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The eight-item treatment-outcome post-traumatic stress disorder scale: a brief measure to assess treatment outcome in post-traumatic stress disorder.

This preliminary report describes a new brief interview based assessment of post-traumatic stress disorder using an 8-item treatment-outcome post-traumatic stress disorder scale (TOP-8). The TOP-8 was developed from a larger post-traumatic stress disorder evaluation scale based on items which occurred frequently in the population and which responded substantially to treatment across time. The 8 resultant items were drawn from all three symptom clusters for post-traumatic stress disorder, and showed an improved ability to detect drug versus placebo differences in comparison with the original scale. The eight-item treatment-outcome post-traumatic stress disorder scale also correlated significantly with a self-rated measure of post-traumatic stress disorder and distinguished at a highly significant level between responders and non-responders on an independently judged Clinical Global Impressions measure. The results of this study are discussed and future directions suggested.

Adult↗

Influence of life stress on immunological reactivity to mild psychological stress.

This study investigated the effects of self-reported life stress and locus of control on reactivity of several immune parameters to a mild and short-lasting interpersonal stressor. Subjects were 86 male teachers aged 24 to 55 years. Immune reactivity was defined as changes in numbers of monocytes. T-lymphocytes and subsets, HLA-DR+ cells, and NK cells as well as changes in (in vitro) proliferative responses of peripheral blood lymphocytes to the antigens PHA and PWM. Multiple regression analysis was used to study the interaction effects of life stress and locus of control by experimental condition on immune reactivity. Life stress, but not locus of control, influences reactivity of the immunological parameters to the stressor. In particular, high numbers of daily hassles were associated with stressor-induced decreases in numbers of T cells and NK cells in peripheral blood. On the other hand, numbers of HLA-DR+ cells in high life stress scorers decreased only slightly during the stressor, whereas they increased in the control condition. The findings suggest that accumulated life stress is related to reactivity of immunological parameters to subsequent experimental stress. Possible physiological explanations and implications of these effects are discussed.

Adult↗

Stress exposure, psychological distress, and physiological stress activation in midlife women with insomnia.

OBJECTIVE: The objective of this study was to describe perceived and polysomnograhic (PSG) sleep patterns and determine whether stress exposure, psychological distress, and physiological stress activation differed among midlife women with psychophysiologic-type (PP-type) or subjective only-type (SO-type) insomnia or no insomnia. METHODS: Women had their sleep monitored, collected urine samples, and completed questionnaires in a week-long field study, and 53 women met criteria for insomnia types or no insomnia based on reported sleep quality and PSG sleep efficiency. RESULTS: As expected, women with PP-type insomnia were found to have the lowest sleep efficiency, took longer to fall asleep, had more wakefulness after sleep onset, and had more fragmented sleep. Perceptions of stress exposure, either for major or minor events, did not differ among groups. Despite there being no differences in perceived stress exposure, women with both types of insomnia scored higher on psychological distress (SCL-90R), especially on the somatization subscale, than women with no insomnia. Of the physiological stress activation indicators tested, a morning-to-evening difference in urinary cortisol statistically differed across the groups (p <.005). Women in the PP-type insomnia group had the highest levels of urinary cortisol in an early morning urine sample. CONCLUSIONS: These data provide support for the hypothesis that, in midlife women, cognitive or emotional arousal with chronic stress neuroendocrine activation underlies chronic insomnia, particularly the PP-type.

Body Mass Index↗

Expression of aluminum-induced genes in transgenic arabidopsis plants can ameliorate aluminum stress and/or oxidative stress.

To examine the biological role of Al-stress-induced genes, nine genes derived from Arabidopsis, tobacco (Nicotiana tabacum L.), wheat (Triticum aestivum L.), and yeast (Saccharomyces cerevisiae) were expressed in Arabidopsis ecotype Landsberg. Lines containing eight of these genes were phenotypically normal and were tested in root elongation assays for their sensitivity to Al, Cd, Cu, Na, Zn, and to oxidative stresses. An Arabidopsis blue-copper-binding protein gene (AtBCB), a tobacco glutathione S-transferase gene (parB), a tobacco peroxidase gene (NtPox), and a tobacco GDP-dissociation inhibitor gene (NtGDI1) conferred a degree of resistance to Al. Two of these genes, AtBCB and parB, and a peroxidase gene from Arabidopsis (AtPox) also showed increased resistance to oxidative stress induced by diamide, while parB conferred resistance to Cu and Na. Al content of Al-treated root tips was reduced in the four Al-resistant plant lines compared with wild-type Ler-0, as judged by morin staining. All four Al-resistant lines also showed reduced staining of roots with 2',7'-dichloro fluorescein diacetate (H(2)DCFDA), an indicator of oxidative stress. We conclude that Al-induced genes can serve to protect against Al toxicity, and also provide genetic evidence for a link between Al stress and oxidative stress in plants.

