindrical sample under creep conditions

    Science.gov (United States)

    Radchenko, V. P.; Saushkin, M. N.; Tsvetkov, V. V.

    2016-05-01

    This paper describes the effect of thermal exposure (high-temperature exposure) ( T = 675°C) on the residual creep stress relaxation in a surface hardened solid cylindrical sample made of ZhS6UVI alloy. The analysis is carried out with the use of experimental data for residual stresses after micro-shot peening and exposures to temperatures equal to T = 675°C during 50, 150, and 300 h. The paper presents the technique for solving the boundary-value creep problem for the hardened cylindrical sample with the initial stress-strain state under the condition of thermal exposure. The uniaxial experimental creep curves obtained under constant stresses of 500, 530, 570, and 600 MPa are used to construct the models describing the primary and secondary stages of creep. The calculated and experimental data for the longitudinal (axial) tensor components of residual stresses are compared, and their satisfactory agreement is determined.

  4. Prenatal fine particulate exposure and early childhood asthma: Effect of maternal stress and fetal sex.

    Science.gov (United States)

    Lee, Alison; Leon Hsu, Hsiao-Hsien; Mathilda Chiu, Yueh-Hsiu; Bose, Sonali; Rosa, Maria José; Kloog, Itai; Wilson, Ander; Schwartz, Joel; Cohen, Sheldon; Coull, Brent A; Wright, Robert O; Wright, Rosalind J

    2018-05-01

    The impact of prenatal ambient air pollution on child asthma may be modified by maternal stress, child sex, and exposure dose and timing. We prospectively examined associations between coexposure to prenatal particulate matter with an aerodynamic diameter of less than 2.5 microns (PM 2.5 ) and maternal stress and childhood asthma (n = 736). Daily PM 2.5 exposure during pregnancy was estimated using a validated satellite-based spatiotemporally resolved prediction model. Prenatal maternal negative life events (NLEs) were dichotomized around the median (high: NLE ≥ 3; low: NLE stress and child sex. Bayesian distributed lag interaction models identified a critical window of exposure (19-23 weeks' gestation, cumulative odds ratio, 1.15; 95% CI, 1.03-1.26; per interquartile range [1.7 μg/m 3 ] increase in prenatal PM 2.5 level) during which children concomitantly exposed to prenatal PM 2.5 and maternal stress had increased risk of asthma. No significant association was seen in children born to women reporting low prenatal stress. When examining modifying effects of prenatal stress and fetal sex, we found that boys born to mothers with higher prenatal stress were most vulnerable (19-21 weeks' gestation; cumulative odds ratio, 1.28; 95% CI, 1.15-1.41; per interquartile range increase in PM 2.5 ). Prenatal PM 2.5 exposure during sensitive windows is associated with increased risk of child asthma, especially in boys concurrently exposed to elevated maternal stress. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  5. Repeated homotypic stress elevates 2-arachidonoylglycerol levels and enhances short-term endocannabinoid signaling at inhibitory synapses in basolateral amygdala.

    Science.gov (United States)

    Patel, Sachin; Kingsley, Philip J; Mackie, Ken; Marnett, Lawrence J; Winder, Danny G

    2009-12-01

    Psychosocial stress is a risk factor for development and exacerbation of neuropsychiatric illness. Repeated stress causes biochemical adaptations in endocannabinoid (eCB) signaling that contribute to stress-response habituation, however, the synaptic correlates of these adaptations have not been examined. Here, we show that the synthetic enzyme for the eCB 2-arachidonoylglycerol (2-AG), diacylglycerol (DAG) lipase alpha, is heterogeneously expressed in the amygdala, and that levels of 2-AG and precursor DAGs are increased in the basolateral amygdala (BLA) after 10 days, but not 1 day, of restraint stress. In contrast, arachidonic acid was decreased after both 1 and 10 days of restraint stress. To examine the synaptic correlates of these alterations in 2-AG metabolism, we used whole-cell electrophysiology to determine the effects of restraint stress on depolarization-induced suppression of inhibition (DSI) in the BLA. A single restraint stress exposure did not alter DSI compared with control mice. However, after 10 days of restraint stress, DSI duration, but not magnitude, was significantly prolonged. Inhibition of 2-AG degradation with MAFP also prolonged DSI duration; the effects of repeated restraint stress and MAFP were mutually occlusive. These data indicate that exposure to repeated, but not acute, stress produces neuroadaptations that confer BLA neurons with an enhanced capacity to elevate 2-AG content and engage in 2-AG-mediated short-term retrograde synaptic signaling. We suggest stress-induced enhancement of eCB-mediated suppression of inhibitory transmission in the BLA could contribute to affective dysregulation associated with chronic stress.

  6. Assessment of Workplace Stress: Occupational Stress, Its Consequences, and Common Causes of Teacher Stress.

    Science.gov (United States)

    Hansen, Jo-Ida; Sullivan, Brandon A.

    This chapter introduces teachers and other education professionals to the assessment of occupational stress. It begins with a brief discussion of what occupational stress is, and overview of the consequences of prolonged stress, and a review of the common causes of teacher stress. Next, it presents methods for reducing occupational stress through…

  7. Prenatal Nitrate Exposure and Childhood Asthma. Influence of Maternal Prenatal Stress and Fetal Sex.

    Science.gov (United States)

    Bose, Sonali; Chiu, Yueh-Hsiu Mathilda; Hsu, Hsiao-Hsien Leon; Di, Qian; Rosa, Maria José; Lee, Alison; Kloog, Itai; Wilson, Ander; Schwartz, Joel; Wright, Robert O; Cohen, Sheldon; Coull, Brent A; Wright, Rosalind J

    2017-12-01

    Impact of ambient pollution upon children's asthma may differ by sex, and exposure dose and timing. Psychosocial stress can also modify pollutant effects. These associations have not been examined for in utero ambient nitrate exposure. We implemented Bayesian-distributed lag interaction models to identify sensitive prenatal windows for the influence of nitrate (NO 3 - ) on child asthma, accounting for effect modification by sex and stress. Analyses included 752 mother-child dyads. Daily ambient NO 3 - exposure during pregnancy was derived using a hybrid chemical transport (Geos-Chem)/land-use regression model and natural log transformed. Prenatal maternal stress was indexed by a negative life events score (high [>2] vs. low [≤2]). The outcome was clinician-diagnosed asthma by age 6 years. Most mothers were Hispanic (54%) or black (29%), had a high school education or less (66%), never smoked (80%), and reported low prenatal stress (58%); 15% of children developed asthma. BDILMs adjusted for maternal age, race, education, prepregnancy obesity, atopy, and smoking status identified two sensitive windows (7-19 and 33-40 wk gestation), during which increased NO 3 - was associated with greater odds of asthma, specifically among boys born to mothers reporting high prenatal stress. Cumulative effects of NO 3 - across pregnancy were also significant in this subgroup (odds ratio = 2.64, 95% confidence interval = 1.27-5.39; per interquartile range increase in ln NO 3 - ). Prenatal NO 3 - exposure during distinct sensitive windows was associated with incident asthma in boys concurrently exposed to high prenatal stress.

  8. [Occupational hazards, DNA damage, and oxidative stress on exposure to waste anesthetic gases].

    Science.gov (United States)

    Lucio, Lorena M C; Braz, Mariana G; do Nascimento Junior, Paulo; Braz, José Reinaldo C; Braz, Leandro G

    The waste anesthetic gases (WAGs) present in the ambient air of operating rooms (OR), are associated with various occupational hazards. This paper intends to discuss occupational exposure to WAGs and its impact on exposed professionals, with emphasis on genetic damage and oxidative stress. Despite the emergence of safer inhaled anesthetics, occupational exposure to WAGs remains a current concern. Factors related to anesthetic techniques and anesthesia workstations, in addition to the absence of a scavenging system in the OR, contribute to anesthetic pollution. In order to minimize the health risks of exposed professionals, several countries have recommended legislation with maximum exposure limits. However, developing countries still require measurement of WAGs and regulation for occupational exposure to WAGs. WAGs are capable of inducing damage to the genetic material, such as DNA damage assessed using the comet assay and increased frequency of micronucleus in professionals with long-term exposure. Oxidative stress is also associated with WAGs exposure, as it induces lipid peroxidation, oxidative damage in DNA, and impairment of the antioxidant defense system in exposed professionals. The occupational hazards related to WAGs including genotoxicity, mutagenicity and oxidative stress, stand as a public health issue and must be acknowledged by exposed personnel and responsible authorities, especially in developing countries. Thus, it is urgent to stablish maximum safe limits of concentration of WAGs in ORs and educational practices and protocols for exposed professionals. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  9. Early Life Trauma Exposure and Stress Sensitivity in Young Children

    OpenAIRE

    Grasso, Damion J.; Ford, Julian D.; Briggs-Gowan, Margaret J.

    2012-01-01

    Objective The current study replicates and extends work with adults that highlights the relationship between trauma exposure and distress in response to subsequent, nontraumatic life stressors. Methods The sample included 213 2–4-year-old children in which 64.3% had a history of potential trauma exposure. Children were categorized into 4 groups based on trauma history and current life stress. Results In a multivariate analysis of variance, trauma-exposed children with current life stressors h...

  10. Reported Exposure and Emotional Reactivity to Daily Stressors: The Roles of Adult-Age and Global Perceived Stress

    Science.gov (United States)

    Stawski, Robert S.; Sliwinski, Martin J.; Almeida, David M.; Smyth, Joshua M.

    2012-01-01

    A central goal of daily stress research is to identify resilience and vulnerability factors associated with exposure and reactivity to daily stressors. The current study examined how age differences and global perceptions of stress relate to exposure and emotional reactivity to daily stressors. Sixty-seven younger (Mage = 20) and 116 older (Mage = 80) adults completed a daily stress diary and measures of positive and negative affect on 6 days over a 14 day period. Participants also completed a measure of global perceived stress. Results revealed that reported exposure to daily stressors is reduced in old age, but that emotional reactivity to daily stressors did not differ between young and older adults. Global perceived stress was associated with greater reported exposure to daily stressors in old adults, and greater stress-related increases in negative affect in younger adults. Furthermore, across days on which daily stressors were reported, intraindividual variability in the number and severity of stressors reported was associated with increased negative affect, but only among younger adults. PMID:18361654

  11. Reported exposure and emotional reactivity to daily stressors: the roles of adult age and global perceived stress.

    Science.gov (United States)

    Stawski, Robert S; Sliwinski, Martin J; Almeida, David M; Smyth, Joshua M

    2008-03-01

    A central goal of daily stress research is to identify resilience and vulnerability factors associated with exposure and reactivity to daily stressors. The present study examined how age differences and global perceptions of stress relate to exposure and emotional reactivity to daily stressors. Sixty-seven younger (M age = 20) and 116 older (M age = 80) adults completed a daily stress diary and measures of positive and negative affect on 6 days over a 14-day period. Participants also completed a measure of global perceived stress. Results revealed that reported exposure to daily stressors is reduced in old age but that emotional reactivity to daily stressors did not differ between younger and older adults. Global perceived stress was associated with greater reported exposure to daily stressors in older adults and greater stress-related increases in negative affect in younger adults. Furthermore, across days on which daily stressors were reported, intraindividual variability in the number and severity of stressors reported was associated with increased negative affect, but only among younger adults. (c) 2008 APA, all rights reserved.

  12. Effect of Prolonged Exposure Therapy Delivered Over 2 Weeks vs 8 Weeks vs Present-Centered Therapy on PTSD Symptom Severity in Military Personnel: A Randomized Clinical Trial.

    Science.gov (United States)

    Foa, Edna B; McLean, Carmen P; Zang, Yinyin; Rosenfield, David; Yadin, Elna; Yarvis, Jeffrey S; Mintz, Jim; Young-McCaughan, Stacey; Borah, Elisa V; Dondanville, Katherine A; Fina, Brooke A; Hall-Clark, Brittany N; Lichner, Tracey; Litz, Brett T; Roache, John; Wright, Edward C; Peterson, Alan L

    2018-01-23

    Effective and efficient treatment is needed for posttraumatic stress disorder (PTSD) in active duty military personnel. To examine the effects of massed prolonged exposure therapy (massed therapy), spaced prolonged exposure therapy (spaced therapy), present-centered therapy (PCT), and a minimal-contact control (MCC) on PTSD severity. Randomized clinical trial conducted at Fort Hood, Texas, from January 2011 through July 2016 and enrolling 370 military personnel with PTSD who had returned from Iraq, Afghanistan, or both. Final follow-up was July 11, 2016. Prolonged exposure therapy, cognitive behavioral therapy involving exposure to trauma memories/reminders, administered as massed therapy (n = 110; 10 sessions over 2 weeks) or spaced therapy (n = 109; 10 sessions over 8 weeks); PCT, a non-trauma-focused therapy involving identifying/discussing daily stressors (n = 107; 10 sessions over 8 weeks); or MCC, telephone calls from therapists (n = 40; once weekly for 4 weeks). Outcomes were assessed before and after treatment and at 2-week, 12-week, and 6-month follow-up. Primary outcome was interviewer-assessed PTSD symptom severity, measured by the PTSD Symptom Scale-Interview (PSS-I; range, 0-51; higher scores indicate greater PTSD severity; MCID, 3.18), used to assess efficacy of massed therapy at 2 weeks posttreatment vs MCC at week 4; noninferiority of massed therapy vs spaced therapy at 2 weeks and 12 weeks posttreatment (noninferiority margin, 50% [2.3 points on PSS-I, with 1-sided α = .05]); and efficacy of spaced therapy vs PCT at posttreatment. Among 370 randomized participants, data were analyzed for 366 (mean age, 32.7 [SD, 7.3] years; 44 women [12.0%]; mean baseline PSS-I score, 25.49 [6.36]), and 216 (59.0%) completed the study. At 2 weeks posttreatment, mean PSS-I score was 17.62 (mean decrease from baseline, 7.13) for massed therapy and 21.41 (mean decrease, 3.43) for MCC (difference in decrease, 3.70 [95% CI,0.72 to 6.68]; P = .02

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

    Science.gov (United States)

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

    2016-06-01

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

  14. Assessing Lifetime Stress Exposure Using the Stress and Adversity Inventory for Adults (Adult STRAIN): An Overview and Initial Validation

    Science.gov (United States)

    Slavich, George M.; Shields, Grant S.

    2018-01-01

    ABSTRACT Objective Numerous theories have proposed that acute and chronic stressors may exert a cumulative effect on life-span health by causing biological “wear and tear,” or allostatic load, which in turn promotes disease. Very few studies have directly tested such models, though, partly because of the challenges associated with efficiently assessing stress exposure over the entire life course. To address this issue, we developed the first online system for systematically assessing lifetime stress exposure, called the Stress and Adversity Inventory (STRAIN), and describe its initial validation here. Methods Adults recruited from the community (n = 205) were administered the STRAIN, Childhood Trauma Questionnaire—Short Form, and Perceived Stress Scale, as well as measures of socioeconomic status, personality, social desirability, negative affect, mental and physical health complaints, sleep quality, computer-assessed executive function, and doctor-diagnosed general health problems and autoimmune disorders. Results The STRAIN achieved high acceptability and was completed relatively quickly (mean = 18 minutes 39 seconds; interquartile range = 12–23 minutes). The structure of the lifetime stress data best fit two latent classes overall and five distinct trajectories over time. Concurrent associations with the Childhood Trauma Questionnaire—Short Form and Perceived Stress Scale were good (r values = .147–.552). Moreover, the STRAIN was not significantly related to personality traits or social desirability characteristics and, in adjusted analyses, emerged as the measure most strongly associated with all six of the health and cognitive outcomes assessed except current mental health complaints (β values = .16–.41; risk ratios = 1.02–1.04). Finally, test-retest reliability for the main stress exposure indices over 2–4 weeks was excellent (r values = .904–.919). Conclusions The STRAIN demonstrated good usability and acceptability; very good concurrent

  15. Assessing Lifetime Stress Exposure Using the Stress and Adversity Inventory for Adults (Adult STRAIN): An Overview and Initial Validation.

    Science.gov (United States)

    Slavich, George M; Shields, Grant S

    2018-01-01

    Numerous theories have proposed that acute and chronic stressors may exert a cumulative effect on life-span health by causing biological "wear and tear," or allostatic load, which in turn promotes disease. Very few studies have directly tested such models, though, partly because of the challenges associated with efficiently assessing stress exposure over the entire life course. To address this issue, we developed the first online system for systematically assessing lifetime stress exposure, called the Stress and Adversity Inventory (STRAIN), and describe its initial validation here. Adults recruited from the community (n = 205) were administered the STRAIN, Childhood Trauma Questionnaire-Short Form, and Perceived Stress Scale, as well as measures of socioeconomic status, personality, social desirability, negative affect, mental and physical health complaints, sleep quality, computer-assessed executive function, and doctor-diagnosed general health problems and autoimmune disorders. The STRAIN achieved high acceptability and was completed relatively quickly (mean = 18 minutes 39 seconds; interquartile range = 12-23 minutes). The structure of the lifetime stress data best fit two latent classes overall and five distinct trajectories over time. Concurrent associations with the Childhood Trauma Questionnaire-Short Form and Perceived Stress Scale were good (r values = .147-.552). Moreover, the STRAIN was not significantly related to personality traits or social desirability characteristics and, in adjusted analyses, emerged as the measure most strongly associated with all six of the health and cognitive outcomes assessed except current mental health complaints (β values = .16-.41; risk ratios = 1.02-1.04). Finally, test-retest reliability for the main stress exposure indices over 2-4 weeks was excellent (r values = .904-.919). The STRAIN demonstrated good usability and acceptability; very good concurrent, discriminant, and predictive validity; and excellent test

  16. Prolonged Corrosion Stability of a Microchip Sensor Implant during In Vivo Exposure

    Directory of Open Access Journals (Sweden)

    Paul Glogener

    2018-02-01

    Full Text Available A microelectronic biosensor was subjected to in vivo exposure by implanting it in the vicinity of m. trapezii (Trapezius muscle from cattle. The implant is intended for the continuous monitoring of glucose levels, and the study aimed at evaluating the biostability of exposed semiconductor surfaces. The sensor chip was a microelectromechanical system (MEMS prepared using 0.25 µm complementary metal–oxide–semiconductor CMOS/BiCMOS technology. Sensing is based on the principle of affinity viscometry with a sensoric assay, which is separated by a semipermeable membrane from the tissue. Outer dimensions of the otherwise hermetically sealed biosensor system were 39 × 49 × 16 mm. The test system was implanted into cattle in a subcutaneous position without running it. After 17 months, the device was explanted and analyzed by comparing it with unexposed chips and systems. Investigations focused on the MEMS chip using SEM, TEM, and elemental analysis by EDX mapping. The sensor chip turned out to be uncorroded and no diminishing of the topmost passivation layer could be determined, which contrasts remarkably with previous results on CMOS biosensors. The negligible corrosive attack is understood to be a side effect of the semipermeable membrane separating the assay from the tissue. It is concluded that the separation has enabled a prolonged biostability of the chip, which will be of relevance for biosensor implants in general.

  17. Trait anxiety mediates the effect of stress exposure on post-traumatic stress disorder and depression risk in cardiac surgery patients

    NARCIS (Netherlands)

    Kok, Lotte; Sep, Milou S; Veldhuijzen, Dieuwke S; Cornelisse, Sandra; Nierich, Arno P; van der Maaten, Joost; Rosseel, Peter M; Hofland, Jan; Dieleman, Jan M; Vinkers, Christiaan H; Joëls, Marian; van Dijk, Diederik; Hillegers, Manon H

    2016-01-01

    BACKGROUND: Post-traumatic stress disorder (PTSD) and depression are common after cardiac surgery. Lifetime stress exposure and personality traits may influence the development of these psychiatric conditions. METHODS: Self-reported rates of PTSD and depression and potential determinants (i.e.,

  18. A simple melatonin treatment protocol attenuates the response to acute stress in the sole Solea senegalensis

    DEFF Research Database (Denmark)

    Gesto, Manuel; Álvarez-Otero, Rosa; Conde-Sieira, Marta

    2016-01-01

    Several compounds have been tested in fish in order to attenuate the effects of different stressors, most often following previous observations in mammals. The hormone melatonin (MEL) and the amino acid L-tryptophan have been tested for this purpose with different degree of success. In Senegalese...... sole (Solea senegalensis) we have previously observed that during prolonged exposure to relatively mild stressors, the presence of MEL in the water helped to reduce the stress response. Here, we aimed to investigate the potential anti-stress effects of a short melatonin exposure that could be easily...... performed in fish farms before an intended manipulative event with the animals. Our results demonstrate that adding MEL to the tanks 30. min before an acute chasing stress is effective in reducing the intensity of the stress response in fish from its beginning, as evidenced by the attenuated and delayed...

  19. Increased precipitation of spasms in an animal model of infantile spasms by prenatal stress exposure.

    Science.gov (United States)

    Shi, Xiu-Yu; Ju, Jun; Zou, Li-Ping; Wang, Juan; Shang, Ning-Xiu; Zhao, Jian-Bo; Wang, Jing; Zhang, Jun-Yan

    2016-05-01

    Infantile spasms (IS) represent a serious epileptic syndrome, called West syndrome (WS) that occurs in the early infantile age. Although several hypotheses and animal models have been proposed to explain the pathogenesis of IS, the pathophysiology of IS has not been elucidated. Recently, we proposed a hypothesis for IS under prenatal stress exposure (also called Zou's hypothesis) by correlating diverse etiologies and prenatal stresses with IS development. This research aims to determine the mechanism through which prenatal stress affects the offspring and establish the potential underlying mechanisms. Pregnant rats were subjected to forced swimming in cold water. Rat pups exposed to prenatal stress were administered with N-methyl-D-aspartate (NMDA). Exposure to prenatal stress sensitized the rats against development of NMDA-induced spasms. However, this phenomenon was altered by administering adrenocorticotropin. Prenatal stress exposure also altered the hormonal levels and neurotransmitter receptor expression of the developing rats as well as influenced the tissue structure of the brain. These findings suggest that maternal stress could alter the level of endogenous glucocorticoid, which is the basis of IS, and cerebral dysplasia, hypoxic-ischemic encephalopathy (HIE), inherited metabolic diseases, and other factors activated this disease in developmental brain. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Differential Impact of Stress Reduction Programs upon Ambulatory Blood Pressure among African American Adolescents: Influences of Endothelin-1 Gene and Chronic Stress Exposure

    Directory of Open Access Journals (Sweden)

    Mathew J. Gregoski

    2012-01-01

    Full Text Available Stress-activated gene × environment interactions may contribute to individual variability in blood pressure reductions from behavioral interventions. We investigated effects of endothelin-1 (ET-1 LYS198ASN SNP and discriminatory stress exposure upon impact of 12-week behavioral interventions upon ambulatory BP (ABP among 162 prehypertensive African American adolescents. Following genotyping, completion of questionnaire battery, and 24-hour ABP monitoring, participants were randomized to health education control (HEC, life skills training (LST, or breathing awareness meditation (BAM. Postintervention ABP was obtained. Significant three-way interactions on ABP changes indicated that among ET-1 SNP carriers, the only group to show reductions was BAM from low chronic stress environments. Among ET-1 SNP noncarriers, under low chronic stress exposure, all approaches worked, especially BAM. Among high stress exposure noncarriers, only BAM resulted in reductions. If these preliminary findings are replicated via ancillary analyses of archival databases and then via efficacy trials, selection of behavioral prescriptions for prehypertensives will be edging closer to being guided by individual's underlying genetic and environmental factors incorporating the healthcare model of personalized preventive medicine.

  1. Exposure to Acute Stress Enhances Decision-Making Competence: Evidence for the Role of DHEA

    Science.gov (United States)

    Shields, Grant S.; Lam, Jovian C. W.; Trainor, Brian C.; Yonelinas, Andrew P.

    2016-01-01

    Exposure to acute stress can impact performance on numerous cognitive abilities, but little is known about how acute stress affects real-world decision-making ability. In the present study, we induced acute stress with a standard laboratory task involving uncontrollable socio-evaluative stress and subsequently assessed decision-making ability using the Adult Decision Making Competence index. In addition, we took baseline and post-test saliva samples from participants to examine associations between decision-making competence and adrenal hormones. Participants in the stress induction group showed enhanced decision-making competence, relative to controls. Further, although both cortisol and dehydroepiandrosterone (DHEA) reactivity predicted decision-making competence when considered in isolation, DHEA was a significantly better predictor than cortisol when both hormones were considered simultaneously. Thus, our results show that exposure to acute stress can have beneficial effects on the cognitive ability underpinning real-world decision-making and that this effect relates to DHEA reactivity more than cortisol. PMID:26874561

  2. Exposure to acute stress enhances decision-making competence: Evidence for the role of DHEA.

    Science.gov (United States)

    Shields, Grant S; Lam, Jovian C W; Trainor, Brian C; Yonelinas, Andrew P

    2016-05-01

    Exposure to acute stress can impact performance on numerous cognitive abilities, but little is known about how acute stress affects real-world decision-making ability. In the present study, we induced acute stress with a standard laboratory task involving uncontrollable socio-evaluative stress and subsequently assessed decision-making ability using the Adult Decision Making Competence index. In addition, we took baseline and post-test saliva samples from participants to examine associations between decision-making competence and adrenal hormones. Participants in the stress induction group showed enhanced decision-making competence, relative to controls. Further, although both cortisol and dehydroepiandrosterone (DHEA) reactivity predicted decision-making competence when considered in isolation, DHEA was a significantly better predictor than cortisol when both hormones were considered simultaneously. Thus, our results show that exposure to acute stress can have beneficial effects on the cognitive ability underpinning real-world decision-making and that this effect relates to DHEA reactivity more than cortisol. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Harm expectancy violation during exposure therapy for posttraumatic stress disorder

    NARCIS (Netherlands)

    Kleine, R.A. de; Hendriks, L.; Becker, E.S.; Broekman, T.G.; Minnen, A. van

    2017-01-01

    Exposure therapy has proven efficacy in the treatment of posttraumatic stress disorder (PTSD). Emotional processing theory proposes that fear habituation is a central mechanism in symptom reduction, but the empirical evidence supporting this is mixed. Recently it has been proposed that violation of

  4. Stress-Triggered Phase Separation Is an Adaptive, Evolutionarily Tuned Response

    Energy Technology Data Exchange (ETDEWEB)

    Riback, Joshua A.; Katanski, Christopher D.; Kear-Scott, Jamie L.; Pilipenko, Evgeny V.; Rojek, Alexandra E.; Sosnick, Tobin R.; Drummond, D. Allan

    2017-03-01

    In eukaryotic cells, diverse stresses trigger coalescence of RNA-binding proteins into stress granules. In vitro, stress-granule-associated proteins can demix to form liquids, hydrogels, and other assemblies lacking fixed stoichiometry. Observing these phenomena has generally required conditions far removed from physiological stresses. We show that poly(A)-binding protein (Pab1 in yeast), a defining marker of stress granules, phase separates and forms hydrogels in vitro upon exposure to physiological stress conditions. Other RNA-binding proteins depend upon low-complexity regions (LCRs) or RNA for phase separation, whereas Pab1’s LCR is not required for demixing, and RNA inhibits it. Based on unique evolutionary patterns, we create LCR mutations, which systematically tune its biophysical properties and Pab1 phase separation in vitro and in vivo. Mutations that impede phase separation reduce organism fitness during prolonged stress. Poly(A)-binding protein thus acts as a physiological stress sensor, exploiting phase separation to precisely mark stress onset, a broadly generalizable mechanism.

  5. Mitochondrial oxidative stress contributes differently to rat pancreatic islet cell apoptosis and insulin secretory defects after prolonged culture in a low non-stimulating glucose concentration.

    Science.gov (United States)

    Roma, L P; Pascal, S M; Duprez, J; Jonas, J-C

    2012-08-01

    Pancreatic beta cells chronically exposed to low glucose concentrations show signs of oxidative stress, loss of glucose-stimulated insulin secretion (GSIS) and increased apoptosis. Our aim was to confirm the role of mitochondrial oxidative stress in rat islet cell apoptosis under these culture conditions and to evaluate whether its reduction similarly improves survival and GSIS. Apoptosis, oxidative stress-response gene mRNA expression and glucose-induced stimulation of mitochondrial metabolism, intracellular Ca(2+) concentration and insulin secretion were measured in male Wistar rat islets cultured for 1 week in RPMI medium containing 5-10 mmol/l glucose with or without manganese(III)tetrakis(4-benzoic acid)porphyrin (MnTBAP) or N-acetyl-L-: cysteine (NAC). Oxidative stress was measured in islet cell clusters cultured under similar conditions using cytosolic and mitochondrial redox-sensitive green fluorescent protein (roGFP1/mt-roGFP1). Prolonged culture in 5 vs 10 mmol/l glucose increased mt-roGFP1 (but not roGFP1) oxidation followed by beta cell apoptosis and loss of GSIS resulting from reduced insulin content, mitochondrial metabolism, Ca(2+) influx and Ca(2+)-induced secretion. Tolbutamide-induced, but not high K(+)-induced, Ca(2+) influx was also suppressed. Under these conditions, MnTBAP, but not NAC, triggered parallel ~50-70% reductions in mt-roGFP1 oxidation and beta cell apoptosis, but failed to protect against the loss of GSIS despite significant improvement in glucose-induced and tolbutamide-induced Ca(2+) influx. Mitochondrial oxidative stress contributes differently to rat pancreatic islet cell apoptosis and insulin secretory defects during culture in a low glucose concentration. Thus, targeting beta cell survival may not be sufficient to restore insulin secretion when beta cells suffer from prolonged mitochondrial oxidative stress, e.g. in the context of reduced glucose metabolism.

  6. Assessing the effects of exposure to environmental stress on some functional properties of Bifidobacterium animalis ssp. lactis.

    Science.gov (United States)

    Amund, O D; Ouoba, L I I; Sutherland, J P; Ghoddusi, H B

    2014-12-01

    This study assessed the effects of exposing a strain of Bifidobacterium animalis ssp. lactis to acid, bile and osmotic stresses on antagonistic properties, biofilm formation and antibiotic susceptibility/resistance profile. Exposure to each stress factor appeared to have no significant effect on the antagonism against Escherichia coli NCTC 12900 and Salmonella enterica serovar Enteritidis PT4. No suppression in biofilm formation due to exposure to stress was observed. Bile and osmotic stresses resulted in significantly higher biofilm formation. Expression of an exopolysaccharide synthesis gene, gtf 01207, was significantly higher when the B. animalis ssp. lactis strain was exposed to osmotic stress. Susceptibility of the B. animalis ssp. lactis strain to chloramphenicol, erythromycin, ampicillin and vancomycin, and resistance to tetracycline remained unchanged when exposed to each stress. The expression of a tetracycline resistance gene, tet(W), was significantly higher when exposed to each stress. These results may suggest that the potential for the B. animalis ssp. lactis strain to provide probiotic benefit, after exposure to the stressful conditions of the gastrointestinal tract, remains intact.

  7. Prenatal exposure to disaster-related traumatic stress and developmental trajectories of temperament in early childhood: Superstorm Sandy pregnancy study.

    Science.gov (United States)

    Zhang, Wei; Rajendran, Khushmand; Ham, Jacob; Finik, Jackie; Buthmann, Jessica; Davey, Kei; Pehme, Patricia M; Dana, Kathryn; Pritchett, Alexandra; Laws, Holly; Nomura, Yoko

    2018-07-01

    Little is known about the impact of prenatal maternal stress (PNMS) on the developmental trajectory of temperament and few studies have been able to incorporate a natural disaster as a quasi-experimental stressor. The current study investigated PNMS related to Superstorm Sandy ('Sandy'), a hurricane that struck the New York metropolitan area in October 2012, in terms of objective exposure during pregnancy, subjective stress reaction as assessed by maternal symptoms of post-traumatic stress, and their impact on the developmental changes in temperament during early childhood. A subsample of 318 mother-child dyads was drawn from the Stress in Pregnancy Study. Temperament was measured at 6, 12, 18, and 24 months of age. Objective exposure was associated with greater High-Intensity Pleasure, Approach, Perceptual Sensitivity and Fearfulness, but lower Cuddliness and Duration of Orientation at 6 months. Objective exposure and its interaction with subjective stress reaction predicted developmental changes in temperament. In particular, objective exposure was linked to greater increases in Activity Level but decreases in High-Intensity Pleasure, Approach, and Fearfulness. The combination of objective exposure and subjective stress reaction was also associated with greater increases in Activity Level. Temperament was measured solely via maternal report. Trimester-specific effects of Sandy on temperament were not examined. This is the first study to examine the effects of prenatal maternal exposure to a natural disaster on trajectories of early childhood temperament. Findings suggest that both objective stress exposure and subjective stress reaction in-utero predict developmental trajectories of temperament in early childhood. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Violence Exposure and Psychopathology in Urban Youth: The Mediating Role of Posttraumatic Stress

    Science.gov (United States)

    Ruchkin, Vladislav; Henrich, Christopher C.; Jones, Stephanie M.; Vermeiren, Robert; Schwab-Stone, Mary

    2007-01-01

    Understanding the mechanisms underlying the development of violence exposure sequelae is essential to providing effective treatments for traumatized youth. This longitudinal study examined the mediating role of posttraumatic stress in the relationship between violence exposure and psychopathology, and compared the mediated models by gender. Urban…

  9. Induction of stress responses by polluting agents which dis-regulate cellular homeostasis

    International Nuclear Information System (INIS)

    Mothersill, Carmel

    2001-01-01

    There is growing concern both in the scientific community and among the general public about the effects of exposure to low levels of radiation and environmental chemicals. The increased incidence of cancer, reproduction disorders and allergies have been associated with ambient environmental exposure to these pollutants. The pollution burden is generally made up of a mixture of agents, occurring at concentrations of the individual compounds which are not considered harmful and which are below the action level. Individual pollutants can act through a variety of primary toxicity mechanisms. However the resulting secondary and tertiary toxicity mechanisms which affect cellular homeostasis might be more common. These resulting stress responses, including oxidative stress, have been associated with effects that include increased level of death during cell division, increased levels of mutation and increased tolerance of mutations in cell populations, increased levels of cytogenetic abnormalities and many other symptoms. These effects are linked to a persistent increase in (oxidative) stress and are particularly evident in the haematopoietic system (possibly due to the high rate self of renewal in that system). Therefore prolonged exposure to mixtures of chemicals and radiation might result in additive and synergistic stress responses which can induce long-term delayed effects, often in progeny or in cells not directly exposed to the agent/s. The existence of a common (oxidative) stress mechanism means that the effects of individual pollutants may not be considered in isolation. Rather the total pollution burden may need to be measured using a response rather than a dose based scoring or ranking system. Improved understanding of toxicity mechanisms and effects underpins improved risk assessment and identification of biomarkers. The immune system plays a pivotal role in maintaining health status, and disruption of immune functions can lead to increased susceptibility to

  10. Sexually dimorphic effects of ancestral exposure to vinclozolin on stress reactivity in rats.

    Science.gov (United States)

    Gillette, Ross; Miller-Crews, Isaac; Nilsson, Eric E; Skinner, Michael K; Gore, Andrea C; Crews, David

    2014-10-01

    How an individual responds to the environment depends upon both personal life history as well as inherited genetic and epigenetic factors from ancestors. Using a 2-hit, 3 generations apart model, we tested how F3 descendants of rats given in utero exposure to the environmental endocrine-disrupting chemical (EDC) vinclozolin reacted to stress during adolescence in their own lives, focusing on sexually dimorphic phenotypic outcomes. In adulthood, male and female F3 vinclozolin- or vehicle-lineage rats, stressed or nonstressed, were behaviorally characterized on a battery of tests and then euthanized. Serum was used for hormone assays, and brains were used for quantitative PCR and transcriptome analyses. Results showed that the effects of ancestral exposure to vinclozolin converged with stress experienced during adolescence in a sexually dimorphic manner. Debilitating effects were seen at all levels of the phenotype, including physiology, behavior, brain metabolism, gene expression, and genome-wide transcriptome modifications in specific brain nuclei. Additionally, females were significantly more vulnerable than males to transgenerational effects of vinclozolin on anxiety but not sociality tests. This fundamental transformation occurs in a manner not predicted by the ancestral exposure or the proximate effects of stress during adolescence, an interaction we refer to as synchronicity.

  11. Prolonged jaundice in newborns is associated with low antioxidant capacity in breast milk.

    Science.gov (United States)

    Uras, Nurdan; Tonbul, Alpaslan; Karadag, Ahmet; Dogan, Derya G; Erel, Ozcan; Tatli, Mustafa M

    2010-10-01

    In breastfeeding newborns who are otherwise healthy, the mechanism of prolonged jaundice remains unclear. The aim of this study was to investigate relations between prolonged jaundice and oxidative parameters in breast milk. Full-term, otherwise healthy newborns with jaundice lasting more than 2 weeks were enrolled prospectively in the study. As a control group, newborns in the same age group but without prolonged jaundice were selected. All newborns in the study were exclusively breastfed. In the newborns with prolonged jaundice, investigations of the etiology of the jaundice included complete blood count, peripheral blood smear, blood typing, direct Coombs test, measurement of serum levels of total and direct bilirubin, tests for liver and thyroid function (TSH, free T4, total T4), urine culture and measurement of urine reducing substances, and determination of glucose 6 phosphate dehydrogenase enzyme levels. Breast milk was collected from the mothers of the newborns in both groups. The antioxidant status of the breast milk was assessed via determination of total antioxidant capacity (TAC). Oxidative stress was also assessed in breast milk by measurement of total oxidation status (TOS) and calculation of the oxidative stress index (OSI). The prolonged jaundice group differed significantly from the control group in terms of mean TAC and OSI (p antioxidant capacity was found to be decreased.

  12. SU-F-I-68: Longitudinal Neurochemical Changes On Rat Prefrontal Cortex of Single Prolonged Stress Model by Using Proton Magnetic Resonance Spectroscopy at 9.4T

    International Nuclear Information System (INIS)

    Lim, S-I; Yoo, C-H; Song, K-H; Choe, B-Y; Woo, D-C

    2016-01-01

    Purpose: Single prolonged stress (SPS) is an animal model of posttraumatic stress disorder (PTSD). However, it has not been known how PTSD develops from the first exposure to traumatic events and neurochemical differences between acute/single stress and PTSD-triggering stress. Therefore, the object of this study is to determine time-dependent neurochemical changes in prefrontal cortex (PFC) of rats using in vivo proton magnetic resonance spectroscopy (1H-MRS). Methods: Male Sprague-Dawley rats (n=14; body weight=200–220g) were used. The SPS protocol was used in this study. Rats were restrained for 2h and then immediately forced to swim for 20min in water (20–24 Celsius). After a 15-min recuperation period, rats were exposed to ether (using a desiccator) until general anesthesia occurred (<5min). In vivo proton MRS was performed 30min before the SPS (Base), approximately 10min after the SPS (D+0), 3 (D+3) and 7 (D+7) days after SPS to investigate time-dependent changes on metabolites levels in the PFC. Acquisition of in vivo MRS spectra and MRI was conducted at the four time points using 9.4 T Agilent Scanner. Concentration of metabolites was quantified by LCModel. Results: Statistical significance was analyzed using one-way ANOVA with post hoc Tukey HSD tests to assess the metabolite changes in the PFC. The SPS resulted in significant stress-induced differences for 7 days in glutamine (F(3,52)=6.750, P=0.001), choline-containing compounds (F(3,52)=16.442, P=0.000), glutamine/glutamate concentrations (F(3,52)=7.352, P=0.000). Conclusion: PTSD in human is associated with decreased neuronal activity in the PFC. In this study, SPS altered total choline, glutamine levels but not NAA levels in the PFC of the rats. Therefore, for the three stressors and quiescent period of seven days, SPS attenuated excitatory tone and membrane turnover but did not affect neural integrity in the PFC.

  13. SU-F-I-68: Longitudinal Neurochemical Changes On Rat Prefrontal Cortex of Single Prolonged Stress Model by Using Proton Magnetic Resonance Spectroscopy at 9.4T

    Energy Technology Data Exchange (ETDEWEB)

    Lim, S-I; Yoo, C-H [Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea College of Medicine, Seoul, Seoul (Korea, Republic of); Asan Institute for Life Sciences, Asan Medical Center, Seoul, Seoul (Korea, Republic of); Song, K-H; Choe, B-Y [Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea College of Medicine, Seoul, Seoul (Korea, Republic of); Woo, D-C [Asan Institute for Life Sciences, Asan Medical Center, Seoul, Seoul (Korea, Republic of)

    2016-06-15

    Purpose: Single prolonged stress (SPS) is an animal model of posttraumatic stress disorder (PTSD). However, it has not been known how PTSD develops from the first exposure to traumatic events and neurochemical differences between acute/single stress and PTSD-triggering stress. Therefore, the object of this study is to determine time-dependent neurochemical changes in prefrontal cortex (PFC) of rats using in vivo proton magnetic resonance spectroscopy (1H-MRS). Methods: Male Sprague-Dawley rats (n=14; body weight=200–220g) were used. The SPS protocol was used in this study. Rats were restrained for 2h and then immediately forced to swim for 20min in water (20–24 Celsius). After a 15-min recuperation period, rats were exposed to ether (using a desiccator) until general anesthesia occurred (<5min). In vivo proton MRS was performed 30min before the SPS (Base), approximately 10min after the SPS (D+0), 3 (D+3) and 7 (D+7) days after SPS to investigate time-dependent changes on metabolites levels in the PFC. Acquisition of in vivo MRS spectra and MRI was conducted at the four time points using 9.4 T Agilent Scanner. Concentration of metabolites was quantified by LCModel. Results: Statistical significance was analyzed using one-way ANOVA with post hoc Tukey HSD tests to assess the metabolite changes in the PFC. The SPS resulted in significant stress-induced differences for 7 days in glutamine (F(3,52)=6.750, P=0.001), choline-containing compounds (F(3,52)=16.442, P=0.000), glutamine/glutamate concentrations (F(3,52)=7.352, P=0.000). Conclusion: PTSD in human is associated with decreased neuronal activity in the PFC. In this study, SPS altered total choline, glutamine levels but not NAA levels in the PFC of the rats. Therefore, for the three stressors and quiescent period of seven days, SPS attenuated excitatory tone and membrane turnover but did not affect neural integrity in the PFC.

  14. Prenatal exposure to escitalopram and/or stress in rats: a prenatal stress model of maternal depression and its treatment

    Science.gov (United States)

    Bourke, Chase H.; Capello, Catherine F.; Rogers, Swati M.; Yu, Megan L.; Boss-Williams, Katherine A.; Weiss, Jay M.; Stowe, Zachary N.; Owens, Michael J.

    2014-01-01

    Rationale A rigorously investigated model of stress and antidepressant administration during pregnancy is needed to evaluate possible effects on the mother. Objective The objective of this study was to develop a model of clinically relevant prenatal exposure to an antidepressant and stress during pregnancy to evaluate the effects on maternal care behavior. Results Female rats implanted with 28 day osmotic minipumps delivering the SSRI escitalopram throughout pregnancy had serum escitalopram concentrations in a clinically observed range (17-65 ng/mL). A separate cohort of pregnant females exposed to a chronic unpredictable mild stress paradigm on gestational days 10-20 showed elevated baseline (305 ng/mL), and acute stress-induced (463 ng/mL), plasma corticosterone concentrations compared to unstressed controls (109 ng/mL). A final cohort of pregnant dams were exposed to saline (control), escitalopram, stress, or stress and escitalopram to determine the effects on maternal care. Maternal behavior was continuously monitored over the first 10 days post parturition. A reduction of 35% in maternal contact and 11% in nursing behavior was observed due to stress during the light cycle. Licking and grooming behavior was unaffected by stress or drug exposure in either the light or dark cycle. Conclusions These data indicate that: 1) clinically relevant antidepressant treatment during human pregnancy can be modeled in rats using escitalopram; 2) chronic mild stress can be delivered in a manner that does not compromise fetal viability; and 3) neither of these prenatal treatments substantially altered maternal care post parturition. PMID:23436130

  15. Prior stress exposure increases pain behaviors in a rat model of full thickness thermal injury.

    Science.gov (United States)

    Nyland, Jennifer E; McLean, Samuel A; Averitt, Dayna L

    2015-12-01

    Thermal burns among individuals working in highly stressful environments, such as firefighters and military Service Members, are common. Evidence suggests that pre-injury stress may exaggerate pain following thermal injury; however current animal models of burn have not evaluated the potential influence of pre-burn stress. This sham-controlled study evaluated the influence of prior stress exposure on post-burn thermal and mechanical sensitivity in male Sprague-Dawley rats. Rats were exposed to 20 min of inescapable swim stress or sham stress once per day for three days. Exposure to inescapable swim stress (1) increased the intensity and duration of thermal hyperalgesia after subsequent burn and (2) accelerated the onset of thermal hyperalgesia and mechanical allodynia after subsequent burn. This stress-induced exacerbation of pain sensitivity was reversed by pretreatment and concurrent treatment with the serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine. These data suggest a better understanding of mechanisms by which prior stress augments pain after thermal burn may lead to improved pain treatments for burn survivors. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

  16. Reef calcifiers are adapted to episodic heat stress but vulnerable to sustained warming.

    Science.gov (United States)

    Stuhr, Marleen; Reymond, Claire E; Rieder, Vera; Hallock, Pamela; Rahnenführer, Jörg; Westphal, Hildegard; Kucera, Michal

    2017-01-01

    Shallow marine ecosystems naturally experience fluctuating physicochemical conditions across spatial and temporal scales. Widespread coral-bleaching events, induced by prolonged heat stress, highlight the importance of how the duration and frequency of thermal stress influence the adaptive physiology of photosymbiotic calcifiers. Large benthic foraminifera harboring algal endosymbionts are major tropical carbonate producers and bioindicators of ecosystem health. Like corals, they are sensitive to thermal stress and bleach at temperatures temporarily occurring in their natural habitat and projected to happen more frequently. However, their thermal tolerance has been studied so far only by chronic exposure, so how they respond under more realistic episodic heat-event scenarios remains unknown. Here, we determined the physiological responses of Amphistegina gibbosa, an abundant western Atlantic foraminifera, to four different treatments--control, single, episodic, and chronic exposure to the same thermal stress (32°C)--in controlled laboratory cultures. Exposure to chronic thermal stress reduced motility and growth, while antioxidant capacity was elevated, and photosymbiont variables (coloration, oxygen-production rates, chlorophyll a concentration) indicated extensive bleaching. In contrast, single- and episodic-stress treatments were associated with higher motility and growth, while photosymbiont variables remained stable. The effects of single and episodic heat events were similar, except for the presumable occurrence of reproduction, which seemed to be suppressed by both episodic and chronic stress. The otherwise different responses between treatments with thermal fluctuations and chronic stress indicate adaptation to thermal peaks, but not to chronic exposure expected to ensue when baseline temperatures are elevated by climate change. This firstly implies that marine habitats with a history of fluctuating thermal stress potentially support resilient

  17. Childhood exposure to violence and lifelong health: clinical intervention science and stress-biology research join forces.

    Science.gov (United States)

    Moffitt, Terrie E

    2013-11-01

    Many young people who are mistreated by an adult, victimized by bullies, criminally assaulted, or who witness domestic violence react to this violence exposure by developing behavioral, emotional, or learning problems. What is less well known is that adverse experiences like violence exposure can lead to hidden physical alterations inside a child's body, alterations that may have adverse effects on life-long health. We discuss why this is important for the field of developmental psychopathology and for society, and we recommend that stress-biology research and intervention science join forces to tackle the problem. We examine the evidence base in relation to stress-sensitive measures for the body (inflammatory reactions, telomere erosion, epigenetic methylation, and gene expression) and brain (mental disorders, neuroimaging, and neuropsychological testing). We also review promising interventions for families, couples, and children that have been designed to reduce the effects of childhood violence exposure. We invite intervention scientists and stress-biology researchers to collaborate in adding stress-biology measures to randomized clinical trials of interventions intended to reduce effects of violence exposure and other traumas on young people.

  18. Deformation and stress in PMMA during hard X-ray exposure for deep lithography

    International Nuclear Information System (INIS)

    Moldovan, N.

