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Biphasic activation of apoptosis signal-regulating kinase 1-stress-activated protein kinase 1-c-Jun N-terminal protein kinase pathway is selectively mediated by Ca2+-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors involving oxidative stress following brain ischemia in rat hippocampus.

Stress-activated protein kinase/extracellular signal-regulated kinase-1 (SEK1/MKK4) was examined in a rat model of global brain ischemia. Western blot assay showed that SEK1 activation was biphasic in CA1 but not CA3/dentate gyrus. The second activation peak (3 days after ischemia) was prevented by pretreatment with l-naphthyl acetyl spermine (Naspm), a channel blocker of Ca(2+)-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors, or N-acetylcysteine (NAC), a free radical scavenger. Concomitantly, the late activation of apoptosis signal-regulating kinase 1 (ASK1) and c-Jun N-terminal protein kinase (JNK) was also prevented by Naspm or NAC. Moreover, phospho-SEK1 and phospho-JNK co-immunoprecipitated with ASK1 and the bindings peaked at 3 days of reperfusion. Together with previous results, these findings indicate that Ca(2+)-permeable AMPA receptors are important routes to mediate the late activation of ASK1-SEK1-JNK pathway involving oxidative stress in hippocampal CA1 region after ischemia.

Acetylcysteine↗

Non-peptidic corticotropin-releasing hormone receptor type 1 antagonist reverses restraint stress-induced shortening of sodium pentobarbital-induced sleeping time of rats: evidence that an increase in arousal induced by stress is mediated through CRH receptor type 1.

Stress shortens sodium pentobarbital (PbNa)-induced sleeping time through corticotropin-releasing hormone (CRH) in rats. We investigated whether this effect of brain CRH is mediated by CRH receptor type 1 (CRHR1) using a non-peptidic CRHR1 antagonist in rats. A 60 min period of restraint significantly shortened PbNa-induced sleeping time. This shortening was completely reversed by peripheral administration of CRHR1 antagonist. These results suggest that the stress-induced increase in arousal is mediated by CRHR1.

Animals↗

Using the psychological stress evaluator in conditions of extreme stress.

The Psychological Stress Evaluator (PSEV) is a machine for detecting signs of stress in the voice. It was tested using tape recordings of negotiators during a prolonged terrorist siege in which a number of death threats were issued. The study aimed to test whether the PSEV could distinguish between the traces of terrorist voices before the death threats from voice traces at other points. A scoring system using the proportion of voice oscillations falling above defined amplitude levels was used. PSEV scores did rise significantly more just before the actual shooting of a hostage. Unfortunately, the apparatus proved to be slow and cumbersome in practice and of limited, or no, use during the course of incidents similar to the one analysed.

Humans↗

Head-to-head comparison of dipyridamole echocardiography and stress perfusion scintigraphy for the detection of coronary artery disease: a meta-analysis. Comparison between stress echo and scintigraphy.

OBJECTIVES: This meta-analysis was performed to assess and compare the diagnostic accuracy of dipyridamole echocardiography test (DET) vs. stress perfusion scintigraphy (SPS) for the diagnosis of coronary artery disease (CAD). METHODS: We performed a meta-analysis of peer reviewed articles, published in English language reporting head-to-head comparison of DET vs. SPS for the diagnosis of CAD. Data of 10 studies comprising 651 patients from 10 different institutions were analyzed. DET dose was 0.56 mg/kg (low dose) in two studies, 0.75 mg/kg in 10 min or 0.84 mg/kg in 10 min (high dose) in six studies, and 0.84 mg/kg in 6 min (accelerated high dose) in one study and 0.84 mg/kg in 10 min + 1 mg atropine co-administration (augmented dose) in one study. SPS was performed with dipyridamole in six studies, with exercise in three studies and with dobutamine in one study. RESULTS: The overall diagnostic accuracy of the two tests was almost similar, 77% (95% CI = 74-81) for DET vs. 81% (95% CI = 78-84) for SPS (p = ns). SPS gave higher sensitivity, 88% (95% CI = 85-89) than DET, 70% (95% CI = 66-75) in cumulative data (p < 0.0001) while DET gave higher specificity, 90% (95% CI = 86-94) vs. 67% (95% CI = 60-73) (p < 0.0001). With state of the art protocols, i.e. accelerated dose and atropine augmented high dose, sensitivity of DET improved and overall accuracy was better than SPS (p < 0.05). CONCLUSION: DET and SPS have a similar diagnostic accuracy. DET has a markedly higher specificity regardless of the dose employed. SPS shows a superior sensitivity, however this sensitivity gap diminishes when more aggressive dipyridamole dosage is used for the stress echocardiography.

