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PubMed2005

ATM deficiency induces oxidative stress and endoplasmic reticulum stress in astrocytes.

ATM kinase, the product of the ataxia telangiectasia mutated (Atm) gene, is activated by genomic damage. ATM plays a crucial role in cell growth and development. Here we report that primary astrocytes isolated from ATM-deficient mice grow slowly, become senescent, and die in culture. However, before reaching senescence, these primary Atm(-/-) astrocytes, like Atm(-/-) lymphocytes, show increased spontaneous DNA synthesis. These astrocytes also show markers of oxidative stress and endoplasmic reticulum (ER) stress, including increased levels of heat shock proteins (HSP70 and GRP78), malondialdehyde adducts, Cu/Zn superoxide dismutase, procaspase 12 cleavage, and redox-sensitive phosphorylation of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2). In addition, HSP70 and ERK1/2 phosphorylation are upregulated in the cerebella of ATM-deficient mice. This increase in ERK1/2 phosphorylation is seen primarily in cerebellar astrocytes, or Bergmann glia, near degenerating Purkinje cells. ERK1/2 activation and astrogliosis are also found in other parts of the brain, for example, the cortex. We conclude that ATM deficiency induces intrinsic growth defects, oxidative stress, ER stress, and ERKs activation in astrocytes.

Animals↗
PubMed1995

Oxidative stress and recovery from oxidative stress are associated with altered ubiquitin conjugating and proteolytic activities in bovine lens epithelial cells.

Roles for ubiquitin (an 8.5 kDa polypeptide) involve its conjugation to proteins as a signal to initiate degradation and as a stress protein. We investigated ubiquitin conjugation and ubiquitin-dependent proteolytic activities in cultured bovine lens epithelial cells (BLECs) upon oxidative challenge. A 44% decrease in intracellular glutathione confirmed oxidative stress upon incubation with 1 mM H2O2. After 30 min incubation, endogenous high-molecular-mass ubiquitin conjugates decreased 73%, and intracellular proteolysis decreased about 50%. In the supernatants of the oxidatively treated BLECs, the ability to form high-molecular-mass ubiquitin conjugates with exogenous 125I-labelled ubiquitin decreased 28%, and ATP-dependent degradation of oxidized alpha-crystallin decreased 36%. When the H2O2-treated BLECs were allowed to recover for 60 min, intracellular proteolysis returned to the level of control cells. There was also a subsequent transient enhancement of intracellular proteolysis and a simultaneous recovery of endogenous high-molecular-mass ubiquitin conjugates. In parallel cell-free experiments, conjugating activity with exogenous 125I-labelled ubiquitin and ATP-dependent degradation of oxidized alpha-crystallin increased 35% and 72% respectively compared with non-oxidatively treated BLECs. ATP-independent proteolysis showed little response to exposure or removal of H2O2. These results indicate that (1) the rate of intracellular proteolysis in BLECs is associated with the level of endogenous high-molecular-mass ubiquitin conjugates and (2) oxidative stress may inactivate the ubiquitin conjugation activity with coordinate depression of proteolytic capability. Enhancement in ubiquitin conjugation and proteolytic activities during recovery from oxidative stress may be important in removal of damaged proteins and restoration of normal function of BLECs. The inactivation of ubiquitin-dependent proteolysis by oxidation may be involved in the accumulation of altered proteins and other adverse sequelae in the oxidatively challenged aging lens.

Adenosine Triphosphate↗
PubMed1995

The Claybury Community Psychiatric Nurse Stress Study: is it more stressful to work in hospital or the community?

The Claybury community psychiatric nurse (CPN) stress study collected data on stress levels in 250 CPNs and 323 ward-based psychiatric nurses (WBPN) in the North East Thames region. Four out of 10 CPNs were found to be experiencing high levels of psychological distress on GHQ scores. Whilst both CPNs and WBPNs scored highly on scores of occupational burnout, especially on emotional exhaustion scores, WBPNs scored worse on emotional detachment from their patients and were achieving less personal fulfilment from their work. Both groups of nurses were more satisfied with direct patient clinical work than with their employment conditions, particularly their working environments and, for CPNs, their relationships with their managers. The different patterns of coping skills are explored and discussed for both groups of nurses, especially the use of social support, time management and organization of tasks. The study concludes that whilst major changes are occurring in the psychiatric arena for both groups of nurses, stress is reaping its toll on mental health nurses, in terms of higher absence rates, lower self-esteem and personal unfulfilment. This could not only affect the quality of patient care but also future career prospects for nurses. The study invites serious consideration of introducing stress-reducing measures in the work-place as well as further research into specific stressors for different groups of nurses.

Adaptation, Psychological↗
PubMed2001

Paradoxical effects of chronic morphine treatment on the temperature and pituitary-adrenal responses to acute restraint stress: a chronic stress paradigm.