    1999-01-01

    The availability of high-energy, high-flux, collimated synchrotrons radiation has extended the application of deep X-ray lithography (DXRL) to thickness values of the PMMA resist of several millimeters. Some of the most severe limitations come from plastic deformation, stress, and cracks induced in PMMA during exposure and development. We have observed and characterized these phenomena quantitatively. Profilometry measurements revealed that the PMMA is subjected either to local shrinkage or to expansion, while compression and expansion evolve over time. Due to material loss and crosslinking, the material undergoes a shrinkage, while the radiation-induced decomposition generates gases expanding the polymer matrix. The overall dynamics of the material microrelief and stress during and after the exposure depend on the balance between compaction and outgassing. These depend in turn on the exposure conditions (spectrum; dose, dose rate, seaming, temperature), post-exposure storage conditions, PMMA material properties and thickness, and also on the size and geometry of the exposed patterns

  19. Neonatal survival after prolonged preterm premature rupture of membranes before 24 weeks of gestation.

    Science.gov (United States)

    Brumbaugh, Jane E; Colaizy, Tarah T; Nuangchamnong, Nina; O'Brien, Emily A; Fleener, Diedre K; Rijhsinghani, Asha; Klein, Jonathan M

    2014-11-01

    To evaluate neonatal survival after prolonged preterm premature rupture of membranes (PROM) in the era of antenatal corticosteroids, surfactant, and inhaled nitric oxide. A single-center retrospective cohort study of neonates born from 2002-2011 after prolonged (1 week or more) preterm (less than 24 weeks of gestation) rupture of membranes was performed. The primary outcome was survival to discharge. Neonates whose membranes ruptured less than 24 hours before delivery (n=116) were matched (2:1) on gestational age at birth, sex, and antenatal corticosteroid exposure with neonates whose membranes ruptured 1 week or more before delivery (n=58). Analysis used conditional logistic regression for categorical data and Wilcoxon signed rank test for continuous data. The prolonged preterm PROM exposed and unexposed cohorts had survival rates of 90% and 95%, respectively, although underpowered to assess the statistical significance (P=.313). Exposed neonates were more likely have pulmonary hypoplasia (26/58 exposed, 1/114 unexposed, Prupture (20.4 weeks exposed, 22.3 weeks unexposed, P=.189), length of rupture (3.7 weeks exposed, 6.4 weeks unexposed, P=.717), and lowest maximal vertical pocket before 24 weeks of gestation (0 cm exposed, 1.4 cm unexposed, P=.114) did not discriminate between survivors and nonsurvivors after exposure to prolonged preterm PROM. With antenatal steroid exposure and aggressive pulmonary management, survival to discharge after prolonged preterm PROM was 90%. Pulmonary morbidities were common. Of note, the data were limited to women who remained pregnant 1 week or longer after rupture of membranes.

  20. Media exposure and associated stress contribute to eating pathology in women with Anorexia Nervosa: Daily and momentary associations.

    Science.gov (United States)

    White, Emily K; Warren, Cortney S; Cao, Li; Crosby, Ross D; Engel, Scott G; Wonderlich, Stephen A; Mitchell, James E; Peterson, Carol B; Crow, Scott J; Le Grange, Daniel

    2016-06-01

    We examined whether media exposure and media-induced stress contributed to eating disorder behaviors immediately and over the course of a day in women with anorexia nervosa (AN). Women with AN (N = 118) completed a 2-week ecological momentary assessment protocol during which they reported on exposure to food, shape, or weight-related media, associated stress, and eating behaviors. Food, weight, or shape-related media exposure alone did not predict more frequent daily eating disorder behaviors. However, stress associated with media exposure was prospectively associated with a greater likelihood of binge eating and vomiting at the next assessment point. In addition, media-induced stress increased the probability of restrictive eating and fluid intake, vomiting, and laxative abuse across the day. Media-induced stress may contribute to increased eating disorder behaviors in women with AN, as women who saw a media image and reported this experience as stressful were more likely to engage in momentary binge eating or vomiting. Reducing stress associated with viewing media images could be a potential target for therapeutic intervention with disordered eating. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:617-621). © 2015 Wiley Periodicals, Inc.

  1. Transcriptional response of stress genes to metal exposure in zebra mussel larvae and adults

    International Nuclear Information System (INIS)

    Navarro, Anna; Faria, Melissa; Barata, Carlos; Pina, Benjamin

    2011-01-01

    Development of stress markers for the invader freshwater zebra mussel (Dreissena polymorpha) is of great interest for both conservation and biomonitoring purposes. Gene expression profiles of several putative or already established gene expression stress markers (Metallothionein, Superoxide dismutase, Catalase, Glutathione S transferase, Glutathione peroxidase, Cytochrome c oxidase, the multixenobiotic resistance P-gp1, and heat shock proteins HSP70 and HSP90) were analyzed by quantitative Real-Time PCR in adults and pediveliger larvae after exposure to metals (Hg, Cu, Cd). A defined pattern of coordinated responses to metal exposure and, presumably, to oxidative stress was observed in gills and digestive gland from adults. A similar, albeit partial response was observed in larvae, indicating an early development of stress-related gene responses in zebra mussel. The tools developed in this study may be useful both for future control strategies and for the use of zebra mussel as sentinel species in water courses with stable populations. - Coordinated expression of stress genes in zebra mussel.

  2. Transcriptional response of stress genes to metal exposure in zebra mussel larvae and adults

    Energy Technology Data Exchange (ETDEWEB)

    Navarro, Anna; Faria, Melissa; Barata, Carlos [Institute of Environmental Assessment and Water Research (IDAEA-CSIC), Jordi Girona 18, 08034 Barcelona (Spain); Pina, Benjamin, E-mail: bpcbmc@cid.csic.e [Institute of Environmental Assessment and Water Research (IDAEA-CSIC), Jordi Girona 18, 08034 Barcelona (Spain)

    2011-01-15

    Development of stress markers for the invader freshwater zebra mussel (Dreissena polymorpha) is of great interest for both conservation and biomonitoring purposes. Gene expression profiles of several putative or already established gene expression stress markers (Metallothionein, Superoxide dismutase, Catalase, Glutathione S transferase, Glutathione peroxidase, Cytochrome c oxidase, the multixenobiotic resistance P-gp1, and heat shock proteins HSP70 and HSP90) were analyzed by quantitative Real-Time PCR in adults and pediveliger larvae after exposure to metals (Hg, Cu, Cd). A defined pattern of coordinated responses to metal exposure and, presumably, to oxidative stress was observed in gills and digestive gland from adults. A similar, albeit partial response was observed in larvae, indicating an early development of stress-related gene responses in zebra mussel. The tools developed in this study may be useful both for future control strategies and for the use of zebra mussel as sentinel species in water courses with stable populations. - Coordinated expression of stress genes in zebra mussel.

  3. Occupational Styrene Exposure Induces Stress-Responsive Genes Involved in Cytoprotective and Cytotoxic Activities

    Science.gov (United States)

    Strafella, Elisabetta; Bracci, Massimo; Staffolani, Sara; Manzella, Nicola; Giantomasi, Daniele; Valentino, Matteo; Amati, Monica; Tomasetti, Marco; Santarelli, Lory

    2013-01-01

    Objective The aim of this study was to evaluate the expression of a panel of genes involved in toxicology in response to styrene exposure at levels below the occupational standard setting. Methods Workers in a fiber glass boat industry were evaluated for a panel of stress- and toxicity-related genes and associated with biochemical parameters related to hepatic injury. Urinary styrene metabolites (MA+PGA) of subjects and environmental sampling data collected for air at workplace were used to estimate styrene exposure. Results Expression array analysis revealed massive upregulation of genes encoding stress-responsive proteins (HSPA1L, EGR1, IL-6, IL-1β, TNSF10 and TNFα) in the styrene-exposed group; the levels of cytokines released were further confirmed in serum. The exposed workers were then stratified by styrene exposure levels. EGR1 gene upregulation paralleled the expression and transcriptional protein levels of IL-6, TNSF10 and TNFα in styrene exposed workers, even at low level. The activation of the EGR1 pathway observed at low-styrene exposure was associated with a slight increase of hepatic markers found in highly exposed subjects, even though they were within normal range. The ALT and AST levels were not affected by alcohol consumption, and positively correlated with urinary styrene metabolites as evaluated by multiple regression analysis. Conclusion The pro-inflammatory cytokines IL-6 and TNFα are the primary mediators of processes involved in the hepatic injury response and regeneration. Here, we show that styrene induced stress responsive genes involved in cytoprotection and cytotoxicity at low-exposure, that proceed to a mild subclinical hepatic toxicity at high-styrene exposure. PMID:24086524

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

    Science.gov (United States)

    Belda, Xavier; Nadal, Roser; Armario, Antonio

    2016-08-11

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

  5. Exposure to Forced Swim Stress Alters Local Circuit Activity and Plasticity in the Dentate Gyrus of the Hippocampus

    Directory of Open Access Journals (Sweden)

    Mouna Maroun

    2008-02-01

    Full Text Available Studies have shown that, depending on its severity and context, stress can affect neural plasticity. Most related studies focused on synaptic plasticity and long-term potentiation (LTP of principle cells. However, evidence suggests that following high-frequency stimulation, which induces LTP in principal cells, modifications also take place at the level of complex interactions with interneurons within the dentate gyrus, that is, at the local circuit level. So far, the possible effects of stress on local circuit activity and plasticity were not studied. Therefore, we set out to examine the possible alterations in local circuit activity and plasticity following exposure to stress. Local circuit activity and plasticity were measured by using frequency dependant inhibition (FDI and commissural modulation protocols following exposure to a 15 minute-forced swim trial. Exposure to stress did not alter FDI. The application of theta-burst stimulation (TBS reduced FDI in both control and stressed rats, but this type of plasticity was greater in stressed rats. Commissural-induced inhibition was significantly higher in stressed rats both before and after applying theta-burst stimulation. These findings indicate that the exposure to acute stress affects aspects of local circuit activity and plasticity in the dentate gyrus. It is possible that these alterations underlie some of the behavioral consequences of the stress experience.

  6. Exposure to Forced Swim Stress Alters Local Circuit Activity and Plasticity in the Dentate Gyrus of the Hippocampus

    Science.gov (United States)

    Yarom, Orli; Maroun, Mouna; Richter-Levin, Gal

    2008-01-01

    Studies have shown that, depending on its severity and context, stress can affect neural plasticity. Most related studies focused on synaptic plasticity and long-term potentiation (LTP) of principle cells. However, evidence suggests that following high-frequency stimulation, which induces LTP in principal cells, modifications also take place at the level of complex interactions with interneurons within the dentate gyrus, that is, at the local circuit level. So far, the possible effects of stress on local circuit activity and plasticity were not studied. Therefore, we set out to examine the possible alterations in local circuit activity and plasticity following exposure to stress. Local circuit activity and plasticity were measured by using frequency dependant inhibition (FDI) and commissural modulation protocols following exposure to a 15 minute-forced swim trial. Exposure to stress did not alter FDI. The application of theta-burst stimulation (TBS) reduced FDI in both control and stressed rats, but this type of plasticity was greater in stressed rats. Commissural-induced inhibition was significantly higher in stressed rats both before and after applying theta-burst stimulation. These findings indicate that the exposure to acute stress affects aspects of local circuit activity and plasticity in the dentate gyrus. It is possible that these alterations underlie some of the behavioral consequences of the stress experience. PMID:18301720

  7. Mediating role of stress reactivity in the effects of prenatal tobacco exposure on childhood mental health outcomes.

    Science.gov (United States)

    Park, Aesoon; O'Malley, Stephanie S; King, Sarah L; Picciotto, Marina R

    2014-02-01

    Prenatal tobacco exposure, through maternal smoking during pregnancy, has been associated with adverse mental health outcomes in childhood. However, the mechanisms by which prenatal tobacco exposure compromises mental health later in life are unclear. We hypothesized that sensitized reactivity to stressful life events in early childhood mediates the effect of prenatal tobacco exposure on mental health outcomes in middle childhood, after accounting for earlier mental health outcomes. Data were from 12,308 mothers and their children drawn from the Avon Longitudinal Study of Parents and Children, a large prospective population-based study. Mothers' self-reports of smoking during pregnancy, mothers' ratings of their child's reactivity to stressful life events, and teachers' and mothers' ratings of the Strengths and Difficulties Questionnaire assessing 5 domains of mental health outcomes were measured. A positive association was found between prenatal tobacco exposure and stress reactivity between the ages of 2 and 6. In turn, stress reactivity was positively associated with peer (isolation), hyperactivity, conduct, and emotional problems (but not prosocial behaviors) between the ages of 7 and 11, after accounting for the mental health outcome at age 4 and other confounders. Heightened stress reactivity in preschool ages mediated the effect of prenatal tobacco exposure on adverse mental health outcomes between the ages of 7 and 11. Interventions to assist children exposed to tobacco smoke during gestation in coping with stressful life events may help mitigate psychiatric symptoms in this population.

  8. Trauma exposure and the mediating role of posttraumatic stress on somatic symptoms in civilian war victims.

    Science.gov (United States)

    Morina, Naser; Schnyder, Ulrich; Klaghofer, Richard; Müller, Julia; Martin-Soelch, Chantal

    2018-04-10

    It has been well documented that the exposure to war has a negative effect on the psychological health of civilian. However, little is known on the impact of war exposure on the physical health of the civilian population. In addition, the link between trauma exposure and somatic symptoms remain poorly understood. This cross-sectional study examined levels of somatic symptoms in the aftermath of war, and the mediating role of posttraumatic stress symptoms in the relationship between trauma exposure and somatic symptoms. Civilian war survivors (N = 142) from Kosovo were assessed for potentially traumatic events, posttraumatic stress symptoms, and somatic symptoms. Data were analyzed using mediation analyses. Posttraumatic stress disorder (PTSD) symptoms were categorized based on King's four factor model (Psychol Assessment. 10: 90-96, 1998). Participants reported on average more than 5 types of traumatic exposure. The cut-off indicative for PTSD was exceeded by 26.1% of participants. Symptom levels of PTSD were associated with somatic symptoms. The relationship between trauma exposure and somatic symptoms was partly mediated by the active avoidance and hyperarousal symptom clusters of PTSD. Active avoidance and hyperarousal symptoms seem to play a key role in traumatized people suffering from somatic symptoms.

  9. A nationwide study on the risk of autism after prenatal stress exposure to maternal bereavement

    DEFF Research Database (Denmark)

    Li, Jiong; Vestergaard, Mogens; Obel, Carsten

    2009-01-01

    OBJECTIVE: Prenatal stress has been linked to several adverse neurobehavioral outcomes, which may share a common pathophysiology with autism. We aimed to examine whether prenatal stress exposure after maternal bereavement is associated with an increased risk of autism later in life. METHODS: We...... compared with those in the unexposed group. RESULTS: Maternal bereavement during the prenatal period was not associated with an increased risk of autism in the offspring. The hazard ratios did not differ by the nature of the exposure (maternal relationship to the deceased or cause of death). The hazard...... ratios were comparable between the 5 prenatal exposure periods under study (7-12 months before pregnancy, 0-6 months before pregnancy, first trimester, second trimester, and third trimester). CONCLUSIONS: This is the first population-based cohort study to examine the effect of prenatal stress on autism...

  10. Why are there lasting effects from exposure to stress during development? An analysis of current models of early stress.

    Science.gov (United States)

    Chaby, Lauren E

    2016-10-01

    The potential for stressful experiences in early life to cause lasting changes in phenotype is well documented, but the functional and evolutionary context of these changes is not well understood. Many hypotheses have been proposed to explain the role of lasting effects of stress exposure during gestation and early development; the purpose of this review is to discuss these hypotheses in the context of human and non-human animal research in the last three decades in order to (i) further dialogues between those approaching early stress from biomedical and evolutionary/ecological perspectives, (ii) outline strengths and limitations of current hypotheses, with respect to species and context-specific effects of exposure to stress in early development, and (iii) address recent evidence suggesting that stress in early development can have beneficial effects in adulthood. It is suggested that the hypotheses discussed are not mutually exclusive, but the applicability of each hypothesis will depend upon the environmental conditions and stability a species, or perhaps even an individual, experiences in their lifetime. Potential investigations to clarify applications of the current hypotheses are discussed, including longitudinal studies that span multiple developmental stages and investigations of species where measures of fitness are possible. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Community violence exposure and post-traumatic stress reactions among Gambian youth: the moderating role of positive school climate.

    Science.gov (United States)

    O'Donnell, Deborah A; Roberts, William C; Schwab-Stone, Mary E

    2011-01-01

    Community violence exposure among youth can lead to various negative outcomes, including post-traumatic stress symptoms. Research in the Western world indicates that a number of social support factors may moderate the relation between violence exposure and internalizing symptoms. Little research has been carried out in non-Western countries. This study aimed to fill this gap by exploring the relations among violence exposure, parental warmth, positive school climate, and post-traumatic stress reactions among youth in The Republic of The Gambia, Africa. A school-based survey of youth behaviors, feelings, attitudes, and perceptions was administered to 653 students at senior secondary schools in four Gambian communities. Students reported high levels of exposure to violence. Over half of students reported witnessing someone threatened with serious physical harm, beaten up or mugged, attacked or stabbed with a knife/piece of glass, or seriously wounded in an incident of violence. Nearly half of students reported being beaten up or mugged during the past year, and nearly a quarter reported being threatened with serious physical harm. There were no sex differences in levels of exposure. Traumatic stress symptoms were common, especially among females. Both violence witnessing and violent victimization significantly predicted post-traumatic stress symptoms, and positive school climate moderated the relationship. Among youth victimized by violence, positive school climate was most strongly correlated with lower levels of post-traumatic stress at low levels of exposure. Among youth who had witnessed violence, positive school climate was most strongly correlated with lower levels of post-traumatic stress at high levels of exposure. Community-based programs that bring together parents, schools, and youth may play an important role in combating the negative effects of some types of violence exposure among Gambian youth. Youth experiencing high levels of violent victimization

  12. Combat exposure, posttraumatic stress symptoms and risk-taking behavior in veterans of the Second Lebanon War.

    Science.gov (United States)

    Svetlicky, Vlad; Solomon, Zahava; Benbenishty, Rami; Levi, Ofir; Lubin, Gadi

    2010-01-01

    Prior research has revealed heightened risk-taking behavior among veterans with posttraumatic stress disorder (PTSD). This study examined whether the risktaking behavior is a direct outcome of the traumatic exposure or whether this relationship is mediated by posttraumatic stress symptoms. The sample was comprised of 180 traumatized Israeli reserve soldiers, who sought treatment in the wake of the Second Lebanon War. Combat exposure was indirectly associated with risk-taking behavior primarily through its relationship with posttraumatic stress symptoms. Results of the multivariate analyses depict the implication of posttraumatic stress symptoms in risk taking behavior, and the role of self-medication and of aggression in traumatized veterans.

  13. Cocaine withdrawal causes delayed dysregulation of stress genes in the hippocampus.

    Directory of Open Access Journals (Sweden)

    M Julia García-Fuster

    Full Text Available Relapse, even following an extended period of withdrawal, is a major challenge in substance abuse management. Delayed neurobiological effects of the drug during prolonged withdrawal likely contribute to sustained vulnerability to relapse. Stress is a major trigger of relapse, and the hippocampus regulates the magnitude and duration of stress responses. Recent work has implicated hippocampal plasticity in various aspects of substance abuse. We asked whether changes in stress regulatory mechanisms in the hippocampus may participate in the neuroadaptations that occur during prolonged withdrawal. We therefore examined changes in the rat stress system during the course of withdrawal from extended daily access (5-hours of cocaine self-administration, an animal model of addiction. Tissue was collected at 1, 14 and 28 days of withdrawal. Plasma corticosterone levels were determined and corticosteroid receptors (GR, MR, MR/GR mRNA ratios and expression of other stress-related molecules (HSP90AA1 and HSP90AB1 mRNA were measured in hippocampal subfields using in situ hybridization. Results showed a delayed emergence of dysregulation of stress genes in the posterior hippocampus following 28 days of cocaine withdrawal. This included increased GR mRNA in DG and CA3, increased MR and HSP90AA1 mRNA in DG, and decreased MR/GR mRNA ratio in DG and CA1. Corticosterone levels progressively decreased during the course of withdrawal, were normalized following 28 days of withdrawal, and were correlated negatively with GR and positively with MR/GR mRNA ratio in DG. These results suggest a role for the posterior hippocampus in the neuroadaptations that occur during prolonged withdrawal, and point to a signaling partner of GR, HSP90AA1, as a novel dysregulated target during cocaine withdrawal. These delayed neurobiological effects of extended cocaine exposure likely contribute to sustained vulnerability to relapse.

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

    Science.gov (United States)

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

    2017-01-01

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

  15. Differential Exposure and Reactivity to Interpersonal Stress Predict Sex Differences in Adolescent Depression

    Science.gov (United States)

    Shih, Josephine H.; Eberhart, Nicole K.; Hammen, Constance L.; Brennan, Patricia A.

    2006-01-01

    This study tested the hypothesis that higher rates of depression in adolescent girls are explained by their greater exposure and reactivity to stress in the interpersonal domain in a large sample of 15-year-olds. Findings indicate that adolescent girls experienced higher levels of total and interpersonal episodic stress, whereas boys experienced…

  16. Childhood exposure to violence and lifelong health: Clinical intervention science and stress biology research join forces

    Science.gov (United States)

    Moffitt, Terrie E.

    2013-01-01

    Many young people who are mistreated by an adult, victimized by bullies, criminally assaulted, or who witness domestic violence react to this violence exposure by developing behavioral, emotional, or learning problems. What is less well known is that adverse experiences like violence exposure can lead to hidden physical alterations inside a child’s body, alterations which may have adverse effects on life-long health. We discuss why this is important for the field of developmental psychopathology and for society, and we recommend that stress-biology research and intervention science join forces to tackle the problem. We examine the evidence base in relation to stress-sensitive measures for the body (inflammatory reactions, telomere erosion, epigenetic methylation, and gene expression) and brain (mental disorders, neuroimaging, and neuropsychological testing). We also review promising interventions for families, couples, and children that have been designed to reduce the effects of childhood violence exposure. We invite intervention scientists and stress-biology researchers to collaborate in adding stress-biology measures to randomized clinical trials of interventions intended to reduce effects of violence exposure and other traumas on young people. PMID:24342859

  17. Community violence exposure and severe posttraumatic stress in suburban American youth: risk and protective factors.

    Science.gov (United States)

    Löfving-Gupta, Sandra; Lindblad, Frank; Stickley, Andrew; Schwab-Stone, Mary; Ruchkin, Vladislav

    2015-04-01

    The psychological effects of community violence exposure among inner-city youth are severe, yet little is known about its prevalence and moderators among suburban middle-class youth. This study aimed to assess the prevalence of community violence exposure among suburban American youth, to examine associated posttraumatic stress and to evaluate factors related to severe vs. less severe posttraumatic stress, such as co-existing internalizing and externalizing problems, as well as the effects of teacher support, parental warmth and support, perceived neighborhood safety and conventional involvement in this context. Data were collected from 780 suburban, predominantly Caucasian middle-class high-school adolescents in the Northeastern US during the Social and Health Assessment (SAHA) study. A substantial number of suburban youth were exposed to community violence and 24% of those victimized by community violence developed severe posttraumatic stress. Depressive symptoms were strongly associated with higher levels and perceived teacher support with lower levels of posttraumatic stress. Similar to urban youth, youth living in suburban areas in North American settings may be affected by community violence. A substantial proportion of these youth reports severe posttraumatic stress and high levels of comorbid depressive symptoms. Teacher support may have a protective effect against severe posttraumatic stress and thus needs to be further assessed as a potential factor that can be used to mitigate the detrimental effects of violence exposure.

  18. Exposure to Acute Stress Enhances Decision-Making Competence: Evidence for the Role of DHEA

    OpenAIRE

    Shields, Grant S.; Lam, Jovian C. W.; Trainor, Brian C.; Yonelinas, Andrew P.

    2016-01-01

    Exposure to acute stress can impact performance on numerous cognitive abilities, but little is known about how acute stress affects real-world decision-making ability. In the present study, we induced acute stress with a standard laboratory task involving uncontrollable socio-evaluative stress and subsequently assessed decision-making ability using the Adult Decision Making Competence index. In addition, we took baseline and post-test saliva samples from participants to examine associations b...

  19. Infectious Disease risks associated with exposure to stressful environments

    Science.gov (United States)

    Meehan, Ichard T.; Smith, Morey; Sams, Clarence

    1993-01-01

    Multiple environmental factors asociated with space flight can increase the risk of infectious illness among crewmembers thereby adversely affecting crew health and mission success. Host defences can be impaired by multiple physiological and psychological stressors including: sleep deprivation, disrupted circadian rhythms, separation from family, perceived danger, radiation exposure, and possibly also by the direct and indirect effects of microgravity. Relevant human immunological data from isolated or stressful environments including spaceflight will be reviewed. Long-duration missions should include reliable hardware which supports sophisticated immunodiagnostic capabilities. Future advances in immunology and molecular biology will continue to provide therapeutic agents and biologic response modifiers which should effectively and selectively restore immune function which has been depressed by exposure to environmental stressors.

  20. Ozone Exposure Increases Circulating Stress Hormones and Lipid Metabolites in Humans

    Science.gov (United States)

    RATIONALE: Air pollution has been associated with increased prevalence of type 2 diabetes; however, the mechanisms remain unknown. We have shown that acute ozone exposure in rats induces release of stress hormones, hyperglycemia, leptinemia, and gluoose intolerance that are assoc...

  1. Reported Exposure and Emotional Reactivity to Daily Stressors: The Roles of Adult-Age and Global Perceived Stress

    OpenAIRE

    Stawski, Robert S.; Sliwinski, Martin J.; Almeida, David M.; Smyth, Joshua M.

    2008-01-01

    A central goal of daily stress research is to identify resilience and vulnerability factors associated with exposure and reactivity to daily stressors. The current study examined how age differences and global perceptions of stress relate to exposure and emotional reactivity to daily stressors. Sixty-seven younger (Mage = 20) and 116 older (Mage = 80) adults completed a daily stress diary and measures of positive and negative affect on 6 days over a 14 day period. Participants also completed ...

  2. Ability to Discriminate Between Sustainable and Unsustainable Heat Stress Exposures-Part 2: Physiological Indicators.

    Science.gov (United States)

    Garzón-Villalba, Ximena P; Wu, Yougui; Ashley, Candi D; Bernard, Thomas E

    2017-07-01

    There are times when it is not practical to assess heat stress using environmental metrics and metabolic rate, and heat strain may provide an alternative approach. Heat strain indicators have been used for decades as tools for monitoring physiological responses to work in hot environments. Common indicators of heat strain are body core temperature (assessed here as rectal temperature Tre), heart rate (HR), and average skin temperature (Tsk). Data collected from progressive heat stress trials were used to (1) demonstrate if physiological heat strain indicators (PHSIs) at the upper limit of Sustainable heat stress were below generally accepted limits; (2) suggest values for PHSIs that demonstrate a Sustainable level of heat stress; (3) suggest alternative PHSIs; and (4) determine if metabolic rate was an effect modifier. Two previous progressive heat stress studies included 176 trials with 352 pairs of Sustainable and Unsustainable exposures over a range of relative humidities and metabolic rates using 29 participants. To assess the discrimination ability of PHSIs, conditional logistic regression and stepwise logistic regression were used to find the best combinations of predictors of Unsustainable exposures. The accuracy of the models was assessed using receiver operating characteristic curves. Current recommendations for physiological heat strain limits were associated with probabilities of Unsustainable greater than 0.5. Screening limits for Sustainable heat stress were Tre of 37.5°C, HR of 105 bpm, and Tsk of 35.8°C. Tsk alone resulted in an area under the curve of 0.85 and the combination of Tsk and HR (area under the curve = 0.88) performed the best. The adjustment for metabolic rate was statistically significant for physiological strain index or ∆Tre-sk as main predictors, but its effect modification was negligible and could be ignored. Based on the receiver operating characteristic curve, PHSIs (Tre, HR, and Tsk) can accurately predict Unsustainable heat

  3. Exposure and non-fear emotions: A randomized controlled study of exposure-based and rescripting-based imagery in PTSD treatment.

    Science.gov (United States)

    Langkaas, Tomas Formo; Hoffart, Asle; Øktedalen, Tuva; Ulvenes, Pål G; Hembree, Elizabeth A; Smucker, Mervin

    2017-10-01

    Interventions involving rescripting-based imagery have been proposed as a better approach than exposure-based imagery when posttraumatic stress disorder (PTSD) is associated with emotions other than fear. Prior research led to the study's hypotheses that (a) higher pretreatment non-fear emotions would predict relatively better response to rescripting as compared to exposure, (b) rescripting would be associated with greater reduction in non-fear emotions, and (c) pretreatment non-fear emotions would predict poor response to exposure. A clinically representative sample of 65 patients presenting a wide range of traumas was recruited from patients seeking and being offered PTSD treatment in an inpatient setting. Subjects were randomly assigned to 10 weeks of treatment involving either rescripting-based imagery (Imagery Rescripting; IR) or exposure-based imagery (Prolonged Exposure; PE). Patients were assessed on outcome and emotion measures at pretreatment, posttreatment and 12 months follow-up. Comparison to control benchmarks indicated that both treatments were effective, but no outcome differences between them appeared. None of the initial hypotheses were supported. The results from this study challenge previous observations and hypotheses about exposure mainly being effective for fear-based PTSD and strengthen the notion that exposure-based treatment is a generally effective treatment for all types of PTSD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Sex Differences in Adolescent Depression: Stress Exposure and Reactivity Models

    Science.gov (United States)

    Hankin, Benjamin L.; Mermelstein, Robin; Roesch, Linda

    2007-01-01

    Stress exposure and reactivity models were examined as explanations for why girls exhibit greater levels of depressive symptoms than boys. In a multiwave, longitudinal design, adolescents' depressive symptoms, alcohol usage, and occurrence of stressors were assessed at baseline, 6, and 12 months later (N=538; 54.5% female; ages 13-18, average…

  5. Brain-derived neurotropic factor polymorphisms, traumatic stress, mild traumatic brain injury, and combat exposure contribute to postdeployment traumatic stress.

    Science.gov (United States)

    Dretsch, Michael N; Williams, Kathy; Emmerich, Tanja; Crynen, Gogce; Ait-Ghezala, Ghania; Chaytow, Helena; Mathura, Venkat; Crawford, Fiona C; Iverson, Grant L

    2016-01-01

    In addition to experiencing traumatic events while deployed in a combat environment, there are other factors that contribute to the development of posttraumatic stress disorder (PTSD) in military service members. This study explored the contribution of genetics, childhood environment, prior trauma, psychological, cognitive, and deployment factors to the development of traumatic stress following deployment. Both pre- and postdeployment data on 231 of 458 soldiers were analyzed. Postdeployment assessments occurred within 30 days from returning stateside and included a battery of psychological health, medical history, and demographic questionnaires; neurocognitive tests; and blood serum for the D2 dopamine receptor (DRD2), apolipoprotein E (APOE), and brain-derived neurotropic factor (BDNF) genes. Soldiers who screened positive for traumatic stress at postdeployment had significantly higher scores in depression (d = 1.91), anxiety (d = 1.61), poor sleep quality (d = 0.92), postconcussion symptoms (d = 2.21), alcohol use (d = 0.63), traumatic life events (d = 0.42), and combat exposure (d = 0.91). BDNF Val66 Met genotype was significantly associated with risk for sustaining a mild traumatic brain injury (mTBI) and screening positive for traumatic stress. Predeployment traumatic stress, greater combat exposure and sustaining an mTBI while deployed, and the BDNF Met/Met genotype accounted for 22% of the variance of postdeployment PTSD scores (R (2)  = 0.22, P PTSD scores. These findings suggest predeployment traumatic stress, genetic, and environmental factors have unique contributions to the development of combat-related traumatic stress in military service members.

  6. Lifetime Exposure to Traumatic and Other Stressful Life Events and Hair Cortisol in a Multi-Racial/Ethnic Sample of Pregnant Women

    Science.gov (United States)

    Schreier, Hannah M. C.; Enlow, Michelle Bosquet; Ritz, Thomas; Coull, Brent A.; Gennings, Chris; Wright, Robert O.; Wright, Rosalind J.

    2016-01-01

    We examined whether lifetime exposure to stressful and traumatic events alters hypothalamic-pituitary-adrenal (HPA) axis functioning, as indexed by hair cortisol, regardless of associated psychopathology, among pregnant women of different racial/ethnic backgrounds. 180 women provided hair samples for measurement of integrated cortisol levels throughout pregnancy and information regarding their lifetime exposure to stressful and traumatic life events. Results indicate that increased lifetime exposure to traumatic events was associated with significantly greater hair cortisol over the course of pregnancy. Similarly, greater lifetime exposure to stressful and traumatic events weighted by reported negative impact (over the previous 12 months) was associated with significantly greater hair cortisol during pregnancy. All analyses controlled for maternal age, education, body mass index (BMI), use of inhaled corticosteroids, race/ethnicity, and posttraumatic stress disorder (PTSD) and depressive symptoms. Following stratification by race/ethnicity, associations between stressful and traumatic life events and hair cortisol were found among Black women only. This is the first study to consider associations between lifetime stress exposures and hair cortisol in a sociodemographically diverse sample of pregnant women. Increased exposure to stressful and traumatic events, independent of PTSD and depressive symptoms, was associated with higher cortisol production, particularly in Black women. Future research should investigate the influence of such increased cortisol exposure on developmental outcomes among offspring. PMID:26551892

  7. Pediatric novice nurses: examining compassion fatigue as a mediator between stress exposure and compassion satisfaction, burnout, and job satisfaction.

    Science.gov (United States)

    Meyer, Rika M L; Li, Angela; Klaristenfeld, Jessica; Gold, Jeffrey I

    2015-01-01

    We investigated whether compassion fatigue mediated associations between nurse stress exposure and job satisfaction, compassion satisfaction, and burnout, controlling for pre-existing stress. The Life Events Checklist was administered to 251 novice pediatric nurses at the start of the nurse residency program (baseline) and 3 months after to assess pre-existing and current stress exposure. Compassion satisfaction, compassion fatigue, and burnout were assessed 3 months after baseline and job satisfaction 6 months after. Stress exposure significantly predicted lower compassion satisfaction and more burnout. Compassion fatigue partially mediated these associations. Results demonstrate a need for hospitals to prevent compassion fatigue in healthcare providers. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Controlled exposure to diesel exhaust and traffic noise - Effects on oxidative stress and activation in mononuclear blood cells

    DEFF Research Database (Denmark)

    Hemmingsen, Jette Gjerke; Møller, Peter; Jantzen, Kim

    2015-01-01

    exhaust (DE) at 276μg/m(3) from a passenger car or filtered air, with co-exposure to traffic noise at 48 or 75dB(A). Gene expression markers of inflammation, (interleukin-8 and tumor necrosis factor), oxidative stress (heme oxygenase (decycling-1)) and DNA repair (8-oxoguanine DNA glycosylase (OGG1)) were...... molecules in leukocyte subtypes. CONCLUSION: 3-h exposure to DE caused no genotoxicity, oxidative stress or inflammation in PBMCs, whereas exposure to noise might cause oxidatively damaged DNA.......Particulate air pollution increases risk of cancer and cardiopulmonary disease, partly through oxidative stress. Traffic-related noise increases risk of cardiovascular disease and may cause oxidative stress. In this controlled random sequence study, 18 healthy subjects were exposed for 3h to diesel...

  9. Asthma and posttraumatic stress symptoms 5 to 6 years following exposure to the World Trade Center terrorist attack.

    Science.gov (United States)

    Brackbill, Robert M; Hadler, James L; DiGrande, Laura; Ekenga, Christine C; Farfel, Mark R; Friedman, Stephen; Perlman, Sharon E; Stellman, Steven D; Walker, Deborah J; Wu, David; Yu, Shengchao; Thorpe, Lorna E

    2009-08-05

    The World Trade Center Health Registry provides a unique opportunity to examine long-term health effects of a large-scale disaster. To examine risk factors for new asthma diagnoses and event-related posttraumatic stress (PTS) symptoms among exposed adults 5 to 6 years following exposure to the September 11, 2001, World Trade Center (WTC) terrorist attack. Longitudinal cohort study with wave 1 (W1) enrollment of 71,437 adults in 2003-2004, including rescue/recovery worker, lower Manhattan resident, lower Manhattan office worker, and passersby eligibility groups; 46,322 adults (68%) completed the wave 2 (W2) survey in 2006-2007. Self-reported diagnosed asthma following September 11; event-related current PTS symptoms indicative of probable posttraumatic stress disorder (PTSD), assessed using the PTSD Checklist (cutoff score > or = 44). Of W2 participants with no stated asthma history, 10.2% (95% confidence interval [CI], 9.9%-10.5%) reported new asthma diagnoses postevent. Intense dust cloud exposure on September 11 was a major contributor to new asthma diagnoses for all eligibility groups: for example, 19.1% vs 9.6% in those without exposure among rescue/recovery workers (adjusted odds ratio, 1.5 [95% CI, 1.4-1.7]). Asthma risk was highest among rescue/recovery workers on the WTC pile on September 11 (20.5% [95% CI, 19.0%-22.0%]). Persistent risks included working longer at the WTC site, not evacuating homes, and experiencing a heavy layer of dust in home or office. Of participants with no PTSD history, 23.8% (95% CI, 23.4%-24.2%) reported PTS symptoms at either W1 (14.3%) or W2 (19.1%). Nearly 10% (9.6% [95% CI, 9.3%-9.8%]) had PTS symptoms at both surveys, 4.7% (95% CI, 4.5%-4.9%) had PTS symptoms at W1 only, and 9.5% (95% CI, 9.3%-9.8%) had PTS symptoms at W2 only. At W2, passersby had the highest rate of PTS symptoms (23.2% [95% CI, 21.4%-25.0%]). Event-related loss of spouse or job was associated with PTS symptoms at W2. Acute and prolonged exposures were both

  10. Effects of lifetime stress exposure on mental and physical health in young adulthood: How stress degrades and forgiveness protects health.

    Science.gov (United States)

    Toussaint, Loren; Shields, Grant S; Dorn, Gabriel; Slavich, George M

    2016-06-01

    To examine risk and resilience factors that affect health, lifetime stress exposure histories, dispositional forgiveness levels, and mental and physical health were assessed in 148 young adults. Greater lifetime stress severity and lower levels of forgiveness each uniquely predicted worse mental and physical health. Analyses also revealed a graded Stress × Forgiveness interaction effect, wherein associations between stress and mental health were weaker for persons exhibiting more forgiveness. These data are the first to elucidate the interactive effects of cumulative stress severity and forgiveness on health, and suggest that developing a more forgiving coping style may help minimize stress-related disorders. © The Author(s) 2014.

  11. Neonatal maternal separation increases susceptibility to experimental colitis and acute stress exposure in male mice

    Directory of Open Access Journals (Sweden)

    Isabella M. Fuentes

    2016-12-01

    Full Text Available Experiencing early life stress can result in maladjusted stress response via dysregulation of the hypothalamic-pituitary-adrenal axis and serves as a risk factor for developing chronic pelvic pain disorders. We investigated whether neonatal maternal separation (NMS would increase susceptibility to experimental colitis or exposure to acute or chronic stress. Male mice underwent NMS from postnatal day 1–21 and as adults were assessed for open field behavior, hindpaw sensitivity, and visceromotor response (VMR to colorectal distension (CRD. VMR was also measured before and after treatment with intracolonic trinitrobenzene sulfonic acid (TNBS or exposure to acute or chronic water avoidance stress (WAS. Myeloperoxidase (MPO activity, proinflammatory gene and corticotropin-releasing factor (CRF receptor expression were measured in distal colon. Baseline VMR was not affected by NMS, but undergoing CRD increased anxiety-like behaviors and mechanical hindpaw sensitivity of NMS mice. Treatment with TNBS dose-dependently decreased body weight and survival only in NMS mice. Following TNBS treatment, IL-6 and artemin mRNA levels were decreased in the distal colon of NMS mice, despite increased MPO activity. A single WAS exposure increased VMR during CRD in NMS mice and increased IL-6 mRNA and CRF2 protein levels in the distal colon of naïve mice, whereas CRF2 protein levels were heightened in NMS colon both at baseline and post-WAS exposure. Taken together, these results suggest that NMS in mice disrupts inflammatory- and stress-induced gene expression in the colon, potentially contributing towards an exaggerated response to specific stressors later in life.

  12. Elodea nuttallii exposure to mercury exposure under enhanced ultraviolet radiation: Effects on bioaccumulation, transcriptome, pigment content and oxidative stress

    International Nuclear Information System (INIS)

    Regier, Nicole; Beauvais-Flück, Rebecca; Slaveykova, Vera I.; Cosio, Claudia

    2016-01-01

    Highlights: • Exposure to UV radiation does not result in co-tolerance to Hg in Elodea nuttallii. • UV radiation increased the stress response to Hg at the transcriptome level. • UV + Hg dysregulated genes of energy and lipid metabolism, nutrition and redox homeostasis. • UV + Hg treatment decreases Hg accumulation in E. nuttallii shoots. • Hg accumulation depends on UV effects on plant metabolism and Hg bioavailability. - Abstract: The hypothesis that increased UV radiation result in co-tolerance to Hg toxicity in aquatic plants was studied at the physiological and transcriptomic level in Elodea nuttallii. At the transcriptomic level, combined exposure to UV + Hg enhanced the stress response in comparison with single treatments, affecting the expression level of transcripts involved in energy metabolism, lipid metabolism, nutrition, and redox homeostasis. Single and combined UV and Hg treatments dysregulated different genes but with similar functions, suggesting a fine regulation of the plant to stresses triggered by Hg, UV and their combination but lack of co-tolerance. At the physiological level, UV + Hg treatment reduced chlorophyll content and depleted antioxidative compounds such as anthocyanin and GSH/GSSG in E. nuttallii. Nonetheless, combined exposure to UV + Hg resulted in about 30% reduction of Hg accumulation into shoots vs exposure to Hg alone, which was congruent with the level of expression of several transporter genes, as well as the UV effect on Hg bioavailability in water. The findings of the present work underlined the importance of performing experimentation under environmentally realistic conditions and to consider the interplay between contaminants and environmental variables such as light that might have confounding effects to better understand and anticipate the effects of multiple stressors in aquatic environment.

  13. Elodea nuttallii exposure to mercury exposure under enhanced ultraviolet radiation: Effects on bioaccumulation, transcriptome, pigment content and oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Regier, Nicole; Beauvais-Flück, Rebecca; Slaveykova, Vera I.; Cosio, Claudia, E-mail: Claudia.Cosio@unige.ch

    2016-11-15

    Highlights: • Exposure to UV radiation does not result in co-tolerance to Hg in Elodea nuttallii. • UV radiation increased the stress response to Hg at the transcriptome level. • UV + Hg dysregulated genes of energy and lipid metabolism, nutrition and redox homeostasis. • UV + Hg treatment decreases Hg accumulation in E. nuttallii shoots. • Hg accumulation depends on UV effects on plant metabolism and Hg bioavailability. - Abstract: The hypothesis that increased UV radiation result in co-tolerance to Hg toxicity in aquatic plants was studied at the physiological and transcriptomic level in Elodea nuttallii. At the transcriptomic level, combined exposure to UV + Hg enhanced the stress response in comparison with single treatments, affecting the expression level of transcripts involved in energy metabolism, lipid metabolism, nutrition, and redox homeostasis. Single and combined UV and Hg treatments dysregulated different genes but with similar functions, suggesting a fine regulation of the plant to stresses triggered by Hg, UV and their combination but lack of co-tolerance. At the physiological level, UV + Hg treatment reduced chlorophyll content and depleted antioxidative compounds such as anthocyanin and GSH/GSSG in E. nuttallii. Nonetheless, combined exposure to UV + Hg resulted in about 30% reduction of Hg accumulation into shoots vs exposure to Hg alone, which was congruent with the level of expression of several transporter genes, as well as the UV effect on Hg bioavailability in water. The findings of the present work underlined the importance of performing experimentation under environmentally realistic conditions and to consider the interplay between contaminants and environmental variables such as light that might have confounding effects to better understand and anticipate the effects of multiple stressors in aquatic environment.

  14. Exposure to workplace bullying and post-traumatic stress disorder symptomology: the role of protective psychological resources.

    Science.gov (United States)

    Spence Laschinger, Heather K; Nosko, Amanda

    2015-03-01

    To examine the relationship between nurses' exposure to workplace bullying and Post-Traumatic Stress Disorder symptomology and the protective role of psychological capital (PsyCap). Workplace bullying has serious organisational and health effects in nursing. Few studies have examined the relation of workplace bullying to serious mental health outcomes, such as Post-Traumatic Stress Disorder. Even fewer have examined the effect of intrapersonal strengths on the health impact of workplace bullying. A survey of 1205 hospital nurses was conducted to test the hypothesized model. Nurses completed standardized measures of bullying, Post-Traumatic Stress Disorder and PsyCap. A moderated regression analysis revealed that more frequent exposure to workplace bullying was significantly related to Post-Traumatic Stress Disorder symptomology regardless of the PsyCap level. That is, PsyCap did not moderate the bullying/PTSD relationship in either group. Bullying exposure and PsyCap were significant independent predictors of Post-Traumatic Stress Disorder symptoms in both groups. Efficacy, a subdimension of PsyCap, moderated the bullying/Post-Traumatic Stress Disorder relationship only among experienced nurses. Workplace bullying appears to be predictive of Post-Traumatic Stress Disorder symptomology, a serious mental health outcome. Workplace bullying is a serious threat to nurses' health and calls for programmes that eliminate bullying and encourage greater levels of positive resources among nurses. © 2013 John Wiley & Sons Ltd.

  15. FEASIBILITY AND EFFECTIVENESS OF DYADIC PROLONGED EXPOSURE INTERVENTION FOR PREVENTING POSTTRAUMATIC GRIEF IN YOUNG CHILDREN: A CASE REPORT OF TWO SIBLINGS.

    Science.gov (United States)

    Rachamim, Lilach

    2017-09-01

    This article highlights the feasibility of a dyadic prolonged exposure (DPE) intervention (L. Rachamim, I. Mirochnik, L. Helpman, N. Nacasch, & E. Yadin, ) in a 3-year-old preschooler and in a 6-year-old kindergartener immediately following the traumatic death of their younger sibling. It presents a detailed case description of the DPE treatment addressing traumatic grief and includes transcribed treatment dialogue. At the time of treatment termination, both children and caregivers resumed normal functioning. The results suggest that DPE intervention may ameliorate posttraumatic grief symptoms in young children. Controlled studies of preventive interventions for this population are clearly warranted. © 2017 Michigan Association for Infant Mental Health.

  16. Biofluid metabotyping of occupationally exposed subjects to air pollution demonstrates high oxidative stress and deregulated amino acid metabolism

    Science.gov (United States)

    Pradhan, Surya Narayan; Das, Aleena; Meena, Ramovatar; Nanda, Ranjan Kumar; Rajamani, Paulraj

    2016-10-01

    Occupational exposure to air pollution induces oxidative stress and prolonged exposure increases susceptibility to cardiovascular and respiratory diseases in several working groups. Biofluid of these subjects may reflect perturbed metabolic phenotypes. In this study we carried out a comparative molecular profiling study using parallel biofluids collected from subjects (n = 85) belonging to auto rickshaw drivers (ARD), traffic cops (TC) and office workers (OW). Higher levels of oxidative stress and inflammation markers in serum of ARD subjects were observed as compared to OW and TC. Uni and multivariate analyses of metabolites identified in urine by 1H NMR revealed 11 deregulated molecules in ARD subjects and involved in phenylalanine, histidine, arginine and proline metabolism. Despite contribution of confounding factors like exposure period, dietary factors including smoking and alcohol status, our results demonstrate existence of exposure specific metabotypes in biofluids of ARD, OW and TC groups. Monitoring serum oxidative stress and inflammation markers and urine metabolites by NMR may be useful to characterize perturbed metabolic phenotypes in populations exposed to urban traffic air pollution.