Coronary Disease↗

Stress exposure and stress generation in children of depressed mothers.

Two hypotheses were tested: (a) One mechanism contributing to the high rate of disorder in children of women with affective disorders is elevated exposure to stressful events and conditions and (b) the children of depressed women, particularly women with unipolar depression, contribute to event occurrence because of increased interpersonal conflict. Life stress interview assessments were made at 6-month intervals for 3 years on 53 children of unipolar, bipolar, medically ill, and normal women. Both hypotheses were confirmed. Transactional models of risk and further studies of the interpersonal functioning of children at risk for depression are needed.

Adaptation, Psychological↗

The relationship between acute stress disorder and posttraumatic stress disorder: a prospective evaluation of motor vehicle accident survivors.

Motor vehicle accident survivors (n = 92) were assessed for acute stress disorder (ASD) within 1 month of the trauma and reassessed (n = 71) for posttraumatic stress disorder (PTSD) 6 months posttrauma. ASD was diagnosed in 13% of participants, and a further 21% had subclinical levels of ASD. At follow-up, 78% of ASD participants and 60% of subclinical ASD participants met criteria for PTSD. The strong predictive power of acute numbing, depersonalization, a sense of relieving the trauma, and motor restlessness, in contrast to the low to moderate predictive power of other symptoms, indicates that only a subset of ASD symptoms is strongly related to the development of chronic PTSD. Although these findings support the use of the ASD diagnosis, they suggest that the dissociative and arousal clusters may require revision.

Accidents, Traffic↗

A comparison of exposure therapy, stress inoculation training, and their combination for reducing posttraumatic stress disorder in female assault victims.

Ninety-six female assault victims with chronic posttraumatic stress disorder (PTSD) were randomly assigned to 4 treatment conditions: prolonged exposure (PE), stress inoculation training (SIT), combined treatment (PE-SIT), or wait-list control (WL). Treatment consisted of 9 twice-weekly, individual sessions. Independent evaluations were conducted at pretreatment; posttreatment; and 3-, 6-, and 12-month follow-ups. All 3 active treatments reduced severity of PTSD and depression compared with WL but did not differ significantly from each other, and these gains were maintained throughout the follow-up period. However, in the intent-to-treat sample, PE was superior to SIT and PE-SIT on posttreatment anxiety and global social adjustment at follow-up and had larger effect sizes on PTSD severity, depression, and anxiety. SIT and PE-SIT did not differ significantly from each other on any outcome measure.

Adolescent↗

Control over stress, type A behavior pattern, and response to stress.

This study was conducted to examine (a) differences in physiological response of Type A and Type B individuals to conditions that varied in both controllability and consistency of controllability over an aversive stimulus and (b) whether Type A relative to Type B individuals employ more denial and/or projection in cognitively coping with arousing situations as well as differ in being preoccupied in such situations. Ninety-six college men were randomly assigned to one of four conditions: no control over shock, consistent control over shock, intermittent control over shock, and low stress. The results indicated that relative to Type B subjects, Type A subjects manifested (a) greater pulse rates and systolic and diastolic blood pressure in the consistent control condition, (b) greater systolic blood pressure in the no-control condition, and (c) greater diastolic blood pressure in the intermittent control condition. Type A subjects relative to Type B subjects also employed more of both denial and projection across the three high-stress conditions but did not differ in how preoccupied they were.

Behavior↗

Traumatic stress, life events, and emotional support in women with metastatic breast cancer: cancer-related traumatic stress symptoms associated with past and current stressors.

This study examined levels of intrusion and avoidance symptoms and their relationships to past life stress, current emotional support, disease-related variables, and age in 125 women with metastatic breast cancer. The results indicate that a sizable proportion of these women experienced clinically significant levels of intrusion and avoidance symptoms related to their cancer, particularly those with both more stressful past life events and higher current levels of aversive emotional support. Additionally, both types of symptoms were associated with shorter time since recurrence, and avoidance symptoms were associated with smaller emotional support networks. These results indicate that metastatic breast cancer is an emotionally traumatic event for a significant proportion of women, particularly those with past life stressors and unsupportive social environments.

Adult↗

Effect of age and long-term stress experience on adaptation to stress analgesia in mature rats: role of opioids.