Body temperature and pituitary-adrenal responses to restraint (15 min or 4 h) stress were evaluated in nondependent and morphine-dependent rats. Male Sprague-Dawley rats were treated twice daily with increasing doses of morphine (10-100 mg/kg, s.c.) for 16 days. Transmitters were implanted in the peritoneal cavity to monitor body temperature and blood was collected for hormone assays. Acute withdrawal from chronic morphine treatment was associated with reduced body weight, increased adrenal weight and decreased thymus weight. Sixteen days after termination of chronic morphine treatment, rats had recovered normal adrenal size, but still displayed marked thymus involution and reduced body weight. Restraint-induced hyperthermia was attenuated in morphine-dependent rats that had undergone 12-h withdrawal. Sixteen days after withdrawal, rats still had not fully recovered the hyperthermic response to restraint. Chronic morphine treatment resulted in a marked elevation of basal corticosterone concentrations. Despite the negative-feedback effects of elevated basal corticosterone concentrations, morphine-dependent rats that had undergone 12-h withdrawal displayed a potentiated and prolonged corticosterone response to restraint stress. In contrast, rats that had undergone 8-day and 16-day morphine withdrawal had recovered normal basal pituitary-adrenal activity, but displayed significantly reduced and shorter adrenocorticotropic hormone and corticosterone responses to restraint. These results suggest that chronic morphine dependence is a chronic stressor, resulting in profound and long-lasting changes in the temperature and pituitary-adrenal responses to acute restraint stress in a time-dependent manner. This morphine-dependence model may be useful in understanding the role that hormonal stress responses play in the maintenance and relapse to opioid use in humans.

Acute Disease↗
PubMed2003

Pups presence eliminates the stress hyporesponsiveness of early lactating females to a psychological stress representing a threat to the pups.

Blunted neuroendocrine responses to stress are reported in lactating females after exposure to various stressors. However, many of the stimuli used in these studies have little ethological relevance for maternal protection of the litter in a threatening environment. The question that arises is whether the relevance of the stressor to the infant is critical in the 'gating' of the neuroendocrine response. We hypothesized that the presence of pups with their mothers at the time of exposure to an intruder or a predator odour is an effective way to increase the emotional salience of the psychological stressor, thus eliminating the stress hyporesponsiveness in lactating females. We first compared neuroendocrine responses [corticotropin-releasing factor (CRF) mRNA in the paraventricular nucleus of the hypothalamus (PVN) and central nucleus of the amygdala (CeA), plasma adrenocorticotropic hormone (ACTH) and corticosterone] between early (EL, PPD3-5), late (LL, PPD 15) lactating and virgin (V) females to a male intruder in the home cage. We next investigated the effect of pups' presence at the time of stressor exposure on the magnitude of the hormonal response to a male intruder in the home cage or to a predator odour (fox urine) in a novel environment. In the male intruder paradigm, levels of CRF mRNA expression in the PVN and CeA were lower in LL compared to EL or V females and plasma ACTH and corticosterone secretion was not as elevated in LL compared to EL females. Aggression towards the intruder was high in EL females in the presence of their pups and a positive correlation was found with the integrated ACTH response. Aggression rapidly declined after pup separation (2.5 h or 48 h) or in LL nursing females. In EL females, the presence of the pups with their mothers (EL + pups) at the time of stress significantly increased plasma ACTH and corticosterone responses to either male intruder or predator odour compared to EL females without their pups for 2.5 h or 48 h (EL - pups). Plasma ACTH response to fox urine in EL + pups females was comparable to that of virgin females, suggesting that increasing the salience of emotionally relevant stimuli by keeping the pups present in the cage could eliminate the hyporesponsiveness detected for EL females without their pups. These studies indicate the critical role of the pups in modulating the maternal response to stressors that represent a threat for the litter. We hypothesize that the amygdala, because of its ability to process olfactory stimuli and stimuli with affective properties, might play an essential role in 'gating' the neuroendocrine response to stress during lactation.

Adrenocorticotropic Hormone↗
PubMed2000

The effect of acute restraint stress on regional brain neurotransmitter levels in stress-susceptible pietrain pigs.