Aluminum↗

Symposium on teacher stress. Occupational stress among vocational teachers.

There is a widespread belief that work related stress among teachers is serious, with implications for teachers' health status and performance. The difficulty with interpreting data on teacher stress is that the measuring instruments used are often neither standardised nor sometimes focused on stressors pertinent to the occupational roles of teachers. This study, therefore, uses a recently developed test instrument called the Occupational Stress Inventory (OSI) which concisely measures occupational stress, strain and coping resources. Data were obtained, using the OSI, from a group of vocational teachers and compared to a group of professional non-teachers. Overall the results showed a significantly higher level of teacher stress, although only one of 10 stress and strain measures contributed to this effect. The implications for teachers, in terms of occupational role, are discussed.

Burnout, Professional↗

Effect of residual stress and heterogeneity on circumferential stress in the arterial wall.

Quantifying the stress distribution through the arterial wall is essential to studies of arterial growth and disease. Previous studies have shown that both residual stress, as measured by opening angle, and differing material properties for the media-intima and the adventitial layers affect the transmural circumferential stress (sigma theta) distribution. Because a lack of comprehensive data on a single species and artery has led to combinations from multiple sources, this study determined the sensitivity of sigma theta to published variations in both opening angle and layer thickness data. We fit material properties to previously published experimental data for pressure-diameter relations and opening angles of rabbit carotid artery, and predicted sigma theta through the arterial wall at physiologic conditions. Using a one-layer model, the ratio of sigma theta at the internal wall to the mean sigma theta decreased from 2.34 to 0.98 as the opening angle increased from 60 to 130 deg. In a two-layer model using a 95 deg opening angle, mean sigma theta in the adventitia increased (112 percent for 25 percent adventitia) and mean sigma theta in the media decreased (47 percent for 25 percent adventitia). These results suggest that both residual stress and wall layers have important effects on transmural stress distribution. Thus, experimental measurements of loading curves, opening angles, and wall composition from the same species and artery are needed to accurately predict the transmural stress distribution in the arterial wall.

Animals↗

Stress induction of the mammalian GRP78/BiP protein gene: in vivo genomic footprinting and identification of p70CORE from human nuclear extract as a DNA-binding component specific to the stress regulatory element.

GRP78, also known as BiP, is one of the better-characterized molecular chaperones. It has been implicated in protein folding and also calcium sequestration in the endoplasmic reticulum. When the cells are subjected to endoplasmic reticulum stress, in particular the depletion of stored calcium and/or the accumulation of abnormal proteins, the rate of transcription of grp78 is enhanced. Previous studies have shown that the core region of the rat grp78 promoter (-170 to -135), which is 95% conserved with the human grp78 core (-133 to -98), is one of the key regulatory elements. Using ligation-mediated PCR, we have found that there are specific changes in factor occupancy after stress induction and the major changes occur within a cluster of bases located in the 3' half of the grp core, whereas other regulatory elements are constitutively occupied. This inducible binding to the 3' half of the human grp78 core region is observed under diverse stress signals, suggesting a common mechanism for the grp stress response. Nonetheless, the lack of constitutive in vivo protection at this region is not due to the absence of a binding factor in nuclear extracts. Using in vitro gel mobility shift assays, we detected a constitutive binding activity which exhibits specificity and affinity to the stress-inducible region. Through sodium dodecyl sulfate-polyacrylamide gel electrophoresis size fractionation and renaturation analysis, the activity is found in polypeptides with molecular sizes of 65 to 75 kDa. After a three-step purification scheme including core affinity column chromatography, we purified p70CORE, which is about 70 kDa in its monomeric form. The purified p70CORE is sufficient to form a complex specific to the stress-inducible region.

Base Sequence↗

Intracellular stress tomography reveals stress focusing and structural anisotropy in cytoskeleton of living cells.