  17. Exposure to bifenthrin causes immunotoxicity and oxidative stress in male mice.

    Science.gov (United States)

    Jin, Yuanxiang; Pan, Xiuhong; Fu, Zhengwei

    2014-09-01

    Bifenthrin (BF) is one of the most commonly used pesticides among the synthetic pyrethroids. The effects of BF exposure on the induction of immunotoxicity and oxidative stress were studied both in adolescent and adult male ICR mice. Both the weights of the spleen and thymus decreased significantly in the adolescent mice when they were treated with 20 mg/kg BF for 3 weeks. We found that the 3-week oral administration of BF during puberty increased the transcriptional levels of the genes TNF and IL2 in the spleen and IL2 as well as IL4 in the thymus. The effect of BF exposure on the induction of oxidative stress was also studied in serum and liver samples. The total antioxidant capacity and activity of superoxide dismutase were altered significantly in the serum of the 20 mg/kg BF-treated adolescent mice, and the activity of glutathione peroxidase (GPX) decreased significantly in the serum of adolescent and adult mice after 3 weeks of oral administration of 20 mg/kg BF. Compared to serum, hepatic GSH content increased significantly in both the adolescent and adult mice exposed to 20 mg/kg BF; hepatic CAT and GPX activities were altered significantly, even in adolescent mice, after treatment with 10 mg/kg BF. Taken together, the results of this study suggest that exposure to BF, especially during puberty, has the potential to induce immunotoxicity accompanied by oxidative stress in male mice. These findings will help in elucidating the mechanism of toxicity induced by BF in mice. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

  18. Early life low-level cadmium exposure is positively associated with increased oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Kippler, Maria [Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm (Sweden); Bakhtiar Hossain, Mohammad [International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka 1212 (Bangladesh); Department of Laboratory Medicine, Section of Occupational and Environmental Medicine, Lund University, Lund (Sweden); Lindh, Christian [International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka 1212 (Bangladesh); Moore, Sophie E. [MRC Keneba, MRC Laboratories (Gambia); Kabir, Iqbal [Department of Laboratory Medicine, Section of Occupational and Environmental Medicine, Lund University, Lund (Sweden); Vahter, Marie [Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm (Sweden); Broberg, Karin, E-mail: karin.broberg_palmgren@med.lu.se [International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka 1212 (Bangladesh)

    2012-01-15

    Environmental exposure to cadmium (Cd) is known to induce oxidative stress, a state of imbalance between the production of reactive oxygen species (ROS) and the ability to detoxify them, in adults. However, data are lacking on potential effects in early-life. We evaluated urinary concentrations of 8-oxo-7,8-dihydro-2 Prime -deoxyguanosine (8-oxodG), a recognized marker of oxidative DNA damage, in relation to Cd exposure in 96 predominantly breast-fed infants (11-17 weeks of age) in rural Bangladesh. Urinary 8-oxodG was measured using liquid chromatography tandem mass spectrometry and Cd in urine and breast milk by inductively coupled plasma mass spectrometry. Median concentration of 8-oxodG was 3.9 nmol/L, urinary Cd 0.30 {mu}g/L, and breast-milk Cd 0.13 {mu}g/L. In linear regression analyses, urinary 8-oxodG was positively associated with Cd in both urine (p=0.00067) and breast milk (p=0.0021), and negatively associated with body weight (kg; p=0.0041). Adjustment for age, body weight, socio-economic status, urinary arsenic, as well as magnesium, calcium, and copper in breast milk did not change the association between Cd exposure and urinary 8-oxodG. These findings suggest that early-life low-level exposure to Cd via breast milk induces oxidative stress. Further studies are warranted to elucidate whether this oxidative stress is associated with impaired child health and development.

  19. Early life low-level cadmium exposure is positively associated with increased oxidative stress

    International Nuclear Information System (INIS)

    Kippler, Maria; Bakhtiar Hossain, Mohammad; Lindh, Christian; Moore, Sophie E.; Kabir, Iqbal; Vahter, Marie; Broberg, Karin

    2012-01-01

    Environmental exposure to cadmium (Cd) is known to induce oxidative stress, a state of imbalance between the production of reactive oxygen species (ROS) and the ability to detoxify them, in adults. However, data are lacking on potential effects in early-life. We evaluated urinary concentrations of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), a recognized marker of oxidative DNA damage, in relation to Cd exposure in 96 predominantly breast-fed infants (11–17 weeks of age) in rural Bangladesh. Urinary 8-oxodG was measured using liquid chromatography tandem mass spectrometry and Cd in urine and breast milk by inductively coupled plasma mass spectrometry. Median concentration of 8-oxodG was 3.9 nmol/L, urinary Cd 0.30 μg/L, and breast-milk Cd 0.13 μg/L. In linear regression analyses, urinary 8-oxodG was positively associated with Cd in both urine (p=0.00067) and breast milk (p=0.0021), and negatively associated with body weight (kg; p=0.0041). Adjustment for age, body weight, socio-economic status, urinary arsenic, as well as magnesium, calcium, and copper in breast milk did not change the association between Cd exposure and urinary 8-oxodG. These findings suggest that early-life low-level exposure to Cd via breast milk induces oxidative stress. Further studies are warranted to elucidate whether this oxidative stress is associated with impaired child health and development.

  20. Israeli adolescents with ongoing exposure to terrorism: suicidal ideation, posttraumatic stress disorder, and functional impairment.

    Science.gov (United States)

    Chemtob, Claude M; Pat-Horenczyk, Ruth; Madan, Anita; Pitman, Seth R; Wang, Yanping; Doppelt, Osnat; Burns, Kelly Dugan; Abramovitz, Robert; Brom, Daniel

    2011-12-01

    In this study, we examined the relationships among terrorism exposure, functional impairment, suicidal ideation, and probable partial or full posttraumatic stress disorder (PTSD) from exposure to terrorism in adolescents continuously exposed to this threat in Israel. A convenience sample of 2,094 students, aged 12 to 18, was drawn from 10 Israeli secondary schools. In terms of demographic factors, older age was associated with increased risk for suicidal ideation, OR = 1.33, 95% CI [1.09, 1.62], p terrorism was associated with increased risk for each of the measured outcomes including probable partial or full PTSD, functional impairment, and suicidal ideation. When age, gender, level of exposure to terrorism, probable partial or full PTSD, and functional impairment were examined together, only terrorism exposure and functional impairment were associated with suicidal ideation. This study underscores the importance and feasibility of examining exposure to terrorism and functional impairment as risk factors for suicidal ideation. Copyright © 2011 International Society for Traumatic Stress Studies.

  1. Effects on respiratory homeostasis of prolonged, continuous hyperoxia at 1.5 to 3.0 ATA in man in Predictive Studies V

    Science.gov (United States)

    Gelfand, R.; Clark, J. M.; Lambertsen, C. J.; Pisarello, J. B.

    1987-01-01

    Prolonged exposures of men to continuous hyperoxia at 3.0, 2.5, 2.0, and 1.5 ATA were conducted to define CNS oxygen tolerance and to investigate the effects of prolonged hyperoxia on CNS and other organ functions. Altered respiratory homeostasis was evident during exposures of men to 2.5 and 3.0 ATA O2 as nonprogressive increment in ventilation and reciprocal decrement in PET(CO2). These changes were progressive during exposure at 1.5 ATA O2. Mean values of respiratory reactivity at CO2 were somewhat increased following prolonged hyperoxia at 1.5 and 2.5 ATA, compared to preexposure mean values. Hypoxic ventilatory response was unchanged or enhanced after oxygen exposures at 1.5 and 2.5 ATA. Observed respiratory and body temperature changes were not of sufficient magnitude to impair function.

  2. Fetal sex modifies effects of prenatal stress exposure and adverse birth outcomes.

    Science.gov (United States)

    Wainstock, Tamar; Shoham-Vardi, Ilana; Glasser, Saralee; Anteby, Eyal; Lerner-Geva, Liat

    2015-01-01

    Prenatal maternal stress is associated with pregnancy complications, poor fetal development and poor birth outcomes. Fetal sex has also been shown to affect the course of pregnancy and its outcomes. The aim of this study was to evaluate whether fetal sex modifies the association between continuous exposure to life-threatening rocket attack alarms and adverse pregnancy outcomes. A retrospective cohort study was conducted in which the exposed group was comprised of 1846 women exposed to rocket-attack alarms before and during pregnancy. The unexposed group, with similar sociodemographic characteristics, delivered during the same period of time at the same medical center, but resided out of rocket-attack range. Multivariable models for each gender separately, controlling for possible confounders, evaluated the risk associated with exposure for preterm births (PTB), low birthweight (LBW), small for gestational age and small head circumference (HC). In both univariable and multivariable analyses exposure status was a significant risk factor in female fetuses only: PTB (adj. OR = 1.43; 1.04-1.96), LBW (adj. OR = 1.41; 1.02-1.95) and HC stress.

  3. Prolonged sedation and/or analgesia and 5-year neurodevelopment outcome in very preterm infants: results from the EPIPAGE cohort.

    Science.gov (United States)

    Rozé, Jean-Christophe; Denizot, Sophie; Carbajal, Ricardo; Ancel, Pierre-Yves; Kaminski, Monique; Arnaud, Catherine; Truffert, Patrick; Marret, Stéphane; Matis, Jaqueline; Thiriez, Gérard; Cambonie, Gilles; André, Monique; Larroque, Béatrice; Bréart, Gérard

    2008-08-01

    To describe the long-term outcome of very preterm infants receiving prolonged sedation and/or analgesia and examine the relationship between prolonged sedation and/or analgesia and this long-term outcome. A prospective population-based study (Etude EPIdémiologique sur les Petits Ages GEstationnels [EPIPAGE]). To reduce bias, the propensity score method was used. Nine regions of France. The study population included very preterm infants of fewer than 33 weeks' gestational age, born in 1997, who received mechanical ventilation and/or surgery. Main Exposure Prolonged exposure to sedative and/or analgesic drugs in the neonatal period, defined as exposure of more than 7 days to sedative and/or opioid drugs. Presence of moderate or severe disability at 5 years of age. The analysis concerns 1572 premature infants who received mechanical ventilation for whom information about exposure to prolonged sedation and/or analgesia in the neonatal period was available. A total of 115 were exposed and 1457 were not exposed. There was no significant difference between the number of patients lost to follow-up from the group of very preterm infants who were exposed to prolonged sedation and/or analgesia and the group who were not. Exposed very preterm infants had severe or moderate disability at 5 years (41/97; 42%) more often than those who were not exposed (324/1248; 26%). After adjustment for gestational age and propensity score, this association was no longer statistically significant (adjusted relative risk, 1.0; 95% confidence interval, 0.8-1.2). Prolonged sedation and/or analgesia is not associated with a poor 5-year neurological outcome after adjustment for the propensity score.

  4. Single-prolonged stress induces endoplasmic reticulum-dependent apoptosis in the hippocampus in a rat model of post-traumatic stress disorder.

    Directory of Open Access Journals (Sweden)

    Fang Han

    Full Text Available BACKGROUND: Our previous research indicated that apoptosis induced atrophy in the hippocampus of post-traumatic stress disorder (PTSD rats. Endoplasmic reticulum (ER stress-induced apoptosis has been implicated in the development of several disorder diseases. The aim of this study was to investigate whether endoplasmic reticulum-related pathway is involved in single-prolonged stress (SPS induces apoptosis in the hippocampus of PTSD rats by examining the expression levels of three important indicators in the ER-related apoptotic pathway: Glucose-regulated protein (GRP 78, caspase-12 and Ca(2+/CaM/CaMkinaseIIα (CaMkIIα. METHODS: Wistar rats were sacrificed at 1, 4 and 7 days after SPS. SPS is a reliable animal model of PTSD. The apoptotic cells in the hippocampus were assessed by TUNEL method and transmission electron microscopy (TEM. Free intracellular Ca(2+ concentration was measured. GRP78 expression was examined by immunohistochemistry, western blotting and RT-PCR. mRNA of caspase-12 and CaM/CaMkIIα were determined by RT-PCR. RESULTS: Our results showed that apoptotic cells were increased in the SPS rats. TEM analysis revealed characteristic morphological changes of apoptosis in these cells. We observed that GRP78 was significantly up-regulated during early PTSD, and then recovered at 7 days after SPS. By RT-PCR, we observed that the change in caspase-12 expression level was similar to that in GRP78. Moreover, the free intracellular Ca(2+ concentration was significantly higher at 1 day after SPS and decreased in 7 days. CaM expression increased significantly, while CaMKIIα expression decreased significantly in the hippocampus at 1 day after SPS. CONCLUSION: SPS induced change in the expression levels of GRP78, caspase-12 and Ca(2+/CaM/CaMkIIα in the hippocampus of PTSD rats indicated that the endoplasmic reticulum pathway may be involved in PTSD-induced apoptosis.

  5. Low cadmium exposure triggers a biphasic oxidative stress response in mice kidneys

    International Nuclear Information System (INIS)

    Thijssen, Sandy; Cuypers, Ann; Maringwa, John; Smeets, Karen; Horemans, Nele; Lambrichts, Ivo; Van Kerkhove, Emmy

    2007-01-01

    Oxidative stress is believed to participate in the early processes of cadmium (Cd)-induced proximal tubular kidney damage. Mice were chronically exposed up to 23 weeks to low Cd concentrations (10 and 100 mg CdCl 2 /l) via the drinking water. Pro- and antioxidant gene expression levels, glutathione, ascorbate and lipid peroxidation levels were measured. Our study provided evidence for an early and a late stress response in the kidney. Metallothioneins were upregulated from 1 week of exposure on and they stayed important during the whole exposure period. After 8 weeks the expression of Bcl2 (anti-apoptotic), Prdx2 and cytosolic superoxide dismutase (Sod1) was reduced in the group exposed to 100 mg CdCl 2 /l, which might indicate a response to Cd-stress. However glutathione, ascorbate and lipid peroxidation levels did not significantly change, and the overall redox balance remained stable. Stable Sod2 transcriptional levels suggested that an increased formation of superoxide anions, which can arise upon Cd-induced mitochondrial free radical generation, was not appearing. A second defence activation was observed after 23 weeks: i.e. an increase of catalase (Cat), glutathione peroxidase 4 (Gpx4) and heme oxygenase 1 (Hmox1), together with NADPH oxidase 4 (Nox4), of which the role has not been studied yet in Cd nephrotoxicity. These findings were in contrast with previous studies, where Cd-induced oxidative stress was detrimental when high Cd concentrations were applied. In conclusion our study provided evidence that a chronic exposure to low Cd concentrations triggered a biphasic defence activation in the kidney that might lead to adaptation and survival

  6. Childhood trauma exposure and toxic stress: what the PNP needs to know.

    Science.gov (United States)

    Hornor, Gail

    2015-01-01

    Trauma exposure in childhood is a major public health problem that can result in lifelong mental and physical health consequences. Pediatric nurse practitioners must improve their skills in the identification of trauma exposure in children and their interventions with these children. This continuing education article will describe childhood trauma exposure (adverse childhood experiences) and toxic stress and their effects on the developing brain and body. Adverse childhood experiences include a unique set of trauma exposures. The adverse childhood experiences or trauma discussed in this continuing education offering will include childhood exposure to emotional abuse, physical abuse, sexual abuse, emotional neglect, physical neglect, domestic violence, household substance abuse, household mental illness, parental separation or divorce, and a criminal household member. Thorough and efficient methods of screening for trauma exposure will be discussed. Appropriate intervention after identification of trauma exposure will be explored. Copyright © 2015 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.

  7. Cognitive reserve and self-efficacy as moderators of the relationship between stress exposure and executive functioning among spousal dementia caregivers.

    Science.gov (United States)

    Pertl, M M; Hannigan, C; Brennan, S; Robertson, I H; Lawlor, B A

    2017-04-01

    A substantial literature has reported that stress negatively impacts on cognitive processes. As dementia caregiving can be stressful, it has been hypothesized that the challenges of dementia care may increase caregivers' own vulnerability to cognitive decline. Prefrontal processes are thought to be most vulnerable to stress; however, few studies have examined whether greater caregiver stress predicts poorer executive dysfunction, and no previous research has considered potential moderators of this relationship. We examined (1) whether greater psychological stress mediated a relationship between caregiver stress exposure and executive functioning and (2) whether greater self-efficacy and cognitive reserve (CR) moderated this relationship. Spousal dementia caregivers (n = 253) completed the Neuropsychiatric Inventory Questionnaire (stress exposure), the Perceived Stress Scale, the National Adult Reading Test (CR), the Fortinsky dementia-specific caregiver self-efficacy scale, and the Color Trails Test (executive functioning). Moderated mediation was tested using the PROCESS macro. Age, gender, and dementia risk factors were included as covariates. Greater stress exposure indirectly predicted executive functioning through psychological stress. Stronger relationships between greater psychological stress and poorer executive functioning were observed among caregivers with lower CR; there was no evidence that self-efficacy moderated the relationship between stress exposure and psychological stress. Our findings are in line with the idea that greater psychological stress in response to challenges associated with dementia care predicts poorer caregiver executive functioning, particularly among caregivers with low CR. However, these findings are cross sectional; it is also possible that poorer executive functioning contributes to greater caregiver stress.

  8. Stress Responses to Heat Exposure in Three Species of Australian Desert Birds.

    Science.gov (United States)

    Xie, Shangzhe; Romero, L Michael; Htut, Zaw Win; McWhorter, Todd J

    Birds need to respond to weather changes quickly and appropriately for their own well-being and survival. The inability to respond appropriately to heat waves can be fatal to individual birds and can translate into large-scale mortality events. We investigated corticosterone (CORT) and heterophil∶lymphocyte (H∶L) ratio responses of budgerigars (Melopsittacus undulatus), zebra finches (Taeniopygia guttata), and diamond doves (Geopelia cuneata) to heat exposures. The birds were exposed to a temperature similar to what they experience during a typical summer day (35°C) and a higher temperature (45°C) similar to that experienced during a heat wave. There were no significant increases between the CORT concentrations before and after heat exposure in zebra finches and budgerigars at 35° and 45°C, but there was a significant increase in CORT concentrations in diamond doves after exposure to 45°C. The H∶L ratios increased significantly after heat exposure in budgerigars at 35° and 45°C and in diamond doves at 35°C. No significant correlation was found between the changes in CORT and H∶L ratios. The data suggest that there are species differences in birds' stress responses to heat exposure that may reflect their ability to detect and adapt to high temperatures. There appear to be differences between the two types of stress measurements, which may reflect differences in the timescales of these responses.

  9. Role of oxidative stress in cadmium toxicity and carcinogenesis

    International Nuclear Information System (INIS)

    Liu Jie; Qu Wei; Kadiiska, Maria B.

    2009-01-01

    Cadmium (Cd) is a toxic metal, targeting the lung, liver, kidney, and testes following acute intoxication, and causing nephrotoxicity, immunotoxicity, osteotoxicity and tumors after prolonged exposures. Reactive oxygen species (ROS) are often implicated in Cd toxicology. This minireview focused on direct evidence for the generation of free radicals in intact animals following acute Cd overload and discussed the association of ROS in chronic Cd toxicity and carcinogenesis. Cd-generated superoxide anion, hydrogen peroxide, and hydroxyl radicals in vivo have been detected by the electron spin resonance spectra, which are often accompanied by activation of redox sensitive transcription factors (e.g., NF-κB, AP-1 and Nrf2) and alteration of ROS-related gene expression. It is generally agreed upon that oxidative stress plays important roles in acute Cd poisoning. However, following long-term Cd exposure at environmentally-relevant low levels, direct evidence for oxidative stress is often obscure. Alterations in ROS-related gene expression during chronic exposures are also less significant compared to acute Cd poisoning. This is probably due to induced adaptation mechanisms (e.g., metallothionein and glutathione) following chronic Cd exposures, which in turn diminish Cd-induced oxidative stress. In chronic Cd-transformed cells, less ROS signals are detected with fluorescence probes. Acquired apoptotic tolerance renders damaged cells to proliferate with inherent oxidative DNA lesions, potentially leading to tumorigenesis. Thus, ROS are generated following acute Cd overload and play important roles in tissue damage. Adaptation to chronic Cd exposure reduces ROS production, but acquired Cd tolerance with aberrant gene expression plays important roles in chronic Cd toxicity and carcinogenesis.

  10. Effect of leucine supplementation on fat free mass with prolonged hypoxic exposure during a 13-day trek to Everest Base Camp: a double-blind randomized study.

    Science.gov (United States)

    Wing-Gaia, Stacie L; Gershenoff, Dana C; Drummond, Micah J; Askew, E Wayne

    2014-03-01

    Loss of body weight and fat-free mass (FFM) are commonly noted with prolonged exposure to hypobaric hypoxia. Recent evidence suggests protein supplementation, specifically leucine, may potentially attenuate loss of FFM in subcaloric conditions during normoxia. The purpose of this study was to determine if leucine supplementation would prevent the loss of FFM in subcaloric conditions during prolonged hypoxia. Eighteen physically active male (n = 10) and female (n = 8) trekkers completed a 13-day trek in Nepal to Everest Base Camp with a mean altitude of 4140 m (range 2810-5364 m). In this double-blind study, participants were randomized to ingest either leucine (LEU) (7 g leucine, 93 kcal, 14.5 g whey-based protein) or an isocaloric isonitrogenous control (CON) (0.3 g LEU, 93 kcal, 11.3 g collagen protein) twice daily prior to meals. Body weight, body composition, and circumferences of bicep, thigh, and calf were measured pre- and post-trek. There was a significant time effect for body weight (-2.2% ± 1.7%), FFM (-1.7% ± 1.5%), fat mass (-4.0% ± 6.9%), and circumferences (p FFM (CON -2.1 ± 1.5%; LEU -1.2 ± 1.6%), fat mass (CON -2.9% ± 5.9%; LEU -5.4% ± 8.1%), or circumferences. Although a significant loss of body weight, FFM, and fat mass was noted in 13 days of high altitude exposure, FFM loss was not attenuated by leucine. Future studies are needed to determine if leucine attenuates loss of FFM with longer duration high altitude exposure.

  11. Mental Health Nurse's Exposure to Workplace Violence Leads to Job Stress, Which Leads to Reduced Professional Quality of Life.

    Science.gov (United States)

    Itzhaki, Michal; Bluvstein, Irit; Peles Bortz, Anat; Kostistky, Hava; Bar Noy, Dor; Filshtinsky, Vivian; Theilla, Miriam

    2018-01-01

    Professional quality of life (ProQOL) reflects how individuals feel about their work as helpers. Psychiatric ward nurses cope with significant psychological and physical challenges, including exposure to verbal and physical violence. This study was based on two aspects of ProQOL, the positive compassion satisfaction, and the negative compassion fatigue, with the aim of investigating the relation of ProQOL to job stress and violence exposure at a large mental health center. Data were collected from 114 mental health nurses (49/63 M/F) who completed a self-administered questionnaire examining violence exposure, ProQOL, and job stress. The results showed that during the last year, almost all nurses (88.6%) experienced verbal violence, and more than half (56.1%) experienced physical violence. Only 2.6% experienced no violence. ProQOL was not associated with violence exposure but was reduced by work stress and by previous exposure to violence; nurses who perceived their work as more stressful had lower satisfaction from their work. In conclusion, although most mental health nurses are exposed to physical and verbal violence, their ProQOL is more related to job stress than to workplace violence (WPV). Hospital managements should conduct work stress reduction intervention programs and promote strategizes to reduce WPV. Further exploration of (a) factors affecting ProQOL and (b) the effect of violence coping workshops on ProQOL is warranted.

  12. Neuropsychology of trauma-exposure: emotional learning, stress responsivity and the glucocorticoid receptor

    OpenAIRE

    Liebscher, Claudia

    2010-01-01

    In the present dissertation the aim was to identify correlates of trauma-exposure in persons who developed symptoms of a posttraumatic stress disorder and in those who were trauma-exposed but do not suffer from PTSD as well as in persons without trauma-exposure. In the first part of the dissertation, mechanisms of context conditioning and the release of glucocorticoids by the Hypothalamus-pituitary-adrenocortical axis were investigated in trauma-exposed and non-exposed persons. In the second ...

  13. Low-Dose Ionizing Radiation Exposure, Oxidative Stress and Epigenetic Programing of Health and Disease.

    Science.gov (United States)

    Tharmalingam, Sujeenthar; Sreetharan, Shayenthiran; Kulesza, Adomas V; Boreham, Douglas R; Tai, T C

    2017-10-01

    Ionizing radiation exposure from medical diagnostic imaging has greatly increased over the last few decades. Approximately 80% of patients who undergo medical imaging are exposed to low-dose ionizing radiation (LDIR). Although there is widespread consensus regarding the harmful effects of high doses of radiation, the biological effects of low-linear energy transfer (LET) LDIR is not well understood. LDIR is known to promote oxidative stress, however, these levels may not be large enough to result in genomic mutations. There is emerging evidence that oxidative stress causes heritable modifications via epigenetic mechanisms (DNA methylation, histone modification, noncoding RNA regulation). These epigenetic modifications result in permanent cellular transformations without altering the underlying DNA nucleotide sequence. This review summarizes the major concepts in the field of epigenetics with a focus on the effects of low-LET LDIR (stress on epigenetic gene modification. In this review, we show evidence that suggests that LDIR-induced oxidative stress provides a mechanistic link between LDIR and epigenetic gene regulation. We also discuss the potential implication of LDIR exposure during pregnancy where intrauterine fetal development is highly susceptible to oxidative stress-induced epigenetic programing.

  14. Computer mouse use predicts acute pain but not prolonged or chronic pain in the neck and shoulder

    DEFF Research Database (Denmark)

    Andersen, Johan Hviid; Harhoff, Mette; Grimstrup, Søren

    2007-01-01

    BACKGROUND: Computer use is one of the commonest work place exposures in modern society. An adverse effect on musculoskeletal outcomes has been claimed for decades, mainly on the basis of self reports of exposure. The purpose of this study was to assess the risk of neck and shoulder pain associat...... psychosocial factors predicted the risk of prolonged pain. CONCLUSIONS: From the NUDATA-study we can conclude that most computer workers have no or minor neck and shoulder pain, few experience prolonged pain, and even fewer, chronic neck and shoulder pain....

  15. Prolonged job strain and subsequent risk of cancer in women–a longitudinal study, based on the Danish Nurse Cohort

    DEFF Research Database (Denmark)

    Vesterlund, Gitte K.; Høeg, Beverley L.; Johansen, Christoffer

    2017-01-01

    Background: The role of psychological stress in cancer risk is continuously debated. Stress at work is the most common form of stress and previous studies have shown inconsistent results regarding cancer risk. In this longitudinal study, we examined the association between prolonged job strain......-related, digestive and lung cancers according to level of prolonged job strain. The women were followed from 1 January 2000 until cancer diagnosis, emigration, death or 31 December 2013 (mean follow-up 13 years) and models were adjusted for potential confounders. Effect modification was examined according to working...... nightshifts and full time. Results: No significant differences in the risk of overall cancer or any of the cancer subgroups were identified in relation to prolonged busyness, speed, influence, or overall job strain. Effect modification by working full time was observed when examining job influence in relation...

  16. Chronic lead exposure induces cochlear oxidative stress and potentiates noise-induced hearing loss.

    Science.gov (United States)

    Jamesdaniel, Samson; Rosati, Rita; Westrick, Judy; Ruden, Douglas M

    2018-08-01

    Acquired hearing loss is caused by complex interactions of multiple environmental risk factors, such as elevated levels of lead and noise, which are prevalent in urban communities. This study delineates the mechanism underlying lead-induced auditory dysfunction and its potential interaction with noise exposure. Young-adult C57BL/6 mice were exposed to: 1) control conditions; 2) 2 mM lead acetate in drinking water for 28 days; 3) 90 dB broadband noise 2 h/day for two weeks; and 4) both lead and noise. Blood lead levels were measured by inductively coupled plasma mass spectrometry analysis (ICP-MS) lead-induced cochlear oxidative stress signaling was assessed using targeted gene arrays, and the hearing thresholds were assessed by recording auditory brainstem responses. Chronic lead exposure downregulated cochlear Sod1, Gpx1, and Gstk1, which encode critical antioxidant enzymes, and upregulated ApoE, Hspa1a, Ercc2, Prnp, Ccl5, and Sqstm1, which are indicative of cellular apoptosis. Isolated exposure to lead or noise induced 8-12 dB and 11-25 dB shifts in hearing thresholds, respectively. Combined exposure induced 18-30 dB shifts, which was significantly higher than that observed with isolated exposures. This study suggests that chronic exposure to lead induces cochlear oxidative stress and potentiates noise-induced hearing impairment, possibly through parallel pathways. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Effects of elevated temperature and cadmium exposure on stress protein response in eastern oysters Crassostrea virginica (Gmelin)

    Energy Technology Data Exchange (ETDEWEB)

    Ivanina, A.V. [Department of Biology, University of North Carolina at Charlotte, 9201 University City Blvd., Charlotte, NC 28223 (United States); Taylor, C. [Department of Biology, University of North Carolina at Charlotte, 9201 University City Blvd., Charlotte, NC 28223 (United States); Johnson C. Smith University, 100 Beatties Ford Rd., Charlotte, NC 28216 (United States); Sokolova, I.M. [Department of Biology, University of North Carolina at Charlotte, 9201 University City Blvd., Charlotte, NC 28223 (United States)], E-mail: isokolov@uncc.edu

    2009-02-19

    Stress proteins such as heat shock proteins (HSPs) and metallothioneins (MTs) play a key role in cellular protection against environmental stress. Marine ectotherms such as eastern oysters Crassostrea virginica are commonly exposed to multiple stressors including temperature and pollution by metals such as cadmium (Cd) in estuaries and coastal zones; however, the combined effects of these stressors on their cellular protection mechanisms are poorly understood. We acclimated C. virginica from populations adapted to different thermal regimes (Washington, North Carolina and Texas) at a common temperature of 12 deg. C, and analyzed their expression of MTs and HSPs (cytosolic HSP69, HSC72-77, HSP90 and mitochondrial HSP60) in response to the combined acute temperature stress and long-term Cd exposure. Overall, HSP and MT induction patterns were similar in oysters from the three studied geographically distant populations. HSP69 and MTs were significantly up-regulated by Cd and temperature stress implying their important role in cellular stress protection. In contrast, HSC72-77, HSP60 and HSP90 were not consistently induced by either acute heat or Cd exposure. The induction temperature for MTs was higher than for HSP69 (>28 deg. C vs. 20 deg. C, respectively), and MTs were more strongly induced by Cd than by temperature stress (to up to 38-94-fold compared by 3.5-7.5-fold, respectively) consistent with their predominant role in metal detoxification. Notably, heat stress did not result in an additional increase in metallothionein expression in Cd-exposed oysters suggesting a capacity limitation during the combined exposure to Cd and temperature stress. Levels of HSP69 and in some cases, HSC72-77 and HSP90 were lower in Cd-exposed oysters as compared to their control counterparts during heat stress indicating that simultaneous exposure to these two stressors may have partially suppressed the cytoprotective upregulation of molecular chaperones. These limitations of stress

  18. Acute exposure to offshore produced water has an effect on stress- and secondary stress responses in three-spined stickleback Gasterosteus aculeatus.

    Science.gov (United States)

    Knag, Anne Christine; Taugbøl, Annette

    2013-09-01

    Pollution is one of today's greatest problems, and the release of contaminants into the environment can cause adverse changes in vitally important biological pathways. In this study, we exposed three-spined stickleback Gasterosteus aculeatus to produced water (PW), i.e. wastewater from offshore petroleum production. PW contains substances such as alkylphenols (APs) and aromatic hydrocarbons (PAHs) known to induce toxicant stress and endocrine disruption in a variety of organisms. Following exposure to PW, a standardized confinement treatment was applied as a second stressor (PW-stress), testing how fish already under stress from the pollutant would respond to an additional stressor. The endpoint for analysis was a combination of blood levels of cortisol and glucose, in addition to transcribed levels of a set of genes related to toxicant stress, endocrine disruption and general stress. The findings of this study indicate that low doses of PW do not induce vitellogenin in immature female stickleback, but do cause an upregulation of cytochrome (CYP1A) and UDP-glucuronsyltransferase (UDP-GT), two biomarkers related to toxicant stress. However, when the second stressor was applied, both genes were downregulated, indicating that the confinement exposure had a suppressive effect on the expression of toxicant biomarkers (CYP1A and UDP-GT). Further, two of the stress related genes, heat shock protein 90 (HSP90) and stress-induced phosphoprotein (STIP), were upregulated in both PW- and PW-stress-treatment, but not in the water control confinement treatment, indicating that PW posed as a larger stress-factor than confinement for these genes. The confinement stressor caused an increased level of glucose in both control and PW-treated fish, indicating hyperglycemia, a commonly reported stress response in fish. © 2013.

  19. Ghrelin mediates stress-induced food-reward behavior in mice.

    Science.gov (United States)

    Chuang, Jen-Chieh; Perello, Mario; Sakata, Ichiro; Osborne-Lawrence, Sherri; Savitt, Joseph M; Lutter, Michael; Zigman, Jeffrey M

    2011-07-01

    The popular media and personal anecdotes are rich with examples of stress-induced eating of calorically dense "comfort foods." Such behavioral reactions likely contribute to the increased prevalence of obesity in humans experiencing chronic stress or atypical depression. However, the molecular substrates and neurocircuits controlling the complex behaviors responsible for stress-based eating remain mostly unknown, and few animal models have been described for probing the mechanisms orchestrating this response. Here, we describe a system in which food-reward behavior, assessed using a conditioned place preference (CPP) task, is monitored in mice after exposure to chronic social defeat stress (CSDS), a model of prolonged psychosocial stress, featuring aspects of major depression and posttraumatic stress disorder. Under this regime, CSDS increased both CPP for and intake of high-fat diet, and stress-induced food-reward behavior was dependent on signaling by the peptide hormone ghrelin. Also, signaling specifically in catecholaminergic neurons mediated not only ghrelin's orexigenic, antidepressant-like, and food-reward behavioral effects, but also was sufficient to mediate stress-induced food-reward behavior. Thus, this mouse model has allowed us to ascribe a role for ghrelin-engaged catecholaminergic neurons in stress-induced eating.

  20. Exposure to excess insulin (glargine) induces type 2 diabetes mellitus in mice fed on a chow diet.

    Science.gov (United States)

    Yang, Xuefeng; Mei, Shuang; Gu, Haihua; Guo, Huailan; Zha, Longying; Cai, Junwei; Li, Xuefeng; Liu, Zhenqi; Cao, Wenhong

    2014-06-01

    We have previously shown that insulin plays an important role in the nutrient-induced insulin resistance. In this study, we tested the hypothesis that chronic exposure to excess long-acting insulin (glargine) can cause typical type 2 diabetes mellitus (T2DM) in normal mice fed on a chow diet. C57BL/6 mice were treated with glargine once a day for 8 weeks, followed by evaluations of food intake, body weight, blood levels of glucose, insulin, lipids, and cytokines, insulin signaling, histology of pancreas, ectopic fat accumulation, oxidative stress level, and cholesterol content in mitochondria in tissues. Cholesterol content in mitochondria and its association with oxidative stress in cultured hepatocytes and β-cells were also examined. Results show that chronic exposure to glargine caused insulin resistance, hyperinsulinemia, and relative insulin deficiency (T2DM). Treatment with excess glargine led to loss of pancreatic islets, ectopic fat accumulation in liver, oxidative stress in liver and pancreas, and increased cholesterol content in mitochondria of liver and pancreas. Prolonged exposure of cultured primary hepatocytes and HIT-TI5 β-cells to insulin induced oxidative stress in a cholesterol synthesis-dependent manner. Together, our results show that chronic exposure to excess insulin can induce typical T2DM in normal mice fed on a chow diet. © 2014 The authors.

  1. Effects of thermal stress and nickel exposure on biomarkers responses in Mytilus galloprovincialis (Lam).

    Science.gov (United States)

    Attig, Hajer; Kamel, Naouel; Sforzini, Susanna; Dagnino, Alessandro; Jamel, Jebali; Boussetta, Hamadi; Viarengo, Aldo; Banni, Mohamed

    2014-03-01

    The present work aimed to assess the Mytilus galloprovincialis digestive gland biomarkers responses to nickel (Ni) exposure along with a heat stress gradient. Mussels were exposed to a sublethal dose of nickel (13 μM) along with a temperature gradient (18 °C, 20 °C, 22 °C, 24 °C and 26 °C) for 4 days. Metallothionein (MTs) content was assessed as specific response to metals. Catalase (CAT), glutathione S-transferase (GST) activities and malondialdehyde (MDA) were measured as biomarkers of oxidative stress and lipid peroxidation. The cholinergic system was monitored using the acetylcholinesterase activity (AChE). Moreover, Ni uptakes along with the exposure temperatures were assessed. A correlation matrix (CM) between the investigated biomarkers and the exposure temperatures and a Principal Component Analysis (PCA) were achieved. Our data showed a negative effect of temperature increase on mussel's antioxidant and detoxification response to Ni exposure being more pronounced in animals exposed to the 24 °C and 26 °C. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Stress Management and Gifted Children

    Science.gov (United States)

    Patel, Vidisha A.

    2009-01-01

    Stress can affect anyone, and gifted children are no exception. Giftedness can sometimes be the cause of the stress. Perfectionism, sensitivity, and intensity are characteristics of gifted children that may exacerbate stress. Stress can be constructive. Prolonged stress, however, with no time to recover becomes detrimental. Continued stress upsets…

  3. Therapists' and patients' stress responses during graduated versus flooding in vivo exposure in the treatment of specific phobia: A preliminary observational study.

    Science.gov (United States)

    Schumacher, Sarah; Miller, Robert; Fehm, Lydia; Kirschbaum, Clemens; Fydrich, Thomas; Ströhle, Andreas

    2015-12-15

    Exposure therapy is considered an effective treatment strategy for phobic anxiety, however, it is rarely applied in clinical practice. The under-usage might be due to various factors of which heightened stress levels not only in patients but also in therapists are presumed to be of particular relevance. The present study aimed to investigate whether different forms of exposure might lead to varying physiological and psychological stress responses in therapists and phobic patients. 25 patients with specific phobia underwent individual cognitive behavioural therapy, performed by 25 psychotherapist trainees, applying exposure sessions in graduated form or the flooding technique. Patients and therapists provided subjective evaluations of stress and five saliva samples for analysis of salivary cortisol and alpha-amylase either during two graduated exposure sessions or during one flooding session, while a regular therapy session served as control condition. Therapists displayed heightened salivary alpha-amylase release during exposure of the flooding, but not the graduated, type. Patients showed elevated salivary cortisol during flooding exposure numerically, however, not on a statistically significant level. Therapists reported more pronounced subjective stress during flooding compared to graduated exposure. Elevated stress levels should be addressed in clinical training in order to improve application of exposure in routine practice. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Effects of fluoxetine on the amygdala and the hippocampus after administration of a single prolonged stress to male Wistar rates: In vivo proton magnetic resonance spectroscopy findings.

    Science.gov (United States)

    Han, Fang; Xiao, Bing; Wen, Lili; Shi, Yuxiu

    2015-05-30

    Posttraumatic stress disorder (PTSD) is an anxiety- and memory-based disorder. The hippocampus and amygdala are key areas in mood regulation. Fluoxetine was found to improve the anxiety-related symptoms of PTSD patients. However, little work has directly examined the effects of fluoxetine on the hippocampus and the amygdala. In the present study, male Wistar rats received fluoxetine or vehicle after exposure to a single prolonged stress (SPS), an animal model of PTSD. In vivo proton magnetic resonance spectroscopy ((1)H-MRS) was performed -1, 1, 4, 7 and 14 days after SPS to examine the effects of fluoxetine on neurometabolite changes in amygdala, hippocampus and thalamus. SPS increased the N-acetylaspartate (NAA)/creatine (Cr) and choline moieties (Cho)/Cr ratios in the bilateral amygdala on day 4, decreased the NAA/Cr ratio in the left hippocampus on day 1, and increased both ratios in the right hippocampus on day 14. But no significant change was found in the thalamus. Fluoxetine treatment corrected the SPS increases in the NAA/Cr and Cho/Cr levels in the amygdala on day 4 and in the hippocampus on day 14, but it failed to normalise SPS-associated decreases in NAA/Cr levels in the left hippocampus on day 1. These results suggested that metabolic abnormalities in the amygdala and the hippocampus were involved in SPS, and different effects of fluoxetine in correcting SPS-induced neurometabolite changes among the three areas. These findings have implications for fluoxetine treatment in PTSD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Personality traits modulate emotional and physiological responses to stress.

    Science.gov (United States)

    Childs, Emma; White, Tara L; de Wit, Harriet

    2014-09-01

    An individual's susceptibility to psychological and physical disorders associated with chronic stress exposure, for example, cardiovascular and infectious disease, may also be predicted by their reactivity to acute stress. One factor associated with both stress resilience and health outcomes is personality. An understanding of how personality influences responses to acute stress may shed light upon individual differences in susceptibility to chronic stress-linked disease. This study examined the relationships between personality and acute responses to stress in 125 healthy adults, using hierarchical linear regression. We assessed personality traits using the Multidimensional Personality Questionnaire (MPQ-BF), and responses to acute stress (cortisol, heart rate, blood pressure, mood) using a standardized laboratory psychosocial stress task, the Trier Social Stress Test. Individuals with high Negative Emotionality exhibited greater emotional distress and lower blood pressure responses to the Trier Social Stress Test. Individuals with high agentic Positive Emotionality exhibited prolonged heart rate responses to stress, whereas those with high communal Positive Emotionality exhibited smaller cortisol and blood pressure responses. Separate personality traits differentially predicted emotional, cardiovascular, and cortisol responses to a psychosocial stressor in healthy volunteers. Future research investigating the association of personality with chronic stress-related disease may provide further clues to the relationship between acute stress reactivity and susceptibility to disease.

  6. Persistent ER stress induces the spliced leader RNA silencing pathway (SLS, leading to programmed cell death in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Hanoch Goldshmidt

    2010-01-01

    Full Text Available Trypanosomes are parasites that cycle between the insect host (procyclic form and mammalian host (bloodstream form. These parasites lack conventional transcription regulation, including factors that induce the unfolded protein response (UPR. However, they possess a stress response mechanism, the spliced leader RNA silencing (SLS pathway. SLS elicits shut-off of spliced leader RNA (SL RNA transcription by perturbing the binding of the transcription factor tSNAP42 to its cognate promoter, thus eliminating trans-splicing of all mRNAs. Induction of endoplasmic reticulum (ER stress in procyclic trypanosomes elicits changes in the transcriptome similar to those induced by conventional UPR found in other eukaryotes. The mechanism of up-regulation under ER stress is dependent on differential stabilization of mRNAs. The transcriptome changes are accompanied by ER dilation and elevation in the ER chaperone, BiP. Prolonged ER stress induces SLS pathway. RNAi silencing of SEC63, a factor that participates in protein translocation across the ER membrane, or SEC61, the translocation channel, also induces SLS. Silencing of these genes or prolonged ER stress led to programmed cell death (PCD, evident by exposure of phosphatidyl serine, DNA laddering, increase in reactive oxygen species (ROS production, increase in cytoplasmic Ca(2+, and decrease in mitochondrial membrane potential, as well as typical morphological changes observed by transmission electron microscopy (TEM. ER stress response is also induced in the bloodstream form and if the stress persists it leads to SLS. We propose that prolonged ER stress induces SLS, which serves as a unique death pathway, replacing the conventional caspase-mediated PCD observed in higher eukaryotes.

  7. Prior exposure to repeated immobilization or chronic unpredictable stress protects from some negative sequels of an acute immobilization.

    Science.gov (United States)

    Pastor-Ciurana, Jordi; Rabasa, Cristina; Ortega-Sánchez, Juan A; Sanchís-Ollè, Maria; Gabriel-Salazar, Marina; Ginesta, Marta; Belda, Xavier; Daviu, Núria; Nadal, Roser; Armario, Antonio

    2014-05-15

    Exposure to chronic unpredictable stress (CUS) is gaining acceptance as a putative animal model of depression. However, there is evidence that chronic exposure to stress can offer non-specific stress protection from some effects of acute superimposed stressors. We then compared in adult male rats the protection afforded by prior exposure to CUS with the one offered by repeated immobilization on boards (IMO) regarding some of the negative consequences of an acute exposure to IMO. Repeated exposure to IMO protected from the negative consequences of an acute IMO on activity in an open-field, saccharin intake and body weight gain. Active coping during IMO (struggling) was markedly reduced by repeated exposure to the same stressor, but it was not affected by a prior history of CUS, suggesting that our CUS protocol does not appear to impair active coping responses. CUS exposure itself caused a strong reduction of activity in the open-field but appeared to protect from the hypo-activity induced by acute IMO. Moreover, prior CUS offered partial protection from acute IMO-induced reduction of saccharin intake and body weight gain. It can be concluded that a prior history of CUS protects from some of the negative consequences of exposure to a novel severe stressor, suggesting the development of partial cross-adaptation whose precise mechanisms remain to be studied. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Mental Health Nurse’s Exposure to Workplace Violence Leads to Job Stress, Which Leads to Reduced Professional Quality of Life

    Directory of Open Access Journals (Sweden)

    Michal Itzhaki

    2018-02-01

    Full Text Available Professional quality of life (ProQOL reflects how individuals feel about their work as helpers. Psychiatric ward nurses cope with significant psychological and physical challenges, including exposure to verbal and physical violence. This study was based on two aspects of ProQOL, the positive compassion satisfaction, and the negative compassion fatigue, with the aim of investigating the relation of ProQOL to job stress and violence exposure at a large mental health center. Data were collected from 114 mental health nurses (49/63 M/F who completed a self-administered questionnaire examining violence exposure, ProQOL, and job stress. The results showed that during the last year, almost all nurses (88.6% experienced verbal violence, and more than half (56.1% experienced physical violence. Only 2.6% experienced no violence. ProQOL was not associated with violence exposure but was reduced by work stress and by previous exposure to violence; nurses who perceived their work as more stressful had lower satisfaction from their work. In conclusion, although most mental health nurses are exposed to physical and verbal violence, their ProQOL is more related to job stress than to workplace violence (WPV. Hospital managements should conduct work stress reduction intervention programs and promote strategizes to reduce WPV. Further exploration of (a factors affecting ProQOL and (b the effect of violence coping workshops on ProQOL is warranted.

  9. Depressive disorders during weaning from prolonged mechanical ventilation.

    Science.gov (United States)

    Jubran, Amal; Lawm, Gerald; Kelly, Joanne; Duffner, Lisa A; Gungor, Gokay; Collins, Eileen G; Lanuza, Dorothy M; Hoffman, Leslie A; Tobin, Martin J

    2010-05-01

    Patients who require mechanical ventilation are at risk of emotional stress because of total dependence on a machine for breathing. The stress may negatively impact ventilator weaning and survival. The purpose of this study was to determine whether depressive disorders in patients being weaned from prolonged mechanical ventilation are linked to weaning failure and decreased survival. A prospective study of 478 consecutive patients transferred to a long-term acute care hospital for weaning from prolonged ventilation was undertaken. A clinical psychologist conducted a psychiatric interview to assess for the presence of depressive disorders. Of the 478 patients, 142 had persistent coma or delirium and were unable to be evaluated for depressive disorders. Of the remaining 336 patients, 142 (42%) were diagnosed with depressive disorders. In multivariate analysis, co-morbidity score [odds ratio (OR), 1.23; P = 0.007], functional dependence before the acute illness (OR, 1.70, P = 0.03) and history of psychiatric disorders (OR, 3.04, P = 0.0001) were independent predictors of depressive disorders. The rate of weaning failure was higher in patients with depressive disorders than in those without such disorders (61 vs. 33%, P = 0.0001), as was mortality (24 vs. 10%, P = 0.0008). The presence of depressive disorders was independently associated with mortality (OR, 4.3; P = 0.0002); age (OR, 1.06; P = 0.001) and co-morbidity score (OR, 1.24; P = 0.02) also predicted mortality. Depressive disorders were diagnosed in 42% of patients who were being weaned from prolonged ventilation. Patients with depressive disorders were more likely to experience weaning failure and death.

  10. Management of prolonged pregnancy

    International Nuclear Information System (INIS)

    Iqbal, S.

    2004-01-01

    Objective: To compare two strategies for management of prolonged pregnancy (= or >294 days) i.e. induction (intervention) versus expectant management (non-intervention) and evaluate the associated feto-maternal risks. Subjects and Methods: One hundred cases of uncomplicated prolonged gestation were selected. The gestational age was confirmed by ultrasound in first trimester. One group (50 patients) was managed by intervention i.e. induction of labour (group A) and other group (50 patients) by non-intervention i.e. expectant management (group B). In group A intervention was done at 42 weeks. In expectant group, the methods of monitoring were fetal kick charting recorded daily by the patient, and ultrasound for amniotic fluid index. The biophysical profile score and NST (non stress test) were performed once a week till 42 weeks and then twice weekly. Results: The frequency of prolonged pregnancy was found to be 10.9%. There was no significant difference in the number of spontaneous vaginal deliveries between the two groups. The rate of LSCS (lower segment caesarean section) was higher in intervention group ( 30% versus 18% ). The neonatal depression at birth was more in group B ( 10% versus 4%) and at 5 minutes almost same between two groups (4% versus 2%). There were 11 cases of meconium aspiration syndrome, leading to one neonatal death. Among nine perinatal deaths two were neonatal deaths. Seven cases of intrauterine deaths in which antepartum deaths occurred because of non compliance of patients. No cause could be detected for the other three fetuses. Conclusion: There was increased LSCS rate in group A. However in expectant group B perinatal mortality was about twice more as compared to intervention group. Active early intervention at 42 weeks is warranted to reduce perinatal morbidity and mortality. (author)

  11. Modifying Exposure-Based CBT for Cambodian Refugees with Posttraumatic Stress Disorder

    Science.gov (United States)

    Otto, Michael W.; Hinton, Devon E.