Concentrations of noradrenaline (NA), adrenaline (A), dopamine (DA), 5-hydroxytryptamine (5-HT), the DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and the main 5-HT metabolite 5-hydroxyindole-3-acetic acid (5-HIAA) were measured using HPLC in 16 brain areas of control and immobilized Pietrain pigs. The animals were immobilized for 15, 30 and 60 min in the prone position. Control pigs showed patterns of regional distribution of brain monoamines similar to those described for rats, dogs and Duroc pigs. However, the absolute values of NA and A in the hypothalamus and preoptic area were much higher than those in rats and dogs, but similar to those in Duroc pigs. The concentrations of dopamine and its metabolites DOPAC and HVA were highest in the caudate nucleus, the nucleus accumbens, the olfactory tubercle and the ventral tegmental area. The distributions of serotonin and its metabolite 5-HIAA were similar in all examined structures. DOPAC/DA and HVA/DA ratios were higher in the cornu ammonis, the hippocampus posterior and the raphe nuclei than in other structures, which suggests brain structure-related differences in dopamine turnover. The greatest decreases in NA and A content were observed in the hypothalamus, the preoptic area and the olfactory tuberculum during the first 30 min of immobilization stress. 5-HT turnover was increased in the raphe nuclei, while DA turnover was affected in the raphe nuclei, the septum, the substantia nigra and the olfactory tubercle. We suggest that acute immobilization stress caused differences in regional patterns of brain biogenic amines, thereby maintaining adequate transmitter levels during stress in stress-susceptible pigs.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

The oxidative stress response in Enterococcus faecalis: relationship between H2O2 tolerance and H2O2 stress proteins.

The hydrogen peroxide (H2O2) stress response in Enterococcus faecalis ATCC19433 was investigated. A 2.4 mmol l-1 H2O2 pretreatment conferred protection against a lethal concentration (45 mmol l-1) of this agent. The relatively high concentrations of H2O2 used for adaptation and challenge treatments in Ent. faecalis emphasised the strong resistance towards oxidative stress in this species. Various stresses (NaCl, heat, ethanol, acidity and alkalinity) induced weak or strong H2O2 cross-protection. This paper describes the involvement of protein synthesis in the active response to lethal dose of H2O2, in addition to the impressive enhancement of synthesis of five H2O2 stress proteins. Combined results suggest that these proteins might play an important role in the H2O2 tolerance response.

Bacterial Proteins↗
PubMedDate not supplied

[The Inflammatory Bowel Disease Stress Inventory (IBD-SI). A measure of psychosocial stress in patients with IBD].

The "Inflammatory Bowel Disease Stress Inventory (IBD-SI)" measures a broad spectrum of disease-specific every day stress factors in patients with inflammatory bowel disease (IBD). Based on a multistage factor analysis on 300 CED patients, the final form comprises 32 items assigned to 8 different domains: depressed mood, doctor-patient relationship, anxiety about loss of bowel control, occupational impairment, worries about deteriovation, stress from medical treatment, impairment of sexuality/partnership and physical complaints. In addition, a global stress score can be obtained. The reliability values of the 8 subscales with 4 items each indicate a good internal consistency (alpha = 0.76 - 0.89) and a high retest reliability (r = 0.75 - 0.92). Significant correlations with medical and psychological variables supports the external validity of this questionnaire.

Adult↗
PubMed1987

[Is there a correlation between the degree of proliferation of vaginal and urethral epithelium and the incidence of stress incontinence? A contribution to estrogen therapy in stress incontinence].

The extent of proliferation of the vaginal and urethral epithelium, as well as urodynamic parameters, were studied in 232 patients in order to determine whether there is a relation between the development of stress incontinence and hormone-related epithelial proliferation. A higher build-up of vaginal than of urethral epithelium was found in 74% of the patients. Even in post-menopause patients, epithelial atrophy in the vagina was only found in 29.3%, while in the urethra it was found in 61.3%. Therefore, the vaginal epithelium cannot with confidence be taken as a basis for conclusions concerning the condition of the urethral epithelium. In the group of 145 patients with urinary stress incontinence no link could be established between the extent of proliferation of the urethral epithelium, the urethral occlusion pressure and the functional length of the urethra: The occurrence of an age-related excessively low urethral occlusion pressure (hypotonic urethra) is independent of the extent of proliferation of the vaginal or urethral epithelium. Sedimentation phenomena are also seen equally frequently in cases with atrophic and eutrophic epithelium. Owing to the high percentage of overweight women among those with stress incontinence, the extent of proliferation of the vaginal and urethral epithelium often corresponds to premenopausal cell pictures even in perimenopausal and postmenopausal women; this is a consequence of increased estrogen production in the peripheral fatty tissue. Therefore, estrogen therapy is unsuccessful in women with pure urinary stress incontinence. However, the efficacy of an equivalent therapy, e.g., with estriol, has been confirmed in cases of active and combined incontinence.

Atrophy↗
PubMed1987

[Interpretation of the stress pressure profile in the diagnosis of female stress incontinence].