We describe a novel synchronous detection approach to map the transmission of mechanical stresses within the cytoplasm of an adherent cell. Using fluorescent protein-labeled mitochondria or cytoskeletal components as fiducial markers, we measured displacements and computed stresses in the cytoskeleton of a living cell plated on extracellular matrix molecules that arise in response to a small, external localized oscillatory load applied to transmembrane receptors on the apical cell surface. Induced synchronous displacements, stresses, and phase lags were found to be concentrated at sites quite remote from the localized load and were modulated by the preexisting tensile stress (prestress) in the cytoskeleton. Stresses applied at the apical surface also resulted in displacements of focal adhesion sites at the cell base. Cytoskeletal anisotropy was revealed by differential phase lags in X vs. Y directions. Displacements and stresses in the cytoskeleton of a cell plated on poly-L-lysine decayed quickly and were not concentrated at remote sites. These data indicate that mechanical forces are transferred across discrete cytoskeletal elements over long distances through the cytoplasm in the living adherent cell.

Cells, Cultured↗

PPARgamma ligands induce ER stress in pancreatic beta-cells: ER stress activation results in attenuation of cytokine signaling.

Peroxisome proliferator-activated receptor (PPAR)gamma ligands are known to have anti-inflammatory properties that include the inhibition of cytokine signaling, transcription factor activation, and inflammatory gene expression. We have recently observed that increased expression of heat shock protein (HSP)70 correlates with, but is not required for, the anti-inflammatory actions of PPARgamma ligands on cytokine signaling. In this study, we provide evidence that the inhibitory actions of PPARgamma ligands on cytokine signaling are associated with endoplasmic reticulum (ER) stress or unfolded protein response (UPR) activation in pancreatic beta-cells. 15-Deoxy-Delta(12,14)-prostaglandin J(2), at concentrations that inhibit cytokine signaling, stimulates phosphorylation of eukaryotic initiation factor-2alpha, and this event is followed by a rapid inhibition of protein translation. Under conditions of impaired translation, PPARgamma ligands stimulate the expression of a number of ER stress-responsive genes, such as GADD 153, BiP, and HSP70. Importantly, ER stress activation in response to PPARgamma ligands or known UPR activators results in the attenuation of IL-1 and IFN-gamma signaling. These findings indicate that PPARgamma ligands induce ER stress, that ER stress activation is associated with an attenuation of cytokine signaling in beta-cells, and that the attenuation of responsiveness to extracellular stimuli appears to be a novel protective action of the UPR in cells undergoing ER stress.

Animals↗

Direct evidence of acute stress-induced facilitation of ACTH response to subsequent stress in rats.

To determine the role of glucocorticoids in the appearance of the facilitatory effect of stress on the ACTH response to a subsequent stress, sham-operated (Sham) rats and rats adrenalectomized (ADX) and supplemented with 50 mg/l corticosterone (B) in the drinking saline (ADX + B) were subjected to 1 min of immobilization stress (Imo) four consecutive times with an interstressor interval of 90 min. Sham rats showed a similar pattern of ACTH response to the first and fourth exposures to Imo. ADX + B rats showed an exacerbated ACTH response to the fourth Imo, despite higher prestress levels than those observed before the first Imo. In another experiment, no facilitatory effect of previous stress on ACTH response was found in ADX rats, but supplementation with B in the drinking saline for 1 wk resulted in facilitation of the ACTH response. We conclude that repeated exposure to a short-time stress induces a facilitatory effect on the ACTH response that is uncovered by eliminating stress-induced glucocorticoid release but needs B doses resulting in approximately basal circulating glucocorticoid levels to be induced or expressed.

Adrenalectomy↗

Aging reduces adaptive capacity and stress protein expression in the liver after heat stress.

A decline in an organism's ability to cope with stress through acute response protein expression may contribute to stress intolerance with aging. We investigated the influence of aging on stress tolerance and the capacity to synthesize the 70-kDa heat shock protein (HSP70) in young and old rats exposed to an environmental heating protocol. Livers were assessed for injury and HSP70 expression after heat stress by use of immunohistochemical and immunoblotting techniques. The inducible HSP70 response in the cytoplasm and nucleus was markedly reduced with age at several time points over a 48-h recovery period, although senescent rats were able to strongly express HSP70 early in recovery. Older animals had extensive zone-specific liver injury, which corresponded to the diminished HSP70 response observed in these regions, and a significant reduction in thermotolerance compared with their young counterparts. These data highlight the regional nature of stress-induced injury and HSP70 expression in the liver and the impact of aging on these responses. Furthermore, the results suggest a functional link between the age-related decrements in the expression of inducible HSP70 and the pathophysiological responses to heat stress.