    2009-01-01

    Cambodian refugees represent a severely traumatized population living in the United States. In this paper, we describe the modification of a cognitive-behavior therapy program to facilitate delivery of an exposure-based treatment for posttraumatic stress disorder while addressing some of the challenges brought by differences in language and culture between providers and patients. Our treatment modifications include the use of metaphors and culturally relevant examples to aid the communication of core concepts by interpreters, an emphasis on teaching the “process” of exposure therapy rather than relying on specific exposure practice in the group setting, a focus on interoceptive exposure to allow more effective group practice and to address culturally specific symptom interpretations, attention to the way in which treatment procedures interacted with culturally specific beliefs, and efforts to integrate treatment services within the community. Although data are limited, results to date suggest that this modified treatment was acceptable to patients and offered benefits on the order of large effect sizes. PMID:20072706

  12. The whole brain diffusion tensor imaging study on acute phase of the posttraumatic stress disorder resulting from the single-prolonged stress based on tract based spatial statistics

    International Nuclear Information System (INIS)

    Xi Yibin; Liu Kang; Zhe Xia; Mu Yunfeng; Yin Hong; Huan Yi; Yang Xiaobin; Du Ping

    2013-01-01

    Objective: To study the changes of the brain white matter microstructure at the acute stage of posttraumatic stress disorder (PTSD) resulting from a single-prolonged stress. Methods: DTI scans were performed on 17 survivors buried more than 190 h in Shanxi Wangjialing mine disaster and 17 cases of normal controls using Siemens 3.0 T MR. The differences of the FA values measured from the whole brain DTI between the two groups were analyzed based on tract based spatial statistics (TBSS). FA data were statistically compared between the two groups based on nonparametric random permutation test (RPT), and the brain areas of the PTSD patients with abnormal FA were defined. Results: Compared with control group, FA values in the PTSD (at acute stage) group decreased in genu, rostral body of corpus callosum, and increased in the left thalamic and corticospinal tract region of bilateral corona radiata and the posterior limb of the left internal capsule, the left cerebral peduncle. The differences were statistically significant (P < 0.01 TFCE-corrected). Conclusions: TBSS is a comprehensive and accurate method for evaluating the changes of whole brain DTI in PTSD cases. The fiber structural abnormalities in the genu, rostral body of bilateral corpus callosum, anterior radiation of left thalamic may be due to stress. TBSS can provide a more objective basis for the early diagnosis and intervention of PTSD. (authors)

  13. Role of Mitochondrial Oxidative Stress in Spaceflight-Induced Tissue Degeneration

    Science.gov (United States)

    Torres, Samantha M.; Schreurs, Ann-Sofie; Truong, Tiffany A.; Tahimic, Candice; Globus, Ruth

    2017-01-01

    Microgravity and ionizing radiation in the spaceflight environment poses multiple challenges to homeostasis and may contribute to cellular stress. Effects may include increased generation of reactive oxygen species (ROS), DNA damage and repair error, cell cycle arrest, cell senescence or death. Our central hypothesis is that prolonged exposure to the spaceflight environment leads to the excess production of ROS and oxidative damage, culminating in accelerated tissue degeneration. The main goal of this project is to determine the importance of cellular redox defense for physiological adaptations and tissue degeneration in the space environment.

  14. Cumulative effects of prenatal-exposure to exogenous chemicals and psychosocial stress on fetal growth: Systematic-review of the human and animal evidence.

    Science.gov (United States)

    Vesterinen, Hanna M; Morello-Frosch, Rachel; Sen, Saunak; Zeise, Lauren; Woodruff, Tracey J

    2017-01-01

    Adverse effects of prenatal stress or environmental chemical exposures on fetal growth are well described, yet their combined effect remains unclear. To conduct a systematic review on the combined impact and interaction of prenatal exposure to stress and chemicals on developmental outcomes. We used the first three steps of the Navigation Guide systematic review. We wrote a protocol, performed a robust literature search to identify relevant animal and human studies and extracted data on developmental outcomes. For the most common outcome (fetal growth), we evaluated risk of bias, calculated effect sizes for main effects of individual and combined exposures, and performed a random effects meta-analysis of those studies reporting on odds of low birthweight (LBW) by smoking and socioeconomic status (SES). We identified 17 human- and 22 animal-studies of combined chemical and stress exposures and fetal growth. Human studies tended to have a lower risk of bias across nine domains. Generally, we found stronger effects for chemicals than stress, and these exposures were associated with reduced fetal growth in the low-stress group and the association was often greater in high stress groups, with limited evidence of effect modification. We found smoking associated with significantly increased odds of LBW, with a greater effect for high stress (low SES; OR 4.75 (2.46-9.16)) compared to low stress (high SES; OR 1.95 (95% CI 1.53-2.48)). Animal studies generally had a high risk of bias with no significant combined effect or effect modification. We found that despite concern for the combined effects of environmental chemicals and stress, this is still an under-studied topic, though limited available human studies indicate chemical exposures exert stronger effects than stress, and this effect is generally larger in the presence of stress.

  15. Exploring violence exposure, stress, protective factors and behavioral problems among inner-city youth.

    Science.gov (United States)

    Youngstrom, Eric; Weist, Mark D; Albus, Kathleen E

    2003-09-01

    This study examined relationships between violence exposure, other stressors, family support, and self-concept on self-reported behavioral problems among 320 urban adolescents (aged 11-18) referred for mental health treatment. Overall, participants reported high levels of violence exposure, with a median of six past encounters with violence as a witness, victim, or through the experiences of associates. All forms of violence exposure (witnessing, being a victim, knowing of victims) were correlated with internalizing and externalizing behavioral problems for males and females. Total violence exposure predicted behavioral problems among participants, even after controlling for the effects of other risk, demographic and protective factors. Family support and self-concept moderated the influence of life stress and cumulative risk on problem behavior outcomes, but these protective variables did not significantly moderate violence exposure.

  16. Increasing adult hippocampal neurogenesis in mice after exposure to unpredictable chronic mild stress may counteract some of the effects of stress.

    Science.gov (United States)

    Culig, Luka; Surget, Alexandre; Bourdey, Marlene; Khemissi, Wahid; Le Guisquet, Anne-Marie; Vogel, Elise; Sahay, Amar; Hen, René; Belzung, Catherine

    2017-11-01

    Major depression is hypothesized to be associated with dysregulations of the hypothalamic-pituitary-adrenal (HPA) axis and impairments in adult hippocampal neurogenesis. Adult-born hippocampal neurons are required for several effects of antidepressants and increasing the rate of adult hippocampal neurogenesis (AHN) before exposure to chronic corticosterone is sufficient to protect against its harmful effects on behavior. However, it is an open question if increasing AHN after the onset of chronic stress exposure would be able to rescue behavioral deficits and which mechanisms might be involved in recovery. We investigated this question by using a 10-week unpredictable chronic mild stress (UCMS) model on a transgenic mouse line (iBax mice), in which the pro-apoptotic gene Bax can be inducibly ablated in neural stem cells following Tamoxifen injection, therefore enhancing the survival of newborn neurons in the adult brain. We did not observe any effect of our treatment in non-stress conditions, but we did find that increasing AHN after 2 weeks of UCMS is sufficient to counteract the effects of UCMS on certain behaviors (splash test and changes in coat state) and endocrine levels and thus to display some antidepressant-like effects. We observed that increasing AHN lowered the elevated basal corticosterone levels in mice exposed to UCMS. This was accompanied by a tamoxifen-induced reversal of the lack of stress-induced decrease in neuronal activation in the anteromedial division of the bed nucleus of the stria terminalis (BSTMA) after intrahippocampal dexamethasone infusion, pointing to a possible mechanism through which adult-born neurons might have exerted their effects. Our results contribute to the neurogenesis hypothesis of depression by suggesting that increasing AHN may be beneficial not just before, but also after exposure to stress by counteracting several of its effects, in part through regulating the HPA axis. Copyright © 2017 Elsevier Ltd. All rights

  17. Gene Transcription and Virulence Potential of Listeria monocytogenes Strains After Exposure to Acidic and NaCl Stress

    DEFF Research Database (Denmark)

    Olesen, Inger; Vogensen, Finn Kvist; Jespersen, Lene

    2009-01-01

    transcription were observed both after exposure to shock (six genes) and after long-term adaptation to stress (18 genes). In the shock experiments, a transient induction of clpC and clpE was seen for both strains, while transient induction of sigB, inlA, and inlB was observed for strain 4140 only; actA was only...... induced in EGD-e after NaCl shock. The longterm stress experiments were included to imitate the stress conditions encountered by L. monocytogenes when present in food products. Long-term adaptation of EGD-e to acidic stress induced transcription of iap and repressed flaA, while genes related to stress......Gene transcription and virulence potential of two strains of Listeria monocytogenes, EGD-e and 4140, were compared by quantitative real-time polymerase chain reaction and in a Caco-2 in vitro model after exposure to acidic (pH 5.5) and NaCl (4.5% w=v) stress. Strain-dependent differences in gene...

  18. Antidepressant-like activity of venlafaxine and clonidine in mice exposed to single prolonged stress - A model of post-traumatic stress disorder. Pharmacodynamic and molecular docking studies.

    Science.gov (United States)

    Malikowska, Natalia; Fijałkowski, Łukasz; Nowaczyk, Alicja; Popik, Piotr; Sałat, Kinga

    2017-10-15

    Post-traumatic stress disorder (PTSD) is a growing issue worldwide characterized by stress and anxiety in response to re-experiencing traumatic events which strongly impair patient's quality of life and social functions. Available antidepressant and anxiolytic drugs are not efficacious in the majority of treated individuals. This necessitates a significant medical demand to develop novel therapeutic strategies for PTSD. Animal model of PTSD was induced using a mouse single prolonged stress protocol (mSPS). To assess the activity of venlafaxine and clonidine, the forced swim test (FST) was used repeatedly 24h, 3days, 8days, 15days and 25days after mSPS. To get insight into a possible mechanism of anti-PTSD action, molecular docking procedure was utilized for the most active drug. This in silico part comprised molecular docking of enantiomers of venlafaxine to human transporters for serotonin (hSERT), norepinephrine (hNET) and dopamine (hDAT). In mSPS-subjected mice FST revealed the effectiveness of venlafaxine, however in non SPS-subjected mice both venlafaxine and clonidine were active. Molecular docking studies indicated that the affinity of venlafaxine to monoamine transporters is growing in the following rank order: hDATPTSD. Its mechanism of action, i.e., SERT, NET and DAT inhibition indicates potential drug targets for PTSD treatment. We expect that these results will contribute to a broader application of VLX in PTSD patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. The temporal relationship between change in symptoms of prolonged grief and posttraumatic stress following old age spousal bereavement

    DEFF Research Database (Denmark)

    O Connor, Maja; Nickerson, Angela; Aderka, Idan M.

    2015-01-01

    Background: High levels of both prolonged grief symptoms (PGS) and posttraumatic stress symptoms (PTSS) are relatively common following bereavement, and the two types of bereavement complications share some of the same features. Little research has studied which of the two precedes the other...... following the death of a loved one. The purpose of this study was to examine the temporal relationship between change in high levels of PGS and PTSS during the first four years following old age spousal loss. Methods: Participants were 237 Danes (40% male; mean age = 73 years, SD = 4.4; range 65-81) who....... Results: Lower-level mediation analyses wereas performed. Results indicated that PGS mediated 83% of the relationship between time and PTSS, while PTSS only mediated 17% of the relationship between time and PGS. These results suggest that changes in PGS mediated changes in PTSS following spousal...

  20. Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

    Energy Technology Data Exchange (ETDEWEB)

    Zago, A. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Leão, R.M.; Carneiro-de-Oliveira, P.E. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos/Universidade Estadual de São Paulo, Araraquara, SP (Brazil); Marin, M.T.; Cruz, F.C. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Planeta, C.S. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos/Universidade Estadual de São Paulo, Araraquara, SP (Brazil)

    2011-11-18

    Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although crosssensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P) 28-37) and adult (P60-67) rats received nicotine (0.4 mg/kg, sc) or saline (0.9% NaCl, sc) and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc) or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats.

  1. Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

    International Nuclear Information System (INIS)

    Zago, A.; Leão, R.M.; Carneiro-de-Oliveira, P.E.; Marin, M.T.; Cruz, F.C.; Planeta, C.S.

    2011-01-01

    Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although crosssensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P) 28-37) and adult (P60-67) rats received nicotine (0.4 mg/kg, sc) or saline (0.9% NaCl, sc) and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc) or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats

  2. Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

    Directory of Open Access Journals (Sweden)

    A. Zago

    2012-01-01

    Full Text Available Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although cross-sensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P 28-37 and adult (P60-67 rats received nicotine (0.4 mg/kg, sc or saline (0.9% NaCl, sc and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats.

  3. Relationship between Type of Trauma Exposure and Posttraumatic Stress Disorder among Urban Children and Adolescents

    Science.gov (United States)

    Luthra, Rohini; Abramovitz, Robert; Greenberg, Rick; Schoor, Alan; Newcorn, Jeffrey; Schmeidler, James; Levine, Paul; Nomura, Yoko; Chemtob, Claude M.

    2009-01-01

    This study examines the association between trauma exposure and posttraumatic stress disorder (PTSD) among 157 help-seeking children (aged 8-17). Structured clinical interviews are carried out, and linear and logistic regression analyses are conducted to examine the relationship between PTSD and type of trauma exposure controlling for age, gender,…

  4. PTSD and PTG among Israeli mothers: Opposite facets of exposure to terrorism.

    Science.gov (United States)

    Shechory Bitton, Mally; Laufer, Avital

    2017-12-01

    The aim of the this study was to test the association between posttraumatic stress disorder (PTSD), posttraumatic growth (PTG), and coping strategies among Israeli mothers with prolonged exposure to rocket missiles. One hundred fifty-two mothers, from the Western Negev region of Israel, took part in the study. Respondents were affected by prolonged exposure to missile attacks even when they themselves had not been hit or injured. A positive correlation was found between PTSD and PTG. Problem-focused coping was found to mediate the relationship between PTSD and PTG; the higher the PTSD, the greater the use of problem-focused coping and the greater the posttraumatic growth. The results help understand the association between PTSD and PTG. The finding whereby problem-focused coping mediates the PTSD-PTG relationship is important for comprehending the association between the variables and the significance of growth in human life and for constructing intervention programs that promote growth following trauma. In addition, the study contributes to raising awareness both of how mothers cope and that they are a separate risk group with distinct growth possibilities. Copyright © 2017 John Wiley & Sons, Ltd.

  5. Particulate air pollution induces arrhythmia via oxidative stress and calcium calmodulin kinase II activation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin-Bae [The Division of Cardiology, Kyung Hee University College of Medicine, 1 Hoegi-dong, Dongdaemun-Gu, Seoul (Korea, Republic of); Kim, Changsoo [The Department of Preventive Medicine, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul (Korea, Republic of); Choi, Eunmi [Cardiovascular Research Institute and Severance Biomedical Science Institute, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul (Korea, Republic of); Park, Sanghoon; Park, Hyelim; Pak, Hui-Nam; Lee, Moon-Hyoung [The Division of Cardiology, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul (Korea, Republic of); Shin, Dong Chun [The Department of Preventive Medicine, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul (Korea, Republic of); Hwang, Ki-Chul [Cardiovascular Research Institute and Severance Biomedical Science Institute, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul (Korea, Republic of); The Division of Cardiology, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul (Korea, Republic of); Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul (Korea, Republic of); Joung, Boyoung, E-mail: cby6908@yuhs.ac [The Division of Cardiology, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul (Korea, Republic of)

    2012-02-15

    Ambient particulate matter (PM) can increase the incidence of arrhythmia. However, the arrhythmogenic mechanism of PM is poorly understood. This study investigated the arrhythmogenic mechanism of PM. In Sprague–Dawley rats, QT interval was increased from 115.0 ± 14.0 to 142.1 ± 18.4 ms (p = 0.02) after endotracheal exposure of DEP (200 μg/ml for 30 min, n = 5). Ventricular premature contractions were more frequently observed after DEP exposure (100%) than baseline (20%, p = 0.04). These effects were prevented by pretreatment of N-acetylcysteine (NAC, 5 mmol/L, n = 3). In 12 Langendorff-perfused rat hearts, DEP infusion of 12.5 μg/ml for 20 min prolonged action potential duration (APD) at only left ventricular base increasing apicobasal repolarization gradients. Spontaneous early afterdepolarization (EAD) and ventricular tachycardia (VT) were observed in 8 (67%) and 6 (50%) hearts, respectively, versus no spontaneous triggered activity or VT in any hearts before DEP infusion. DEP-induced APD prolongation, EAD and VT were successfully prevented with NAC (5 mmol/L, n = 5), nifedipine (10 μmol/L, n = 5), and active Ca{sup 2+}/calmodulin-dependent protein kinase II (CaMKII) blockade, KN 93 (1 μmol/L, n = 5), but not by thapsigargin (200 nmol/L) plus ryanodine (10 μmol/L, n = 5) and inactive CaMKII blockade, KN 92 (1 μmol/L, n = 5). In neonatal rat cardiomyocytes, DEP provoked ROS generation in dose dependant manner. DEP (12.5 μg/ml) induced apoptosis, and this effect was prevented by NAC and KN 93. Thus, this study shows that in vivo and vitro exposure of PM induced APD prolongation, EAD and ventricular arrhythmia. These effects might be caused by oxidative stress and CaMKII activation. -- Highlights: ► The ambient PM consistently prolonged repolarization. ► The ambient PM induced triggered activity and ventricular arrhythmia. ► These effects were prevented by antioxidants, I{sub CaL} blockade and CaMKII blockade. ► The ambient PM can induce

  6. How to quantify exposure to traumatic stress? Reliability and predictive validity of measures for cumulative trauma exposure in a post-conflict population.

    Science.gov (United States)

    Wilker, Sarah; Pfeiffer, Anett; Kolassa, Stephan; Koslowski, Daniela; Elbert, Thomas; Kolassa, Iris-Tatjana

    2015-01-01

    While studies with survivors of single traumatic experiences highlight individual response variation following trauma, research from conflict regions shows that almost everyone develops posttraumatic stress disorder (PTSD) if trauma exposure reaches extreme levels. Therefore, evaluating the effects of cumulative trauma exposure is of utmost importance in studies investigating risk factors for PTSD. Yet, little research has been devoted to evaluate how this important environmental risk factor can be best quantified. We investigated the retest reliability and predictive validity of different trauma measures in a sample of 227 Ugandan rebel war survivors. Trauma exposure was modeled as the number of traumatic event types experienced or as a score considering traumatic event frequencies. In addition, we investigated whether age at trauma exposure can be reliably measured and improves PTSD risk prediction. All trauma measures showed good reliability. While prediction of lifetime PTSD was most accurate from the number of different traumatic event types experienced, inclusion of event frequencies slightly improved the prediction of current PTSD. As assessing the number of traumatic events experienced is the least stressful and time-consuming assessment and leads to the best prediction of lifetime PTSD, we recommend this measure for research on PTSD etiology.

  7. Expedited patient-specific assessment of contact stress exposure in the ankle joint following definitive articular fracture reduction.

    Science.gov (United States)

    Kern, Andrew M; Anderson, Donald D

    2015-09-18

    Acute injury severity, altered joint kinematics, and joint incongruity are three important mechanical factors linked to post-traumatic osteoarthritis (PTOA). Finite element analysis (FEA) was previously used to assess the influence of increased contact stress due to joint incongruity on PTOA development. While promising agreement with PTOA development was seen, the inherent complexities of contact FEA limited the numbers of subjects that could be analyzed. Discrete element analysis (DEA) is a simplified methodology for contact stress computation, which idealizes contact surfaces as a bed of independent linear springs. In this study, DEA was explored as an expedited alternative to FEA contact stress exposure computation. DEA was compared to FEA using results from a previously completed validation study of two cadaveric human ankles, as well as a previous study of post-operative contact stress exposure in 11 patients with tibial plafond fracture. DEA-computed maximum contact stresses were within 19% of those experimentally measured, with 90% of the contact area having computed contact stress values within 1MPa of those measured. In the 11 fractured ankles, maximum contact stress and contact area differences between DEA and FEA were 0.85 ± 0.64 MPa and 22.5 ± 11.5mm(2). As a predictive measure for PTOA development, both DEA and FEA had 100% concordance with presence of OA (KL grade ≥ 2) and >95% concordance with KL grade at 2 years. These results support DEA as a reasonable alternative to FEA for computing contact stress exposures following surgical reduction of a tibial plafond fracture. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Re-modeling Chara action potential: II. The action potential form under salinity stress

    Directory of Open Access Journals (Sweden)

    Mary Jane Beilby

    2017-04-01

    Full Text Available In part I we established Thiel-Beilby model of the Chara action potential (AP. In part II the AP is investigated in detail at the time of saline stress. Even very short exposure of salt-sensitive Chara cells to artificial pond water with 50 mM NaCl (Saline APW modified the AP threshold and drastically altered the AP form. Detailed modeling of 14 saline APs from 3 cells established that both the Ca2+ pump and the Ca2+ channels on internal stores seem to be affected, with the changes sometimes cancelling and sometimes re-enforcing each other, leading to APs with long durations and very complex forms. The exposure to salinity offers further insights into AP mechanism and suggests future experiments. The prolonged APs lead to greater loss of chloride and potassium ions, compounding the effects of saline stress.

  9. Neuroplasticity to a single-episode traumatic stress revealed by resting-state fMRI in awake rats.

    Science.gov (United States)

    Liang, Zhifeng; King, Jean; Zhang, Nanyin

    2014-12-01

    Substantial evidence has suggested that the brain structures of the medial prefrontal cortex (mPFC) and amygdala (AMYG) are implicated in the pathophysiology of stress-related disorders. However, little is known with respect to the system-level adaptation of their neural circuitries to the perturbations of traumatic stressors. By utilizing behavioral tests and an awake animal imaging approach, in the present study we non-invasively investigated the impact of single-episode predator odor exposure in an inescapable environment on behaviors and neural circuits in rodents. We found that predator odor exposure significantly increased the freezing behavior. In addition, animals exhibited heightened anxiety levels seven days after the exposure. Intriguingly, we also found that the intrinsic functional connectivity within the AMYG-mPFC circuit was considerably compromised seven days after the traumatic event. Our data provide neuroimaging evidence suggesting that prolonged neuroadaptation induced by a single episode of traumatic stress can be non-invasively detected in rodents. These results also support the face validity and construction validity of using the paradigm of single trauma exposure in an inescapable environment as an animal model for post-traumatic stress disorder. Taken together, the present study has opened a new avenue to investigating animal models of stress-related mental disorders by going beyond static neuroanatomy, and ultimately bridging the gap between basic biomedical and human imaging research. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Cognitions in prolonged exposure therapy for posttraumatic stress disorder

    Directory of Open Access Journals (Sweden)

    Muriel A. Hagenaars

    2010-01-01

    Full Text Available Este estudio cuasi-experimental investiga el impacto del tratamiento de exposición prolongada en los cambios cognitivos en pacientes con trastorno por estrés postraumático (TEPT. Setenta y siete pacientes con TEPT con traumas mixtos pasaron por 8-12 sesiones de exposición en imaginación y en vivo, sin ninguna intervención cognitiva. La reexperimentación de los síntomas y las cogniciones más importantes (i.e. su frecuencia y credibilidad fueron evaluadas semanalmente. El tratamiento de exposición redujo de forma significativa las cogniciones negativas relacionadas con el trauma, aunque no se prestó atención a éstas durante el tratamiento. La reducción en cogniciones se relacionó con la reducción en los síntomas del TEPT. La reducción en las cogniciones pre y post-tratamiento no predijo el TEPT en el seguimiento habiendo controlado la reducción en los síntomas del TEPT pre y post-tratamiento. Finalmente, la disminución en la frecuencia de la reexperimentación y de las cogniciones relacionadas con el trauma fue precedida por la reducción del sufrimiento causado por la reexperimentación. La credibilidad de las cogniciones relacionadas con el trauma fue la última variable que disminuyó. El hecho de que el sufrimiento causado por la reexperimentación fuera el primer síntoma en disminuir puede significar que la reducción de las cogniciones relacionadas con el trauma es el resultado de la reducción de los síntomas del TEPT. Esta complicada relación entre las cogniciones y el cambio en los síntomas, sin duda, merece ser explorada en el futuro.

  11. Prenatal psychosocial stress exposure is associated with subsequent working memory performance in young women.

    Science.gov (United States)

    Entringer, Sonja; Buss, Claudia; Kumsta, Robert; Hellhammer, Dirk H; Wadhwa, Pathik D; Wüst, Stefan

    2009-08-01

    The aim of the present study was to examine the association between prenatal psychosocial stress exposure and subsequent prefrontal cortex-dependent working memory performance in human adults. Working memory performance was assessed using an item-recognition task under 10 mg hydrocortisone (cortisol) and placebo conditions in a sample of 32 healthy young women (mean age = 25 +/- 4.34 years) whose mothers experienced a major negative life event during their pregnancy (Prenatal Stress, PS group), and in a comparison group of 27 healthy young women (mean age = 24 +/- 3.4 years). The two groups did not differ in the placebo condition, however, subjects in the PS group showed longer reaction times after hydrocortisone administration compared with subjects in the comparison group (p = .02). These findings provide support for an association between prenatal stress exposure and the potential modulatory effect of cortisol on working memory performance in young adults, which may reflect compromised development of the prefrontal cortex in prenatal life. 2009 APA, all rights reserved

  12. Using c-Jun to identify fear extinction learning-specific patterns of neural activity that are affected by single prolonged stress.

    Science.gov (United States)

    Knox, Dayan; Stanfield, Briana R; Staib, Jennifer M; David, Nina P; DePietro, Thomas; Chamness, Marisa; Schneider, Elizabeth K; Keller, Samantha M; Lawless, Caroline

    2018-04-02

    Neural circuits via which stress leads to disruptions in fear extinction is often explored in animal stress models. Using the single prolonged stress (SPS) model of post traumatic stress disorder and the immediate early gene (IEG) c-Fos as a measure of neural activity, we previously identified patterns of neural activity through which SPS disrupts extinction retention. However, none of these stress effects were specific to fear or extinction learning and memory. C-Jun is another IEG that is sometimes regulated in a different manner to c-Fos and could be used to identify emotional learning/memory specific patterns of neural activity that are sensitive to SPS. Animals were either fear conditioned (CS-fear) or presented with CSs only (CS-only) then subjected to extinction training and testing. C-Jun was then assayed within neural substrates critical for extinction memory. Inhibited c-Jun levels in the hippocampus (Hipp) and enhanced functional connectivity between the ventromedial prefrontal cortex (vmPFC) and basolateral amygdala (BLA) during extinction training was disrupted by SPS in the CS-fear group only. As a result, these effects were specific to emotional learning/memory. SPS also disrupted inhibited Hipp c-Jun levels, enhanced BLA c-Jun levels, and altered functional connectivity among the vmPFC, BLA, and Hipp during extinction testing in SPS rats in the CS-fear and CS-only groups. As a result, these effects were not specific to emotional learning/memory. Our findings suggest that SPS disrupts neural activity specific to extinction memory, but may also disrupt the retention of fear extinction by mechanisms that do not involve emotional learning/memory. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Impact of Combined Prenatal Ethanol and Prenatal Stress Exposures on Markers of Activity-Dependent Synaptic Plasticity in Rat Dentate Gyrus

    OpenAIRE

    Staples, Miranda C.; Porch, Morgan W.; Savage, Daniel D.

    2014-01-01

    Prenatal ethanol exposure and prenatal stress can each cause long-lasting deficits in hippocampal synaptic plasticity and disrupt learning and memory processes. However, the mechanisms underlying these perturbations following a learning event are still poorly understood. We examined the effects of prenatal ethanol exposure and prenatal stress exposure, either alone or in combination, on the cytosolic expression of activity-regulated cytoskeletal (ARC) protein and the synaptosomal expression o...

  14. Influence of chitosan and melanin-glucan complex onto gamma-exposure with low doses and acute stressful reaction

    International Nuclear Information System (INIS)

    Senyuk, O.F.; Tarasenko, P.D.; Pazukhin, Eh.M.; Gorovoj, L.F.; Varlamov, V.P.

    2004-01-01

    Possibilities of prevention and reduction of consequences of acute exposure on the background of immobilization stress with the help of chitosan preparations and of melanin - glucan complex of highest bazidiomicetes (fungi) were studied. Tested preparations were capable to protect hematological and immunological homeostasis of line BALB/c mice from stressful reaction provoked by acute exposure and two-hour immobilization. The most expressed normalizing and adapting effect had the mixture composed of chitosan and melanin-glucan complex

  15. Biomarkers of oxidative stress and inflammation after wood smoke exposure in a reconstructed Viking Age house

    DEFF Research Database (Denmark)

    Jensen, Annie; Karottki, Dorina Gabriela; Christensen, Jannie Marie

    2014-01-01

    Exposure to particles from combustion of wood is associated with respiratory symptoms, whereas there is limited knowledge about systemic effects. We investigated effects on systemic inflammation, oxidative stress and DNA damage in humans who lived in a reconstructed Viking Age house, with indoor...... expression levels of CD11b, CD49d, and CD62L on monocytes after the stay in the house. In conclusion, even a high inhalation exposure to wood smoke was associated with limited systemic effects on markers of oxidative stress, DNA damage, inflammation, and monocyte activation....

  16. Trauma-related shame and guilt as time-varying predictors of posttraumatic stress disorder symptoms during imagery exposure and imagery rescripting--A randomized controlled trial.

    Science.gov (United States)

    Øktedalen, Tuva; Hoffart, Asle; Langkaas, Tomas Formo

    2015-01-01

    The specific aims of this study are to examine trauma-related shame and guilt as time-varying predictors of symptoms of posttraumatic stress disorder (PTSD). Sixty-five patients were included in the statistical analyses and the multilevel modeling analyses supported three major findings. (i) Patients with a higher level of shame and guilt at the start of treatment displayed a higher level of PTSD symptoms over the course of treatment compared to other patients. (ii) Time-specific change in shame and guilt predicted the level of PTSD symptoms 3 days later from session to session during treatment. (iii) No significant differences were evident between prolonged exposure (PE) and modified PE to include imagery rescripting in the within-person process of change in PTSD symptoms from session to session during therapy. This trial reports the first evidence that within-person change in shame and guilt predicts change in PTSD symptoms from session to session during treatment.

  17. Predator Exposure/Psychosocial Stress Animal Model of Post-Traumatic Stress Disorder Modulates Neurotransmitters in the Rat Hippocampus and Prefrontal Cortex

    Science.gov (United States)

    Wilson, C. Brad; Ebenezer, Philip J.; McLaughlin, Leslie D.; Francis, Joseph

    2014-01-01

    Post-Traumatic Stress Disorder (PTSD) can develop in response to a traumatic event involving a threat to life. To date, no diagnostic biomarkers have been identified for PTSD. Recent research points toward physiological abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis, sympathoadrenal medullary and immune system that may be implicated in the disorder. The modulation of neurotransmitters is another possible mechanism, but their role in the progression of PTSD is poorly understood. Low serotonin (5-HT) may be a factor, but it may not be the only neurotransmitter affected as modulation affects levels of other neurotransmitters. In this study, we hypothesized the predator exposure/psychosocial stress rodent model of PTSD may alter levels of 5-HT and other neurotransmitters in the rat hippocampus and prefrontal cortex (PFC). Male Sprague-Dawley rats were used in this experiment. We induced PTSD via a predator exposure/psychosocial stress model, whereby rats were placed in a cage with a cat for 1 hour on days 1 and 11 of the 31-day experiment. Rats also received psychosocial stress via daily cage cohort changes. On day 32, the rats were sacrificed and the brains dissected to remove the hippocampus and PFC. Norepinephrine (NE), 5-Hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), dopamine (DA), and 3,4-Dihydroxyphenylacetic acid (DOPAC), and 5-HT levels in the hippocampus and PFC were measured with high-performance liquid chromatography (HPLC). In the hippocampus, 5-HT and HVA were lower, while NE and DOPAC were higher, in the PTSD group vs. controls. In the PFC, only 5-HT was lower, while NE, DA, and DOPAC were higher, in the PTSD group vs. controls. The rate limiting enzymes tyrosine hydroxylase and tryptophan hydroxylase were also examined and confirmed our findings. These results demonstrate that the predator exposure/psychosocial stress model of PTSD produces neurotransmitter changes similar to those seen in human patients and may cause a

  18. Predator exposure/psychosocial stress animal model of post-traumatic stress disorder modulates neurotransmitters in the rat hippocampus and prefrontal cortex.

    Directory of Open Access Journals (Sweden)

    C Brad Wilson

    Full Text Available Post-Traumatic Stress Disorder (PTSD can develop in response to a traumatic event involving a threat to life. To date, no diagnostic biomarkers have been identified for PTSD. Recent research points toward physiological abnormalities in the hypothalamic-pituitary-adrenal (HPA axis, sympathoadrenal medullary and immune system that may be implicated in the disorder. The modulation of neurotransmitters is another possible mechanism, but their role in the progression of PTSD is poorly understood. Low serotonin (5-HT may be a factor, but it may not be the only neurotransmitter affected as modulation affects levels of other neurotransmitters. In this study, we hypothesized the predator exposure/psychosocial stress rodent model of PTSD may alter levels of 5-HT and other neurotransmitters in the rat hippocampus and prefrontal cortex (PFC. Male Sprague-Dawley rats were used in this experiment. We induced PTSD via a predator exposure/psychosocial stress model, whereby rats were placed in a cage with a cat for 1 hour on days 1 and 11 of the 31-day experiment. Rats also received psychosocial stress via daily cage cohort changes. On day 32, the rats were sacrificed and the brains dissected to remove the hippocampus and PFC. Norepinephrine (NE, 5-Hydroxyindoleacetic acid (5-HIAA, homovanillic acid (HVA, dopamine (DA, and 3,4-Dihydroxyphenylacetic acid (DOPAC, and 5-HT levels in the hippocampus and PFC were measured with high-performance liquid chromatography (HPLC. In the hippocampus, 5-HT and HVA were lower, while NE and DOPAC were higher, in the PTSD group vs. controls. In the PFC, only 5-HT was lower, while NE, DA, and DOPAC were higher, in the PTSD group vs. controls. The rate limiting enzymes tyrosine hydroxylase and tryptophan hydroxylase were also examined and confirmed our findings. These results demonstrate that the predator exposure/psychosocial stress model of PTSD produces neurotransmitter changes similar to those seen in human patients and may

  19. Oxidative stress generated damage to DNA by gastrointestinal exposure to insoluble particles

    DEFF Research Database (Denmark)

    Møller, Peter; Folkmann, J K; Danielsen, P H

    2012-01-01

    that gastrointestinal exposure to single-walled carbon nanotubes (SWCNT), fullerenes C60, carbon black, titanium dioxide and diesel exhaust particles generates oxidized DNA base lesions in organs such as the bone marrow, liver and lung. Oral exposure to nanosized carbon black has also been associated with increased...... level of lipid peroxidation derived exocyclic DNA adducts in the liver, suggesting multiple pathways of oxidative stress for particle-generated damage to DNA. At equal dose, diesel exhaust particles (SRM2975) generated larger levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine in rat liver than carbon black...

  20. Does prolonged pneumoperitoneum affect the kidney? Oxidative stress, stereological and electron microscopy study in a rat model

    Directory of Open Access Journals (Sweden)

    Diogo B. de Souza

    2013-01-01

    Full Text Available Purpose: Pneumoperitoneum (Pp at 12 to 15 mmHg in rats is associated with kidney damage. However, Pp at 8 mmHg is now known to best correlate to working pressures used in humans. Thus the aim of this work was to study the kidney of rats submitted to prolonged Pp at 8 mmHg. Materials and Methods: Rats were divided into a Sham group (n = 14, submitted to anesthesia, and a Pp group (n = 14, submitted to Pp at 8 mmHg, followed by deflation. In both groups, 7 animals were immediately killed and their kidneys were used for oxidative stress analyses. The remaining 7 rats in each group were evaluated after 6 weeks for the number of glomeruli and podocyte morphology. Results: For all analyzed parameters Sham and Pp groups presented no statistical difference. Conclusion: When submitted to adequate Pp pressures (8 mmHg, no kidney damage occurs in rats.

  1. Does uranium exposure induce oxidative stress and genotoxicity in the teleostean Danio rerio? first experimental results

    International Nuclear Information System (INIS)

    Barillet, S.; Devaux, A.; Simon, O.; Buet, A.; Pradines, C.

    2004-01-01

    Within the Envirhom research program, key advances have been obtained in uranium bioaccumulation and underlying mechanisms understanding in various biological models at the individual level. However, considering different scales of biological effects (from early to delayed ones, from low to high level of organization) is crucial to provide ecologically relevant indicators. Organisms counteract stress induced by pollutant exposure through a wide range of physiological responses being both dose and time dependent. Effects at higher hierarchical levels are always preceded by early changes in biological processes, from subtle biochemical disturbances to impaired physiological functions, increased susceptibility to other stresses, reduced life-span Within this global context, preliminary experiments were carried out on adult zebra fish (Danio rerio), to assess early changes after short-term uranium exposure. Among the subsequent primary subcellular damages oxidative stress and genotoxicity (characterizing both chemo-toxicity and radiotoxicity) are relevant endpoints, thus requiring the knowledge of dose-effects relationships as a first operational approach to provide useful tool in predicting possible effects of U exposure. Zebra fish has been selected due to its small size (facilitating its maintenance) and its extended use in eco-toxicological studies. Moreover, its short life-cycle will allow to carry out chronic exposure experiments (along the whole life-cycle). Four uranium concentrations (0, 20, 100 and 500μg.L -1 ) and five sampling times (0, 0.5, 1, 5 and 10 days) were selected. Catalase, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were measured as oxidative stress bio-markers. DNA damage level was assessed in zebra fish erythrocytes using the comet assay. Uranium bioaccumulation was concurrently studied to understand observed bio-marker responses. Further experiments, dedicated to the assessment of the impact of chronic uranium

  2. Overexpressed cyclophilin B suppresses apoptosis associated with ROS and Ca2+ homeostasis after ER stress.

    Science.gov (United States)

    Kim, Jinhwan; Choi, Tae Gyu; Ding, Yan; Kim, Yeonghwan; Ha, Kwon Soo; Lee, Kyung Ho; Kang, Insug; Ha, Joohun; Kaufman, Randal J; Lee, Jinhwa; Choe, Wonchae; Kim, Sung Soo

    2008-11-01

    Prolonged accumulation of misfolded proteins in the endoplasmic reticulum (ER) results in ER stress-mediated apoptosis. Cyclophilins are protein chaperones that accelerate the rate of protein folding through their peptidyl-prolyl cis-trans isomerase (PPIase) activity. In this study, we demonstrated that ER stress activates the expression of the ER-localized cyclophilin B (CypB) gene through a novel ER stress response element. Overexpression of wild-type CypB attenuated ER stress-induced cell death, whereas overexpression of an isomerase activity-defective mutant, CypB/R62A, not only increased Ca(2+) leakage from the ER and ROS generation, but also decreased mitochondrial membrane potential, resulting in cell death following exposure to ER stress-inducing agents. siRNA-mediated inhibition of CypB expression rendered cells more vulnerable to ER stress. Finally, CypB interacted with the ER stress-related chaperones, Bip and Grp94. Taken together, we concluded that CypB performs a crucial function in protecting cells against ER stress via its PPIase activity.

  3. Early life exposure to a rodent carcinogen propiconazole fungicide induces oxidative stress and hepatocarcinogenesis in medaka fish

    Energy Technology Data Exchange (ETDEWEB)

    Tu, Tzu-Yi; Hong, Chwan-Yang [Department of Agricultural Chemistry, College of Bio-Resources and Agriculture, National Taiwan University, Taipei, Taiwan (China); Sasado, Takao [Laboratory of Bioresources, National Institute for Basic Biology, Okazaki (Japan); Kashiwada, Shosaku [Research Center for Life and Environmental Sciences, Department of Life Sciences, the Toyo University, Gunma (Japan); Chen, Pei-Jen, E-mail: chenpj@ntu.edu.tw [Department of Agricultural Chemistry, College of Bio-Resources and Agriculture, National Taiwan University, Taipei, Taiwan (China)

    2016-01-15

    Highlights: • Propiconazole initiates ROS-induced oxidative stress and damage in medaka fish. • Early life exposure to propiconazole increases incidence of hepatocarcionogensis in p53{sup −/−} medaka. • Oxidative stress and CYP induction involved in p53 regulation are key events in propiconazole-induced hepatotumorigenesis. • Propiconazole-induced toxic response in medaka is compatible with that in rodents. - Abstract: Conazole pollution is an emerging concern to human health and environmental safety because of the broad use of conazole fungicides in agriculture and medicine and their frequent occurrence in aquifers. The agricultural pesticide propiconazole has received much regulatory interest because it is a known rodent carcinogen with evidence of multiple adverse effects in mammals and non-targeted organisms. However, the carcinogenic effect and associated mechanism of propiconazole in fish under microgram-per-liter levels of environmental-relevant exposure remains unclear. To explore whether early life of propiconzaole exposure would induce oxidative stress and latent carcinogenic effects in fish, we continuously exposed larvae of wild type or p53{sup −/−} mutant of medaka fish (Oryzias latipes) to propiconazole (2.5–250 μg/L) for 3, 7, 14 or 28 days and assessed liver histopathology and/or the oxidative stress response and gene expression during exposure and throughout adulthood. Propiconazole dose-dependently induced reactive oxygen species (ROS) level, altered homeostasis of antioxidant superoxide dismutase, catalase and glutathione S-transferase and caused lipid and protein peroxidation during early life exposure in wild type medaka. Such exposure also significantly upregulated gene expression of the cytochrome P450 CYP1A, but marginally suppressed that of tumor suppressor p53 in adults. Furthermore, histopathology revealed that p53{sup −/−} mutant medaka with early life exposure to propiconazole showed increased incidence of

  4. Early life exposure to a rodent carcinogen propiconazole fungicide induces oxidative stress and hepatocarcinogenesis in medaka fish

    International Nuclear Information System (INIS)

    Tu, Tzu-Yi; Hong, Chwan-Yang; Sasado, Takao; Kashiwada, Shosaku; Chen, Pei-Jen

    2016-01-01

    Highlights: • Propiconazole initiates ROS-induced oxidative stress and damage in medaka fish. • Early life exposure to propiconazole increases incidence of hepatocarcionogensis in p53"−"/"− medaka. • Oxidative stress and CYP induction involved in p53 regulation are key events in propiconazole-induced hepatotumorigenesis. • Propiconazole-induced toxic response in medaka is compatible with that in rodents. - Abstract: Conazole pollution is an emerging concern to human health and environmental safety because of the broad use of conazole fungicides in agriculture and medicine and their frequent occurrence in aquifers. The agricultural pesticide propiconazole has received much regulatory interest because it is a known rodent carcinogen with evidence of multiple adverse effects in mammals and non-targeted organisms. However, the carcinogenic effect and associated mechanism of propiconazole in fish under microgram-per-liter levels of environmental-relevant exposure remains unclear. To explore whether early life of propiconzaole exposure would induce oxidative stress and latent carcinogenic effects in fish, we continuously exposed larvae of wild type or p53"−"/"− mutant of medaka fish (Oryzias latipes) to propiconazole (2.5–250 μg/L) for 3, 7, 14 or 28 days and assessed liver histopathology and/or the oxidative stress response and gene expression during exposure and throughout adulthood. Propiconazole dose-dependently induced reactive oxygen species (ROS) level, altered homeostasis of antioxidant superoxide dismutase, catalase and glutathione S-transferase and caused lipid and protein peroxidation during early life exposure in wild type medaka. Such exposure also significantly upregulated gene expression of the cytochrome P450 CYP1A, but marginally suppressed that of tumor suppressor p53 in adults. Furthermore, histopathology revealed that p53"−"/"− mutant medaka with early life exposure to propiconazole showed increased incidence of

  5. Induction of oxidative stress related responses in Arabidopsis thaliana after uranium exposure

    International Nuclear Information System (INIS)

    Vanhoudt, N.

    2009-01-01

    Uranium contamination in the environment has resulted from releases linked with nuclear fuel cycle activities and from industries extracting and processing materials containing naturally occurring radionuclides (for example phosphate industry). Uranium toxicity effects are predominantly studied on man and animal species, but little information is available for plants. If phytomanagement of uranium contaminated soils is considered, biological effects on the vegetation have to be investigated. Information on the contamination impact can also be used for risk assessment and derivation of clean-up standards. Plants can experience oxidative stress when they are exposed to environmental stress situations (for example exposure to heavy metals). Reactive oxygen species (ROS) are produced in both stressed and unstressed cells potentially leading to cellular damage. Consequently, plants have developed an antioxidative defence system comprising ROS-scavenging enzymes (e.g. SOD (superoxide dismutase), CAT (catalase) and metabolites (e.g. ascorbate, glutathione). Previous results showed that uranium exposure can cause an imbalance between the oxidative and antioxidative capacities of the plant cells. The present study aimed to analyse biological effects induced in Arabidopsis thaliana after bioaccumulation of uranium and to define possible dose-effect relationships. Subtle effects on the antioxidative defence system (enzymes, metabolites viewed as early responses for individual disturbances (growth, nutrient profile) were analysed

  6. Exposure to prenatal psychobiological stress exerts programming influences on the mother and her fetus.

    Science.gov (United States)

    Sandman, Curt A; Davis, Elysia P; Buss, Claudia; Glynn, Laura M

    2012-01-01

    Accumulating evidence from a relatively small number of prospective studies indicates that exposure to prenatal stress profoundly influences the developing human fetus with consequences that persist into childhood and very likely forever. Maternal/fetal dyads are assessed at ∼20, ∼25, ∼31 and ∼36 weeks of gestation. Infant assessments begin 24 h after delivery with the collection of cortisol and behavioral responses to the painful stress of the heel-stick procedure and measures of neonatal neuromuscular maturity. Infant cognitive, neuromotor development, stress and emotional regulation are evaluated at 3, 6 12 and 24 months of age. Maternal psychosocial stress and demographic information is collected in parallel with infant assessments. Child neurodevelopment is assessed with cognitive tests, measures of adjustment and brain imaging between 5 and 8 years of age. Psychobiological markers of stress during pregnancy, especially early in gestation, result in delayed fetal maturation, disrupted emotional regulation and impaired cognitive performance during infancy and decreased brain volume in areas associated with learning and memory in 6- to 8-year-old children. We review findings from our projects that maternal endocrine alterations that accompany pregnancy and influence fetal/infant/child development are associated with decreased affective responses to stress, altered memory function and increased risk for postpartum depression. Our findings indicate that the mother and her fetus both are influenced by exposure to psychosocial and biological stress. The findings that fetal and maternal programming occur in parallel may have important implications for long-term child development and mother/child interactions. Copyright © 2011 S. Karger AG, Basel.

  7. Recent life stress exposure is associated with poorer long-term memory, working memory, and self-reported memory.

    Science.gov (United States)

    Shields, Grant S; Doty, Dominique; Shields, Rebecca H; Gower, Garrett; Slavich, George M; Yonelinas, Andrew P

    2017-11-01

    Although substantial research has examined the effects of stress on cognition, much of this research has focused on acute stress (e.g. manipulated in the laboratory) or chronic stress (e.g. persistent interpersonal or financial difficulties). In contrast, the effects of recent life stress on cognition have been relatively understudied. To address this issue, we examined how recent life stress is associated with long-term, working memory, and self-reported memory in a sample of 142 healthy young adults who were assessed at two time points over a two-week period. Recent life stress was measured using the newly-developed Stress and Adversity Inventory for Daily Stress (Daily STRAIN), which assesses the frequency of relatively common stressful life events and difficulties over the preceding two weeks. To assess memory performance, participants completed both long-term and working memory tasks. Participants also provided self-reports of memory problems. As hypothesized, greater recent life stress exposure was associated with worse performance on measures of long-term and working memory, as well as more self-reported memory problems. These associations were largely robust while controlling for possible confounds, including participants' age, sex, and negative affect. The findings indicate that recent life stress exposure is broadly associated with worse memory. Future studies should thus consider assessing recent life stress as a potential predictor, moderator, or covariate of memory performance.

  8. Early Maternal Deprivation Enhances Voluntary Alcohol Intake Induced by Exposure to Stressful Events Later in Life

    Directory of Open Access Journals (Sweden)

    Sara Peñasco

    2015-01-01

    Full Text Available In the present study, we aimed to assess the impact of early life stress, in the form of early maternal deprivation (MD, 24 h on postnatal day, pnd, 9, on voluntary alcohol intake in adolescent male and female Wistar rats. During adolescence, from pnd 28 to pnd 50, voluntary ethanol intake (20%, v/v was investigated using the two-bottle free choice paradigm. To better understand the relationship between stress and alcohol consumption, voluntary alcohol intake was also evaluated following additional stressful events later in life, that is, a week of alcohol cessation and a week of alcohol cessation combined with exposure to restraint stress. Female animals consumed more alcohol than males only after a second episode of alcohol cessation combined with restraint stress. MD did not affect baseline voluntary alcohol intake but increased voluntary alcohol intake after stress exposure, indicating that MD may render animals more vulnerable to the effects of stress on alcohol intake. During adolescence, when animals had free access to alcohol, MD animals showed lower body weight gain but a higher growth rate than control animals. Moreover, the higher growth rate was accompanied by a decrease in food intake, suggesting an altered metabolic regulation in MD animals that may interact with alcohol intake.

  9. Concomitant stress potentiates the preference for, and consumption of, ethanol induced by chronic pre-exposure to ethanol.