The effects of aging and previous long-term stress on development of tolerance to stress-induced analgesia were evaluated in male Sprague-Dawley rats exposed to intermittent cold water swims (ICWS) in 2 degrees C water (eighteen 10-s exposure, three/min) on 15 consecutive days. Analgesia was measured by the tail-flick test prior to and 30 min after ICWS. In young rats (4 months), tolerance developed faster and asymptotic tolerance was acquired sooner and was more complete than in older rats (15-16 months). Previous long-term exposure (but not the age at which it occurred) accelerated the development and acquisition of asymptotic tolerance to reexposure. Naltrexone (10 mg/kg, ip) partially and completely reversed tolerance to ICWS analgesia in 4- and 9-10-month-old rats, respectively, results suggesting that the opioids are involved in ICWS-analgesia tolerance in both young and old mature rats. In young animals, a second mechanism, naltrexone-insensitive, may be responsible for at least some of the differences in ICWS tolerance found between young and old mature adult rats.

Aging↗

Aging and cardiovascular reactivity to stress: longitudinal evidence for changes in stress reactivity.

Although age differences in cardiovascular function are well documented, little research has provided longitudinal evidence for age-related changes in cardiovascular reactivity to stress. In this study, the authors report such data from a follow-up of their prior work (B. N. Uchino, D. Uno, J. Holt-Lunstad, & J. B. Flinders, 1999) with participants between the ages of 30 to 70 (n=108, mean follow-up=10 months, range=7 to 16 months). Results revealed longitudinal evidence for an age-related increase in systolic blood-pressure reactivity and parasympathetic withdrawal to acute stress. The implications of these findings are discussed in light of the increased cardiovascular disease risk with age, as well as the links between aging, emotions, and physiology.

Adult↗

Induction of the mammalian stress response gene GADD153 by oxidative stress: role of AP-1 element.

GADD153 is a CCAAT/enhancer-binding-protein-related gene that may function to control cellular growth in response to stress signals. In this study, a variety of oxidant treatments were shown to stimulate endogenous GADD153 mRNA expression and to transcriptionally activate a GADD153 promoter-reporter gene construct in transfected HeLa cells. Both commonalities and distinctions in the induction of GADD153 by H2O2 and the thiol-reactive compound arsenite were demonstrated. GADD153 mRNA induction by both H2O2 and arsenite was potentiated by GSH depletion, and completely inhibited by N-acetyl-cysteine. o-Phenanthroline and mannitol blocked GADD153 induction by H2O2, indicating that iron-generated hydroxyl radical mediates this induction. Concordantly, GSH peroxidase overexpression in WI38 cells attenuated GADD153 mRNA induction by H2O2. However, GADD153 induction by arsenite was only modestly reduced in the same cells, suggesting a lesser contribution of peroxides to gene activation by arsenite. We also demonstrated that oxidative stress participates in the induction of GADD153 by UVC (254 nm) irradiation. Finally, both promoter-deletion analysis and point mutation of the AP-1 site in an otherwise intact promoter support a significant role for AP-1 in transcriptional activation of GADD153 by UVC or oxidant treatment. Indeed, exposure of cells to oxidants or UVC stimulated binding of Fos and Jun to the GADD153 AP-1 element. Together, these results demonstrate that both free-radical generation and thiol modification can transcriptionally activate GADD153, and that AP-1 is critical to oxidative regulation of this gene. This study further supports a role for the GADD153 gene product in the cellular response to oxidant injury.

Arsenites↗

Exercise stress testing, myocardial perfusion imaging and stress echocardiography for detecting restenosis after successful percutaneous transluminal coronary angioplasty: a review of performance.

When chest symptoms recur in a patient who underwent percutaneous transluminal coronary angioplasty (PTCA), it is necessary to rule out restenosis (R). Three main noninvasive tests suggest the presence of R: exercise stress test (XT), myocardial perfusion imaging (MPI) and stress echocardiography (s-echo). The objectives of this review were: (1) to estimate the pretest probability of R as a function of time after PTCA in symptomatic patients and (2) to obtain an approximation of the diagnostic parameters of the XT, MPI and s-echo for detecting R. A MEDLINE search (English-language, years: 1980-2001) was conducted to identify studies examining post-PTCA functional testing for diagnosing R. Data from the studies were pooled. Comparing studies was often difficult due to varying methodology in the studies. Pretest probability of R in symptomatic patients increases in a nonlinear fashion from 20% or less at 1 month, to nearly 90% at 1-year postangioplasty. The approximated accuracy of the XT, MPI, and s-echo for detecting R was 62, 82 and 84%, respectively. During the first month after PTCA, none of the noninvasive modalities is able to accurately detect R. Late (7-9 months) after PTCA, the pretest probability of R is high and therefore the noninvasive measure may be spared. Our analysis suggests that MPI and s-echo should be preferred over the XT for diagnosing R.

Angioplasty, Balloon, Coronary↗

Vasopressin released within the septal brain area during swim stress modulates the behavioural stress response in rats.