Adaptation, Physiological↗

Differential involvement of opioid receptors in stress-induced antinociception caused by repeated exposure to forced walking stress in mice.

We examined the effects of repeated exposure to forced walking stress for 6 h once a day for 0, 6 and 9 consecutive days on formalin-induced paw licking in mice. In each observation period, stress-induced antinociception (SIA) was observed only in the late phase (from 10 to 30 min), but not in the early phase (from 0 to 10 min) of formalin-induced paw licking in mice. Moreover, it was hard to develop tolerance even by daily exposure to stress for 6 days, although SIA for 9 days decreased compared with those for 0 and 6 days. Naloxone (10 mg/kg), an opioid-receptor antagonist, was effective in reducing the SIA induced by forced walking stress for 6 days and/or 9 days, but not for 0 days. Furthermore, the experiments with selective opioid-receptor antagonists, beta-funaltrexamine (mu) naltrindol (delta), or nor-binaltorphimine (kappa) demonstrated that SIA induced by forced walking stress for 9 successive days may be mediated through opioid delta- and kappa-receptors. Finally, although SIA seemed to be a unitary phenomenon, the present results strengthened the idea that SIA is induced by exposure to forced walking stress with characteristics dependent on the duration of exposure.

Animals↗

Dobutamine stress echo is superior to exercise stress testing in achieving target heart rate among patients on beta blockers.

Published guidelines recommend continuing beta-adrenergic receptor blockade in patients undergoing stress testing. We evaluated the role of pharmacological versus exercise stress testing in achieving target heart rate (THR) among patients on beta-adrenergic blockade. We compared data from 140 patients who underwent dobutamine stress echo (DSE) and 143 patients who underwent exercise treadmill testing (ETT). In both groups, beta-adrenergic blocker was continued at the time of stress testing. Overall, patients undergoing DSE achieved THR more frequently than ETT. With beta-adrenergic blockade, DSE patients met THR more frequently than ETT patients (p < 0.001). Without beta-adrenergic blockade, there was no difference between either modality in achieving THR. In both DSE and ETT patients, absence of beta-adrenergic blockade increased the odds of achieving THR [odds ratio (OR): 2.46, p = 0.042 and OR: 7.44, p < 0.001, respectively]. Atropine use with DSE increased the odds of achieving THR (OR: 3.76, p = 0.006). In conclusion, pharmacological stress testing appears to be superior to exercise stress testing in achieving THR among patients on beta-adrenergic blockade.

Adrenergic beta-Antagonists↗

Impact of cumulative lifetime trauma and recent stress on current posttraumatic stress disorder symptoms in holocaust survivors.

OBJECTIVE: The purpose of this study was to examine the relationships among cumulative lifetime trauma, recent stressful events, and presence and severity of current posttraumatic stress disorder (PTSD) symptoms in Holocaust survivors and nonexposed comparison subjects. METHOD: Lifetime trauma, recent stressful events, and presence and severity of PTSD were assessed in Holocaust survivors (N=72) and comparison subjects ( N=19). RESULTS: Survivors with PTSD (N =40) reported significantly greater cumulative trauma and recent stress than survivors without PTSD (N=32) and comparison subjects. Severity of PTSD symptoms, cumulative trauma, and recent stress were significantly associated. CONCLUSIONS: The presence and severity of current PTSD were related to having experienced stressful events in addition to the Holocaust.

Aged↗

The effect of an integrated stress management program on the psychologic and physiologic stress reactions of peptic ulcer in Korea.

The purpose of this study was to identify the effects of an integrated stress management program on symptoms of stress and ulcer healing in a sample of Koreans at a major medical center in Seoul. The study employed an experimental design with two treatment groups. One treatment group (n = 23) participated in an integrated stress management program (ISMP) that consisted of seven 1-hour sessions over a 4-week period. A second treatment group (n = 24) was only given a tape on progressive muscle relaxation (PMR). The ISMP treatment group reported significantly lower stress symptom scores than the PMR only group (t = 3.66, p < .001). The ISMP group also demonstrated greater improvement in ulcer healing than the PMR group (t = 1.95, p < .05). The integrated stress management program was more effective in decreasing self-reported stress symptoms and resulted in more significant ulcer healing than the progressive muscle relaxation treatment.

Adaptation, Psychological↗

Urocortin 3 modulates the neuroendocrine stress response and is regulated in rat amygdala and hypothalamus by stress and glucocorticoids.