    Science.gov (United States)

    Morais-Silva, G; Fernandes-Santos, J; Moreira-Silva, D; Marin, M T

    2016-01-01

    Ethanol abuse is linked to several acute and chronic injuries that can lead to health problems. Ethanol addiction is one of the most severe diseases linked to the abuse of this drug. Symptoms of ethanol addiction include compulsive substance intake and withdrawal syndrome. Stress exposure has an important role in addictive behavior for many drugs of abuse (including ethanol), but the consequences of stress and ethanol in the organism when these factors are concomitant results in a complex interaction. We investigated the effects of concomitant, chronic administration of ethanol and stress exposure on the withdrawal and consumption of, as well as the preference for, ethanol in mice. Male Swiss mice (30-35 g, 8-10 per group) were exposed to an ethanol liquid diet as the only source of food for 15 days. In the final 5 days, they were exposed to forced swimming stress. Twelve hours after removal of the ethanol liquid diet, animals were evaluated for ethanol withdrawal by measuring anxiety-related behaviors and locomotor activity. Twenty-four hours after evaluation of ethanol withdrawal, they were evaluated for voluntary consumption of ethanol in a "three-bottle choice" paradigm. Mice exposed to chronic consumption of ethanol had decreased locomotor activity during withdrawal. Contrary to our expectations, a concomitant forced swimming stress did not aggravate ethanol withdrawal. Nevertheless, simultaneous ethanol administration and stress exposure increased voluntary consumption of ethanol, mainly solutions containing high concentrations of ethanol. These results showed that stressful situations during ethanol intake may aggravate specific addiction-related behaviors.

  10. Concomitant stress potentiates the preference for, and consumption of, ethanol induced by chronic pre-exposure to ethanol

    Directory of Open Access Journals (Sweden)

    G. Morais-Silva

    2016-01-01

    Full Text Available Ethanol abuse is linked to several acute and chronic injuries that can lead to health problems. Ethanol addiction is one of the most severe diseases linked to the abuse of this drug. Symptoms of ethanol addiction include compulsive substance intake and withdrawal syndrome. Stress exposure has an important role in addictive behavior for many drugs of abuse (including ethanol, but the consequences of stress and ethanol in the organism when these factors are concomitant results in a complex interaction. We investigated the effects of concomitant, chronic administration of ethanol and stress exposure on the withdrawal and consumption of, as well as the preference for, ethanol in mice. Male Swiss mice (30–35 g, 8-10 per group were exposed to an ethanol liquid diet as the only source of food for 15 days. In the final 5 days, they were exposed to forced swimming stress. Twelve hours after removal of the ethanol liquid diet, animals were evaluated for ethanol withdrawal by measuring anxiety-related behaviors and locomotor activity. Twenty-four hours after evaluation of ethanol withdrawal, they were evaluated for voluntary consumption of ethanol in a “three-bottle choice” paradigm. Mice exposed to chronic consumption of ethanol had decreased locomotor activity during withdrawal. Contrary to our expectations, a concomitant forced swimming stress did not aggravate ethanol withdrawal. Nevertheless, simultaneous ethanol administration and stress exposure increased voluntary consumption of ethanol, mainly solutions containing high concentrations of ethanol. These results showed that stressful situations during ethanol intake may aggravate specific addiction-related behaviors.

  11. Increase in oxidative stress levels following welding fume inhalation: a controlled human exposure study.

    Science.gov (United States)

    Graczyk, Halshka; Lewinski, Nastassja; Zhao, Jiayuan; Sauvain, Jean-Jacques; Suarez, Guillaume; Wild, Pascal; Danuser, Brigitta; Riediker, Michael

    2016-06-10

    Tungsten inert gas (TIG) welding represents one of the most widely used metal joining processes in industry. It has been shown to generate a large majority of particles at the nanoscale and to have low mass emission rates when compared to other types of welding. Despite evidence that TIG fume particles may produce reactive oxygen species (ROS), limited data is available for the time course changes of particle-associated oxidative stress in exposed TIG welders. Twenty non-smoking male welding apprentices were exposed to TIG welding fumes for 60 min under controlled, well-ventilated settings. Exhaled breathe condensate (EBC), blood and urine were collected before exposure, immediately after exposure, 1 h and 3 h post exposure. Volunteers participated in a control day to account for oxidative stress fluctuations due to circadian rhythm. Biological liquids were assessed for total reducing capacity, hydrogen peroxide (H2O2), malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations at each time point. A linear mixed model was used to assess within day and between day differences. Significant increases in the measured biomarkers were found at 3 h post exposure. At 3 h post exposure, we found a 24 % increase in plasma-H2O2 concentrations ([95%CI: 4 % to 46 %], p = 0.01); a 91 % increase in urinary-H2O2 ([2 % to 258 %], p = 0.04); a 14 % increase in plasma-8-OHdG ([0 % to 31 %], p = 0.049); and a 45 % increase in urinary-8-OHdG ([3 % to 105 %], p = 0.03). Doubling particle number concentration (PNC) exposure was associated with a 22 % increase of plasma-8-OHdG at 3 h post exposure (p = 0.01). A 60-min exposure to TIG welding fume in a controlled, well-ventilated setting induced acute oxidative stress at 3 h post exposure in healthy, non-smoking apprentice welders not chronically exposed to welding fumes. As mass concentration of TIG welding fume particles is very low when compared to other types of welding, it is

  12. The Role of Musk in Relieving the Neurodegenerative Changes Induced After Exposure to Chronic Stress.

    Science.gov (United States)

    Abd El Wahab, Manal Galal; Ali, Soad Shaker; Ayuob, Nasra Naeim

    2018-06-01

    This study aimed to evaluate the effect induced by musk on Alzheimer's disease-such as neurodegenerative changes in mice exposed to chronic unpredictable mild stress (CUMS). Forty male Swiss albino mice were divided into 4 groups (n = 10); control, CUMS, CUMS + fluoxetine, CUMS + musk. At the end of the experiment, behavior of the mice was assessed. Serum corticosterone level, hippocampal protein level of the glucocorticoid receptors, and brain-derived neurotropic factor were also assessed. Hippocampus was histopathologically examined. Musk improved depressive status induced after exposure to CUMS as evidenced by the forced swimming and open field tests and improved the short-term memory as evidenced by the elevated plus maze test. Musk reduced both corticosterone levels and the hippocampal neurodegenerative changes observed after exposure to CUMS. These improvements were comparable to those induced by fluoxetine. Musk alleviated the memory impairment and neurodegenerative changes induced after exposure to the chronic stress.

  13. El Salvador earthquakes: relationships among acute stress disorder symptoms, depression, traumatic event exposure, and resource loss.

    Science.gov (United States)

    Sattler, David N; de Alvarado, Ana Maria Glower; de Castro, Norma Blandon; Male, Robert Van; Zetino, A M; Vega, Raphael

    2006-12-01

    Four and seven weeks after powerful earthquakes in El Salvador, the authors examined the relationships among demographics, traumatic event exposure, social support, resource loss, acute stress disorder (ASD) symptoms, depression, and posttraumatic growth. Participants were 253 college students (Study 1) and 83 people in the community (Study 2). In Study 1, female gender, traumatic event exposure, low social support, and loss of personal characteristic, condition, and energy resources contributed to ASD symptoms and depression. In Study 2, damage to home and loss of personal characteristic and object resources contributed to ASD symptoms and depression. Posttraumatic growth was not associated with ASD symptoms or depression. Findings support the conservation of resources stress theory (Hobfoll, 1998). Resource loss spirals, excessive demands on coping, and exposure to multiple disasters are discussed.

  14. Lung volumes identify an at-risk group in persons with prolonged secondhand tobacco smoke exposure but without overt airflow obstruction.

    Science.gov (United States)

    Arjomandi, Mehrdad; Zeng, Siyang; Geerts, Jeroen; Stiner, Rachel K; Bos, Bruce; van Koeverden, Ian; Keene, Jason; Elicker, Brett; Blanc, Paul D; Gold, Warren M

    2018-01-01

    Exposure to secondhand smoke (SHS) is associated with occult obstructive lung disease as evident by abnormal airflow indices representing small airway disease despite having preserved spirometry (normal forced expiratory volume in 1 s-to-forced vital capacity ratio, FEV 1 /FVC). The significance of lung volumes that reflect air trapping in the presence of preserved spirometry is unclear. To investigate whether lung volumes representing air trapping could determine susceptibility to respiratory morbidity in people with SHS exposure but without spirometric chronic obstructive pulmonary disease, we examined a cohort of 256 subjects with prolonged occupational SHS exposure and preserved spirometry. We elicited symptom prevalence by structured questionnaires, examined functional capacity (maximum oxygen uptake, VO 2max ) by exercise testing, and estimated associations of those outcomes with air trapping (plethysmography-measured residual volume-to-total lung capacity ratio, RV/TLC), and progressive air trapping with exertion (increase in fraction of tidal breathing that is flow limited on expiration during exercise (per cent of expiratory flow limitation, %EFL)). RV/TLC was within the predicted normal limits, but was highly variable spanning 22%±13% and 16%±8% across the increments of FEV 1 /FVC and FEV 1 , respectively. Respiratory complaints were prevalent (50.4%) with the most common symptom being ≥2 episodes of cough per year (44.5%). Higher RV/TLC was associated with higher OR of reporting respiratory symptoms (n=256; r 2 =0.03; p=0.011) and lower VO 2max (n=179; r 2 =0.47; p=0.013), and %EFL was negatively associated with VO 2max (n=32; r 2 =0.40; p=0.017). In those at risk for obstruction due to SHS exposure but with preserved spirometry, higher RV/TLC identifies a subgroup with increased respiratory symptoms and lower exercise capacity.

  15. Hypoxia Stress Test Reveals Exaggerated Cardiovascular Effects in Hypertensive Rats after Exposure to the Air Pollutant Acrolein

    Science.gov (United States)

    Exposure to air pollution increases the risk of cardiovascular morbidity and mortality, especially in susceptible populations with cardiovascular disease. Stress tests are useful in assessing cardiovascular risk and manifesting latent effects of exposure. The goal of this study w...

  16. An Agent-Based Modeling Framework for Simulating Human Exposure to Environmental Stresses in Urban Areas

    Directory of Open Access Journals (Sweden)

    Liang Emlyn Yang

    2018-04-01

    Full Text Available Several approaches have been used to assess potential human exposure to environmental stresses and achieve optimal results under various conditions, such as for example, for different scales, groups of people, or points in time. A thorough literature review in this paper identifies the research gap regarding modeling approaches for assessing human exposure to environment stressors, and it indicates that microsimulation tools are becoming increasingly important in human exposure assessments of urban environments, in which each person is simulated individually and continuously. The paper further describes an agent-based model (ABM framework that can dynamically simulate human exposure levels, along with their daily activities, in urban areas that are characterized by environmental stresses such as air pollution and heat stress. Within the framework, decision-making processes can be included for each individual based on rule-based behavior in order to achieve goals under changing environmental conditions. The ideas described in this paper are implemented in a free and open source NetLogo platform. A basic modeling scenario of the ABM framework in Hamburg, Germany, demonstrates its utility in various urban environments and individual activity patterns, as well as its portability to other models, programs, and frameworks. The prototype model can potentially be extended to support environmental incidence management through exploring the daily routines of different groups of citizens, and comparing the effectiveness of different strategies. Further research is needed to fully develop an operational version of the model.

  17. Prenatal nicotinic exposure upregulates pulmonary C-fiber NK1R expression to prolong pulmonary C-fiber-mediated apneic response

    International Nuclear Information System (INIS)

    Zhao, Lei; Zhuang, Jianguo; Zang, Na; Lin, Yong; Lee, Lu-Yuan; Xu, Fadi

    2016-01-01

    Prenatal nicotinic exposure (PNE) prolongs bronchopulmonary C-fiber (PCF)-mediated apneic response to intra-atrial bolus injection of capsaicin in rat pups. The relevant mechanisms remain unclear. Pulmonary substance P and adenosine and their receptors (neurokinin-A receptor, NK1R and ADA 1 receptor, ADA 1 R) and transient receptor potential cation channel subfamily V member 1 (TRPV1) expressed on PCFs are critical for PCF sensitization and/or activation. Here, we compared substance P and adenosine in BALF and NK1R, ADA 1 R, and TRPV1 expression in the nodose/jugular (N/J) ganglia (vagal pulmonary C-neurons retrogradely labeled) between Ctrl and PNE pups. We found that PNE failed to change BALF substance P and adenosine content, but significantly upregulated both mRNA and protein TRPV1 and NK1R in the N/J ganglia and only NK1R mRNA in pulmonary C-neurons. To define the role of NK1R in the PNE-induced PCF sensitization, the apneic response to capsaicin (i.v.) without or with pretreatment of SR140333 (a peripheral and selective NK1R antagonist) was compared and the prolonged apnea by PNE significantly shortened by SR140333. To clarify if the PNE-evoked responses depended on action of nicotinic acetylcholine receptors (nAChRs), particularly α7nAChR, mecamylamine or methyllycaconitine (a general nAChR or a selective α7nAChR antagonist) was administrated via another mini-pump over the PNE period. Mecamylamine or methyllycaconitine eliminated the PNE-evoked mRNA and protein responses. Our data suggest that PNE is able to elevate PCF NK1R expression via activation of nAChRs, especially α7nAChR, which likely contributes to sensitize PCFs and prolong the PCF-mediated apneic response to capsaicin. - Highlights: • PNE upregulated NK1R and TRPV1 gene and protein expression in the N/J ganglia. • PNE only elevated NK1R mRNA in vagal pulmonary C-neurons. • Blockage of peripheral NK1R reduced the PNE-induced PCF sensitization. • PNE induced gene and protein changes in

  18. How to quantify exposure to traumatic stress? Reliability and predictive validity of measures for cumulative trauma exposure in a post-conflict population

    Directory of Open Access Journals (Sweden)

    Sarah Wilker

    2015-11-01

    Full Text Available Background: While studies with survivors of single traumatic experiences highlight individual response variation following trauma, research from conflict regions shows that almost everyone develops posttraumatic stress disorder (PTSD if trauma exposure reaches extreme levels. Therefore, evaluating the effects of cumulative trauma exposure is of utmost importance in studies investigating risk factors for PTSD. Yet, little research has been devoted to evaluate how this important environmental risk factor can be best quantified. Methods: We investigated the retest reliability and predictive validity of different trauma measures in a sample of 227 Ugandan rebel war survivors. Trauma exposure was modeled as the number of traumatic event types experienced or as a score considering traumatic event frequencies. In addition, we investigated whether age at trauma exposure can be reliably measured and improves PTSD risk prediction. Results: All trauma measures showed good reliability. While prediction of lifetime PTSD was most accurate from the number of different traumatic event types experienced, inclusion of event frequencies slightly improved the prediction of current PTSD. Conclusions: As assessing the number of traumatic events experienced is the least stressful and time-consuming assessment and leads to the best prediction of lifetime PTSD, we recommend this measure for research on PTSD etiology.

  19. Functional Connectivity During Exposure to Favorite-Food, Stress, and Neutral-Relaxing Imagery Differs Between Smokers and Nonsmokers.

    Science.gov (United States)

    Garrison, Kathleen A; Sinha, Rajita; Lacadie, Cheryl M; Scheinost, Dustin; Jastreboff, Ania M; Constable, R Todd; Potenza, Marc N

    2016-09-01

    Tobacco-use disorder is a complex condition involving multiple brain networks and presenting with multiple behavioral correlates including changes in diet and stress. In a previous functional magnetic resonance imaging (fMRI) study of neural responses to favorite-food, stress, and neutral-relaxing imagery, smokers versus nonsmokers demonstrated blunted corticostriatal-limbic responses to favorite-food cues. Based on other recent reports of alterations in functional brain networks in smokers, the current study examined functional connectivity during exposure to favorite-food, stress, and neutral-relaxing imagery in smokers and nonsmokers, using the same dataset. The intrinsic connectivity distribution was measured to identify brain regions that differed in degree of functional connectivity between groups during each imagery condition. Resulting clusters were evaluated for seed-to-voxel connectivity to identify the specific connections that differed between groups during each imagery condition. During exposure to favorite-food imagery, smokers versus nonsmokers showed lower connectivity in the supramarginal gyrus, and differences in connectivity between the supramarginal gyrus and the corticostriatal-limbic system. During exposure to neutral-relaxing imagery, smokers versus nonsmokers showed greater connectivity in the precuneus, and greater connectivity between the precuneus and the posterior insula and rolandic operculum. During exposure to stress imagery, smokers versus nonsmokers showed lower connectivity in the cerebellum. These findings provide data-driven insights into smoking-related alterations in brain functional connectivity patterns related to appetitive, relaxing, and stressful states. This study uses a data-driven approach to demonstrate that smokers and nonsmokers show differential patterns of functional connectivity during guided imagery related to personalized favorite-food, stress, and neutral-relaxing cues, in brain regions implicated in attention

  20. Acute stress exposure preceding transient global brain ischemia exacerbates the decrease in cortical remodeling potential in the rat retrosplenial cortex.

    Science.gov (United States)

    Kutsuna, Nobuo; Yamashita, Akiko; Eriguchi, Takashi; Oshima, Hideki; Suma, Takeshi; Sakatani, Kaoru; Yamamoto, Takamitsu; Yoshino, Atsuo; Katayama, Yoichi

    2014-01-01

    Doublecortin (DCX)-immunoreactive (-ir) cells are candidates that play key roles in adult cortical remodeling. We have previously reported that DCX-ir cells decrease after stress exposure or global brain ischemia (GBI) in the cingulate cortex (Cg) of rats. Herein, we investigate whether the decrease in DCX-ir cells is exacerbated after GBI due to acute stress exposure preconditioning. Twenty rats were divided into 3 groups: acute stress exposure before GBI (Group P), non-stress exposure before GBI (Group G), and controls (Group C). Acute stress or GBI was induced by a forced swim paradigm or by transient bilateral common carotid artery occlusion, respectively. DCX-ir cells were investigated in the anterior cingulate cortex (ACC) and retrosplenial cortex (RS). The number of DCX-ir cells per unit area (mm(2)) decreased after GBI with or without stress preconditioning in the ACC and in the RS (ANOVA followed by a Tukey-type test, P<0.001). Moreover, compared to Group G, the number in Group P decreased significantly in RS (P<0.05), though not significantly in ACC. Many of the DCX-ir cells were co-localized with the GABAergic neuronal marker parvalbumin. The present study indicates that cortical remodeling potential of GABAergic neurons of Cg decreases after GBI, and moreover, the ratio of the decrease is exacerbated by acute stress preconditioning in the RS. Copyright © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  1. Elodea nuttallii exposure to mercury exposure under enhanced ultraviolet radiation: Effects on bioaccumulation, transcriptome, pigment content and oxidative stress.

    Science.gov (United States)

    Regier, Nicole; Beauvais-Flück, Rebecca; Slaveykova, Vera I; Cosio, Claudia

    2016-11-01

    The hypothesis that increased UV radiation result in co-tolerance to Hg toxicity in aquatic plants was studied at the physiological and transcriptomic level in Elodea nuttallii. At the transcriptomic level, combined exposure to UV+Hg enhanced the stress response in comparison with single treatments, affecting the expression level of transcripts involved in energy metabolism, lipid metabolism, nutrition, and redox homeostasis. Single and combined UV and Hg treatments dysregulated different genes but with similar functions, suggesting a fine regulation of the plant to stresses triggered by Hg, UV and their combination but lack of co-tolerance. At the physiological level, UV+Hg treatment reduced chlorophyll content and depleted antioxidative compounds such as anthocyanin and GSH/GSSG in E. nuttallii. Nonetheless, combined exposure to UV+Hg resulted in about 30% reduction of Hg accumulation into shoots vs exposure to Hg alone, which was congruent with the level of expression of several transporter genes, as well as the UV effect on Hg bioavailability in water. The findings of the present work underlined the importance of performing experimentation under environmentally realistic conditions and to consider the interplay between contaminants and environmental variables such as light that might have confounding effects to better understand and anticipate the effects of multiple stressors in aquatic environment. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Dysfunction of serotoninergic and dopaminergic neuronal systems in the antidepressant-resistant impairment of social behaviors induced by social defeat stress exposure as juveniles.

    Science.gov (United States)

    Hasegawa, Sho; Miyake, Yuriko; Yoshimi, Akira; Mouri, Akihiro; Hida, Hirotake; Yamada, Kiyofumi; Ozaki, Norio; Nabeshima, Toshitaka; Noda, Yukihiro

    2018-03-29

    Extensive studies have been performed on the role of monoaminergic neuronal systems in rodents exposed to social defeat stress as adults. In the present study, we investigated the role of monoaminergic neuronal systems in the impairment of social behaviors induced by social defeat stress exposure as juveniles. Juvenile, male C57BL/6J mice were exposed to social defeat stress for 10 consecutive days. From 1 day after the last stress exposure, desipramine, sertraline, and aripiprazole, were administered for 15 days. Social behaviors were assessed at 1 and 15 days after the last stress exposure. Monoamine turnover was determined in specific regions of the brain in the mice exposed to the stress. Stress exposure as juveniles induced the impairment of social behaviors in adolescent mice. In mice that showed the impairment of social behaviors, turnover of the serotonin and dopamine, but not noradrenaline was decreased in specific brain regions. Acute and repeated administration of desipramine, sertraline, and aripiprazole failed to attenuate the impairment of social behaviors, whereas repeated administration of a combination of sertraline and aripiprazole showed additive attenuating effects. These findings suggest that social defeat stress exposure as juveniles induces the treatment-resistant impairment of social behaviors in adolescents through dysfunction in the serotoninergic and dopaminergic neuronal systems. The combination of sertraline and aripiprazole may be used as a new treatment strategy for treatment-resistant stress-related psychiatric disorders in adolescents with adverse juvenile experiences.

  3. Associations between Prenatal Exposure to Black Carbon and Memory Domains in Urban Children: Modification by Sex and Prenatal Stress.

    Science.gov (United States)

    Cowell, Whitney J; Bellinger, David C; Coull, Brent A; Gennings, Chris; Wright, Robert O; Wright, Rosalind J

    2015-01-01

    Whether fetal neurodevelopment is disrupted by traffic-related air pollution is uncertain. Animal studies suggest that chemical and non-chemical stressors interact to impact neurodevelopment, and that this association is further modified by sex. To examine associations between prenatal traffic-related black carbon exposure, prenatal stress, and sex with children's memory and learning. Analyses included N = 258 mother-child dyads enrolled in a Boston, Massachusetts pregnancy cohort. Black carbon exposure was estimated using a validated spatiotemporal land-use regression model. Prenatal stress was measured using the Crisis in Family Systems-Revised survey of negative life events. The Wide Range Assessment of Memory and Learning (WRAML2) was administered at age 6 years; outcomes included the General Memory Index and its component indices [Verbal, Visual, and Attention Concentration]. Relationships between black carbon and WRAML2 index scores were examined using multivariable-adjusted linear regression including effect modification by stress and sex. Mothers were primarily minorities (60% Hispanic, 26% Black); 67% had ≤12 years of education. The main effect for black carbon was not significant for any WRAML2 index; however, in stratified analyses, among boys with high exposure to prenatal stress, Attention Concentration Index scores were on average 9.5 points lower for those with high compared to low prenatal black carbon exposure (P3-way interaction = 0.04). The associations between prenatal exposure to black carbon and stress with children's memory scores were stronger in boys than in girls. Studies assessing complex interactions may more fully characterize health risks and, in particular, identify vulnerable subgroups.

  4. Escitalopram or novel herbal mixture treatments during or following exposure to stress reduce anxiety-like behavior through corticosterone and BDNF modifications.

    Directory of Open Access Journals (Sweden)

    Ravid Doron

    Full Text Available Anxiety disorders are a major public health concern worldwide. Studies indicate that repeated exposure to adverse experiences early in life can lead to anxiety disorders in adulthood. Current treatments for anxiety disorders are characterized by a low success rate and are associated with a wide variety of side effects. The aim of the present study was to evaluate the anxiolytic effects of a novel herbal treatment, in comparison to treatment with the selective serotonin reuptake inhibitor escitalopram. We recently demonstrated the anxiolytic effects of these treatments in BALB mice previously exposed to one week of stress. In the present study, ICR mice were exposed to post natal maternal separation and to 4 weeks of unpredictable chronic mild stress in adolescence, and treated during or following exposure to stress with the novel herbal treatment or with escitalopram. Anxiety-like behavior was evaluated in the elevated plus maze. Blood corticosterone levels were evaluated using radioimmunoassay. Brain derived neurotrophic factor levels in the hippocampus were evaluated using enzyme-linked immunosorbent assay. We found that (1 exposure to stress in childhood and adolescence increased anxiety-like behavior in adulthood; (2 the herbal treatment reduced anxiety-like behavior, both when treated during or following exposure to stress; (3 blood corticosterone levels were reduced following treatment with the herbal treatment or escitalopram, when treated during or following exposure to stress; (4 brain derived neurotrophic factor levels in the hippocampus of mice treated with the herbal treatment or escitalopram were increased, when treated either during or following exposure to stress. This study expands our previous findings and further points to the proposed herbal compound's potential to be highly efficacious in treating anxiety disorders in humans.

  5. Long-term effect of early-life stress from earthquake exposure on working memory in adulthood.

    Science.gov (United States)

    Li, Na; Wang, Yumei; Zhao, Xiaochuan; Gao, Yuanyuan; Song, Mei; Yu, Lulu; Wang, Lan; Li, Ning; Chen, Qianqian; Li, Yunpeng; Cai, Jiajia; Wang, Xueyi

    2015-01-01

    The present study aimed to investigate the long-term effect of 1976 Tangshan earthquake exposure in early life on performance of working memory in adulthood. A total of 907 study subjects born and raised in Tangshan were enrolled in this study. They were divided into three groups according to the dates of birth: infant exposure (3-12 months, n=274), prenatal exposure (n=269), and no exposure (born at least 1 year after the earthquake, n=364). The prenatal group was further divided into first, second, and third trimester subgroups based on the timing of exposure during pregnancy. Hopkins Verbal Learning Test-Revised and Brief Visuospatial Memory Test-Revised (BVMT-R) were used to measure the performance of working memory. Unconditional logistic regression analysis was used to analyze the influential factors for impaired working memory. The Hopkins Verbal Learning Test-Revised scores did not show significant difference across the three groups. Compared with no exposure group, the BVMT-R scores were slightly lower in the prenatal exposure group and markedly decreased in the infant exposure group. When the BVMT-R scores were analyzed in three subgroups, the results showed that the subjects whose mothers were exposed to earthquake in the second and third trimesters of pregnancy had significantly lower BVMT-R scores compared with those in the first trimester. Education level and early-life earthquake exposure were identified as independent risk factors for reduced performance of visuospatial memory indicated by lower BVMT-R scores. Infant exposure to earthquake-related stress impairs visuospatial memory in adulthood. Fetuses in the middle and late stages of development are more vulnerable to stress-induced damage that consequently results in impaired visuospatial memory. Education and early-life trauma can also influence the performance of working memory in adulthood.

  6. Chironomus riparius exposure to fullerene-contaminated sediment results in oxidative stress and may impact life cycle parameters

    International Nuclear Information System (INIS)

    Waissi, G.C.; Bold, S.; Pakarinen, K.; Akkanen, J.; Leppänen, M.T.; Petersen, E.J.; Kukkonen, J.V.K.

    2017-01-01

    Highlights: • FullerenesC_6_0 were tested to C. riparius with acute and chronic exposures. • The rapid uptake of fullerenes by C. riparius observed after an acute experiment. • Oxidative stress was localized in tissues under microvilli layer. - Abstract: A key component of understanding the potential environmental risks of fullerenes (C_6_0) is their potential effects on benthic invertebrates. Using the sediment dwelling invertebrate Chironomus riparius we explored the effects of acute (12 h and 24 h) and chronic (10 d, 15 d, and 28 d) exposures of sediment associated fullerenes. The aims of this study were to assess the impact of exposure to C_6_0 in the sediment top layer ((0.025, 0.18 and 0.48) C_6_0 mg/cm"2) on larval growth, oxidative stress and emergence rates and to quantify larval body burdens in similarly exposed organisms. Oxidative stress localization was observed in the tissues next to the microvilli and exoskeleton through a method for identifying oxidative stress reactions generated by reactive oxygen species. Rapid intake of fullerenes was shown in acute experiments, whereas body residues decreased after chronic exposure. Transmission electron microscopy analysis revealed oxidative damage and structural changes in cells located between the lipid droplets and next to the microvilli layer in fullerene exposed samples. Fullerene associated sediments also caused changes in the emergence rate of males and females, suggesting that the cellular interactions described above or other effects from the fullerenes may influence reproduction rates.

  7. Chronic low dose radiation exposure and oxidative stress in radiation workers

    International Nuclear Information System (INIS)

    Ali, S.S.; Bhatt, M.B.; Kulkarni, MM.; Rajan, R.; Singh, B.B.; Venkataraman, G.

    1996-01-01

    Free radicals have been implicated in the pathogenesis of several human diseases. In this study free radical stress due to low dose chronic radiation exposures of radiation workers was examined as a possible atherogenic risk factor. Data on lipid profiles, lipid peroxidation and reduced glutathione content in blood indicated an absence of correlation with radiation doses up to 125 mSv. (author). 13 refs., 1 fig

  8. Prolonged fasting activates Nrf2 in post-weaned elephant seals.

    Science.gov (United States)

    Vázquez-Medina, José Pablo; Soñanez-Organis, José G; Rodriguez, Ruben; Viscarra, Jose A; Nishiyama, Akira; Crocker, Daniel E; Ortiz, Rudy M

    2013-08-01

    Elephant seals naturally experience prolonged periods of absolute food and water deprivation (fasting). In humans, rats and mice, prolonged food deprivation activates the renin-angiotensin system (RAS) and increases oxidative damage. In elephant seals, prolonged fasting activates RAS without increasing oxidative damage likely due to an increase in antioxidant defenses. The mechanism leading to the upregulation of antioxidant defenses during prolonged fasting remains elusive. Therefore, we investigated whether prolonged fasting activates the redox-sensitive transcription factor Nrf2, which controls the expression of antioxidant genes, and if such activation is potentially mediated by systemic increases in RAS. Blood and skeletal muscle samples were collected from seals fasting for 1, 3, 5 and 7 weeks. Nrf2 activity and nuclear content increased by 76% and 167% at week 7. Plasma angiotensin II (Ang II) and transforming growth factor β (TGF-β) were 5000% and 250% higher at week 7 than at week 1. Phosphorylation of Smad2, an effector of Ang II and TGF signaling, increased by 120% at week 7 and by 84% in response to intravenously infused Ang II. NADPH oxidase 4 (Nox4) mRNA expression, which is controlled by smad proteins, increased 430% at week 7, while Nox4 protein expression, which can activate Nrf2, was 170% higher at week 7 than at week 1. These results demonstrate that prolonged fasting activates Nrf2 in elephant seals and that RAS stimulation can potentially result in increased Nox4 through Smad phosphorylation. The results also suggest that Nox4 is essential to sustain the hormetic adaptive response to oxidative stress in fasting seals.

  9. Effects of Chronic Interpersonal Stress Exposure on Depressive Symptoms are Moderated by Genetic Variation at IL6 and IL1β in Youth

    Science.gov (United States)

    Tartter, Margaret; Hammen, Constance; Bower, Julienne E.; Brennan, Patricia A.; Cole, Steven

    2015-01-01

    Aims Close to one third of patients with major depression show increases in pro-inflammatory cytokines, which are in turn associated with risk for inflammatory disease. Genetic variants that enhance immune reactivity may thus enhance inflammatory and depressive reactions to stress. The aim of the present study was to investigate a trio of functional SNPs in the promoter regions of IL6 (-174G>C, rs1800795), IL1β (-511C>T, rs16944), and TNF (-308G>A, rs1800629) as moderators of the relationship between chronic stress exposure and elevations in depressive symptoms. Methods Participants were 444 Australian youth (mean age = 20.12) whose exposure to chronic stress in the past 6 months was assessed using the semi-structured UCLA Life Stress Interview, and who completed the Beck Depression Inventory II at ages 15 and 20. Between ages 22 and 25, all participants in the selected sample provided blood samples for genotyping. Results In line with a hypothesized moderation effect, -174G allele carriers at IL6 had fewer depressive symptoms following interpersonal stress, relative to C/C homozygotes with equal interpersonal stress exposure. However, IL6 genotype did not moderate the effects of non-interpersonal stress exposure (i.e., financial, work and health-related difficulties) on depression. Also in line with hypotheses, the -511C allele in IL1β, previously associated with higher IL-1β expression, was associated with more severe depression following chronic interpersonal stress exposure, relative to T/T homozygotes. Again, the moderating effect was specific to interpersonal stressors and did not generalize to non-interpersonal stress. TNF was not a moderator of the effects of either interpersonal or non-interpersonal stress on later depression outcomes. Conclusion Findings were consistent with the hypothesis that pro-inflammatory genetic variation increases the risk of stress-induced depression. The present results provide evidence of a genetic mechanism contributing to

  10. Prenatal Exposure to Maternal Obesity Alters Anxiety and Stress Coping Behaviors in Aged Mice

    OpenAIRE

    Balsevich, G.; Baumann, V.; Uribe, A.; Chen, A.; Schmidt, M.

    2016-01-01

    Background: There is growing evidence that maternal obesity and prenatal exposure to a high-fat diet program fetal development to regulate the physiology and behavior of the offspring in adulthood. Yet the extent to which the maternal dietary environment contributes to adult disease vulnerability remains unclear. In the current study we tested whether prenatal exposure to maternal obesity increases the offspring's vulnerability to stress-related psychiatric disorders. Methods: We used a mouse...

  11. Pain-related stress in the Neonatal Intensive Care Unit and salivary cortisol reactivity to socio-emotional stress in 3-month-old very preterm infants.

    Science.gov (United States)

    Provenzi, Livio; Giusti, Lorenzo; Fumagalli, Monica; Tasca, Hilarj; Ciceri, Francesca; Menozzi, Giorgia; Mosca, Fabio; Morandi, Francesco; Borgatti, Renato; Montirosso, Rosario

    2016-10-01

    Very preterm (VPT) infants are hospitalized in the Neonatal Intensive Care Unit (NICU) and exposed to varying levels of skin-breaking procedures (pain-related stress), even in absence of severe clinical conditions. Repeated and prolonged pain exposure may alter hypothalamic-pituitary-adrenal (HPA) axis reactivity in VPT infants. During the post-discharge period, altered HPA axis reactivity has been documented in response to non-social stressors, using salivary cortisol as a biomarker. However, little is known about the effects of NICU pain-related stress on subsequent HPA axis reactivity to socio-emotional stress in infants. We examined the relationship between pain-related stress in NICU and HPA axis reactivity (i.e., salivary cortisol reactivity) to an age-appropriate socio-emotional condition in 37 healthy VPT infants compared to 53 full-term (FT) controls. The number of skin-breaking procedures was obtained across NICU stay for VPT infants. At 3 months (corrected age for prematurity), all infants participated in the maternal Face-to-Face Still-Face (FFSF) procedure, in order to assess HPA axis reactivity to socio-emotional stress (i.e., maternal unresponsiveness). VPT infants exhibited a blunted salivary cortisol reactivity, which was associated with the amount of skin-breaking procedures during NICU: greater pain-related stress predicted lower salivary cortisol reactivity, adjusting for neonatal confounders. These findings further advance our knowledge of how early exposure to pain-related stress in NICU contributes to the programming of an altered HPA axis reactivity to socio-emotional stress in 3-month-old VPT infants, even in the absence of major perinatal complications. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Prenatal maternal stress in relation to the effects of prenatal lead exposure on toddler cognitive development.

    Science.gov (United States)

    Zhou, Leilei; Xu, Jian; Zhang, Jinsong; Yan, Chonghuai; Lin, Yanfen; Jia, Yinan; Hu, Wenjing

    2017-03-01

    To evaluate the effects of maternal lead exposure during pregnancy on toddler cognitive development and the potential effect modification by maternal stress. We conducted a prospective birth-cohort study in Shanghai from 2010 to 2012 and investigated 225 mother-infant pairs. The mothers were recruited in mid-to-late pregnancy and children were followed up until 24-36 months old. A self-administered Symptom Checklist-90-Revised Scale (SCL-90-R) was used to assess maternal emotional stress during pregnancy. Maternal whole blood lead levels were measured during gestational weeks 28-36. The toddlers' cognitive levels were assessed using the Gesell Development Scale. Multiple linear regression models were established to explore the main effects of prenatal lead exposure on toddlers' cognitive abilities and the modifying effects of maternal stress. Covariate information was collected through interviews, questionnaires and medical records. The mean maternal blood lead concentration was 3.30 (95%CI: 3.05, 3.57) μg/dL. After adjusting for relevant confounders, no significant associations of maternal blood lead concentrations with toddlers' cognitive levels were observed in all five domains of the Gesell scale (P>0.05). However, the interaction between prenatal maternal blood lead and stress was significant in the domains of adaptive behavior, language and social behavior. When stratified by maternal stress levels, compared with non-significant associations (P>0.05) among low (P1-P75) prenatal stress group, adverse associations between maternal blood lead concentrations (log10-transformed) and toddlers' cognitive levels were observed among high (P75-P100) prenatal stress group in the domains of language (β=-33.82, 95%CI: -60.04, -7.59), social behavior (β=-41.00, 95%CI: -63.11, -18.89) and adaptive behavior (β=-17.93, 95%CI: -35.83, -0.03). Prenatal maternal stress may exacerbate the deleterious effects of prenatal exposure to lead on toddler cognitive development

  13. Virtual nature environment with nature sound exposure induce stress recovery by enhanced parasympathetic activity

    DEFF Research Database (Denmark)

    Annerstedt, Matilda; Jönsson, Peter; Wallergård, Mattias

    2013-01-01

    . The group that recovered in virtual nature without sound and the control group displayed no particular autonomic activation or deactivation. The results demonstrate a potential mechanistic link between nature, the sounds of nature, and stress recovery, and suggest the potential importance of virtual reality......Experimental research on stress recovery in natural environments is limited, as is study of the effect of sounds of nature. After inducing stress by means of a virtual stress test, we explored physiological recovery in two different virtual natural environments (with and without exposure to sounds...... of nature) and in one control condition. Cardiovascular data and saliva cortisol were collected. Repeated ANOVA measurements indicated parasympathetic activation in the group subjected to sounds of nature in a virtual natural environment, suggesting enhanced stress recovery may occur in such surroundings...

  14. Effects of low-level exposure to xenobiotics present in paints on oxidative stress in workers.

    Science.gov (United States)

    Moro, Angela M; Charão, Mariele; Brucker, Natália; Bulcão, Rachel; Freitas, Fernando; Guerreiro, Gilian; Baierle, Marília; Nascimento, Sabrina; Waechter, Fernanda; Hirakata, Vânia; Linden, Rafael; Thiesen, Flávia V; Garcia, Solange Cristina

    2010-09-15

    Paints are composed of an extensive variety of hazardous substances, such as organic solvents and heavy metals. Biomonitoring is an essential tool for assessing the risk to occupational health. Thus, this study analyzed the levels of biomarkers of exposure for toluene, xylene, styrene, ethylbenzene, and lead, as well as the oxidative stress biomarker alterations in painters of an industry. Lipid peroxidation biomarker (MDA), delta-aminolevulinate dehydratase (ALA-D), nonprotein thyol groups, superoxide dismutase and catalase (CAT) were analyzed in exposed and nonexposed subjects. We estimated which of the paint constituents have the greatest influence on the changes in the biomarkers of oxidative stress in this case of co-exposure. The results demonstrated that despite the fact that all the biomarkers of exposure were below the biological exposure limits, the MDA levels and antioxidant enzyme activities were increased, while nonprotein thyol groups and ALA-D levels were decreased in painters when compared with nonexposed subjects. After statistic test, toluene could be suggested as the principal factor responsible for increased lipid peroxidation and inhibition of ALA-D enzyme; however, further studies on the inhibition of ALA-D enzyme by toluene are necessary. Copyright 2010 Elsevier B.V. All rights reserved.

  15. Activation of the HPA axis and depression of feeding behavior induced by restraint stress are separately regulated by PACAPergic neurotransmission in the mouse.

    Science.gov (United States)

    Jiang, Sunny Zhihong; Eiden, Lee E

    2016-07-01

    We measured serum CORT elevation in wild-type and PACAP-deficient C57BL/6N male mice after acute (1 h) or prolonged (2-3 h) daily restraint stress for 7 d. The PACAP dependence of CORT elevation was compared to that of stress-induced hypophagia. Daily restraint induced unhabituated peak CORT elevation, and hypophagia/weight loss, of similar magnitude for 1, 2, and 3 h of daily restraint, in wild-type mice. Peak CORT elevation, and hypophagia, were both attenuated in PACAP-deficient mice for 2 and 3 h daily restraint. Hypophagia induced by 1-h daily restraint was also greatly reduced in PACAP-deficient mice, however CORT elevation, both peak and during recovery from stress, was unaffected. Thus, hypothalamic PACAPergic neurotransmission appears to affect CRH gene transcription and peptide production, but not CRH release, in response to psychogenic stress. A single exposure to restraint sufficed to trigger hypophagia over the following 24 h. PACAP deficiency attenuated HPA axis response (CORT elevation) to prolonged (3 h) but not acute (1 h) single-exposure restraint stress, while hypophagia induced by either a single 1 h or a single 3 h restraint were both abolished in PACAP-deficient mice. These results suggest that PACAP's actions to promote suppression of food intake following an episode of psychogenic stress is unrelated to the release of CRH into the portal circulation to activate the pituitary-adrenal axis. Furthermore, demonstration of suppressed food intake after a single 1-h restraint stress provides a convenient assay for investigating the location of the synapses and circuits mediating the effects of PACAP on the behavioral sequelae of psychogenic stress.

  16. Photobiomodulation Therapy Decreases Oxidative Stress in the Lung Tissue after Formaldehyde Exposure: Role of Oxidant/Antioxidant Enzymes

    Directory of Open Access Journals (Sweden)

    Rodrigo Silva Macedo

    2016-01-01

    Full Text Available Formaldehyde is ubiquitous pollutant that induces oxidative stress in the lung. Several lung diseases have been associated with oxidative stress and their control is necessary. Photobiomodulation therapy (PBMT has been highlighted as a promissory treatment, but its mechanisms need to be better investigated. Our objective was to evaluate the effects of PBMT on the oxidative stress generated by FA exposure. Male Wistar rats were submitted to FA exposure of 1% or vehicle (3 days and treated or not with PBMT (1 and 5 h after each FA exposure. Rats treated only with laser were used as control. Twenty-four hours after the last FA exposure, we analyzed the effects of PBMT on the generation of nitrites and hydrogen peroxide, oxidative burst, glutathione reductase, peroxidase, S-transferase enzyme activities, the gene expression of nitric oxide, cyclooxygenase, superoxide dismutase, the catalase enzyme, and heme oxygenase-1. PBMT reduced the generation of nitrites and hydrogen peroxide and increased oxidative burst in the lung cells. A decreased level of oxidant enzymes was observed which were concomitantly related to an increased level of antioxidants. This study provides new information about the antioxidant mechanisms of PBMT in the lung and might constitute an important tool for lung disease treatment.

  17. Exposure to mercuric chloride induces developmental damage, oxidative stress and immunotoxicity in zebrafish embryos-larvae.

    Science.gov (United States)

    Zhang, Qun-Fang; Li, Ying-Wen; Liu, Zhi-Hao; Chen, Qi-Liang

    2016-12-01

    Mercury (Hg) is a widespread environmental pollutant that can produce severe negative effects on fish even at very low concentrations. However, the mechanisms underlying inorganic Hg-induced oxidative stress and immunotoxicity in the early development stage of fish still need to be clarified. In the present study, zebrafish (Danio rerio) embryos were exposed to different concentrations of Hg 2+ (0, 1, 4 and 16μg/L; added as mercuric chloride, HgCl 2 ) from 2h post-fertilization (hpf) to 168hpf. Developmental parameters and total Hg accumulation were monitored during the exposure period, and antioxidant status and the mRNA expression of genes related to the innate immune system were examined at 168hpf. The results showed that increasing Hg 2+ concentration and time significantly increased total Hg accumulation in zebrafish embryos-larvae. Exposure to 16μg/L Hg 2+ caused developmental damage, including increased mortality and malformation, decreased body length, and delayed hatching period. Meanwhile, HgCl 2 exposure (especially in the 16μg/L Hg 2+ group) induced oxidative stress affecting antioxidant enzyme (CAT, GST and GPX) activities, endogenous GSH and MDA contents, as well as the mRNA levels of genes (cat1, sod1, gstr, gpx1a, nrf2, keap1, hsp70 and mt) encoding antioxidant proteins. Moreover, the transcription levels of several representative genes (il-1β, il-8, il-10, tnfα2, lyz and c3) involved in innate immunity were up-regulated by HgCl 2 exposure, suggesting that inorganic Hg had the potential to induce immunotoxicity. Taken together, the present study provides evidence that waterborne HgCl 2 exposure can induce developmental impairment, oxidative stress and immunotoxicity in the early development stage of fish, which brings insights into the toxicity mechanisms of inorganic Hg in fish. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Molecular and Genetic Basis of Stress

    Directory of Open Access Journals (Sweden)

    Bakir Mehić

    2012-05-01

    Full Text Available A person’s reaction to trauma depends on the traumatic situation itself, personality characteristics of the person exposed to trauma, and posttraumatic social environment. Stressor must be extreme event that is extremely dangerous or fatal nature, and which is outside normal human experience [1].Studies investigating psychological consequences of military and civil trauma confirmed the correlation between the nature and intensity of trauma, previous traumatic experience, and psychological consequences. Stress causes the autonomic nervous system hyperactivity. If the stress is extreme or constant symptoms of hyperactivity, increased heart rate, increased respiration, sweating, muscle tension, insomnia and increased anxiety are becoming significant for the prolonging the symptoms of PTSD. Our cells are well adapted to exposure to a mild stress for a short time. In contrast there are potentially serious consequences of exposure to the prolonged stress[2].Various damages arising from the war in Bosnia (1992 - 1995 are almost undetectable, and the consequences for the mental health of the population of Bosnia and Herzegovina are long and painful. It is estimated that in Bosnia and Herzegovina there are 1.75 million people who have some stress-related mental disorders, of which 1 million in the Federation.PTSD may be represented by mutations that must be carried by many genes. There may even be epigenetic reasons for the disorder that have nothing to do with heritable mutations per se. Epigenetic means related to functional changes in the genome that can be regulated by external environmental events that do not involve alterations in the genetic code. One epigenetic mechanism is called “methylation,” a molecular process that affects the activity of a large percentage of genes. Epigenetic investigations say that methylation may be involved in the development of stress regulation in early life[3].A number of longitudinal studies have looked at

  19. Perfluorooctanoic acid exposure induces endoplasmic reticulum stress in the liver and its effects are ameliorated by 4-phenylbutyrate.

    Science.gov (United States)

    Yan, Shengmin; Zhang, Hongxia; Wang, Jianshe; Zheng, Fei; Dai, Jiayin

    2015-10-01

    Perfluoroalkyl acids (PFAAs) are a group of widely used anthropogenic compounds. As one of the most dominant PFAAs, perfluorooctanoic acid (PFOA) has been suggested to induce hepatotoxicity and several other toxicological effects. However, details on the mechanisms for PFOA-induced hepatotoxicity still need to be elucidated. In this study, we observed the occurrence of endoplasmic reticulum (ER) stress in mouse livers and HepG2 cells after PFOA exposure using several familiar markers for the unfolded protein response (UPR). ER stress in HepG2 cells after PFOA exposure was not significantly influenced by autophagy inhibition or stimulation. The antioxidant defense system was significantly disturbed in mouse livers after PFOA exposure, and reactive oxygen species (ROS) were increased in cells exposed to PFOA for 24 h. However, N-acetyl-L-cysteine (NAC) pretreatment did not satisfactorily alleviate the UPR in cells exposed to PFOA even though the increase of ROS was less evident. Furthermore, exposure of HepG2 cells to PFOA in the presence of sodium 4-phenylbutyrate (4-PBA), a chemical chaperone and ER stress inhibitor, suggested that 4-PBA alleviated the UPR and autophagosome accumulation induced by PFOA in cells. In addition, several toxicological effects attributed to PFOA exposure, including cell cycle arrest, proteolytic activity impairment, and neutral lipid accumulation, were also improved by 4-PBA cotreatment in cells. In vivo study demonstrated that PFOA-induced lipid metabolism perturbation and liver injury were partially ameliorated by 4-PBA in mice after 28 days of exposure. These findings demonstrated that PFOA-induced ER stress leading to UPR might play an important role in PFOA-induced hepatotoxic effects, and chemical chaperone 4-PBA could ameliorate the effects. Copyright © 2015. Published by Elsevier Inc.