The aim of the present study was to investigate the physiological significance of the neuropeptide arginine vasopressin (AVP) released within the septum, in the behavioural response of rats to stress. In the first experiment, rats were chronically implanted with a microdialysis probe aimed at the mediolateral or ventral septum to monitor the local release of AVP in response to 10 min of forced swimming in 20 degrees C warm water. Exposure to this stressor caused a significant increase in AVP release in both the mediolateral (174 +/- 21%, P < 0.01) and ventral septum (220 +/- 33%, P < 0.01). In contrast, microdialysates collected outside the mediolateral septum or in the lateral ventricle remained at prestress levels throughout the dialysis period. Furthermore, unstressed control animals failed to show significant alterations in vasopressin release in the mediolateral septum. In a second experiment, the introduction of the V1 receptor antagonist d(CH2)5Tyr(Me)AVP into the mediolateral septum via inverse microdialysis concomitant with stressor exposure caused the rats to spend an increased time floating and a reduced time swimming compared to vehicle-treated rats. This effect was acute and also detected 24 h after antagonist administration. Taken together, these findings demonstrate a significant activation of the septal vasopressinergic system in response to swim stress. Furthermore, our data support the view that AVP released within this brain area is involved in the generation of active behavioural strategies aimed at coping with new and challenging situations.

Adaptation, Psychological↗

NDP kinase 2 interacts with two oxidative stress-activated MAPKs to regulate cellular redox state and enhances multiple stress tolerance in transgenic plants.

NDP kinases (NDPKs) are multifunctional proteins that regulate a variety of eukaryotic cellular activities, including cell proliferation, development, and differentiation. However, much less is known about the functional significance of NDPKs in plants. We show here that NDPK is associated with H(2)O(2)-mediated mitogen-activated protein kinase signaling in plants. H(2)O(2) stress strongly induces the expression of the NDPK2 gene in Arabidopsis thaliana (AtNDPK2). Proteins from transgenic plants overexpressing AtNDPK2 showed high levels of autophosphorylation and NDPK activity, and they have lower levels of reactive oxygen species (ROS) than wild-type plants. Mutants lacking AtNDPK2 had higher levels of ROS than wild type. H(2)O(2) treatment induced the phosphorylation of two endogenous proteins whose molecular weights suggested they are AtMPK3 and AtMPK6, two H(2)O(2)-activated A. thaliana mitogen-activated protein kinases. In the absence of H(2)O(2) treatment, phosphorylation of these proteins was slightly elevated in plants overexpressing AtNDPK2 but markedly decreased in the AtNDPK2 deletion mutant. Yeast two-hybrid and in vitro protein pull-down assays revealed that AtNDPK2 specifically interacts with AtMPK3 and AtMPK6. Furthermore, AtNDPK2 also enhances the myelin basic protein phosphorylation activity of AtMPK3 in vitro. Finally, constitutive overexpression of AtNDPK2 in Arabidopsis plants conferred an enhanced tolerance to multiple environmental stresses that elicit ROS accumulation in situ. Thus, AtNDPK2 appears to play a previously uncharacterized regulatory role in H(2)O(2)-mediated MAPK signaling in plants.

Arabidopsis↗

Regeneration of peroxiredoxins during recovery after oxidative stress: only some overoxidized peroxiredoxins can be reduced during recovery after oxidative stress.

Peroxiredoxins (prx) are redox enzymes using an activated cysteine as their active site. This activated cysteine can be easily overoxidized to cysteine sulfinic acid or cysteine sulfonic acid, especially under oxidative stress conditions. The regeneration of peroxiredoxins after a short, intense oxidative stress was studied, using a proteomics approach. Important differences in regeneration speed were found, prx2 being the fastest regenerated protein, followed by prx1, whereas prx3 and prx6 were regenerated very slowly. Further study of the mechanism of this regeneration by pulse-chase experiments using stable isotope labeling and cycloheximide demonstrated that the fast-regenerating peroxiredoxins are regenerated at least in part by a retroreduction mechanism. This demonstrates that the overoxidation can be reversible under certain conditions. The pathway of this retroreduction and the reasons explaining the various regeneration speeds of the peroxiredoxins remain to be elucidated.

Binding Sites↗

How you know when you're stressed: self-evaluations of stress.

One hundred participants were asked to list 5 cues that they use to determine their level of stress. The responses were tabulated, and the 25 most frequent responses were retained for further analyses. A sorting task was used to assess the relationships among cues, and a similarity matrix was developed from the responses. This similarity matrix was subjected to cluster analysis. The results yielded a taxonomy of cues to stress.

Adaptation, Psychological↗