The endogenous corticotropin-releasing factor (CRF) type 2 receptor (CRFR2)-selective ligand urocortin 3 is expressed in discrete subcortical brain regions with fibers distributed mainly to hypothalamic and limbic structures. Close anatomical association between major urocortin 3 terminal fields and CRFR2 in hypothalamus, lateral septum, and medial amygdala (MEA) suggest it is well placed to modulate behavioral and hormonal responses to stress. Urocortin 3 was administered intracerebroventricularly to male rats under basal conditions or before a restraint stress, and circulating ACTH, corticosterone, glucose, and insulin were measured. Urocortin 3 activated the hypothalamic-pituitary-adrenal axis under basal conditions and augmented ACTH responses to restraint stress. Elevated blood glucose with lowered insulin to glucose ratios in both groups suggested increased sympathetic activity. Circulating catecholamines were also increased by urocortin 3, providing additional evidence for sympathoadrenomedullary stimulation. Intracerebroventricular urocortin 3 increased vasopressin mRNA expression in the parvocellular division of the hypothalamic paraventricular nucleus, whereas CRF expression was unchanged, providing a possible mechanism by which urocortin 3 mediates its actions. Urocortin 3 mRNA expression was examined after exposure to stress-related paradigms. Restraint increased levels in MEA with a trend to increased expression in the rostral perifornical hypothalamic area, whereas hemorrhage and food deprivation decreased expression in MEA. Adrenalectomy markedly increased expression in the rostral perifornical hypothalamic area, and high-level corticosterone replacement restored this to control levels. The evidence that urocortin 3 has the potential to influence hormonal components of the stress response and the changes in its expression levels after stressors is consistent with a potential function for the endogenous peptide in modulating stress responses.

Adrenalectomy↗

Oxidative stress during stressful heat exposure and recovery in the North Sea eelpout Zoarces viviparus L.

The interplay between antioxidants, heat shock proteins and hypoxic signaling is supposed to be important for passive survival of critical temperature stress, e.g. during unfavorable conditions in hot summers. We investigated the effect of mild (18 degrees C), critical (22 degrees C) and severe (26 degrees C) experimental heat stress, assumed to induce different degrees of functional hypoxia, as well as the effect of recovery following heat stress on these parameters in liver samples of the common eelpout Zoarces viviparus. Upon heat exposure to critical and higher temperatures we found an increase in oxidative damage markers such as TBARS (thiobarbituric reactive substances) and a more oxidized cellular redox potential, combined with reduced activities of the antioxidant enzyme superoxide dismutase at 26 degrees C. Together, these point to higher oxidative stress levels during hyperthermia. In a recovery-time series, heat-induced hypoxia and subsequent reoxygenation upon return of the fishes to 12 degrees C led to increased protein oxidation and chemiluminescence rates within the first 12 h of recovery, therein resembling ischemia/reperfusion injury in mammals. HSP70 levels were found to be only slightly elevated after recovery from sub-lethal heat stress, indicating minor importance of the heat shock response in this species. The DNA binding activity of the hypoxia-inducible transcription factor (HIF-1) was elevated only during mild heat exposure (18 degrees C), but appeared impaired at more severe heat stress. We suppose that the more oxidized redox state during extreme heat may interfere with the hypoxic signaling response.

Animals↗

[Changes of the function of the heart of SART stressed (repeated cold stressed) mice and the action of neurotropin on these changes].

Electrocardiography (ECG) was performed for SART stressed (repeated cold stressed) mice which had changes in blood pressure and blood flow to examine the effects of this treatment on heart function. In the ECG of mice subjected to SART stress for 5 days, potentiations of the R and T voltage, a shortening of the PQ interval, a prolongation of the QRS interval, and a slight increase of the heart rate were observed; and such changes in the ECG were maintained for several days. Recovery from all these changes was observed after a single dose or consecutive administration of propranolol. From these results, it is considered that sympathetic nerve activity may be increased in the function of the heart in SART stressed mice, as contrasted to the partial vagotonia in the duodenum. Neurotropin (NSP), a nerve sedative, was then administered to mice once daily for 5 days during the sart stress. NSP prevented the changes of the PQ and QRS interval in SART stressed mice, but could not prevent the potentiation of the R and T voltage and the heart rate increase. In particular, the potentiations of the R and T voltages were thought to be induced by the increase of sympathetic nerve activity; therefore, it is thought that NSP may not have direct actions at least on the sympathetic nerve sites in autonomic nervous systems.

Animals↗