  20. Pharmacokinetics of prolonged-release tacrolimus and implications for use in solid organ transplant recipients.

    Science.gov (United States)

    Tanzi, Maria G; Undre, Nasrullah; Keirns, James; Fitzsimmons, William E; Brown, Malcolm; First, M Roy

    2016-08-01

    Prolonged-release tacrolimus was developed as a once-daily formulation with ethylcellulose as the excipient, resulting in slower release and reduction in peak concentration (Cmax ) for a given dose compared with immediate-release tacrolimus, which is administered twice daily. This manuscript reviews pharmacokinetic information on prolonged-release tacrolimus in healthy subjects, in transplant recipients converted from immediate-release tacrolimus, and in de novo kidney and liver transplant recipients. As with the immediate-release formulation, prolonged-release tacrolimus shows a strong correlation between trough concentration (Cmin ) and area under the 24-hour time-concentration curve (AUC24 ), indicating that trough whole blood concentrations provide an accurate measure of drug exposure. We present the pharmacokinetic similarities and differences between the two formulations, so that prescribing physicians will have a better understanding of therapeutic drug monitoring in patients receiving prolonged-release tacrolimus. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Animal models for posttraumatic stress disorder: An overview of what is used in research.

    Science.gov (United States)

    Borghans, Bart; Homberg, Judith R

    2015-12-22

    Posttraumatic stress disorder (PTSD) is a common anxiety disorder characterised by its persistence of symptoms after a traumatic experience. Although some patients can be cured, many do not benefit enough from the psychological therapies or medication strategies used. Many researchers use animal models to learn more about the disorder and several models are available. The most-used physical stressor models are single-prolonged stress, restraint stress, foot shock, stress-enhanced fear learning, and underwater trauma. Common social stressors are housing instability, social instability, early-life stress, and social defeat. Psychological models are not as diverse and rely on controlled exposure to the test animal's natural predator. While validation of these models has been resolved with replicated symptoms using analogous stressors, translating new findings to human patients remains essential for their impact on the field. Choosing a model to experiment with can be challenging; this overview of what is possible with individual models may aid in making a decision.

  2. Deficits in water maze performance and oxidative stress in the hippocampus and striatum induced by extremely low frequency magnetic field exposure.

    Directory of Open Access Journals (Sweden)

    Yonghua Cui

    Full Text Available The exposures to extremely low frequency magnetic field (ELF-MF in our environment have dramatically increased. Epidemiological studies suggest that there is a possible association between ELF-MF exposure and increased risks of cardiovascular disease, cancers and neurodegenerative disorders. Animal studies show that ELF-MF exposure may interfere with the activity of brain cells, generate behavioral and cognitive disturbances, and produce deficits in attention, perception and spatial learning. Although, many research efforts have been focused on the interaction between ELF-MF exposure and the central nervous system, the mechanism of interaction is still unknown. In this study, we examined the effects of ELF-MF exposure on learning in mice using two water maze tasks and on some parameters indicative of oxidative stress in the hippocampus and striatum. We found that ELF-MF exposure (1 mT, 50 Hz induced serious oxidative stress in the hippocampus and striatum and impaired hippocampal-dependent spatial learning and striatum-dependent habit learning. This study provides evidence for the association between the impairment of learning and the oxidative stress in hippocampus and striatum induced by ELF-MF exposure.

  3. Susceptibility patterns and the role of extracellular DNA in Staphylococcus epidermidis biofilm resistance to physico-chemical stress exposure.

    Science.gov (United States)

    Olwal, Charles Ochieng'; Ang'ienda, Paul Oyieng'; Onyango, David Miruka; Ochiel, Daniel Otieno

    2018-05-02

    Over 65% of human infections are ascribed to bacterial biofilms that are often highly resistant to antibiotics and host immunity. Staphylococcus epidermidis is the predominant cause of recurrent nosocomial and biofilm-related infections. However, the susceptibility patterns of S. epidermidis biofilms to physico-chemical stress induced by commonly recommended disinfectants [(heat, sodium chloride (NaCl), sodium hypochlorite (NaOCl) and hydrogen peroxide (H 2 O 2 )] in domestic and human healthcare settings remains largely unknown. Further, the molecular mechanisms of bacterial biofilms resistance to the physico-chemical stresses remain unclear. Growing evidence demonstrates that extracellular DNA (eDNA) protects bacterial biofilms against antibiotics. However, the role of eDNA as a potential mechanism underlying S. epidermidis biofilms resistance to physico-chemical stress exposure is yet to be understood. Therefore, this study aimed to evaluate the susceptibility patterns of and eDNA release by S. epidermidis biofilm and planktonic cells to physico-chemical stress exposure. S. epidermidis biofilms exposed to physico-chemical stress conditions commonly recommended for disinfection [heat (60 °C), 1.72 M NaCl, solution containing 150 μL of waterguard (0.178 M NaOCl) in 1 L of water or 1.77 M H 2 O 2 ] for 30 and 60 min exhibited lower log reductions of CFU/mL than the corresponding planktonic cells (p chemical stress induced by the four commonly recommended disinfectants than the analogous planktonic cells. Further, S. epidermidis biofilms enhanced eDNA release in response to the sub-lethal heat and oxidative stress exposure than the corresponding planktonic cells suggesting a role of eDNA in biofilms resistance to the physico-chemical stresses.

  4. Stress Exposure and Physical, Mental, and Behavioral Health among American Indian Adults with Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Melissa L. Walls

    2017-09-01

    Full Text Available American Indian (AI communities experience disproportionate exposure to stressors and health inequities including type 2 diabetes. Yet, we know little about the role of psychosocial stressors for AI diabetes-related health outcomes. We investigated associations between a range of stressors and psychological, behavioral, and physical health for AIs with diabetes. This community-based participatory research with 5 AI tribes includes 192 AI adult type 2 diabetes patients recruited from clinical records at tribal clinics. Data are from computer-assisted interviews and medical charts. We found consistent bivariate relationships between chronic to discrete stressors and mental and behavioral health outcomes; several remained even after accounting for participant age, gender, and income. Fewer stressors were linked to physical health. We also document a dose–response relationship between stress accumulation and worse health. Findings underscore the importance of considering a broad range of stressors for comprehensive assessment of stress burden and diabetes. Policies and practices aimed at reducing stress exposure and promoting tools for stress management may be mechanisms for optimal health for AI diabetes patients.

  5. Stress Exposure and Physical, Mental, and Behavioral Health among American Indian Adults with Type 2 Diabetes.

    Science.gov (United States)

    Walls, Melissa L; Sittner, Kelley J; Aronson, Benjamin D; Forsberg, Angie K; Whitbeck, Les B; al'Absi, Mustafa

    2017-09-16

    American Indian (AI) communities experience disproportionate exposure to stressors and health inequities including type 2 diabetes. Yet, we know little about the role of psychosocial stressors for AI diabetes-related health outcomes. We investigated associations between a range of stressors and psychological, behavioral, and physical health for AIs with diabetes. This community-based participatory research with 5 AI tribes includes 192 AI adult type 2 diabetes patients recruited from clinical records at tribal clinics. Data are from computer-assisted interviews and medical charts. We found consistent bivariate relationships between chronic to discrete stressors and mental and behavioral health outcomes; several remained even after accounting for participant age, gender, and income. Fewer stressors were linked to physical health. We also document a dose-response relationship between stress accumulation and worse health. Findings underscore the importance of considering a broad range of stressors for comprehensive assessment of stress burden and diabetes. Policies and practices aimed at reducing stress exposure and promoting tools for stress management may be mechanisms for optimal health for AI diabetes patients.

  6. Moderate Thermal Stress Causes Active and Immediate Expulsion of Photosynthetically Damaged Zooxanthellae (Symbiodinium from Corals.

    Directory of Open Access Journals (Sweden)

    Lisa Fujise

    Full Text Available The foundation of coral reef biology is the symbiosis between corals and zooxanthellae (dinoflagellate genus Symbiodinium. Recently, coral bleaching, which often results in mass mortality of corals and the collapse of coral reef ecosystems, has become an important issue around the world as coral reefs decrease in number year after year. To understand the mechanisms underlying coral bleaching, we maintained two species of scleractinian corals (Acroporidae in aquaria under non-thermal stress (27°C and moderate thermal stress conditions (30°C, and we compared the numbers and conditions of the expelled Symbiodinium from these corals. Under non-thermal stress conditions corals actively expel a degraded form of Symbiodinium, which are thought to be digested by their host coral. This response was also observed at 30°C. However, while the expulsion rates of Symbiodinium cells remained constant, the proportion of degraded cells significantly increased at 30°C. This result indicates that corals more actively digest and expel damaged Symbiodinium under thermal stress conditions, likely as a mechanism for coping with environmental change. However, the increase in digested Symbiodinium expulsion under thermal stress may not fully keep up with accumulation of the damaged cells. There are more photosynthetically damaged Symbiodinium upon prolonged exposure to thermal stress, and corals release them without digestion to prevent their accumulation. This response may be an adaptive strategy to moderate stress to ensure survival, but the accumulation of damaged Symbiodinium, which causes subsequent coral deterioration, may occur when the response cannot cope with the magnitude or duration of environmental stress, and this might be a possible mechanism underlying coral bleaching during prolonged moderate thermal stress.

  7. Moderate Thermal Stress Causes Active and Immediate Expulsion of Photosynthetically Damaged Zooxanthellae (Symbiodinium) from Corals.

    Science.gov (United States)

    Fujise, Lisa; Yamashita, Hiroshi; Suzuki, Go; Sasaki, Kengo; Liao, Lawrence M; Koike, Kazuhiko

    2014-01-01

    The foundation of coral reef biology is the symbiosis between corals and zooxanthellae (dinoflagellate genus Symbiodinium). Recently, coral bleaching, which often results in mass mortality of corals and the collapse of coral reef ecosystems, has become an important issue around the world as coral reefs decrease in number year after year. To understand the mechanisms underlying coral bleaching, we maintained two species of scleractinian corals (Acroporidae) in aquaria under non-thermal stress (27°C) and moderate thermal stress conditions (30°C), and we compared the numbers and conditions of the expelled Symbiodinium from these corals. Under non-thermal stress conditions corals actively expel a degraded form of Symbiodinium, which are thought to be digested by their host coral. This response was also observed at 30°C. However, while the expulsion rates of Symbiodinium cells remained constant, the proportion of degraded cells significantly increased at 30°C. This result indicates that corals more actively digest and expel damaged Symbiodinium under thermal stress conditions, likely as a mechanism for coping with environmental change. However, the increase in digested Symbiodinium expulsion under thermal stress may not fully keep up with accumulation of the damaged cells. There are more photosynthetically damaged Symbiodinium upon prolonged exposure to thermal stress, and corals release them without digestion to prevent their accumulation. This response may be an adaptive strategy to moderate stress to ensure survival, but the accumulation of damaged Symbiodinium, which causes subsequent coral deterioration, may occur when the response cannot cope with the magnitude or duration of environmental stress, and this might be a possible mechanism underlying coral bleaching during prolonged moderate thermal stress.

  8. Endoplasmic reticulum: ER stress regulates mitochondrial bioenergetics

    Science.gov (United States)

    Bravo, Roberto; Gutierrez, Tomás; Paredes, Felipe; Gatica, Damián; Rodriguez, Andrea E.; Pedrozo, Zully; Chiong, Mario; Parra, Valentina; Quest, Andrew F.G.; Rothermel, Beverly A.; Lavandero, Sergio

    2014-01-01

    Endoplasmic reticulum (ER) stress activates an adaptive unfolded protein response (UPR) that facilitates cellular repair, however, under prolonged ER stress, the UPR can ultimately trigger apoptosis thereby terminating damaged cells. The molecular mechanisms responsible for execution of the cell death program are relatively well characterized, but the metabolic events taking place during the adaptive phase of ER stress remain largely undefined. Here we discuss emerging evidence regarding the metabolic changes that occur during the onset of ER stress and how ER influences mitochondrial function through mechanisms involving calcium transfer, thereby facilitating cellular adaptation. Finally, we highlight how dysregulation of ER–mitochondrial calcium homeostasis during prolonged ER stress is emerging as a novel mechanism implicated in the onset of metabolic disorders. PMID:22064245

  9. Programming of stress-related behavior and epigenetic neural gene regulation in mice offspring through maternal exposure to predator odor

    Science.gov (United States)

    St-Cyr, Sophie; McGowan, Patrick O.

    2015-01-01

    Perinatal stress mediated through the mother can lead to long-term alterations in stress-related phenotypes in offspring. The capacity for adaptation to adversity in early life depends in part on the life history of the animal. This study was designed to examine the behavioral and neural response in adult offspring to prenatal exposure to predator odor: an ethologically-relevant psychological stressor. Pregnant mice were exposed daily to predator odors or distilled water control over the second half of the pregnancy. Predator odor exposure lead to a transient decrease in maternal care in the mothers. As adults, the offspring of predator odor-exposed mothers showed increased anti-predator behavior, a predator-odor induced decrease in activity and, in female offspring, an increased corticosterone (CORT) response to predator odor exposure. We found a highly specific response among stress-related genes within limbic brain regions. Transcript abundance of Corticotropin-releasing hormone receptor 1 (CRHR1) was elevated in the amygdala in adult female offspring of predator odor-exposed mothers. In the hippocampus of adult female offspring, decreased Brain-derived neurotrophic factor (BDNF) transcript abundance was correlated with a site-specific decrease in DNA methylation in Bdnf exon IV, indicating the potential contribution of this epigenetic mechanism to maternal programming by maternal predator odor exposure. These data indicate that maternal predator odor exposure alone is sufficient to induce an altered stress-related phenotype in adulthood, with implications for anti-predator behavior in offspring. PMID:26082698

  10. Physiologic effects of prolonged conducted electrical weapon discharge in ethanol-intoxicated adults.

    Science.gov (United States)

    Moscati, Ronald; Ho, Jeffrey D; Dawes, Donald M; Miner, James R

    2010-06-01

    This study examines the physiologic effects of prolonged conducted electrical weapon (CEW) exposure on alcohol-intoxicated adult subjects. Adult volunteers were recruited at a TASER International training conference. All subjects ingested mixed drinks until clinical intoxication or until a minimum breath alcohol level of 0.08 mg/dL was achieved. Blood samples for venous pH, Pco(2), bicarbonate, and lactate were measured in all subjects at baseline, immediately after alcohol ingestion, immediately after exposure to a 15-second TASER X26 discharge (Taser International Inc, Scottsdale, AZ), and 24 hours post-alcohol ingestion. Laboratory values were compared at sampling times using repeated-measure analysis of variance. A focused analysis comparing time points within groups was then performed using paired t tests. Twenty-two subjects were enrolled into the study. There was a decrease in pH and bicarbonate and an increase in lactate after alcohol ingestion. There was a further increase in lactate and drop in pH after CEW exposure. No subject experienced a significant adverse event. All values had returned to baseline levels at 24 hours except lactate, which demonstrated a small but clinically insignificant increase. Prolonged continuous CEW exposure in the setting of acute alcohol intoxication has no clinically significant effect on subjects in terms of markers of metabolic acidosis. The acidosis seen is consistent with what occurs with ethanol intoxication or moderate exertion. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  11. Chironomus riparius exposure to fullerene-contaminated sediment results in oxidative stress and may impact life cycle parameters

    Energy Technology Data Exchange (ETDEWEB)

    Waissi, G.C., E-mail: greta.waissi@uef.fi [Department of Environmental and Biological Sciences, University of Eastern Finland, Joensuu (Finland); Bold, S. [GEOMAR Helmholtz Centre of Ocean for Research Kiel (Germany); Pakarinen, K.; Akkanen, J. [Department of Environmental and Biological Sciences, University of Eastern Finland, Joensuu (Finland); Leppänen, M.T. [Finnish Environment Institute, Jyväskylä (Finland); Petersen, E.J. [Material Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, MD (United States); Kukkonen, J.V.K. [University of Jyväskylä, Department of Biological and Environmental Science, Jyväskylä (Finland)

    2017-01-15

    Highlights: • FullerenesC{sub 60} were tested to C. riparius with acute and chronic exposures. • The rapid uptake of fullerenes by C. riparius observed after an acute experiment. • Oxidative stress was localized in tissues under microvilli layer. - Abstract: A key component of understanding the potential environmental risks of fullerenes (C{sub 60}) is their potential effects on benthic invertebrates. Using the sediment dwelling invertebrate Chironomus riparius we explored the effects of acute (12 h and 24 h) and chronic (10 d, 15 d, and 28 d) exposures of sediment associated fullerenes. The aims of this study were to assess the impact of exposure to C{sub 60} in the sediment top layer ((0.025, 0.18 and 0.48) C{sub 60} mg/cm{sup 2}) on larval growth, oxidative stress and emergence rates and to quantify larval body burdens in similarly exposed organisms. Oxidative stress localization was observed in the tissues next to the microvilli and exoskeleton through a method for identifying oxidative stress reactions generated by reactive oxygen species. Rapid intake of fullerenes was shown in acute experiments, whereas body residues decreased after chronic exposure. Transmission electron microscopy analysis revealed oxidative damage and structural changes in cells located between the lipid droplets and next to the microvilli layer in fullerene exposed samples. Fullerene associated sediments also caused changes in the emergence rate of males and females, suggesting that the cellular interactions described above or other effects from the fullerenes may influence reproduction rates.

  12. Exposure to tributyltin induces endoplasmic reticulum stress and the unfolded protein response in zebrafish.

    Science.gov (United States)

    Komoike, Yuta; Matsuoka, Masato

    2013-10-15

    Tributyltin (TBT) is a major marine contaminant and causes endocrine disruption, hepatotoxicity, immunotoxicity, and neurotoxicity. However, the molecular mechanisms underlying the toxicity of TBT have not been fully elucidated. We examined whether exposure to TBT induces the endoplasmic reticulum (ER) stress response in zebrafish, a model organism. Zebrafish-derived BRF41 fibroblast cells were exposed to 0.5 or 1 μM TBT for 0.5-16 h and subsequently lysed and immunoblotted to detect ER stress-related proteins. Zebrafish embryos, grown until 32 h post fertilization (hpf), were exposed to 1 μM TBT for 16 h and used in whole mount in situ hybridization and immunohistochemistry to visualize the expression of ER chaperones and an ER stress-related apoptosis factor. Exposure of the BRF41 cells to TBT caused phosphorylation of the zebrafish homolog of protein kinase RNA-activated-like ER kinase (PERK), eukaryotic translation initiation factor 2 alpha (eIF2α), and inositol-requiring enzyme 1 (IRE1), characteristic splicing of X-box binding protein 1 (XBP1) mRNA, and enhanced expression of activating transcription factor 4 (ATF4) protein. In TBT-exposed zebrafish embryos, ectopic expression of the gene encoding zebrafish homolog of the 78 kDa glucose-regulating protein (GRP78) and gene encoding CCAAT/enhancer-binding protein homologous protein (CHOP) was detected in the precursors of the neuromast, which is a sensory organ for detecting water flow and vibration. Our in vitro and in vivo studies revealed that exposure of zebrafish to TBT induces the ER stress response via activation of both the PERK-eIF2α and IRE1-XBP1 pathways of the unfolded protein response (UPR) in an organ-specific manner. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Diazepam administration prevents testosterone decrease and lipofuscin accumulation in testis of mouse exposed to chronic noise stress.

    Science.gov (United States)

    Ruffoli, R; Carpi, A; Giambelluca, M A; Grasso, L; Scavuzzo, M C; Giannessi F, F

    2006-10-01

    Lipofuscin is an autofluorescent and undegradable material, which accumulates in tissues during ageing and under different types of stress. Among these, oxidative stress represents a major trigger for lipofuscin formation. However, prolonged noise exposure is also an effective stressful stimuli. Diazepam may inhibit lipofuscinogenesis in liver and prevent the noise-induced reduction of the steroidogenesis in the adrenal gland. The aim of the study was to ascertain whether chronic noise exposure causes lipofuscin accumulation in mouse testis, and to evaluate the effects of diazepam administration. Eight-week old mice were either exposed for 6 weeks (6 h day(-1)) to white-noise (group A), or received diazepam (3 mg kg(-1), i.p.) before noise exposures (group B), while a further group was used as control (group C). Light fluorescence and transmission electron microscopy revealed lipofuscin in large amounts in the Leydig cells in mice of group A, which concomitantly had low serum testosterone levels; pre-treatment with diazepam occluded both effects. The present study indicates that: (i) chronic noise exposure causes lipofuscin accumulation at the level of the Leydig cells and a decrease in testosterone; (ii) all these effects are suppressed by pre-treatment with diazepam. As the Leydig cells represent the only cellular type of the interstitial testicular tissue having peripheral benzodiazepine receptors, these results could be explained by the capacity of the peripheral benzodiazepine receptors to prevent reactive oxygen species damage and to increase the resistance of these cells to oxidative stress.

  14. Stress hormonal changes in the brain and plasma after acute noise exposure in mice.

    Science.gov (United States)

    Jin, Sang Gyun; Kim, Min Jung; Park, So Young; Park, Shi Nae

    2017-06-01

    To investigate the effects of acute noise stress on two amine stress hormones, norepinephrine (NE) and 5-hydroxyindoleacetic acid (5-HIAA) in the brain and plasma of mice after noise exposure. Mice were grouped into the control and noise groups. Mice in the noise group were exposed to white noise of 110dB sound pressure level for 60min. Auditory brainstem response thresholds, distortion product otoacoustic emissions, the organ of Corti grading scores, western blots of NE/5-HIAA in the whole brain and hippocampus, and the plasma levels of NE/5-HIAA were compared between the two groups. Significant hearing loss and cochlear damage were demonstrated in the noise group. NE and 5-HIAA in the hippocampus were elevated in the noise group (p=0.019/0.022 for NE/5-HIAA vs. the control). Plasma levels of NE and 5-HIAA were not statistically different between the groups (p=0.052/0.671 for NE/5-HIAA). Hearing loss with outer hair cell dysfunction and morphological changes of the organ of Corti after noise exposure in C57BL/6 mice proved the reliability of our animal model as an acute noise stress model. NE and 5-HIAA are suggested to be the potential biomarkers for acute noise stress in the hippocampus. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Scrambled and fried: Cigarette smoke exposure causes antral follicle destruction and oocyte dysfunction through oxidative stress

    International Nuclear Information System (INIS)

    Sobinoff, A.P.; Beckett, E.L.; Jarnicki, A.G.; Sutherland, J.M.; McCluskey, A.; Hansbro, P.M.; McLaughlin, E.A.

    2013-01-01

    Cigarette smoke is a reproductive hazard associated with pre-mature reproductive senescence and reduced clinical pregnancy rates in female smokers. Despite an increased awareness of the adverse effects of cigarette smoke exposure on systemic health, many women remain unaware of the adverse effects of cigarette smoke on female fertility. This issue is compounded by our limited understanding of the molecular mechanisms behind cigarette smoke induced infertility. In this study we used a direct nasal exposure mouse model of cigarette smoke-induced chronic obstructive pulmonary disease to characterise mechanisms of cigarette-smoke induced ovotoxicity. Cigarette smoke exposure caused increased levels of primordial follicle depletion, antral follicle oocyte apoptosis and oxidative stress in exposed ovaries, resulting in fewer follicles available for ovulation. Evidence of oxidative stress also persisted in ovulated oocytes which escaped destruction, with increased levels of mitochondrial ROS and lipid peroxidation resulting in reduced fertilisation potential. Microarray analysis of ovarian tissue correlated these insults with a complex mechanism of ovotoxicity involving genes associated with detoxification, inflammation, follicular activation, immune cell mediated apoptosis and membrane organisation. In particular, the phase I detoxifying enzyme cyp2e1 was found to be significantly up-regulated in developing oocytes; an enzyme known to cause molecular bioactivation resulting in oxidative stress. Our results provide a preliminary model of cigarette smoke induced sub-fertility through cyp2e1 bioactivation and oxidative stress, resulting in developing follicle depletion and oocyte dysfunction. - Highlights: • Cigarette smoke exposure targets developing follicle oocytes. • The antral follicle oocyte is a primary site of ovarian cigarette smoke metabolism. • Cyp2e1 is a major enzyme involved in ameliorating smoke-induced ovotoxicity. • Cigarette smoke causes oocyte

  16. Scrambled and fried: Cigarette smoke exposure causes antral follicle destruction and oocyte dysfunction through oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Sobinoff, A.P. [Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308 (Australia); Priority Research Centre for Chemical Biology, University of Newcastle, Callaghan, NSW 2308 (Australia); Beckett, E.L.; Jarnicki, A.G. [Centre for Asthma and Respiratory Disease, The University of Newcastle and Hunter Medical Research Institute, Callaghan, NSW 2308 (Australia); Sutherland, J.M. [Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308 (Australia); Priority Research Centre for Chemical Biology, University of Newcastle, Callaghan, NSW 2308 (Australia); McCluskey, A. [Priority Research Centre for Chemical Biology, University of Newcastle, Callaghan, NSW 2308 (Australia); Hansbro, P.M. [Centre for Asthma and Respiratory Disease, The University of Newcastle and Hunter Medical Research Institute, Callaghan, NSW 2308 (Australia); McLaughlin, E.A., E-mail: eileen.mclaughlin@newcastle.edu.au [Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308 (Australia); Priority Research Centre for Chemical Biology, University of Newcastle, Callaghan, NSW 2308 (Australia)

    2013-09-01

    Cigarette smoke is a reproductive hazard associated with pre-mature reproductive senescence and reduced clinical pregnancy rates in female smokers. Despite an increased awareness of the adverse effects of cigarette smoke exposure on systemic health, many women remain unaware of the adverse effects of cigarette smoke on female fertility. This issue is compounded by our limited understanding of the molecular mechanisms behind cigarette smoke induced infertility. In this study we used a direct nasal exposure mouse model of cigarette smoke-induced chronic obstructive pulmonary disease to characterise mechanisms of cigarette-smoke induced ovotoxicity. Cigarette smoke exposure caused increased levels of primordial follicle depletion, antral follicle oocyte apoptosis and oxidative stress in exposed ovaries, resulting in fewer follicles available for ovulation. Evidence of oxidative stress also persisted in ovulated oocytes which escaped destruction, with increased levels of mitochondrial ROS and lipid peroxidation resulting in reduced fertilisation potential. Microarray analysis of ovarian tissue correlated these insults with a complex mechanism of ovotoxicity involving genes associated with detoxification, inflammation, follicular activation, immune cell mediated apoptosis and membrane organisation. In particular, the phase I detoxifying enzyme cyp2e1 was found to be significantly up-regulated in developing oocytes; an enzyme known to cause molecular bioactivation resulting in oxidative stress. Our results provide a preliminary model of cigarette smoke induced sub-fertility through cyp2e1 bioactivation and oxidative stress, resulting in developing follicle depletion and oocyte dysfunction. - Highlights: • Cigarette smoke exposure targets developing follicle oocytes. • The antral follicle oocyte is a primary site of ovarian cigarette smoke metabolism. • Cyp2e1 is a major enzyme involved in ameliorating smoke-induced ovotoxicity. • Cigarette smoke causes oocyte

  17. Stress-induced changes of hippocampal NMDA receptors: modulation by duloxetine treatment.

    Directory of Open Access Journals (Sweden)

    Francesca Calabrese

    Full Text Available It is now well established that the glutamatergic system contributes to the pathophysiology of depression. Exposure to stress, a major precipitating factor for depression, enhances glutamate release that can contribute to structural abnormalities observed in the brain of depressed subjects. On the other hand, it has been demonstrated that NMDA antagonists, like ketamine, exert an antidepressant effect at preclinical and clinical levels. On these bases, the purpose of our study was to investigate whether chronic mild stress is associated with specific alterations of the NMDA receptor complex, in adult rats, and to establish whether concomitant antidepressant treatment could normalize such deficits. We found that chronic stress increases the expression of the obligatory GluN1 subunit, as well as of the accessory subunits GluN2A and GluN2B at transcriptional and translational levels, particularly in the ventral hippocampus. Concomitant treatment with the antidepressant duloxetine was able to normalize the increase of glutamatergic receptor subunit expression, and correct the changes in receptor phosphorylation produced by stress exposure. Our data suggest that prolonged stress, a condition that has etiologic relevance for depression, may enhance glutamate activity through post-synaptic mechanisms, by regulating NMDA receptors, and that antidepressants may in part normalize such changes. Our results provide support to the notion that antidepressants may exert their activity in the long-term also via modulation of the glutamatergic synapse.

  18. Alterations in glucocorticoid negative feedback following maternal Pb, prenatal stress and the combination: A potential biological unifying mechanism for their corresponding disease profiles

    International Nuclear Information System (INIS)

    Rossi-George, A.; Virgolini, M.B.; Weston, D.; Cory-Slechta, D.A.

    2009-01-01

    Combined exposures to maternal lead (Pb) and prenatal stress (PS) can act synergistically to enhance behavioral and neurochemical toxicity in offspring. Maternal Pb itself causes permanent dysfunction of the body's major stress system, the hypothalamic pituitary adrenal (HPA) axis. The current study sought to determine the potential involvement of altered negative glucocorticoid feedback as a mechanistic basis of the effects in rats of maternal Pb (0, 50 or 150 ppm in drinking water beginning 2 mo prior to breeding), prenatal stress (PS; restraint on gestational days 16-17) and combined maternal Pb + PS in 8 mo old male and female offspring. Corticosterone changes were measured over 24 h following an i.p. injection stress containing vehicle or 100 or 300 μg/kg (females) or 100 or 150 μg/kg (males) dexamethasone (DEX). Both Pb and PS prolonged the time course of corticosterone reduction following vehicle injection stress. Pb effects were non-monotonic, with a greater impact at 50 vs. 150 ppm, particularly in males, where further enhancement occurred with PS. In accord with these findings, the efficacy of DEX in suppressing corticosterone was reduced by Pb and Pb + PS in both genders, with Pb efficacy enhanced by PS in females, over the first 6 h post-administration. A marked prolongation of DEX effects was found in males. Thus, Pb, PS and Pb + PS, sometimes additively, produced hypercortisolism in both genders, followed by hypocortisolism in males, consistent with HPA axis dysfunction. These findings may provide a plausible unifying biological mechanism for the reported links between Pb exposure and stress-associated diseases and disorders mediated via the HPA axis, including obesity, hypertension, diabetes, anxiety, schizophrenia and depression. They also suggest broadening of Pb screening programs to pregnant women in high stress environments

  19. Effect of prolonged exposure to sublethal concentrations of DDT and DDE on protein expression in human pancreatic beta cells.

    Science.gov (United States)

    Pavlikova, Nela; Smetana, Pavel; Halada, Petr; Kovar, Jan

    2015-10-01

    Pollution of the environment represents one of less explored potential reasons for the worldwide epidemic of type 2 diabetes. One of the most prevalent organochlorine pollutants remains the pesticide DDT and its degradation product DDE. Despite some epidemiologic correlations between levels of DDT and DDE in human organism and the prevalence of diabetes, there is almost no information about the exact targets of these compounds inside pancreatic beta cells. To detect functional areas of pancreatic beta cells that could be affected by exposure to DDT and DDE, we analyzed changes in protein expression in the NES2Y human pancreatic beta cell line exposed to three sublethal concentrations (0.1 μM, 1 μM, 10 μM) of DDT and DDE for 1 month. Protein separation and identification was achieved using high-resolution 2D-electrophoresis, computer analysis and mass spectrometry. With these techniques, four proteins were found downregulated after exposure to 10 μM DDT: three cytoskeletal proteins (cytokeratin 8, cytokeratin 18 and actin) and one protein involved in glycolysis (alpha-enolase). Two proteins were downregulated after exposure to 10 μM DDE: cytokeratin 18 and heterogenous nuclear ribonucleoprotein H1 (HNRH1). These changes correlate with previously described effects of other stress conditions (e.g. exposure to palmitate, hyperglycemia, imidazoline derivative, and cytokines) on protein expression in pancreatic beta cells. We conclude that cytoskeletal proteins and their processing, glucose metabolism, and mRNA processing may represent targets affected by exposure to conditions hostile to pancreatic beta cells, including exposure to DDT and DDE. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Long-Term Effectiveness of Stress Management at Work: Effects of the Changes in Perceived Stress Reactivity on Mental Health and Sleep Problems Seven Years Later.

    Science.gov (United States)

    Herr, Raphael M; Barrech, Amira; Riedel, Natalie; Gündel, Harald; Angerer, Peter; Li, Jian

    2018-02-03

    The reduction of stress reactivity resulting from stress management interventions prevents disorders and improves mental health, however, its long-term sustainability has been little examined. The objective of this study was, therefore, to determine the effectiveness of a stress management intervention, designed to improve stress reactivity, for mental health and sleep problems seven years later, using longitudinal data from 101 male industrial workers. Linear regressions estimated the adjusted effects of the changes in stress reactivity in general as well as in its six subdimensions (work overload, social conflict, social stress, failure at work, and anticipatory and prolonged reactivity) on depression, anxiety, and sleep problems seven years later. The improvement of the prolonged reactivity had positive effects on depression, anxiety, and sleep problems (unstandardized regression coefficients [ Bs ] ≥ 0.35, all p -values ≤ 0.01). Depression and sleep problems were further improved by a reduction of the reactivity to social conflicts ( Bs ≥ 0.29, p -values stress reactivity resulting from a work stress intervention was effective and generally long-lasting in preventing mental health and sleep problems. The reduction of the prolonged reactivity seems of particular importance and efficient in inhibiting negative stress manifestations.

  1. Decision-making about chronic radiation exposure to the public. New recommendations from the ICRP

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez, A.J. [Division of Radiation and Waste Safety, International Atomic Energy Agency, Vienna (Austria)

    2000-05-01

    The paper discusses decision-making in situations of chronic exposure within the framework of a forthcoming related ICRP report on the subject which has been produced by an ICRP Task Group chaired by the author. This ICRP report will provide guidance on the application of the ICRP System of Radiological Protection to prolonged exposure situations afflicting members of the public. It will address the general application of the System to the control of prolonged exposures resulting from practices and to the undertaking of interventions in prolonged exposure situations, and will provide recommendations on generic reference levels for such interventions. It will also consider some specific situations and will discuss a number of issues that have been of concern, namely: natural radiation sources that may give rise to high doses; the restoration and rehabilitation of sites where human activities involving radioactive substances have been carried out; the return to 'normality' following an accident that has released radioactive substances to the environment; and the global marketing of commodities for public consumption that contain relatively high levels of radioactive substances. Annexes will provide some examples of prolonged exposure situations and will discuss the radiological protection quantities, radiation-induced health effects and aspects of the System of Radiological Protection relevant to prolonged exposure. The quantitative recommendations for prolonged exposures provided in the report will be as follows: generic reference levels for intervention, in terms of existing annual doses, of < or approx. 100 mSv, above which intervention is almost always justifiable (situations for which the annual dose threshold for deterministic effects in relevant organs is exceeded will almost always require intervention), and of < or approx.10 mSv, below which intervention is not likely to be justifiable (and above which it may be necessary); intervention exemption

  2. Prenatal nonylphenol exposure, oxidative and nitrative stress, and birth outcomes: A cohort study in Taiwan

    International Nuclear Information System (INIS)

    Wang, Pei-Wei; Chen, Mei-Lien; Huang, Li-Wei; Yang, Winnie; Wu, Kuen-Yuh; Huang, Yu-Fang

    2015-01-01

    Data concerning the effects of prenatal exposures to nonylphenol (NP) and oxidative stress on neonatal birth outcomes from human studies are limited. A total of 146 pregnant women were studied (1) to investigate the association between prenatal NP exposure and maternal oxidative/nitrative stress biomarkers of DNA damage (8-hydroxy-2’-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO 2 Gua)) and lipid peroxidation (8-iso-prostaglandin F 2α (8-isoPF 2α ), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)) and (2) to explore the associations among oxidative stress biomarkers, NP exposure, and neonatal birth outcomes, including gestational age, birth weight, length, Ponderal index, and head and chest circumferences. NP significantly increased the 8-OHdG and 8-NO 2 Gua levels. All infants born to mothers with urinary 8-OHdG levels above the median exhibited a significantly shorter gestational duration (B adjusted  = −4.72 days; 95% CI: −8.08 to −1.36 days). No clear association was found between NP levels and birth outcomes. Prenatal 8-OHdG levels might be a novel biomarker for monitoring fetal health related to NP exposure. - Highlights: • A cohort of pregnant women was established and followed until delivery. • NP significantly increased 8-OHdG and 8-NO 2 Gua levels. • Maternal 8-OHdG levels were associated with significantly decreased gestational duration. • No clear association was observed between NP and birth outcomes. - NP increased 8-OHdG and 8-NO 2 Gua levels; high 8-OHdG levels significantly decreased gestation length.

  3. Intrauterine ethanol exposure results in hypothalamic oxidative stress and neuroendocrine alterations in adult rat offspring.

    Science.gov (United States)

    Dembele, Korami; Yao, Xing-Hai; Chen, Li; Nyomba, B L Grégoire

    2006-09-01

    Prenatal ethanol (EtOH) exposure is associated with low birth weight, followed by increased appetite, catch-up growth, insulin resistance, and impaired glucose tolerance in the rat offspring. Because EtOH can induce oxidative stress, which is a putative mechanism of insulin resistance, and because of the central role of the hypothalamus in the regulation of energy homeostasis and insulin action, we investigated whether prenatal EtOH exposure causes oxidative damage to the hypothalamus, which may alter its function. Female rats were given EtOH by gavage throughout pregnancy. At birth, their offspring were smaller than those of non-EtOH rats. Markers of oxidative stress and expression of neuropeptide Y and proopiomelanocortin (POMC) were determined in hypothalami of postnatal day 7 (PD7) and 3-mo-old (adult) rat offspring. In both PD7 and adult rats, prenatal EtOH exposure was associated with decreased levels of glutathione and increased expression of MnSOD. The concentrations of lipid peroxides and protein carbonyls were normal in PD7 EtOH-exposed offspring, but were increased in adult EtOH-exposed offspring. Both PD7 and adult EtOH-exposed offspring had normal neuropeptide Y and POMC mRNA levels, but the adult offspring had reduced POMC protein concentration. Thus only adult offspring preexposed to EtOH had increased hypothalamic tissue damage and decreased levels of POMC, which could impair melanocortin signaling. We conclude that prenatal EtOH exposure causes hypothalamic oxidative stress, which persists into adult life and alters melanocortin action during adulthood. These neuroendocrine alterations may explain weight gain and insulin resistance in rats exposed to EtOH early in life.

  4. Prenatal nicotinic exposure upregulates pulmonary C-fiber NK1R expression to prolong pulmonary C-fiber-mediated apneic response

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Lei; Zhuang, Jianguo; Zang, Na; Lin, Yong [Pathophysiology Program, Lovelace Respiratory Research Institute, Albuquerque, NM (United States); Lee, Lu-Yuan [Department of Physiology, University of Kentucky, Lexington, KY (United States); Xu, Fadi, E-mail: fxu@lrri.org [Pathophysiology Program, Lovelace Respiratory Research Institute, Albuquerque, NM (United States); Department of Physiology, University of Kentucky, Lexington, KY (United States)

    2016-01-01

    Prenatal nicotinic exposure (PNE) prolongs bronchopulmonary C-fiber (PCF)-mediated apneic response to intra-atrial bolus injection of capsaicin in rat pups. The relevant mechanisms remain unclear. Pulmonary substance P and adenosine and their receptors (neurokinin-A receptor, NK1R and ADA{sub 1} receptor, ADA{sub 1}R) and transient receptor potential cation channel subfamily V member 1 (TRPV1) expressed on PCFs are critical for PCF sensitization and/or activation. Here, we compared substance P and adenosine in BALF and NK1R, ADA{sub 1}R, and TRPV1 expression in the nodose/jugular (N/J) ganglia (vagal pulmonary C-neurons retrogradely labeled) between Ctrl and PNE pups. We found that PNE failed to change BALF substance P and adenosine content, but significantly upregulated both mRNA and protein TRPV1 and NK1R in the N/J ganglia and only NK1R mRNA in pulmonary C-neurons. To define the role of NK1R in the PNE-induced PCF sensitization, the apneic response to capsaicin (i.v.) without or with pretreatment of SR140333 (a peripheral and selective NK1R antagonist) was compared and the prolonged apnea by PNE significantly shortened by SR140333. To clarify if the PNE-evoked responses depended on action of nicotinic acetylcholine receptors (nAChRs), particularly α7nAChR, mecamylamine or methyllycaconitine (a general nAChR or a selective α7nAChR antagonist) was administrated via another mini-pump over the PNE period. Mecamylamine or methyllycaconitine eliminated the PNE-evoked mRNA and protein responses. Our data suggest that PNE is able to elevate PCF NK1R expression via activation of nAChRs, especially α7nAChR, which likely contributes to sensitize PCFs and prolong the PCF-mediated apneic response to capsaicin. - Highlights: • PNE upregulated NK1R and TRPV1 gene and protein expression in the N/J ganglia. • PNE only elevated NK1R mRNA in vagal pulmonary C-neurons. • Blockage of peripheral NK1R reduced the PNE-induced PCF sensitization. • PNE induced gene and protein

  5. The constant threat of terrorism: stress levels and coping strategies amongst university students of Karachi.

    Science.gov (United States)

    Ahmed, Ayesha Ejaz; Masood, Komal; Dean, Sohni Vicky; Shakir, Tanzila; Kardar, Ahmed Abdul Hafeez; Barlass, Usman; Imam, Syed Haider; Mohmand, Mohammad Ghawar Khan; Ibrahim, Hussain; Khan, Imad Saeed; Akram, Usman; Hasnain, Farid

    2011-04-01

    To assess the levels of stress in the face of terrorism and the adopted coping strategies, amongst the student population of universities in Karachi. A descriptive, cross sectional study was conducted on undergraduate students from four universities of Karachi. Self-administered questionnaires were filled out by 291 students. Pearson Chi-Square test was used to assess associations between stress levels and different variables at a level of significance of 0.05%. A total of 65.8% of the students had mild stress levels, 91.5% of university students were exposed to terrorism through television, while only 26.5% students reported personal exposure to terrorism. 67.4% students were forbidden by their parents to go out (p = 0.002). Most of those who had self exposure to an attack were the ones whose parents forbade them from going out (p = 0.00). Most commonly used coping strategy was increased faith in religion. Irritability was the most common stress symptom. A majority of students studying in universities of Karachi had mild stress levels due to the constant threat of terrorism whereas a minority had severe stress levels. Possible reasons for resilience and only mild stress levels could be the history of Karachi's internal conflicts and its prolonged duration of being exposed to terrorism. These students who are positive for stress need to be targeted for counseling either through the media or through their universities. More extensive research is needed in this area.

  6. Cognitive abnormalities and neural mechanisms in post-traumatic stress disorder

    Directory of Open Access Journals (Sweden)

    Ting HU

    2017-10-01

    Full Text Available Post-traumatic stress disorder (PTSD is an anxiety disorder that develops usually in response to an overwhelmingly terrifying or a life-threatening event. The symptoms including intrusion, flashback, re-experiencing, hyperarousal and avoidance can seriously impair the cognitive functions. At present, the researches have found PTSD patients had the difficulty in retrieving autobiographical memory and narrative disorder, attention bias toward traumatic stimulus and intellectual decline. Decrease in hippocampus and amygdala's volumes, excess endoplasmic reticulum stress, medial prefrontal cortex's low activation and highly excited response of the amygdala to the traumatic stimulus may be the neural mechanisms of cognitive abnormalities. In- depth research on cognitive abnormalities provides directions for PTSD prevention and treatment, and the cognitive treatment by prolonged exposure and attention control may be the effective method. DOI: 10.11855/j.issn.0577-7402.2017.09.14

  7. Prolonged ultraviolet light-induced erythema and the cutaneous carcinoma phenotype

    International Nuclear Information System (INIS)

    Tanenbaum, L.; Parrish, J.A.; Haynes, H.A.; Fitzpatrick, T.B.; Pathak, M.A.

    1976-01-01

    A considerable amount of evidence exists in support of the role of ultraviolet radiation as a major etiologic factor in human skin cancer, both melanoma and carcinoma types. On the basis of epidemiologic studies a phenotype has been described which helps to identify the persons who are more susceptible to skin cancer. In an attempt to further define this population, patients with cutaneous carcinoma and a normal control group were exposed to artificial ultraviolet light (UVL) and the erythema and tanning responses of each group were measured over a 21-day period. UVL-induced erythema was prolonged in a significantly higher percentage of patients with skin cancer than in control patients, lasting two to three weeks after single exposures to 6 and 8 times the patient's minimal erythema dose. The presence of prolonged erythema correlated with this history of previous skin cancer but did not correlate with other established risk factors for cutaneous carcinoma, i.e., fair skin, light hair and light eyes, easy sunburning and poor tanning, and Celtic ancestry. Prolonged erythema following UVL radiation may therefore represent an additional risk factor and help to identify the skin cancer-susceptible population

  8. Parameters for measurement of oxidative stress in diabetes mellitus: applicability of enzyme-linked immunosorbent assay for clinical evaluation.

    Science.gov (United States)

    Noiri, Eisei; Tsukahara, Hirokazu

    2005-05-01

    Investigations of the mechanisms involved in the onset and progression of diabetes have recently confronted the role of reactive oxygen species (ROS) and oxidative stress. Prolonged exposure to hyperglycemic conditions induces nonenzymatic glycation of protein via the so-called Maillard reaction, resulting in Schiff-base products and Amadori products that engender ROS production. These processes initiate and exacerbate micro- and macrovascular complications in diabetes. Increased oxidative stress is induced by excessive ROS production and inadequate antioxidant defenses. Recently, oxidative stress status markers have been associated directly with the severity and prognosis of diabetes. To examine oxidative stress, reliable and high-throughput methods are needed to examine large numbers of clinical samples. The emerging availability of enzyme-linked immunosorbent assay (ELISA) for oxidative stress status markers allows its application to assessment of various pathophysiologic conditions, including diabetes. This review outlines the recent achievements of ELISA application for clinical studies elucidating oxidative stress. It introduces the potential applicability of ELISA for investigating oxidative stress in diabetes.

  9. Cumulative Exposure to Prior Collective Trauma and Acute Stress Responses to the Boston Marathon Bombings

    OpenAIRE

    Garfin, DR; Holman, EA; Silver, RC

    2015-01-01

    © The Author(s) 2015 The role of repeated exposure to collective trauma in explaining response to subsequent community-wide trauma is poorly understood. We examined the relationship between acute stress response to the 2013 Boston Marathon bombings and prior direct and indirect media-based exposure to three collective traumatic events: the September 11, 2001 (9/11) terrorist attacks, Superstorm Sandy, and the Sandy Hook Elementary School shooting. Representative samples of residents of metrop...

  10. Comparison of exposure to stress and analysis of ways of coping with stress among freight transport and public transport drivers

    Directory of Open Access Journals (Sweden)

    Katarzyna Urbańska

    2016-08-01

    Full Text Available Background: Fast progress in a lot of economic sectors has greatly contributed to a growing role of road transportation systems, including freight transport and passenger transport. The job of professional drivers is regarded as extremely hard and dangerous, it is associated with high risk of health loss and even life loss. This profession is also associated with mental burden, the main cause of the absence at work and alarming number of road accidents. The aim of study was to compare exposure to stress, check the level of stress and ways to cope with stress in 2 groups of drivers (N = 187. Material and Methods: The study was carried out among public transport drivers and freight transport drivers. The authors’ own questionnaire and 2 psychological tests: Perceived Stress Scale (PSS-10 and Posttraumatic Growth Inventory and Inventory to Measure Coping Strategies with Stress (Mini-COPE were used as the study tools. Results: The level of stress is high in both groups, mostly due to a similar type of work. Both groups practice similar ways to cope with stress, but active ways predominate. Conclusions: The work of a professional driver is considered as extremely stressful. The level of stress among professional drivers should be under continuous control. Employers should introduce preventive programs and educate employees about some professional ways to cope with stress. Med Pr 2016;67(4:455–466

  11. Hair cortisol and work stress : Importance of workload and stress model (JDCS or ERI)

    NARCIS (Netherlands)

    van der Meij, L.; Gubbels, N.; Schaveling, J.; Almela, M.; van Vugt, M.

    2018-01-01

    Hair cortisol concentrations (HCCs) are a potential physiological indicator of work related stress. However, studies that tested the relationship between HCC and self-reported stress in a work setting show mixed findings. This may be because few studies used worker samples that experience prolonged

  12. Posttraumatic Stress Symptoms and Nonmedical Prescription Drug Use Among College Students With Trauma Exposure.

    Science.gov (United States)

    Ham, Lindsay S; Wiersma-Mosley, Jacquelyn D; Feldner, Matthew T; Melkonian, Alexander J; Milner, Lauren A; Lewis, Sarah F

    2016-01-01

    Nonmedical prescription drug use, defined as using the drug without a prescription or in ways for which it is not prescribed, and traumatic event exposure are highly prevalent among college students. Despite evidence that posttraumatic stress symptoms could place college students at risk for nonmedical prescription drug problems, no studies have examined this relationship. This study was a preliminary examination of posttraumatic stress symptoms, lifetime nonmedical prescription drug use, hazardous use, and dependence symptoms among college students with trauma exposure. Participants were students attending a rural college in Virginia, recruited through psychology classes, flyers, LISTSERVs, and announcements at student events. All students who reported experiencing at least one traumatic event were included (N = 119); participants' mean age was 19.7 years (SD = 1.90), about half were women (n = 63, 53%), and most were Caucasian (n = 103, 87%). Nearly 60% of participants (n = 71) reported using nonmedical prescription drugs at least once during their lifetime and were more likely than those with no use to report hazardous alcohol use (p drugs. Regression analyses showed that posttraumatic stress symptom frequency was positively associated with hazardous nonmedical prescription drug use, after controlling for gender, depressive symptoms, and hazardous alcohol use (p stress symptom frequency was higher for those with any nonmedical prescription drug dependence symptoms (p drug use. Findings suggest that consideration of the types of behaviors and problems a college student is experiencing related to nonmedical prescription drug use may be more relevant to posttraumatic stress symptom frequency than dichotomous measures of nonmedical prescription drug use alone. Further, the association between the frequency of posttraumatic stress symptoms and both hazardous nonmedical prescription drug use and dependence symptoms among college students with a trauma history

  13. High environmental ammonia exposure has developmental-stage specific and long-term consequences on the cortisol stress response in zebrafish.

    Science.gov (United States)

    Williams, Tegan A; Bonham, Luke A; Bernier, Nicholas J

    2017-12-01

    The capacity for early life environmental stressors to induce programming effects on the endocrine stress response in fish is largely unknown. In this study we determined the effects of high environmental ammonia (HEA) exposure on the stress response in larval zebrafish, assessed the tolerance of embryonic and larval stages to HEA, and evaluated whether early life HEA exposure has long-term consequences on the cortisol response to a novel stressor. Exposure to 500-2000μM NH 4 Cl for 16h did not affect the gene expression of corticotropin-releasing factor (CRF) system components in 1day post-fertilization (dpf) embryos, but differentially increased crfa, crfb and CRF binding protein (crfbp) expression and stimulated both dose- and time-dependent increases in the whole body cortisol of 5dpf larvae. Pre-acclimation to HEA at 1dpf did not affect the cortisol response to a subsequent NH 4 Cl exposure at 5dpf. In contrast, pre-acclimation to HEA at 5dpf caused a small but significant reduction in the cortisol response to a second NH 4 Cl exposure at 10dpf. While continuous exposure to 500-2000μM NH 4 Cl between 0 and 5dpf had a modest effect on mean survival time, exposure to 400-1000μM NH 4 Cl between 10 and 14dpf decreased mean survival time in a dose-dependent manner. Moreover, pre-acclimation to HEA at 5dpf significantly decreased the risk of mortality to continuous NH 4 Cl exposure between 10 and 14dpf. Finally, while HEA at 1dpf did not affect the cortisol stress response to a novel vortex stressor at 5dpf, the same HEA treatment at 5dpf abolished vortex stressor-induced increases in whole body cortisol at 10 and 60dpf. Together these results show that the impact of HEA on the cortisol stress response during development is life-stage specific and closely linked to ammonia tolerance. Further, we demonstrate that HEA exposure at the larval stage can have persistent effects on the capacity to respond to stressors in later life. Copyright © 2017 Elsevier Inc. All

  14. Early growth rates and their relationships to mortalities of five breeds of chickens following exposure to acute gamma radiation stress

    International Nuclear Information System (INIS)

    Latimer, B.E.; Brisbin, I.L. Jr.

    1987-01-01

    Growth and mortality responses were recorded for 541 chicks, representing five different breeds of chickens, following acute exposures to gamma radiation stress at two days of age. Although there were no statistically significant differences in the LD50/30 of the five breeds studied, Cobb broilers showed the highest (1580R) and White Leghorn bantams the lowest (980R) levels, respectively. Other breeds studied included the standard White Leghorn, Athens Randombreds and a strain of feral bantam. Growth rates of body weights were proportionately more depressed by radiation stress than were body sizes, as measured by the lengths of the culmen, tarsus, middle toe and longest primary wing feather of all 32 day-old survivors. Among these structures, the length of the culmen seemed to be the least affected by radiation stress in all of the breeds studied. Feral bantams were able to tolerate the greatest depression in weight gain before exhibiting mortality at exposures below their LD50/30' while Cobb broilers tolerated the greatest depression of weight gain at higher exposure levels. There was a suggestion that those characteristics which were strongly selected for in the course of a particular breed's development were those which experienced the greatest proportional depressions following exposure to gamma radiation stress

  15. Evaluation of benzodiazepines and zolpidem in nails and their stability after prolonged exposure to chlorinated water.

    Science.gov (United States)

    Moretti, Matteo; Andrello, Luisa; Visonà, Silvia; Vignali, Claudia; Groppi, Angelo; Freni, Francesca; Osculati, Antonio; Tajana, Luca; Morini, Luca

    2018-04-15

    The study aims the development and validation of a LC-MS/MS method for the identification and quantification of benzodiazepines and zolpidem in nails as alternative keratinized matrix to hair in long-term monitoring of anxiolytic and hypnotic drugs. Both fingernail and toenail samples (1-2 mm) were collected by clipping the excess overhang of the nail from volunteers and from postmortem cases. They were washed twice with organic solvents, dried under nitrogen stream, pulverized, immersed in a methanol solution (internal standard: diazepam-D5) and sonicated up to two hours. The solution was then direct injected in the LC-MS/MS system. Mass spectrometry was set in MRM mode, selecting two transitions for each substance. 32 analytes among benzodiazepines, metabolites and hypnotics were included in the list. The method fulfilled the internationally required criteria for validation. Limits of detection ranged from 0.03 pg/mg (zolpidem) to 13.1 pg/mg (bromazepam). 9 subjects under therapy were positive at 7 different benzodiazepines and/or metabolites (lorazepam, desalkylflurazepam, bromazepam, diazepam, alprazolam, lormetazepam and prazepam), while 5 molecules were measured in 4 postmortem cases (diazepam, desmethyldiazepam, delorazepam, 7-aminoclonazepam and zolpidem). In vitro experiments on eight authentic samples suggested that benzodiazepines in nails are influenced by the prolonged exposure to chlorinated water. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Monitoring and control of occupational radiation exposure in Switzerland

    International Nuclear Information System (INIS)

    Moser, M.

    1997-01-01

    Occupational exposure is the most prominent example for the prolonged exposure to low level ionizing radiation characterized by low doses and dose rates. In this paper the occupational exposure in Switzerland is presented and the regulatory control of this exposure in the framework of the new radiation protection regulations is discussed. (author)

  17. Sub-acute nickel exposure impairs behavior, alters neuronal microarchitecture, and induces oxidative stress in rats' brain.

    Science.gov (United States)

    Ijomone, Omamuyovwi Meashack; Okori, Stephen Odey; Ijomone, Olayemi Kafilat; Ebokaiwe, Azubike Peter

    2018-02-26

    Nickel (Ni) is a heavy metal with wide industrial uses. Environmental and occupational exposures to Ni are potential risk factors for neurological symptoms in humans. The present study investigated the behavior and histomorphological alterations in brain of rats sub-acutely exposed to nickel chloride (NiCl 2 ) and the possible involvement of oxidative stress. Rats were administered with 5, 10 or 20 mg/kg NiCl 2 via intraperitoneal injections for 21 days. Neurobehavioral assessment was performed using the Y-maze and open field test (OFT). Histomorphological analyses of brain tissues, as well as biochemical determination of oxidative stress levels were performed. Results showed that Ni treatments significantly reduced body weight and food intake. Cognitive and motor behaviors on the Y-maze and OFT, respectively, were compromised following Ni treatments. Administration of Ni affected neuronal morphology in the brain and significantly reduced percentage of intact neurons in both hippocampus and striatum. Additionally, markers of oxidative stress levels and nitric oxide (NO) levels were significantly altered following Ni treatments. These data suggest that compromised behavior and brain histomorphology following Ni exposures is associated with increase in oxidative stress.

  18. Perceived Workplace Stress Is Associated with an Increased Risk of Prostate Cancer before Age 65.

    Science.gov (United States)

    Blanc-Lapierre, Audrey; Rousseau, Marie-Claude; Parent, Marie-Elise

    2017-01-01

    Evidence is lacking regarding the potential role of chronic psychological stress on cancer incidence. The workplace is reported to be the main source of stress among Canadian men. We examined the association between perceived lifetime workplace stress and prostate cancer (PCa) risk in a large case-control study. Cases were 1,933 men, aged ≤ 75 years, newly diagnosed with PCa in 2005-2009 across hospitals in Montreal, Canada. Concurrently, 1994 population controls frequency-matched on age were randomly selected from the electoral list based on cases' residential districts. Detailed lifestyle and work histories (including perceived stress, from any type of work stressor, for each job held) were collected during in-person interviews. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between work-related stress and PCa risk in multivariate analyses. Over the lifetime, 58% of subjects reported at least one job as stressful. Occupations described as stressful were most often among white-collar workers. Perceived workplace stress duration was associated with a higher risk of PCa (OR = 1.12, 95% CI:1.04-1.20 per 10-year increase) among men younger than 65 years, but not among older men. Associations were similar irrespective of PCa aggressiveness. Frequent or recent screening for PCa, age at first exposure and time since exposure to work-related stress, and socioeconomic and lifestyle factors, had little influence on risk estimates. Findings are in line with an association between reporting prolonged workplace stress and an increase in risk of PCa before age 65.

  19. The Effect of Heart Rate on Exposure Window and Best Phase for Stress Perfusion Computed Tomography: Lessons From the CORE320 Study.

    Science.gov (United States)

    Steveson, Chloe; Schuijf, Joanne D; Vavere, Andrea L; Mather, Richard T; Caton, Teresa; Mehra, Vishal; Betoko, Aisha; Cox, Christopher; Lima, Joao Ac; George, Richard T

    The aim of this study is to evaluate the effect of heart rate on exposure window, best phase, and image quality for stress computed tomography perfusion (CTP) in the CORE320 study. The CTP data sets were analyzed to determine the best phase for perfusion analysis. A predefined exposure window covering 75% to 95% of the R-R cycle was used. Of the 368 patients included in the analysis, 93% received oral β blockade before the rest scan. The median heart rate during the stress acquisition was 69 bpm (interquartile range [IQR], 60-77). The median best phase was 81% (IQR, 76-90), and length of exposure window was 22% (IQR, 19-24). The best phase was significantly later in the cardiac cycle with higher heart rates (P stress scan was 5.3 mSv (IQR, 3.8-6.1). Stress myocardial CTP imaging can be performed using prospective electrocardiography triggering, an exposure window of 75% to 95%, and β-blockade resulting in good or excellent image quality in the majority (80%) of patients while maintaining a low effective radiation dose.

  20. The Effect of Parenting Stress on Child Behavior Problems in High-Risk Children with Prenatal Drug Exposure

    Science.gov (United States)

    Bagner, Daniel M.; Sheinkopf, Stephen J.; Miller-Loncar, Cynthia; LaGasse, Linda L.; Lester, Barry M.; Liu, Jing; Bauer, Charles R.; Shankaran, Seetha; Bada, Henrietta; Das, Abhik

    2009-01-01

    Objective: To examine the relationship between early parenting stress and later child behavior in a high-risk sample and measure the effect of drug exposure on the relationship between parenting stress and child behavior. Methods: A subset of child-caregiver dyads (n = 607) were selected from the Maternal Lifestyle Study (MLS), which is a large…

  1. Synergistic interaction between prolonged increased glycemic exposure and mildly increased urinary albumin excretion on diabetic retinopathy.

    Science.gov (United States)

    Moon, Shinje; Yoo, Hyung-Joon; Ahn, You-Hern; Kim, Gheun-Ho; Yu, Jae Myung; Park, Joon-Sung

    2018-01-01

    The association of mild increase in urinary albumin excretion with diabetic retinopathy (DR) in clinical studies is controversial. The aim of this study is to clarify the interaction between increased glycemic exposure and mild increase in urinary albumin excretion on risk of DR.Data were collected from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2012. Overall, data from 953 participants without microalbuminuria (477 men and 476 women) were assessed. Logistic regression analysis was constructed to evaluate the association between DR and related clinical parameters, including urinary albumin-creatinine ratio (UACR, mg/g creatinine). The biological interaction of glycemic status and UACR on DR was evaluated by 3 indices: RERI, the relative excess risk due to the interaction; AP, the attributable proportion due to the interaction; and S, the additive interaction index of synergy.We found that UACR, glycated hemoglobin (HbA1c), and diabetic duration were deeply associated with increased risk of DR (UACR, odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.02-1.07; HbA1c, OR = 1.16, 95% CI = 1.04-1.30; diabetic duration, OR = 1.06, 95% CI = 1.04-1.07). Furthermore, our interaction analysis demonstrated that synergistic interaction between HbA1c and UACR on development of DR was prominent in participants with diabetic duration of ≥10 years (adjusted RERI = 0.92, 95% CI = 0.10-1.74; adjusted AP = 0.29, 95% CI = -0.82-1.41; adjusted S = 1.76, 95% CI = 1.27-2.25), but not subjects with shorter diabetic duration.These findings imply that there is the interaction between prolonged hyperglycemic exposure and increased urinary albumin excretion may exert additive synergistic effect on vascular endothelial dysfunction in the eye, even before the appearance of overt diabetic nephropathy. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  2. Antenatal exposure to Ureaplasma species exacerbates bronchopulmonary dysplasia synergistically with subsequent prolonged mechanical ventilation in preterm infants.

    Science.gov (United States)

    Inatomi, Tadashi; Oue, Shinya; Ogihara, Tohru; Hira, Seigo; Hasegawa, Masashi; Yamaoka, Shigeo; Yasui, Masako; Tamai, Hiroshi

    2012-03-01

    The presence of microorganisms in gastric fluid in neonates at birth is postulated to reflect antenatal infection and also to be associated with the development of bronchopulmonary dysplasia (BPD). A logistic regression analysis, after controlling for other risk factors, indicated that Ureaplasma-positive infants were not at increased risk for moderate/severe BPD (adjusted odds ratio (OR): 2.58, 95% confidence interval (CI): 0.57-6.89, P = 0.12). However, the association between the presence of Ureaplasma species and the risk for moderate/severe BPD increased significantly in infants on mechanical ventilation (MV) ≥2 wk (adjusted OR: 4.17, 95% CI: 1.62-44.1, P = 0.009). An analysis using a lung injury marker indicated that Ureaplasma-positive infants with MV ≥2 wk, but not other infants, showed higher serum KL-6 levels in samples taken from cord blood, and that KL-6 levels increased time-dependently up to 4 wk of age. Antenatal exposure to Ureaplasma species induces lung injury prior to birth and synergistically contributes to the development of BPD in infants requiring prolonged MV (≥2 wk). We recovered gastric fluid specimens from 122 infants with gestational age (GA) Ureaplasma-positive or Ureaplasma-negative infants.

  3. Toxic stress and child refugees.

    Science.gov (United States)

    Murray, John S

    2018-01-01

    The purpose of this article was to describe the phenomenon of toxic stress and its impact on the physical and mental health of child refugees. Almost two decades ago, researchers found that recurring adverse childhood events (ACEs; e.g., physical, psychological, and sexual abuse, neglect, and household dysfunction such as substance abuse, mental illness, and criminal behavior) were associated with a significant increase in serious illnesses during adulthood. Illnesses include heart, lung, and liver disease, cancer, and bone fractures. The scientists reported that experiencing four or more ACEs during childhood significantly increases the risk for toxic stress. Toxic stress is defined as the exposure to extreme, frequent, and persistent adverse events without the presence of a supportive caretaker. There is a paucity of literature related to toxic stress and child refugees. However, it has been clearly established that the prolonged brutal and traumatizing war in Syria is having a profound impact on the physical and mental health of child refugees at a distressing rate. Prevention of toxic stress should be a primary goal of all pediatric healthcare professionals working with child refugees. While this seems daunting given the population, and the seemingly insurmountable stressors they experience, some basic interventions should be considered. Providing basic anticipatory guidance to parents and caregivers of child refugees, to encourage positive parenting and strengthening support networks, will be highly effective in developing the requisite buffers that mitigate the effects of stress and avoid toxic stress. Efforts should also be focused on addressing caregiver stress and improving their ability to provide safe, reliable, and nurturing care that will help to mitigate any stress response experienced by a child. It is critical that greater awareness be placed on the effects of toxic stress on child refugees who are exposed to significant adverse events early in life

  4. Prolonged Exposure of Cortical Neurons to Oligomeric Amyloid-β Impairs NMDA Receptor Function Via NADPH Oxidase-Mediated ROS Production: Protective Effect of Green Tea (--Epigallocatechin-3-Gallate

    Directory of Open Access Journals (Sweden)

    Yan He

    2011-01-01

    Full Text Available Excessive production of Aβ (amyloid β-peptide has been shown to play an important role in the pathogenesis of AD (Alzheimer's disease. Although not yet well understood, aggregation of Aβ is known to cause toxicity to neurons. Our recent study demonstrated the ability for oligomeric Aβ to stimulate the production of ROS (reactive oxygen species in neurons through an NMDA (N-methyl-D-aspartate-dependent pathway. However, whether prolonged exposure of neurons to aggregated Aβ is associated with impairment of NMDA receptor function has not been extensively investigated. In the present study, we show that prolonged exposure of primary cortical neurons to Aβ oligomers caused mitochondrial dysfunction, an attenuation of NMDA receptor-mediated Ca2+ influx and inhibition of NMDA-induced AA (arachidonic acid release. Mitochondrial dysfunction and the decrease in NMDA receptor activity due to oligomeric Aβ are associated with an increase in ROS production. Gp91ds-tat, a specific peptide inhibitor of NADPH oxidase, and Mn(III-tetrakis(4-benzoic acid-porphyrin chloride, an ROS scavenger, effectively abrogated Aβ-induced ROS production. Furthermore, Aβ-induced mitochondrial dysfunction, impairment of NMDA Ca2+ influx and ROS production were prevented by pretreatment of neurons with EGCG [(–-epigallocatechin-3-gallate], a major polyphenolic component of green tea. Taken together, these results support a role for NADPH oxidase-mediated ROS production in the cytotoxic effects of Aβ, and demonstrate the therapeutic potential of EGCG and other dietary polyphenols in delaying onset or retarding the progression of AD.

  5. Time course of systemic oxidative stress and inflammatory response induced by an acute exposure to Residual Oil Fly Ash

    Energy Technology Data Exchange (ETDEWEB)

    Marchini, T.; Magnani, N.D. [Cátedra de Química General e Inorgánica, Instituto de Bioquímica y Medicina Molecular (IBIMOL UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 954, C1113AAB Buenos Aires (Argentina); Paz, M.L. [Cátedra de Inmunología, Instituto de Estudios de la Inmunidad Humoral (IDEHU UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 954, C1113AAB Buenos Aires (Argentina); Vanasco, V. [Cátedra de Química General e Inorgánica, Instituto de Bioquímica y Medicina Molecular (IBIMOL UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 954, C1113AAB Buenos Aires (Argentina); Tasat, D. [CESyMA, Facultad de Ciencia Tecnología, Universidad Nacional de General San Martín, Martín de Irigoyen 3100, 1650 San Martín, Buenos Aires (Argentina); González Maglio, D.H. [Cátedra de Inmunología, Instituto de Estudios de la Inmunidad Humoral (IDEHU UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 954, C1113AAB Buenos Aires (Argentina); and others

    2014-01-15

    It is suggested that systemic oxidative stress and inflammation play a central role in the onset and progression of cardiovascular diseases associated with the exposure to particulate matter (PM). The aim of this work was to evaluate the time changes of systemic markers of oxidative stress and inflammation, after an acute exposure to Residual Oil Fly Ash (ROFA). Female Swiss mice were intranasally instilled with a ROFA suspension (1.0 mg/kg body weight) or saline solution, and plasma levels of oxidative damage markers [thiobarbituric acid reactive substances (TBARSs) and protein carbonyls], antioxidant status [reduced (GSH) and oxidized (GSSG) glutathione, ascorbic acid levels, and superoxide dismutase (SOD) activity], cytokines levels, and intravascular leukocyte activation were evaluated after 1, 3 or 5 h of exposure. Oxidative damage to lipids and decreased GSH/GSSG ratio were observed in ROFA-exposed mice as early as 1 h. Afterwards, increased protein oxidation, decreased ascorbic acid content and SOD activity were found in this group at 3 h. The onset of an adaptive response was observed at 5 h after the ROFA exposure, as indicated by decreased TBARS plasma content and increased SOD activity. The observed increase in oxidative damage to plasma macromolecules, together with systemic antioxidants depletion, may be a consequence of a systemic inflammatory response triggered by the ROFA exposure, since increased TNF-α and IL-6 plasma levels and polymorphonuclear leukocytes activation was found at every evaluated time point. These findings contribute to the understanding of the increase in cardiovascular morbidity and mortality, in association with environmental PM inhalation. - Highlights: • An acute exposure to ROFA triggers the occurrence of systemic oxidative stress. • Changes in plasmatic oxidative stress markers appear as early as 1 h after exposure. • ROFA induces proinflammatory cytokines release and intravascular leukocyte activation. • PMN

  6. Compensation processes of Aleppo pine (Pinus halepensis Mill.) to ozone exposure and drought stress

    International Nuclear Information System (INIS)

    Inclan, R.; Gimeno, B.S.; Dizengremel, P.; Sanchez, M.

    2005-01-01

    A long-term experiment was performed to study the effects of O 3 and drought-stress (DS) on Aleppo pine seedlings (Pinus halepensis Mill.) exposed in open-top chambers. Ozone reduced gas exchange rates, ribulose-1,5-biphosphate carboxylase/oxygenase activity (Rubisco), aboveground C and needle N concentrations and C/N ratio and Ca concentrations of the twigs under 3 mm (twigs Pd ), C/N ratio, twigs<3 Ca, plant growth, aerial biomass and increased N, twigs with a diameter above 3 mm P and Mg concentrations. The combined exposure to both stresses increased N concentrations of twigs<3 and roots and aboveground biomass K content and decreased root C, maximum daily assimilation rate and instantaneous water use efficiency. The sensitivity of Aleppo pine to both stresses is determined by plant internal resource allocation and compensation mechanisms to cope with stress. - Ozone and drought stress induce the activation of similar processes related to C and N metabolism

  7. Maternal posttraumatic stress disorder and depression in pediatric primary care: association with child maltreatment and frequency of child exposure to traumatic events.

    Science.gov (United States)

    Chemtob, Claude M; Gudiño, Omar G; Laraque, Danielle

    2013-11-01

    Maternal posttraumatic stress disorder (PTSD) may be associated with increased risk for child maltreatment and child exposure to traumatic events. Exposure to multiple traumatic events is associated with a wide range of adverse health and social outcomes in children. To examine the association of probable maternal depression, PTSD, and comorbid PTSD and depression with the risk for child maltreatment and parenting stress and with the number of traumatic events to which preschool children are exposed. Cross-sectional observational design. We used analysis of variance to determine whether probable maternal psychopathology groups differed on child maltreatment, parenting stress, and children's exposure to traumatic events. Hierarchical regression analyses were used to examine the unique and interactive effects of depression and PTSD severity scores on these outcomes. Urban pediatric primary care outpatient clinic. Ninety-seven mothers of children aged 3 to 5 years. Pediatric primary care visit. Probable maternal depression and/or PTSD, parenting stress, child exposure to traumatic events, and child maltreatment. Mothers with probable comorbid PTSD and depression reported greater child-directed psychological aggression and physical assault and greater parenting stress. The children of mothers with PTSD (mean number of events the child was exposed to, 5.0) or with comorbid PTSD and depression (3.5 events) experienced more traumatic events than those of mothers with depression (1.2 events) or neither disorder (1.4 events). Severity of depressive symptoms uniquely predicted physical assault and neglect. Symptom scores for PTSD and depression interacted to predict psychological aggression and child exposure to traumatic events. When PTSD symptom severity scores were high, psychological aggression and the number of traumatic events children experienced rose. Depressive symptom severity scores predicted the risk for psychological aggression and exposure to traumatic events

  8. DNA repair and cell cycle biomarkers of radiation exposure and inflammation stress in human blood.

    Directory of Open Access Journals (Sweden)

    Helen Budworth

    Full Text Available DNA damage and repair are hallmarks of cellular responses to ionizing radiation. We hypothesized that monitoring the expression of DNA repair-associated genes would enhance the detection of individuals exposed to radiation versus other forms of physiological stress. We employed the human blood ex vivo radiation model to investigate the expression responses of DNA repair genes in repeated blood samples from healthy, non-smoking men and women exposed to 2 Gy of X-rays in the context of inflammation stress mimicked by the bacterial endotoxin lipopolysaccharide (LPS. Radiation exposure significantly modulated the transcript expression of 12 genes of 40 tested (2.2E-06exposure, and LPS co-treatment significantly affected their radiation responses. At the protein level, BAX and pCHK2-thr68 were elevated after radiation exposure, but the pCHK2-thr68 response was significantly decreased in the presence of LPS. Our combined panel yields an estimated 4-group accuracy of ∼90% to discriminate between radiation alone, inflammation alone, or combined exposures. Our findings suggest that DNA repair gene expression may be helpful to identify biodosimeters of exposure to radiation, especially within high-complexity exposure scenarios.

  9. Effect of Mitochondrial Oxidative Stress and Age on the Signaling Pathway of Ultrafine Particulate Matter Exposure in Murine Aorta

    Science.gov (United States)

    Epidemiological studies have linked ultrafine particulate matter (PM) exposure and adverse cardiovascular events. PM-induced oxidative stress is believed to be a key mechanism contributing to the adverse short-term vascular effects of air pollution exposure. Advanced age is one ...

  10. A New Stress-Based Model of Political Extremism: Personal Exposure to Terrorism, Psychological Distress, and Exclusionist Political Attitudes

    Science.gov (United States)

    Canetti-Nisim, Daphna; Halperin, Eran; Sharvit, Keren; Hobfoll, Stevan E.

    2009-01-01

    Does exposure to terrorism lead to hostility toward minorities? Drawing on theories from clinical and social psychology, we propose a stress-based model of political extremism in which psychological distress--which is largely overlooked in political scholarship--and threat perceptions mediate the relationship between exposure to terrorism and…

  11. Oxidative stress mediated toxicity of TiO2 nanoparticles after a concentration and time dependent exposure of the aquatic macrophyte Hydrilla verticillata.

    Science.gov (United States)

    Spengler, Annette; Wanninger, Lena; Pflugmacher, Stephan

    2017-09-01

    The present study focused on oxidative stress effects in the aquatic macrophyte Hydrilla verticillata after exposure to titanium dioxide nanoparticles (TiO 2 -NPs). Experiments were conducted with different TiO 2 -NPs and concentrations (0.1 mg/L and 10 mg/L) in a time-dependent manner (0 h, 24 h, 48 h, 96 h, 168 h). To assess various levels of the oxidative stress response in H. verticillata, the level of hydrogen peroxide (H 2 O 2 ), the ratio of reduced to oxidized glutathione (GSH/GSSG), and activities of the antioxidative enzymes catalase (CAT) and glutathione reductase (GR) were evaluated. Study results imply oxidative stress effects after TiO 2 -NP exposure as adaptations in plant metabolism became apparent to counteract increased ROS formation. All TiO 2 -NPs caused elevated activities of the enzymes CAT and GR. Moreover, decreased ratios of GSH/GSSG indicated an activation of GSH-dependent pathways counteracting ROS formation. Plants exposed to a bulk-sized control revealed a size-dependent influence on the antioxidative stress response. As H 2 O 2 level increases were solely detected after exposure to 10 mg/L TiO 2 -NPs and nano-exposed plants showed normalization in its antioxidative stress response after 168h of exposure, it can be suggested that macrophytes are able to cope with currently predicted low-level exposures to TiO 2 -NPs. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. OXIDATIVE STRESS-DEPENDENT ALTERED IMMUNE RESPONSES AND CELL DEATH IN SUBSTANTIA NIGRA AFTER OZONE EXPOSURE IN RAT

    Directory of Open Access Journals (Sweden)

    Selva eRivas - Arancibia

    2015-05-01

    Full Text Available Parkinson’s disease has been associated with the selective loss of neurons in the substantia nigra pars compacta. Increasing evidence suggests that oxidative stress plays a major role. The resulting increase in reactive oxygen species triggers a sequence of events that leads to cell damage, activation of microglia cells and neuroinflammatory responses. Our objective was to study whether chronic exposure to low doses of ozone, which produces oxidative stress itself, induces progressive cell death in conjunction with glial alterations in the substantia nigra. Animals were exposed to an ozone-free air stream (control or to low doses of ozone for 7, 15, 30, 60, or 90 days. Each group underwent 1 spectrophotometric analysis for protein oxidation; 2 western blot testing for microglia reactivity and nuclear factor kappa B expression levels; and 3 immunohistochemistry for cytochrome c, GFAP, Iba-1, NFkB and COX-2. Our results indicate that ozone induces an increase in protein oxidation levels, changes in activated astrocytes and microglia, and cell death. NFkB and cytochrome c showed an increase until 30 days of exposure, while cyclooxygenase 2 in the substantia nigra increased from 7 days up to 90 days of repetitive ozone exposure. These results suggest that oxidative stress caused by ozone exposure induces changes in inflammatory responses and progressive cell death in the substantia nigra in rats, which could also be occurring in Parkinson’s disease.

  13. The effects of stress exposure on prefrontal cortex: Translating basic research into successful treatments for post-traumatic stress disorder

    Directory of Open Access Journals (Sweden)

    Amy F.T. Arnsten

    2015-01-01

    Full Text Available Research on the neurobiology of the stress response in animals has led to successful new treatments for Post-Traumatic Stress Disorder (PTSD in humans. Basic research has found that high levels of catecholamine release during stress rapidly impair the top-down cognitive functions of the prefrontal cortex (PFC, while strengthening the emotional and habitual responses of the amygdala and basal ganglia. Chronic stress exposure leads to dendritic atrophy in PFC, dendritic extension in the amygdala, and strengthening of the noradrenergic (NE system. High levels of NE release during stress engage low affinity alpha-1 adrenoceptors, (and likely beta-1 adrenoceptors, which rapidly reduce the firing of PFC neurons, but strengthen amygdala function. In contrast, moderate levels of NE release during nonstress conditions engage higher affinity alpha-2A receptors, which strengthen PFC, weaken amygdala, and regulate NE cell firing. Thus, either alpha-1 receptor blockade or alpha-2A receptor stimulation can protect PFC function during stress. Patients with PTSD have signs of PFC dysfunction. Clinical studies have found that blocking alpha-1 receptors with prazosin, or stimulating alpha-2A receptors with guanfacine or clonidine can be useful in reducing the symptoms of PTSD. Placebo-controlled trials have shown that prazosin is helpful in veterans, active duty soldiers and civilians with PTSD, including improvement of PFC symptoms such as impaired concentration and impulse control. Open label studies suggest that guanfacine may be especially helpful in treating children and adolescents who have experienced trauma. Thus, understanding the neurobiology of the stress response has begun to help patients with stress disorders.

  14. Embryo-larval exposure to atrazine reduces viability and alters oxidative stress parameters in Drosophila melanogaster.

    Science.gov (United States)

    Figueira, Fernanda Hernandes; Aguiar, Lais Mattos de; Rosa, Carlos Eduardo da

    2017-01-01

    The herbicide atrazine has been used worldwide with subsequent residual contamination of water and food, which may cause adverse effects on non-target organisms. Animal exposure to this herbicide may affect development, reproduction and energy metabolism. Here, the effects of atrazine regarding survival and redox metabolism were assessed in the fruit fly D. melanogaster exposed during embryonic and larval development. The embryos (newly fertilized eggs) were exposed to different atrazine concentrations (10μM and 100μM) in the diet until the adult fly emerged. Pupation and emergence rates, developmental time and sex ratio were determined as well as oxidative stress parameters and gene expression of the antioxidant defence system were evaluated in newly emerged male and female flies. Atrazine exposure reduced pupation and emergence rates in fruit flies without alterations to developmental time and sex ratio. Different redox imbalance patterns were observed between males and females exposed to atrazine. Atrazine caused an increase in oxidative damage, reactive oxygen species generation and antioxidant capacity and decreased thiol-containing molecules. Further, atrazine exposure altered the mRNA expression of antioxidant genes (keap1, sod, sod2, cat, irc, gss, gclm, gclc, trxt, trxr-1 and trxr-2). Reductions in fruit fly larval and pupal viability observed here are likely consequences of the oxidative stress induced by atrazine exposure. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Ecotoxicity of bisphenol A to Caenorhabditis elegans by multigenerational exposure and variations of stress response in vivo across generations

    International Nuclear Information System (INIS)

    Zhou, Dong; Yang, Jie; Li, Hui; Lu, Qiang; Liu, Yong-di; Lin, Kuang-fei

    2016-01-01

    In order to understand how bisphenol A (BPA) exposure acts on the evolutionary dynamics of populations and changes of stress response across generations, the model animal Caenorhabditis elegans was used to conduct the multigenerational testing. Multiple endpoints at the physiological (growth, reproduction, and locomotion behaviors) and molecular (stress-related gene expressions) levels were examined by multigenerational exposure to low-concentration BPA (0.001–10 μM) across four generations. The results showed that changes of physiological-level effects across four generations varied in magnitude and direction, depending on the exposure concentrations. C. elegans individuals in the first generation grew smaller, moved slower, and produced less offsprings than the controls by BPA exposure. As for each trait tested, the first generation response could be commonly mirrored in the subsequent generations at the highest concentration of 10 μM. However, at lower concentrations, response of parental generation was a relatively poor predictor of the effects on progeny, as acclimation or cumulative damage could occur in the subsequent generations. The integrated gene expression profiles visually illustrated that the tested gene expressions at low concentrations (0.001–0.01 μM) were more obviously changed in both G_1 and G_4 generations, and the G_1 generation showed a much greater degree of increase in stress-related gene expressions than the G_4 generation. The multigenerational toxicity data emphasize the need of considering biological effects over multiple generations to conduct accurate assessment of environmental risks of toxicants on population dynamics. - Highlights: • Multigenerational exposure was conducted to evaluate effects of BPA on C. elegans. • Changes of biological effects varied in magnitude and direction across generations. • A more significant induction in stress-related gene expressions was found in G_1. • Multigenerational tests have

  16. Prolonged oxidative stress down-regulates Early B cell factor 1 with inhibition of its tumor suppressive function against cholangiocarcinoma genesis

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    Napat Armartmuntree

    2018-04-01

    Full Text Available Early B cell factor 1 (EBF1 is a transcription factor involved in the differentiation of several stem cell lineages and it is a negative regulator of estrogen receptors. EBF1 is down-regulated in many tumors, and is believed to play suppressive roles in cancer promotion and progression. However, the functional roles of EBF1 in carcinogenesis are unclear. Liver fluke-infection-associated cholangiocarcinoma (CCA is an oxidative stress-driven cancer of bile duct epithelium. In this study, we investigated EBF1 expression in tissues from CCA patients, CCA cell lines (KKU-213, KKU-214 and KKU-156, cholangiocyte (MMNK1 and its oxidative stress-resistant (ox-MMNK1-L cell lines. The formation of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG was used as an oxidative stress marker. Our results revealed that EBF1 expression was suppressed in cancer cells compared with the individual normal bile duct cells at tumor adjacent areas of CCA tissues. CCA patients with low EBF1 expression and high formation of 8-oxodG were shown to correlate with poor survival. Moreover, EBF1 was suppressed in the oxidative stress-resistant cell line and all of CCA cell lines compared to the cholangiocyte cell line. This suggests that prolonged oxidative stress suppressed EBF1 expression and the reduced EBF1 level may facilitate CCA genesis. To elucidate the significance of EBF1 suppression in CCA genesis, EBF1 expression of the MMNK1 cell line was down-regulated by siRNA technique, and its effects on stem cell properties (CD133 and Oct3/4 expressions, tumorigenic properties (cell proliferation, wound healing and cell migration, estrogen responsive gene (TFF1, estrogen-stimulated wound healing, and cell migration were examined. The results showed that CD133, Oct3/4 and TFF1 expression levels, wound healing, and cell migration of EBF1 knockdown-MMNK1 cells were significantly increased. Also, cell migration of EBF1-knockdown cells was significantly enhanced after 17

  17. Long-Term Effects of Subchronic Exposure to Sarin, Alone and With Stress or Other Chemicals

    National Research Council Canada - National Science Library

    Abou-Donia, Mohamed

    2002-01-01

    ...) and stress on the development of chronic and neurologic deficits. An important finding from our studies is that brain AChE and plasma BChE inhibition might be used as a biomarker for exposure, not for sarin-induced neurologic deficits...

  18. Effect of prolonged exposure to sublethal concentrations of DDT and DDE on protein expression in human pancreatic beta cells

    Energy Technology Data Exchange (ETDEWEB)

    Pavlikova, Nela, E-mail: nela.pavlikova@lf3.cuni.cz [Department of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague (Czech Republic); Smetana, Pavel [Department of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague (Czech Republic); Halada, Petr [Laboratory of Molecular Structure Characterization, Institute of Microbiology, Academy of Sciences of the Czech Republic, Prague (Czech Republic); Kovar, Jan [Department of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague (Czech Republic)

    2015-10-15

    Pollution of the environment represents one of less explored potential reasons for the worldwide epidemic of type 2 diabetes. One of the most prevalent organochlorine pollutants remains the pesticide DDT and its degradation product DDE. Despite some epidemiologic correlations between levels of DDT and DDE in human organism and the prevalence of diabetes, there is almost no information about the exact targets of these compounds inside pancreatic beta cells. To detect functional areas of pancreatic beta cells that could be affected by exposure to DDT and DDE, we analyzed changes in protein expression in the NES2Y human pancreatic beta cell line exposed to three sublethal concentrations (0.1 μM, 1 μM, 10 μM) of DDT and DDE for 1 month. Protein separation and identification was achieved using high-resolution 2D-electrophoresis, computer analysis and mass spectrometry. With these techniques, four proteins were found downregulated after exposure to 10 μM DDT: three cytoskeletal proteins (cytokeratin 8, cytokeratin 18 and actin) and one protein involved in glycolysis (alpha-enolase). Two proteins were downregulated after exposure to 10 μM DDE: cytokeratin 18 and heterogenous nuclear ribonucleoprotein H1 (HNRH1). These changes correlate with previously described effects of other stress conditions (e.g. exposure to palmitate, hyperglycemia, imidazoline derivative, and cytokines) on protein expression in pancreatic beta cells. We conclude that cytoskeletal proteins and their processing, glucose metabolism, and mRNA processing may represent targets affected by exposure to conditions hostile to pancreatic beta cells, including exposure to DDT and DDE. - Highlights: • Epidemiologic studies connect pollution with incidence of diabetes mellitus. • We explored the effect of DDT and DDE on protein expression in the NES2Y pancreatic beta cell line. • One month exposure to three sublethal concentrations of DDT and DDE was employed. • Expression of alpha-enolase, actin

  19. Effect of prolonged exposure to sublethal concentrations of DDT and DDE on protein expression in human pancreatic beta cells

    International Nuclear Information System (INIS)

    Pavlikova, Nela; Smetana, Pavel; Halada, Petr; Kovar, Jan

    2015-01-01

    Pollution of the environment represents one of less explored potential reasons for the worldwide epidemic of type 2 diabetes. One of the most prevalent organochlorine pollutants remains the pesticide DDT and its degradation product DDE. Despite some epidemiologic correlations between levels of DDT and DDE in human organism and the prevalence of diabetes, there is almost no information about the exact targets of these compounds inside pancreatic beta cells. To detect functional areas of pancreatic beta cells that could be affected by exposure to DDT and DDE, we analyzed changes in protein expression in the NES2Y human pancreatic beta cell line exposed to three sublethal concentrations (0.1 μM, 1 μM, 10 μM) of DDT and DDE for 1 month. Protein separation and identification was achieved using high-resolution 2D-electrophoresis, computer analysis and mass spectrometry. With these techniques, four proteins were found downregulated after exposure to 10 μM DDT: three cytoskeletal proteins (cytokeratin 8, cytokeratin 18 and actin) and one protein involved in glycolysis (alpha-enolase). Two proteins were downregulated after exposure to 10 μM DDE: cytokeratin 18 and heterogenous nuclear ribonucleoprotein H1 (HNRH1). These changes correlate with previously described effects of other stress conditions (e.g. exposure to palmitate, hyperglycemia, imidazoline derivative, and cytokines) on protein expression in pancreatic beta cells. We conclude that cytoskeletal proteins and their processing, glucose metabolism, and mRNA processing may represent targets affected by exposure to conditions hostile to pancreatic beta cells, including exposure to DDT and DDE. - Highlights: • Epidemiologic studies connect pollution with incidence of diabetes mellitus. • We explored the effect of DDT and DDE on protein expression in the NES2Y pancreatic beta cell line. • One month exposure to three sublethal concentrations of DDT and DDE was employed. • Expression of alpha-enolase, actin

  20. Cortisol response mediates the effect of post-reactivation stress exposure on contextualization of emotional memories.

    Science.gov (United States)

    Bos, Marieke G N; Jacobs van Goethem, Tessa H; Beckers, Tom; Kindt, Merel

    2014-12-01

    Retrieval of traumatic experiences is often accompanied by strong feelings of distress. Here, we examined in healthy participants whether post-reactivation stress experience affects the context-dependency of emotional memory. First, participants studied words from two distinctive emotional categories (i.e., war and disease) presented against a category-related background picture. One day later, participants returned to the lab and received a reminder of the words of one emotional category followed by exposure to a stress task (Stress group, n=22) or a control task (Control group, n=24). Six days later, memory contextualization was tested using a word stem completion task. Half of the word stems were presented against the encoding context (i.e., congruent context) and the other half of the word stems were presented against the other context (i.e., incongruent context). The results showed that participants recalled more words in the congruent context than in the incongruent context. Interestingly, cortisol mediated the effect of stress exposure on memory contextualization. The stronger the post-reactivation cortisol response, the more memory performance relied on the contextual embedding of the words. Taken together, the current findings suggest that a moderate cortisol response after memory reactivation might serve an adaptive function in preventing generalization of emotional memories over contexts. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Novel biochemical markers of psychosocial stress in women.

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    Marie Asberg

    Full Text Available BACKGROUND: Prolonged psychosocial stress is a condition assessed through self-reports. Here we aimed to identify biochemical markers for screening and early intervention in women. METHODS: Plasma concentrations of interleukin (IL 1-alpha, IL1-beta, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma (INF-gamma, tumor necrosis factor-alpha (TNF-alpha, monocyte chemotactic protein-1 (MCP-1, epidermal growth factor (EGF, vascular endothelial growth factor (VEGF, thyroid stimulating hormone (TSH, total tri-iodothyronine (TT3, total thyroxine (TT4, prolactin, and testosterone were measured in: 195 women on long-term sick-leave for a stress-related affective disorder, 45 women at risk for professional burnout, and 84 healthy women. RESULTS: We found significantly increased levels of MCP-1, VEGF and EGF in women exposed to prolonged psychosocial stress. Statistical analysis indicates that they independently associate with a significant risk for being classified as ill. CONCLUSIONS: MCP-1, EGF, and VEGF are potential markers for screening and early intervention in women under prolonged psychosocial stress.

  2. Greater physiological and behavioral effects of interrupted stress pattern compared to daily restraint stress in rats.

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    Full Text Available Repeated stress can trigger a range of psychiatric disorders, including anxiety. The propensity to develop abnormal behaviors after repeated stress is related to the severity, frequency and number of stressors. However, the pattern of stress exposure may contribute to the impact of stress. In addition, the anxiogenic nature of repeated stress exposure can be moderated by the degree of coping that occurs, and can be reflected in homotypic habituation to the repeated stress. However, expectations are not clear when a pattern of stress presentation is utilized that diminishes habituation. The purpose of these experiments is to test whether interrupted stress exposure decreases homotypic habituation and leads to greater effects on anxiety-like behavior in adult male rats. We found that repeated interrupted restraint stress resulted in less overall homotypic habituation compared to repeated daily restraint stress. This was demonstrated by greater production of fecal boli and greater corticosterone response to restraint. Furthermore, interrupted restraint stress resulted in a lower body weight and greater adrenal gland weight than daily restraint stress, and greater anxiety-like behavior in the elevated plus maze. Control experiments demonstrated that these effects of the interrupted pattern could not be explained by differences in the total number of stress exposures, differences in the total number of days that the stress periods encompased, nor could it be explained as a result of only the stress exposures after an interruption from stress. These experiments demonstrate that the pattern of stress exposure is a significant determinant of the effects of repeated stress, and that interrupted stress exposure that decreases habituation can have larger effects than a greater number of daily stress exposures. Differences in the pattern of stress exposure are therefore an important factor to consider when predicting the severity of the effects of repeated

  3. An inducer of VGF protects cells against ER stress-induced cell death and prolongs survival in the mutant SOD1 animal models of familial ALS.

    Directory of Open Access Journals (Sweden)

    Masamitsu Shimazawa

    2010-12-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is the most frequent adult-onset motor neuron disease, and recent evidence has suggested that endoplasmic reticulum (ER stress signaling is involved in the pathogenesis of ALS. Here we identified a small molecule, SUN N8075, which has a marked protective effect on ER stress-induced cell death, in an in vitro cell-based screening, and its protective mechanism was mediated by an induction of VGF nerve growth factor inducible (VGF: VGF knockdown with siRNA completely abolished the protective effect of SUN N8075 against ER-induced cell death, and overexpression of VGF inhibited ER-stress-induced cell death. VGF level was lower in the spinal cords of sporadic ALS patients than in the control patients. Furthermore, SUN N8075 slowed disease progression and prolonged survival in mutant SOD1 transgenic mouse and rat models of ALS, preventing the decrease of VGF expression in the spinal cords of ALS mice. These data suggest that VGF plays a critical role in motor neuron survival and may be a potential new therapeutic target for ALS, and SUN N8075 may become a potential therapeutic candidate for treatment of ALS.

  4. Stress affects a gastrin-releasing peptide system in the spinal cord that mediates sexual function: implications for psychogenic erectile dysfunction.

    Directory of Open Access Journals (Sweden)

    Hirotaka Sakamoto

    Full Text Available Many men suffering from stress, including post-traumatic stress disorder (PTSD, report sexual dysfunction, which is traditionally treated via psychological counseling. Recently, we identified a gastrin-releasing peptide (GRP system in the lumbar spinal cord that is a primary mediator for male reproductive functions.To ask whether an acute severe stress could alter the male specific GRP system, we used a single-prolonged stress (SPS, a putative rat model for PTSD in the present study. Exposure of SPS to male rats decreases both the local content and axonal distribution of GRP in the lower lumbar spinal cord and results in an attenuation of penile reflexes in vivo. Remarkably, pharmacological stimulation of GRP receptors restores penile reflexes in SPS-exposed males, and induces spontaneous ejaculation in a dose-dependent manner. Furthermore, although the level of plasma testosterone is normal 7 days after SPS exposure, we found a significant decrease in the expression of androgen receptor protein in this spinal center.We conclude that the spinal GRP system appears to be a stress-vulnerable center for male reproductive functions, which may provide new insight into a clinical target for the treatment of erectile dysfunction triggered by stress and psychiatric disorders.

  5. Intrauterine Exposure to Maternal Stress Alters Bdnf IV DNA Methylation and Telomere Length in the Brain of Adult Rat Offspring

    Science.gov (United States)

    Blaze, Jennifer; Asok, Arun; Borrelli, Kristyn; Tulbert, Christine; Bollinger, Justin; Ronca Finco, April E.; Roth, Tania L.

    2017-01-01

    DNA methylation (addition of methyl groups to cytosines which normally represses gene transcription) and changes in telomere length (TTAGGG repeats on the ends of chromosomes) are two molecular modifications that result from stress and could contribute to the long-term effects of intrauterine exposure to maternal stress on offspring behavioral outcomes. Here, we measured methylation of Brain-derived neurotrophic factor (Bdnf), a gene important in development and plasticity, and telomere length in the brains of adult rat male and female offspring whose mothers were exposed to unpredictable and variable stressors throughout gestation. Males exposed to prenatal stress had greater methylation (Bdnf IV) in the medial prefrontal cortex (mPFC) compared to non-stressed controls. Further, prenatally-stressed males had shorter telomeres than controls in the mPFC. This study provides the first evidence in a rodent model of an association between prenatal stress exposure and subsequent shorter brain telomere length. Together findings indicate a long-term impact of prenatal stress on DNA methylation and telomere biology with relevance for behavioral and health outcomes, and contribute to a growing literature linking stress to intergenerational epigenetic alterations and changes in telomere length.

  6. Perinatal BPA Exposure Induces Hyperglycemia, Oxidative Stress and Decreased Adiponectin Production in Later Life of Male Rat Offspring

    Directory of Open Access Journals (Sweden)

    Shunzhe Song

    2014-04-01

    Full Text Available The main object of the present study was to explore the effect of perinatal bisphenol A (BPA exposure on glucose metabolism in early and later life of male rat offspring, and to establish the potential mechanism of BPA-induced dysglycemia. Pregnant rats were treated with either vehicle or BPA by drinking water at concentrations of 1 and 10 µg/mL BPA from gestation day 6 through the end of lactation. We measured the levels of fasting serum glucose, insulin, adiponectin and parameters of oxidative stress on postnatal day (PND 50 and PND100 in male offspring, and adiponectin mRNA and protein expression in adipose tissue were also examined. Our results showed that perinatal exposure to 1 or 10 µg/mL BPA induced hyperglycemia with insulin resistance on PND100, but only 10 µg/mL BPA exposure had similar effects as early as PND50. In addition, increased oxidative stress and decreased adiponectin production were also observed in BPA exposed male offspring. Our findings indicated that perinatal exposure to BPA resulted in abnormal glucose metabolism in later life of male offspring, with an earlier and more exacerbated effect at higher doses. Down-regulated expression of adiponectin gene and increased oxidative stress induced by BPA may be associated with insulin resistance.

  7. Cumulative Effects of Exposure to Violence on Posttraumatic Stress in Palestinian and Israeli Youth

    Science.gov (United States)

    Dubow, Eric F.; Boxer, Paul; Huesmann, L. Rowell; Landau, Simha; Dvir, Shira; Shikaki, Khalil; Ginges, Jeremy

    2012-01-01

    We examine cumulative and prospective effects of exposure to conflict and violence across four contexts (ethnic-political, community, family, school) on posttraumatic stress (PTS) symptoms in Palestinian and Israeli youth. Interviews were conducted with 600 Palestinian and 901 Israeli (Jewish and Arab) children (ages 8, 11, and 14) and their…

  8. The effect of chronic ozone exposure on the activation of endoplasmic reticulum stress and apoptosis in rat hippocampus

    Directory of Open Access Journals (Sweden)

    Erika Rodríguez-Martínez

    2016-10-01

    Full Text Available The chronic exposure to low doses of ozone, like in environmental pollution, leads to a state of oxidative stress, which has been proposed to contribute to neurodegenerative disorders, including Alzheimer's disease. It induces an increase of calcium in the endoplasmic reticulum (ER, which produces ER stress. On the other hand, different studies show that, in diseases such as Alzheimer’s, there exist disturbances in protein folding where ER plays an important role. The objective of this study was to evaluate the state of chronic oxidative stress on ER stress and its relationship with apoptotic death in the hippocampus of rats exposed to low doses of ozone. We used 108 male Wistar rats randomly divided into five groups. The groups received one of the following treatments: 1 Control (air, 2 Ozone (O3 7 days, 3 O3 15 days, 4 O3 30 days, 5 O3 60 days, and 6 O3 90 days. Two hours after each treatment, the animals were sacrificed and the hippocampus was extracted. Afterwards, the tissue was processed for western blot and immunohistochemistry using the following antibodies: ATF6, GRP8 and caspase 12. It was also performed TUNEL assay and electronic microscopy. Our results show an increase in ATF6, GRP78 and caspase 12 as well as ER ultrastructural alterations and an increase of TUNEL positive cells after 60 and 90 days of exposure to ozone. With the obtained results, we can conclude that oxidative stress induced by chronic exposure to low doses of ozone leads to ER stress. ER stress activates ATF6 inducing the increase of GRP78 in the cytoplasm, which leads to the increase in the nuclear translocation of ATF6. Finally, the translocation creates a vicious cycle that, together with the activation of the cascade for apoptotic cell death, contributes to the maintenance of ER stress. These events potentially contribute in the neurodegeneration processes in diseases like Alzheimer’s Disease.

  9. Violence Exposure, Posttraumatic Stress, and Subjective Well-Being in a Sample of Russian Adults: A Facebook-Based Study.

    Science.gov (United States)

    Bogolyubova, Olga; Tikhonov, Roman; Ivanov, Victor; Panicheva, Polina; Ledovaya, Yanina

    2017-03-01

    Exposure to violence has been shown to negatively affect mental health and well-being. The goal of this Facebook-based study was to describe the rates of exposure to violence in a sample of Russian adults and to assess the impact of these experiences on subjective well-being and victimization-related psychological distress. Three types of victimization were assessed: physical assault by a stranger, physical assault by someone known to victim, and nonconsensual sexual experiences. The 5-item World Health Organization Well-Being Index (WHO-5) was used to assess subjective well-being, and Primary Care PTSD Screen (PC-PTSD) was employed as an indicator of victimization-related psychological distress. Data were obtained from 6,724 Russian-speaking Facebook users. Significant levels of lifetime victimization were reported by the study participants. Lifetime physical assault by a stranger, physical assault by someone known to victim, and sexual assault were reported by 56.9%, 64.2%, and 54.1% of respondents, respectively. Respondents exposed to violence were more likely to report posttraumatic stress symptoms and lower levels of subjective well-being. Participants who were exposed to at least one type of violence were more likely to experience symptoms of traumatic stress ( U = 1,794,250.50, p violence was associated with more severe traumatic stress symptoms ( r s = .257, p violence ( t = 8.37, p violence exposure is associated with reduced well-being among Russian adults. Our findings highlight the negative impact of violence exposure on subjective well-being and underscore the necessity to develop programs addressing violence exposure in Russian populations.

  10. Hypoxic ventilatory sensitivity in men is not reduced by prolonged hyperoxia (Predictive Studies V and VI)

    Science.gov (United States)

    Gelfand, R.; Lambertsen, C. J.; Clark, J. M.; Hopkin, E.

    1998-01-01

    Potential adverse effects on the O2-sensing function of the carotid body when its cells are exposed to toxic O2 pressures were assessed during investigations of human organ tolerance to prolonged continuous and intermittent hyperoxia (Predictive Studies V and VI). Isocapnic hypoxic ventilatory responses (HVR) were determined at 1.0 ATA before and after severe hyperoxic exposures: 1) continuous O2 breathing at 1.5, 2.0, and 2.5 ATA for 17.7, 9.0, and 5.7 h and 2) intermittent O2 breathing at 2.0 ATA (30 min O2-30 min normoxia) for 14.3 O2 h within 30-h total time. Postexposure curvature of HVR hyperbolas was not reduced compared with preexposure controls. The hyperbolas were temporarily elevated to higher ventilations than controls due to increments in respiratory frequency that were proportional to O2 exposure time, not O2 pressure. In humans, prolonged hyperoxia does not attenuate the hypoxia-sensing function of the peripheral chemoreceptors, even after exposures that approach limits of human pulmonary and central nervous system O2 tolerance. Current applications of hyperoxia in hyperbaric O2 therapy and in subsea- and aerospace-related operations are guided by and are well within these exposure limits.

  11. Differential effects of 5-HTTLPR genotypes on mood, memory, and attention bias following acute tryptophan depletion and stress exposure.

    Science.gov (United States)

    Firk, Christine; Markus, C Rob

    2009-05-01

    Polymorphisms of the serotonin transporter gene (5-HTTLPR) may be associated with increased vulnerability to acute tryptophan depletion (ATD) and depression vulnerability especially following stressful life events. The aim of the present study was to investigate the effects of ATD in subjects with different 5-HTTLPR profiles before and after stress exposure on affective and cognitive-attentional changes. Eighteen subjects with homozygotic short alleles (S'/S') and 17 subjects with homozygotic long alleles (L'/L') of the 5-HTTLPR participated in a double-blind, placebo-controlled, crossover design to measure the effects of ATD on mood, memory, and attention before and after acute stress exposure. ATD lowered mood in all subjects independent of genotype. In S'/S' genotypes, mild acute stress increased depressive mood and in L'/L' genotypes increased feelings of vigor. Furthermore, S'/S' genotypes differed from L'/L' genotypes on measures of attention independent of treatment and memory following ATD. Polymorphisms of the 5-HTTLPR differentially affect responses to mild stress and ATD, suggesting greater vulnerability of S'/S' carriers to serotonergic manipulations and supporting increased depression vulnerability.

  12. Low Vagal Tone Magnifies the Association Between Psychosocial Stress Exposure and Internalizing Psychopathology in Adolescents

    Science.gov (United States)

    McLaughlin, Katie A.; Rith-Najarian, Leslie; Dirks, Melanie A.; Sheridan, Margaret A.

    2014-01-01

    Vagal tone is a measure of cardiovascular function that facilitates adaptive responses to environmental challenge. Low vagal tone is associated with poor emotional and attentional regulation in children and has been conceptualized as a marker of sensitivity to stress. We investigated whether the associations of a wide range of psychosocial stressors with internalizing and externalizing psychopathology were magnified in adolescents with low vagal tone. Resting heart period data were collected from a diverse community sample of adolescents (ages 13–17; N =168). Adolescents completed measures assessing internalizing and externalizing psychopathology and exposure to stressors occurring in family, peer, and community contexts. Respiratory sinus arrhythmia (RSA) was calculated from the interbeat interval time series. We estimated interactions between RSA and stress exposure in predicting internalizing and externalizing symptoms and evaluated whether interactions differed by gender. Exposure to psychosocial stressors was associated strongly with psychopathology. RSA was unrelated to internalizing or externalizing problems. Significant interactions were observed between RSA and child abuse, community violence, peer victimization, and traumatic events in predicting internalizing but not externalizing symptoms. Stressors were positively associated with internalizing symptoms in adolescents with low RSA but not in those with high RSA. Similar patterns were observed for anxiety and depression. These interactions were more consistently observed for male than female individuals. Low vagal tone is associated with internalizing psychopathology in adolescents exposed to high levels of stressors. Measurement of vagal tone in clinical settings might provide useful information about sensitivity to stress in child and adolescent clients. PMID:24156380

  13. Effects of Prolonged Silver Nanoparticle Exposure on the Contextual Cognition and Behavior of Mammals

    Directory of Open Access Journals (Sweden)

    Anna Antsiferova

    2018-04-01

    Full Text Available Silver nanoparticles have been widely used in the lighting and food industries, in medicine, and in pharmaceutics as an antiseptic agent. Recent research demonstrates that, after prolonged oral administration, silver nanoparticles may cross the blood-brain barrier and accumulate in the brain in rather high amounts. In ex vivo experiments, it has also been shown that silver nanoparticles demonstrate neurotoxicity. The objective of this work was to answer the questions whether silver nanoparticles change cognitive and behavioral functions of mammals after prolonged administration if silver nanoparticles have accumulated in the brain. C57Bl/6 male mice were orally exposed to PVP-coated silver nanoparticles daily for 30, 60, 120 and 180 days. Control mice were exposed to distilled water. After that they were tested in the Open Field, Elevated Plus Maze, Light-Dark Box and contextual fear conditioning task. The data have shown that the experimental mice went through three periods of switching in the behavior caused by adaptation to the toxic silver nanoparticles: anxiety, appearance of research instinct and impairment of long-term memory. This provides evidence of the hazardous effect of silver nanoparticles, which appears after long periods of silver nanoparticle oral administration.

  14. The role of peri-traumatic stress and disruption distress in predicting symptoms of major depression following exposure to a natural disaster.

    Science.gov (United States)

    Bell, Caroline J; Boden, Joseph M; Horwood, L John; Mulder, Roger T

    2017-07-01

    Few studies have examined the contribution of specific disaster-related experiences to symptoms of depression. The aims of this study were to do this by examining the roles of peri-traumatic stress and distress due to lingering disaster-related disruption in explaining linkages between disaster exposure and major depressive disorder symptoms among a cohort exposed to the 2010-2011 Canterbury (New Zealand) earthquakes. Structural equation models were fitted to data obtained from the Christchurch Health and Development Study at age 35 ( n = 495), 20-24 months following the onset of the disaster. Measures included earthquake exposure, peri-traumatic stress, disruption distress and symptoms of major depressive disorder. The associations between earthquake exposure and major depression were explained largely by the experience of peri-traumatic stress during the earthquakes (β = 0.180, p < 0.01) and not by disruption distress following the earthquakes (β = 0.048, p = 0.47). The results suggest that peri-traumatic stress has been under-recognised as a predictor of major depressive disorder.

  15. Eggshell appearance does not signal maternal corticosterone exposure in Japanese quail: an experimental study with brown-spotted eggs.

    Directory of Open Access Journals (Sweden)

    Camille Duval

    Full Text Available Reproduction is a critical period for birds as they have to cope with many stressful events. One consequence of an acute exposure to stress is the release of corticosterone, the avian stress hormone. Prolonged stress can have negative impacts on the immune system, resulting in, for example, increased oxidative stress. Through maternal effects, females are known to modulate their investment in eggs content according to their own physiological condition. Less is known about maternal investment in eggshells, especially in pigments. The two main eggshell pigments may possess opposite antioxidant properties: protoporphyrin (brown is a pro-oxidant, whereas biliverdin (blue-green is an antioxidant. In Japanese quail, we know that the deposition of both pigments is related to female body condition. Thus, a chronic stress response may be reflected in eggshell coloration. Using female Japanese quails that lay brown-spotted eggs, we explored whether physiological exposure to corticosterone induces a change in female basal stress and antioxidant factors, and eggshell pigment concentration, spectrophotometric reflectance, and maculation coverage. We supplemented adult females over a 2 week period with either peanut oil (control or corticosterone (treatment. We collected pre- and post-supplementation eggs and analysed the effect of corticosterone treatment on female physiology and eggshell appearance parameters. Except for corticosterone-fed birds which laid eggs with brighter spots, supplementation had no significant effect on female physiology or eggshell pigment concentration, reflectance and maculation. The change in eggshell spot brightness was not detected by a photoreceptor noise-limited color opponent model of avian visual perception. Our data confirms that eggshell reflectance in spotted eggs varies over the laying sequence, and spot reflectance may be a key factor that is affected by females CORT exposure, even if the changes are not detected by an

  16. The Mind-Body Connection - Can Prolonged Stress Affect Whether Breast Cancer Returns?

    Science.gov (United States)

    ... traumatic stress to some stress to no significant stress. According to David Spiegel, M.D., one of the study's authors and a faculty member at the Stanford University School of Medicine, there were marked differences. "Comparisons ...

  17. Narrative reconstruction therapy for prolonged grief disorder—rationale and case study

    Directory of Open Access Journals (Sweden)

    Tuvia Peri

    2016-05-01

    Full Text Available Background: Prolonged grief disorder (PGD is a potentially disabling condition affecting approximately 10% of bereaved people. It has been suggested that the impaired integration of the loss memory, as expressed in recurrent memories of the loss and disorganization of memory, is involved in the development of PGD. Narrative reconstruction (NR, originally designed for the treatment of posttraumatic stress disorder (PTSD in an integrative therapy module, and consisting of exposure to the loss memory, detailed written reconstruction of the loss memory narrative and an elaboration of the personal significance of that memory for the bereaved, has been shown to be effective in the treatment of intrusion symptoms. Objective: In light of findings that cognitive behavior therapy (CBT, including cognitive restructuring and exposure, is effective in the treatment of PGD, we suggest the implementation of a somewhat novel therapy module, NR, for the treatment of intrusive phenomena in bereaved patients. Method: The rationale for the implementation of NR for PGD and a case study of the treatment of a woman suffering from PGD after the death of her father are presented. Therapy took place in a university outpatient training clinic. Results: Evaluations conducted before and after treatment and at a 3-month follow-up demonstrated the effectiveness of NR in reducing symptoms of PGD and depression. The analysis of spontaneous narratives recorded before and after treatment showed an increased organization of the narratives. Conclusions: This case report demonstrates an adaptation of NR for the treatment of PGD. The results provide preliminary support for the effectiveness of NR for PGD. The significance of the study and its limitations are discussed.

  18. Stress Exposure in Significant Relationships Is Associated with Lymph Node Status in Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Chiara Renzi

    Full Text Available Life stress exposure may impact on health and disease. Previous literature showed that stressful life events are associated with cancer incidence, survival and mortality. In animal models, patterns of maternal care have been shown to critically affect stress sensitivity and immunity trajectories later in life, by modifying DNA methylation during critical periods early in life. However, the role of parental care in breast cancer progression and survival has only limitedly been explored. Here, we investigated whether these factors may be linked to biological prognostic variables.One hundred twenty-three women hospitalized for surgery of primary breast cancer completed a questionnaire assessing parental bonding. Stressful events throughout the life span were also assessed.We found that the absence of optimal parental relationships is significantly associated with an increased risk of lymph node involvement, adjusting for confounders, while cumulative stress in the area of sentimental relationships is borderline significantly associated with the same prognostic factor.Our results suggest that parental bonding and sentimental relations may have a role in breast cancer progression. These variables represent an important evolutionary aspect which may modulate cancer progression through psycho-physiological stress pathways and influence the immune system.

  19. Persistent effects of prior chronic exposure to corticosterone on reward-related learning and motivation in rodents.

    Science.gov (United States)

    Olausson, Peter; Kiraly, Drew D; Gourley, Shannon L; Taylor, Jane R

    2013-02-01

    Repeated or prolonged exposure to stress has profound effects on a wide spectrum of behavioral and neurobiological processes and has been associated with the pathophysiology of depression. The multifaceted nature of this disorder includes despair, anhedonia, diminished motivation, and disrupted cognition, and it has been proposed that depression is also associated with reduced reward-motivated learning. We have previously reported that prior chronic corticosterone exposure to mice produces a lasting depressive-like state that can be reversed by chronic antidepressant treatment. In the present study, we tested the effects of prior chronic exposure to corticosterone (50 μg/ml) administered to rats or to mice in drinking water for 14 days followed by dose-tapering over 9 days. The exposure to corticosterone produced lasting deficits in the acquisition of reward-related learning tested on a food-motivated instrumental task conducted 10-20 days after the last day of full dose corticosterone exposure. Rats exposed to corticosterone also displayed reduced responding on a progressive ratio schedule of reinforcement when tested on day 21 after exposure. Amitriptyline (200 mg/ml in drinking water) exposure for 14 days to mice produced the opposite effect, enhancing food-motivated instrumental acquisition and performance. Repeated treatment with amitriptyline (5 mg/kg, intraperitoneally; bid) subsequent to corticosterone exposure also prevented the corticosterone-induced deficits in rats. These results are consistent with aberrant reward-related learning and motivational processes in depressive states and provide new evidence that stress-induced neuroadaptive alterations in cortico-limbic-striatal brain circuits involved in learning and motivation may play a critical role in aspects of mood disorders.

  20. Neuronal cellular responses to extremely low frequency electromagnetic field exposure: implications regarding oxidative stress and neurodegeneration.

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    Marcella Reale

    Full Text Available Neurodegenerative diseases comprise both hereditary and sporadic conditions characterized by an identifying progressive nervous system dysfunction and distinctive neuopathophysiology. The majority are of non-familial etiology and hence environmental factors and lifestyle play key roles in their pathogenesis. The extensive use of and ever increasing worldwide demand for electricity has stimulated societal and scientific interest on the environmental exposure to low frequency electromagnetic fields (EMFs on human health. Epidemiological studies suggest a positive association between 50/60-Hz power transmission fields and leukemia or lymphoma development. Consequent to the association between EMFs and induction of oxidative stress, concerns relating to development of neurodegenerative diseases, such as Alzheimer disease (AD, have been voiced as the brain consumes the greatest fraction of oxygen and is particularly vulnerable to oxidative stress. Exposure to extremely low frequency (ELF-EMFs are reported to alter animal behavior and modulate biological variables, including gene expression, regulation of cell survival, promotion of cellular differentiation, and changes in cerebral blood flow in aged AD transgenic mice. Alterations in inflammatory responses have also been reported, but how these actions impact human health remains unknown. We hence evaluated the effects of an electromagnetic wave (magnetic field intensity 1 mT; frequency, 50-Hz on a well-characterized immortalized neuronal cell model, human SH-SY5Y cells. ELF-EMF exposure elevated the expession of NOS and O2(-, which were countered by compensatory changes in antioxidant catylase (CAT activity and enzymatic kinetic parameters related to CYP-450 and CAT activity. Actions of ELF-EMFs on cytokine gene expression were additionally evaluated and found rapidly modified. Confronted with co-exposure to H2O2-induced oxidative stress, ELF-EMF proved not as well counteracted and resulted in a

  1. Good stress, bad stress and oxidative stress: insights from anticipatory cortisol reactivity.

    Science.gov (United States)

    Aschbacher, Kirstin; O'Donovan, Aoife; Wolkowitz, Owen M; Dhabhar, Firdaus S; Su, Yali; Epel, Elissa

    2013-09-01

    Chronic psychological stress appears to accelerate biological aging, and oxidative damage is an important potential mediator of this process. However, the mechanisms by which psychological stress promotes oxidative damage are poorly understood. This study investigates the theory that cortisol increases in response to an acutely stressful event have the potential to either enhance or undermine psychobiological resilience to oxidative damage, depending on the body's prior exposure to chronic psychological stress. In order to achieve a range of chronic stress exposure, forty-eight post-menopausal women were recruited in a case-control design that matched women caring for spouses with dementia (a chronic stress model) with similarly aged control women whose spouses were healthy. Participants completed a questionnaire assessing perceived stress over the previous month and provided fasting blood. Three markers of oxidative damage were assessed: 8-iso-prostaglandin F(2α) (IsoP), lipid peroxidation, 8-hydroxyguanosine (8-oxoG) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), reflecting oxidative damage to RNA/DNA respectively. Within approximately one week, participants completed a standardized acute laboratory stress task while salivary cortisol responses were measured. The increase from 0 to 30 min was defined as "peak" cortisol reactivity, while the increase from 0 to 15 min was defined as "anticipatory" cortisol reactivity, representing a cortisol response that began while preparing for the stress task. Women under chronic stress had higher 8-oxoG, oxidative damage to RNA (pstress and elevated oxidative stress damage, but only among women under chronic stress. Consistent with this model, bootstrapped path analysis found significant indirect paths from perceived stress to 8-oxoG and IsoP (but not 8-OHdG) via anticipatory cortisol reactivity, showing the expected relations among chronically stressed participants (p≤.01) Intriguingly, among those with low chronic stress

  2. Oxidative stress induces senescence in human mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Brandl, Anita [Department of Anesthesiology, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg (Germany); Meyer, Matthias; Bechmann, Volker [Department of Trauma Surgery, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg (Germany); Nerlich, Michael [Department of Anesthesiology, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg (Germany); Angele, Peter, E-mail: Peter.Angele@klinik.uni-regensburg.de [Department of Trauma Surgery, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg (Germany)

    2011-07-01

    Mesenchymal stem cells (MSCs) contribute to tissue repair in vivo and form an attractive cell source for tissue engineering. Their regenerative potential is impaired by cellular senescence. The effects of oxidative stress on MSCs are still unknown. Our studies were to investigate into the proliferation potential, cytological features and the telomere linked stress response system of MSCs, subject to acute or prolonged oxidant challenge with hydrogen peroxide. Telomere length was measured using the telomere restriction fragment assay, gene expression was determined by rtPCR. Sub-lethal doses of oxidative stress reduced proliferation rates and induced senescent-morphological features and senescence-associated {beta}-galactosidase positivity. Prolonged low dose treatment with hydrogen peroxide had no effects on cell proliferation or morphology. Sub-lethal and prolonged low doses of oxidative stress considerably accelerated telomere attrition. Following acute oxidant insult p21 was up-regulated prior to returning to initial levels. TRF1 was significantly reduced, TRF2 showed a slight up-regulation. SIRT1 and XRCC5 were up-regulated after oxidant insult and expression levels increased in aging cells. Compared to fibroblasts and chondrocytes, MSCs showed an increased tolerance to oxidative stress regarding proliferation, telomere biology and gene expression with an impaired stress tolerance in aged cells.

  3. Dietary antioxidant and anti-inflammatory intake modifies the effect of cadmium exposure on markers of systemic inflammation and oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Colacino, Justin A.; Arthur, Anna E.; Ferguson, Kelly K.; Rozek, Laura S., E-mail: rozekl@umich.edu

    2014-05-01

    Chronic cadmium exposure may cause disease through induction of systemic oxidative stress and inflammation. Factors that mitigate cadmium toxicity and could serve as interventions in exposed populations have not been well characterized. We used data from the 2003–2010 National Health and Nutrition Examination Survey to quantify diet's role in modifying associations between cadmium exposure and oxidative stress and inflammation. We created a composite antioxidant and anti-inflammatory diet score (ADS) by ranking participants by quintile of intake across a panel of 19 nutrients. We identified associations and effect modification between ADS, urinary cadmium, and markers of oxidative stress and inflammation by multiple linear regression. An interquartile range increase in urinary cadmium was associated with a 47.5%, 8.8%, and 3.7% increase in C-reactive protein (CRP), gamma glutamyl transferase (GGT), and alkaline phosphatase (ALP), respectively. An interquartile range increase in ADS was associated with an 7.4%, 3.3%, 5.2%, and 2.5% decrease in CRP, GGT, ALP, and total white blood cell count respectively, and a 3.0% increase in serum bilirubin. ADS significantly attenuated the association between cadmium exposure, CRP and ALP. Dietary interventions may provide a route to reduce the impact of cadmium toxicity on the population level. - Highlights: • Cadmium may cause chronic disease through oxidative stress or inflammation. • We developed a score to quantify dietary antioxidant and anti-inflammatory intake. • Cadmium was associated with markers of oxidative stress and inflammation. • Antioxidant and anti-inflammatory intake mitigated the effects of cadmium exposure. • Dietary interventions may be effective against chronic cadmium toxicity.

  4. Dietary antioxidant and anti-inflammatory intake modifies the effect of cadmium exposure on markers of systemic inflammation and oxidative stress

    International Nuclear Information System (INIS)

    Colacino, Justin A.; Arthur, Anna E.; Ferguson, Kelly K.; Rozek, Laura S.

    2014-01-01

    Chronic cadmium exposure may cause disease through induction of systemic oxidative stress and inflammation. Factors that mitigate cadmium toxicity and could serve as interventions in exposed populations have not been well characterized. We used data from the 2003–2010 National Health and Nutrition Examination Survey to quantify diet's role in modifying associations between cadmium exposure and oxidative stress and inflammation. We created a composite antioxidant and anti-inflammatory diet score (ADS) by ranking participants by quintile of intake across a panel of 19 nutrients. We identified associations and effect modification between ADS, urinary cadmium, and markers of oxidative stress and inflammation by multiple linear regression. An interquartile range increase in urinary cadmium was associated with a 47.5%, 8.8%, and 3.7% increase in C-reactive protein (CRP), gamma glutamyl transferase (GGT), and alkaline phosphatase (ALP), respectively. An interquartile range increase in ADS was associated with an 7.4%, 3.3%, 5.2%, and 2.5% decrease in CRP, GGT, ALP, and total white blood cell count respectively, and a 3.0% increase in serum bilirubin. ADS significantly attenuated the association between cadmium exposure, CRP and ALP. Dietary interventions may provide a route to reduce the impact of cadmium toxicity on the population level. - Highlights: • Cadmium may cause chronic disease through oxidative stress or inflammation. • We developed a score to quantify dietary antioxidant and anti-inflammatory intake. • Cadmium was associated with markers of oxidative stress and inflammation. • Antioxidant and anti-inflammatory intake mitigated the effects of cadmium exposure. • Dietary interventions may be effective against chronic cadmium toxicity

  5. Effect of environmental enrichment exposure on neuronal morphology of streptozotocin-induced diabetic and stressed rat hippocampus

    Directory of Open Access Journals (Sweden)

    Narendra Pamidi

    2014-08-01

    Full Text Available Background: Environmental enrichment (EE exposure is known to influence the structural changes in the neuronal network of hippocampus. In the present study, we evaluated the effects of EE exposure on the streptozotocin (STZ-induced diabetic and stressed rat hippocampus. Methods: Male albino rats of Wistar strain (4-5 weeks old were grouped into normal control (NC, vehicle control (VC, diabetes (DI, diabetes + stress (DI + S, diabetes + EE (DI + E, and diabetes + stress + EE (DI + S + E groups (n = 8 in each group. Rats were exposed to stress and EE after inducing diabetes with STZ (40 mg/kg. Rats were sacrificed on Day 30 and brain sections were processed for cresyl violet staining to quantify the number of surviving neurons in the CA1, CA3, and dentate hilus (DH regions of hippocampus. Results: A significant (p < 0.001 decrease in the number of survived neurons was noticed in DI (CA1, 34.06 ± 3.2; CA3, 36.1 ± 3.62; DH, 9.83 ± 2.02 as well as DI + S (CA1, 14.03 ± 3.12; CA3, 20.27 ± 4.09; DH, 6.4 ± 1.21 group rats compared to NC rats (CA1, 53.64 ± 2.96; CA3, 62.1 ± 3.34; DH, 21.11 ± 1.03. A significant (p < 0.001 increase in the number of survived neurons was observed in DI + E (CA1, 42.3 ± 3.66; CA3, 46.73 ± 4.74; DH, 17.03 ± 2.19 and DI + S + E (CA1, 29.69 ± 4.47; CA3, 36.73 ± 3.89; DH, 12.23 ± 2.36 group rats compared to DI and DI + S groups, respectively. Conclusions: EE exposure significantly reduced the amount of neuronal damage caused by complications of diabetes and stress to the neurons of hippocampus.

  6. Long-term effects of prenatal atrazine exposure on physiology, body composition, and stress reactivity in rats

    Science.gov (United States)

    Low birth weight in humans is associated with increased risk of coronary heart disease, hypertension, and diabetes in adulthood. Experimental studies have also reported that undernutrition, stress or exposure to glucocorticoids during pregnancy is associated with hypertension, gl...

  7. Sugar consumption produces effects similar to early life stress exposure on hippocampal markers of neurogenesis and stress response

    Directory of Open Access Journals (Sweden)

    Jayanthi eManiam

    2016-01-01

    Full Text Available Adverse early life experience is a known risk factor for psychiatric disorders. It is also known that stress influences food preference. We were interested in exploring whether the choice of diet following early life stress exerts long-lasting molecular changes in the brain, particularly the hippocampus, a region critically involved in stress regulation and behavioural outcomes. Here, we examined the impact of early life stress induced by limited nesting material (LN and chronic sucrose availability post-weaning on an array of hippocampal genes related to plasticity, neurogenesis, stress and inflammatory responses and mitochondrial biogenesis. To examine mechanisms underlying the impact of LN and sugar intake on hippocampal gene expression, we investigated the role of DNA methylation. As females are more likely to experience adverse life events, we studied female Sprague-Dawley rats. After mating LN was imposed from days 2-9 postpartum. From 3-15 weeks of age, female Control and LN siblings had unlimited to access to either chow and water, or chow, water and 25% sucrose solution. LN markedly reduced glucocorticoid receptor (GR and neurogenic differentiation 1 (Neurod1 mRNA, markers involved in stress and hippocampal plasticity respectively, by more than 40%, with a similar effect of sugar intake in control rats. However, no further impact was observed in LN rats consuming sugar. Hippocampal Akt3 mRNA expression was similarly affected by LN and sucrose consumption. Interestingly, DNA methylation across 4 CpG sites of the GR and Neurod1 promoters was similar in LN and control rats. In summary, early life stress and post-weaning sugar intake produced long-term effects on hippocampal GR and Neurod1 expression. Moreover we found no evidence of altered promoter DNA methylation. We demonstrate for the first time that chronic sucrose consumption alone produces similar detrimental effects on the expression of hippocampal genes as LN exposure.

  8. Impact of Workplace Exposure and Stress on Neck Pain and Disabilities in Women-A Longitudinal Follow-up After a Rehabilitation Intervention.

    Science.gov (United States)

    Svedmark, Åsa; Björklund, Martin; Häger, Charlotte K; Sommar, Johan Nilsson; Wahlström, Jens

    2018-05-28

    The aim was to evaluate if pain, disability, and work productivity are influenced by physical and psychosocial work exposures as well as by stress, up to 1 year after a randomized controlled trial treatment intervention, and to determine whether any such association differed between treatment and control groups. Ninety-seven working women suffering non-specific neck pain (n = 67 treatment group, n = 30 control group) were followed from end of treatment intervention and at 9- and 15-month follow-ups, respectively. Physical and psychosocial exposures, as well as perceived stress, were assessed after the treatment intervention. Pain, neck disability, and work productivity were assessed at baseline, after intervention 3 months later and at 9- and 15-month follow-ups. Longitudinal assessment was conducted using the exposure level at 3 months as predictor of pain, disability, and work productivity at 3, 9, and 15 months, respectively. Mixed models were used to estimate longitudinal associations, accounting for within-individual correlation of repeated outcome measures by incorporation of a random intercept. Age and duration of neck pain were adjusted for in all models. To evaluate group differences, interactions between exposures and treatment groups were estimated. High perceived stress was associated with more neck pain, more neck disability, and decreased work productivity in both cross-sectional and longitudinal analyses. High 'control of decision' was associated with less neck pain, less neck disability, and higher work productivity in cross-sectional analyses but only to less disability and higher productivity in longitudinal analyses. Shoulder/arm load was the only physical exposure variable that was significantly associated with work productivity in the univariate analyses. Only small differences were observed between treatment and control groups. High perceived stress and low 'control of decision' were associated with more neck pain, increased neck disability

  9. Exposure to Political Conflict and Violence and Posttraumatic Stress in Middle East Youth: Protective Factors

    Science.gov (United States)

    Dubow, Eric F.; Huesmann, L. Rowell; Boxer, Paul; Landau, Simha; Dvir, Shira; Shikaki, Khalil; Ginges, Jeremy

    2012-01-01

    We examine the role of family- and individual-level protective factors in the relation between exposure to ethnic-political conflict and violence and posttraumatic stress among Israeli and Palestinian youth. Specifically, we examine whether parental mental health (lack of depression), positive parenting, children's self-esteem, and academic…

  10. Quantifying Cyclic Thermal Stresses Due to Solar Exposure in Rock Fragments in Gale Crater, Mars

    Science.gov (United States)

    Hallet, B.; Mackenzie-Helnwein, P.; Sletten, R. S.

    2017-12-01

    Curiosity and earlier rovers on Mars have revealed in detail rocky landscapes with decaying outcrops, rubble, stone-littered regolith, and bedrock exposures that reflect the weathering processes operating on rock exposed to Mars' cold and hyperarid environment. Evidence from diverse sources points to the importance of thermal stresses driven by cyclic solar exposure in contributing to the mechanical weathering of exposed rock and generation of regolith in various settings on Earth [1,2,3], and even more so on extraterrestrial bodies where large, rapid cyclic temperature variations are frequent (e.g. Mars [4], as well as comets [5], asteroids [6] and other airless bodies [7]). To study these thermal stresses, we use a 3d finite element (FE) model constrained by ground-based surface temperature measurements from Curiosity's Environmental Monitoring Station (REMS). The numerical model couples radiation and conduction with elastic response to determine the temperature and stress fields in individual rocks on the surface of Mars based on rock size and thermo-mechanical properties. We provide specific quantitative results for boulder-size basalt rocks resting on the ground using a realistic thermal forcing that closely matches the REMS temperature observations, and related thermal inertia data. Moreover, we introduce analytical studies showing that these numerical results can readily be generalized. They are quite universal, informing us about thermal stresses due to cyclic solar exposure in general, for rock fragments of different sizes, lithologies, and fracture- thermal- and mechanical-properties. Using Earth-analogue studies to gain insight, we also consider how the shapes, fractures, and surface details of rock fragments imaged by Curiosity likely reflect the importance of rock breakdown due to thermal stresses relative to wind-driven rock erosion and other surface processes on Mars. References:[1] McFadden L et al. (2005) Geol. Soc.Am. Bull. 117(1-2): 161-173 [2

  11. Impact of military trauma exposures on posttraumatic stress and depression in female veterans.

    Science.gov (United States)

    Goldstein, Lizabeth A; Dinh, Julie; Donalson, Rosemary; Hebenstreit, Claire L; Maguen, Shira

    2017-03-01

    Previous research has demonstrated the deleterious effects of traumatic military experiences on symptoms of posttraumatic stress disorder (PTSD) and depression in female veterans. However, more research is needed to identify the unique predictors of distressing psychological symptoms when both combat-related and sexual trauma are considered, particularly as women's combat exposure in the military increases. Female veterans who had attended at least one appointment at a large Veterans Health Administration medical center were invited to complete questionnaires about traumatic military exposures and psychiatric symptoms. A total of 403 veterans responded, with 383 respondents' data used in analyses. Multiple regression analyses were conducted with trauma exposure items entered simultaneously to determine their association with symptoms of (1) PTSD and (2) depression. Sexual assault had the strongest relationship with both posttraumatic and depressive symptoms. Sexual assault, sexual harassment, feeling in danger of being killed, and seeing others killed/injured were associated with symptoms of PTSD, but only sexual assault and sexual harassment were associated with symptoms of depression, even when accounting for several aspects of combat exposure. Improving assessment for trauma exposure and developing treatments personalized to type of trauma experienced are important clinical research priorities as female service members' roles in the military expand. Published by Elsevier B.V.

  12. Acute and sub-lethal exposure to copper oxide nanoparticles causes oxidative stress and teratogenicity in zebrafish embryos.

    Science.gov (United States)

    Ganesan, Santhanamari; Anaimalai Thirumurthi, Naveenkumar; Raghunath, Azhwar; Vijayakumar, Savitha; Perumal, Ekambaram

    2016-04-01

    Nano-copper oxides are a versatile inorganic material. As a result of their versatility, the immense applications and usage end up in the environment causing a concern for the lifespan of various beings. The ambiguities surround globally on the toxic effects of copper oxide nanoparticles (CuO-NPs). Hence, the present study endeavored to study the sub-lethal acute exposure effects on the developing zebrafish embryos. The 48 hpf LC50 value was about 64 ppm. Therefore, we have chosen the sub-lethal dose of 40 and 60 ppm for the study. Accumulation of CuO-NPs was evidenced from the SEM-EDS and AAS analyzes. The alterations in the AChE and Na(+)/K(+)-ATPase activities disrupted the development process. An increment in the levels of oxidants with a concomitant decrease in the antioxidant enzymes confirmed the induction of oxidative stress. Oxidative stress triggered apoptosis in the exposed embryos. Developmental anomalies were observed with CuO-NPs exposure in addition to oxidative stress in the developing embryos. Decreased heart rate and hatching delay hindered the normal developmental processes. Our work has offered valuable data on the connection between oxidative stress and teratogenicity leading to lethality caused by CuO-NPs. A further molecular mechanism unraveling the uncharted connection between oxidative stress and teratogenicity will aid in the safe use of CuO-NPs. Copyright © 2015 John Wiley & Sons, Ltd.

  13. The teacher under stress

    OpenAIRE

    Krnjajić Stevan B.

    2003-01-01

    Empirical records consistently point to the fact that the phenomenon of stress is characteristic of service professions, especially of teacher’s. Although stress in teachers is a problem of public interest, it is still a relatively new field of empirical investigations. Data available show that stress in teachers can have negative effects on school as an organization teacher professional achievement, his/her and his/her family psychosocial status. The most frequent symptoms of a prolonged pro...

  14. Response of heat shock protein genes of the oriental fruit moth under diapause and thermal stress reveals multiple patterns dependent on the nature of stress exposure.

    Science.gov (United States)

    Zhang, Bo; Peng, Yu; Zheng, Jincheng; Liang, Lina; Hoffmann, Ary A; Ma, Chun-Sen

    2016-07-01

    Heat shock protein gene (Hsp) families are thought to be important in thermal adaptation, but their expression patterns under various thermal stresses have still been poorly characterized outside of model systems. We have therefore characterized Hsp genes and their stress responses in the oriental fruit moth (OFM), Grapholita molesta, a widespread global orchard pest, and compared patterns of expression in this species to that of other insects. Genes from four Hsp families showed variable expression levels among tissues and developmental stages. Members of the Hsp40, 70, and 90 families were highly expressed under short exposures to heat and cold. Expression of Hsp40, 70, and Hsc70 family members increased in OFM undergoing diapause, while Hsp90 was downregulated. We found that there was strong sequence conservation of members of large Hsp families (Hsp40, Hsp60, Hsp70, Hsc70) across taxa, but this was not always matched by conservation of expression patterns. When the large Hsps as well as small Hsps from OFM were compared under acute and ramping heat stress, two groups of sHsps expression patterns were apparent, depending on whether expression increased or decreased immediately after stress exposure. These results highlight potential differences in conservation of function as opposed to sequence in this gene family and also point to Hsp genes potentially useful as bioindicators of diapause and thermal stress in OFM.

  15. Translating QT interval prolongation from conscious dogs to humans.

    Science.gov (United States)

    Dubois, Vincent F S; Smania, Giovanni; Yu, Huixin; Graf, Ramona; Chain, Anne S Y; Danhof, Meindert; Della Pasqua, Oscar

    2017-02-01

    In spite of screening procedures in early drug development, uncertainty remains about the propensity of new chemical entities (NCEs) to prolong the QT/QTc interval. The evaluation of proarrhythmic activity using a comprehensive in vitro proarrhythmia assay does not fully account for pharmacokinetic-pharmacodynamic (PKPD) differences in vivo. In the present study, we evaluated the correlation between drug-specific parameters describing QT interval prolongation in dogs and in humans. Using estimates of the drug-specific parameter, data on the slopes of the PKPD relationships of nine compounds with varying QT-prolonging effects (cisapride, sotalol, moxifloxacin, carabersat, GSK945237, SB237376 and GSK618334, and two anonymized NCEs) were analysed. Mean slope estimates varied between -0.98 ms μM -1 and 6.1 ms μM -1 in dogs and -10 ms μM -1 and 90 ms μM -1 in humans, indicating a wide range of effects on the QT interval. Linear regression techniques were then applied to characterize the correlation between the parameter estimates across species. For compounds without a mixed ion channel block, a correlation was observed between the drug-specific parameter in dogs and humans (y = -1.709 + 11.6x; R 2  = 0.989). These results show that per unit concentration, the drug effect on the QT interval in humans is 11.6-fold larger than in dogs. Together with information about the expected therapeutic exposure, the evidence of a correlation between the compound-specific parameter in dogs and in humans represents an opportunity for translating preclinical safety data before progression into the clinic. Whereas further investigation is required to establish the generalizability of our findings, this approach can be used with clinical trial simulations to predict the probability of QT prolongation in humans. © 2016 The British Pharmacological Society.

  16. Posttraumatic Stress Among Syrian Refugees: Trauma Exposure Characteristics, Trauma Centrality, and Emotional Suppression.

    Science.gov (United States)

    Chung, Man Cheung; Shakra, Mudar; AlQarni, Nowf; AlMazrouei, Mariam; Al Mazrouei, Sara; Al Hashimi, Shurooq

    2018-03-01

    This study revisited the prevalence of posttraumatic stress disorder (PTSD) and examined a hypothesized model describing the interrelationship between trauma exposure characteristics, trauma centrality, emotional suppression, PTSD, and psychiatric comorbidity among Syrian refugees. A total of 564 Syrian refugees participated in the study and completed the Harvard Trauma Questionnaire, General Health Questionnaire (GHQ-28), Centrality of Event Scale, and Courtauld Emotional Control Scale. Of the participants, 30% met the cutoff for PTSD. Trauma exposure characteristics (experiencing or witnessing horror and murder, kidnapping or disappearance of family members or friends) were associated with trauma centrality, which was associated with emotional suppression. Emotional suppression was associated with PTSD and psychiatric comorbid symptom severities. Suppression mediated the path between trauma centrality and distress outcomes. Almost one-third of refugees can develop PTSD and other psychiatric problems following exposure to traumatic events during war. A traumatized identity can develop, of which life-threatening experiences is a dominant feature, leading to suppression of depression with associated psychological distress.

  17. Inflammation and oxidative stress are elevated in the brain, blood, and adrenal glands during the progression of post-traumatic stress disorder in a predator exposure animal model.

    Science.gov (United States)

    Wilson, C Brad; McLaughlin, Leslie D; Nair, Anand; Ebenezer, Philip J; Dange, Rahul; Francis, Joseph

    2013-01-01

    This study sought to analyze specific pathophysiological mechanisms involved in the progression of post-traumatic stress disorder (PTSD) by utilizing an animal model. To examine PTSD pathophysiology, we measured damaging reactive oxygen species and inflammatory cytokines to determine if oxidative stress and inflammation in the brain, adrenal glands, and systemic circulation were upregulated in response to constant stress. Pre-clinical PTSD was induced in naïve, male Sprague-Dawley rats via a predator exposure/psychosocial stress regimen. PTSD group rats were secured in Plexiglas cylinders and placed in a cage with a cat for one hour on days 1 and 11 of a 31-day stress regimen. In addition, PTSD group rats were subjected to psychosocial stress whereby their cage cohort was changed daily. This model has been shown to cause heightened anxiety, exaggerated startle response, impaired cognition, and increased cardiovascular reactivity, all of which are common symptoms seen in humans with PTSD. At the conclusion of the predator exposure/psychosocial stress regimen, the rats were euthanized and their brains were dissected to remove the hippocampus, amygdala, and pre-frontal cortex (PFC), the three areas commonly associated with PTSD development. The adrenal glands and whole blood were also collected to assess systemic oxidative stress. Analysis of the whole blood, adrenal glands, and brain regions revealed oxidative stress increased during PTSD progression. In addition, examination of pro-inflammatory cytokine (PIC) mRNA and protein demonstrated neurological inflammatory molecules were significantly upregulated in the PTSD group vs. controls. These results indicate oxidative stress and inflammation in the brain, adrenal glands, and systemic circulation may play a critical role in the development and further exacerbation of PTSD. Thus, PTSD may not be solely a neurological pathology but may progress as a systemic condition involving multiple organ systems.

  18. The combined effects of developmental lead and ethanol exposure on hippocampus dependent spatial learning and memory in rats: Role of oxidative stress.

    Science.gov (United States)

    Soleimani, Elham; Goudarzi, Iran; Abrari, Kataneh; Lashkarbolouki, Taghi

    2016-10-01

    Either developmental lead or ethanol exposure can impair learning and memory via induction of oxidative stress, which results in neuronal damage. we examined the effect of combined exposure with lead and ethanol on spatial learning and memory in offspring and oxidative stress in hippocampus. Rats were exposed to lead (0.2% in drinking water) or ethanol (4 g/kg) either individually or in combination in 5th day gestation through weaning. On postnatal days (PD) 30, rats were trained with six trials per day for 6 consecutive days in the water maze. On day 37, a probe test was done. Also, oxidative stress markers in the hippocampus were also evaluated. Results demonstrated that lead + ethanol co-exposed rats exhibited higher escape latency during training trials and reduced time spent in target quadrant, higher escape location latency and average proximity in probe trial test. There was significant decrease in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities and increase of malondialdehyde (MDA) levels in hippocampus of animals co-exposed to lead and ethanol compared with their individual exposures. We suggest that maternal consumption of ethanol during lead exposure has pronounced detrimental effects on memory, which may be mediated by oxidative stress. Copyright © 2016. Published by Elsevier Ltd.

  19. AN EVALUATION OF OZONE EXPOSURE METRICS FOR A SEASONALLY DROUGHT STRESSED PONDEROSA PINE ECOSYSTEM. (R826601)

    Science.gov (United States)

    Ozone stress has become an increasingly significant factor in cases of forest decline reported throughout the world. Current metrics to estimate ozone exposure for forest trees are derived from atmospheric concentrations and assume that the forest is physiologically active at ...

  20. Thermoregulatory responses to environmental toxicants: The interaction of thermal stress and toxicant exposure

    International Nuclear Information System (INIS)

    Leon, Lisa R.

    2008-01-01

    Thermal stress can have a profound impact on the physiological responses that are elicited following environmental toxicant exposure. The efficacy by which toxicants enter the body is directly influenced by thermoregulatory effector responses that are evoked in response to high ambient temperatures. In mammals, the thermoregulatory response to heat stress consists of an increase in skin blood flow and moistening of the skin surface to dissipate core heat to the environment. These physiological responses may exacerbate chemical toxicity due to increased permeability of the skin, which facilitates the cutaneous absorption of many environmental toxicants. The core temperature responses that are elicited in response to high ambient temperatures, toxicant exposure or both can also have a profound impact on the ability of an organism to survive the insult. In small rodents, the thermoregulatory response to thermal stress and many environmental toxicants (such as organophosphate compounds) is often biphasic in nature, consisting initially of a regulated reduction in core temperature (i.e., hypothermia) followed by fever. Hypothermia is an important thermoregulatory survival strategy that is used by small rodents to diminish the effect of severe environmental insults on tissue homeostasis. The protective effect of hypothermia is realized by its effects on chemical toxicity as molecular and cellular processes, such as lipid peroxidation and the formation of reactive oxygen species, are minimized at reduced core temperatures. The beneficial effects of fever are unknown under these conditions. Perspective is provided on the applicability of data obtained in rodent models to the human condition