In 94 stress pressure profiles the electronically measured occlusion pressure under stress with a bladder filling of 100 ml in dorsosacral position and 300 ml in sitting position was compared with the computed value in the proximal and medial thirds of the urethra. Electronic measurement furnishes low, statistically confirmed occlusion pressure values. With a bladder filling of 300 ml in sitting position, urodynamic assessment of incontinence on the basis of the electronic occlusion pressure furnishes corresponding findings in over 70% of patients, while the extent of agreement with the computed values seems unsatisfactory. In stress pressure profiles, in accordance with clinical considerations and radiological studies, the proximal urethra should also be assessed as the first portion of the continence-preserving zones. The occlusion pressure, electronically measured under routine conditions, is the parameter which furnishes the most information for the urodynamic diagnosis of stress incontinence.

Female↗
PubMed1985

Congruent stress-preventing factors and anxiety in a long-term stress situation.

The relationship of state anxiety to personal and social stress-preventing factors and to criterion measure was examined in 38 family men who were recent immigrants to Israel from Western countries. As predicted, state anxiety accounted for more variance in the criterion measure of stated intention of remaining in Israel than all the stress-preventing factors combined. Moreover, approximately half of the effect of the latter factors on the criterion was achieved through the anxiety variable. Given the modest sample size, the specific findings are regarded as tentative, but the general conclusion of the study appears to be amply supported. Namely, the level of state anxiety in the individual may be regarded as an index of the effectiveness of the various stress-preventing factors operating in the situation and as a stress-preventing factor in its own right that directly affects problem-solving behavior and outcomes.

Adaptation, Psychological↗
PubMed2003

Stress discourse and Western biomedical ideology: rewriting stress.

Popular psychosocial theories of stress and coping are based on an empiricist paradigm and a Western biomedical framework that reflect Western ideologies and values about health and illness. Problems associated with this discourse lie mainly in the ideologies that emphasize naturalism, individualism, rationalism, and objectivity. We suggest that stress and coping theory should be concerned with the ways in which power relations and social institutions produce the meaning of stress. The inclusion of alternative discourses that attend to the micro and macro social and historical factors is necessary for the further development of stress and coping theory and practice.

Communication↗
PubMed2006

Life stress, coping and comorbid youth: an examination of the stress-vulnerability model for substance relapse.

The stress-vulnerability model of addiction relapse states that the impact of life stress on alcohol and other drug use is influenced by several types of psychosocial risk and protective factors. Coping skills have been shown to be protective against alcohol or other drug use in adolescents and adults. To date, the influence of life stress and coping on addiction relapse has not been investigated among substance use disordered youth with comorbid Axis I psychopathology. In the present study, 80 adolescents, ages 13 to 17, were followed six months after treatment for substance use and Axis I disorders. Participants completed measures of psychopathology, substance use, life stressors and coping during treatment and at three and six months following treatment. Coping ability best predicted youth substance use at six months. Negative life events moderated the relation between coping and frequency of substance use. These results suggest that coping is a protective factor for return to substance involvement post-treatment, particularly for comorbid youth who have experienced high levels of life stress.

Adaptation, Psychological↗
PubMed2001

GP stress and patient dissatisfaction with nights on call: an exploratory study. GP stress and patient satisfaction.

OBJECTIVES: To compare the relative effects of being on or off duty at night on general practitioners' (GPs') levels of stress, and the satisfaction of their patients with daytime consultations surrounding these nights. DESIGN: A within-subjects, counterbalanced design was used. Two "on-call" and two "off-duty" nights were studied per GP over 4 weeks. SETTING: Primary health care in the UK. PARTICIPANTS: 26 GPs and their patients seen in consultations either side of nights studied. MAIN OUTCOME MEASURES: GPs completed validated stress questionnaires at the beginning and end of the consultation sessions immediately before and after nights on call and off duty. RESULTS: GPs experienced elevated levels of stress when on call, compared to when they were off duty. Patients seen in the consultation sessions before and after a night on call were less satisfied than patients seen before and after a night off duty. CONCLUSION: Being on call at night raised GP stress levels from at least the start of the afternoon consultation session before until the end of the morning consultation after the night on call. Daytime patient satisfaction is also reduced in periods surrounding nights on call.

Adult↗
PubMed1993

The role of chemical-induced stress responses in immunosuppression: a review of quantitative associations and cause-effect relationships between chemical-induced stress responses and immunosuppression.

Although there is an increasing awareness that drugs and chemicals can modulate the immune system by indirect mechanisms, few compounds have been thoroughly evaluated in this regard. Several environmentally relevant chemicals induce stresslike responses, as indicated by elevated glucocorticoid levels. Comparable glucocorticoid levels induced by physical or psychological stressors are consistently associated with suppression of one or more immunological parameters. Thus, it seems likely that stress-related neuroendocrine mechanisms are important in immunosuppression by some environmental chemicals. Distinguishing direct and indirect (stress-related) mechanisms of immunosuppression is generally possible, and this could be done as a routine part of immunotoxicity assessment. Although it is clear that glucocorticoids can contribute to such immunosuppression, it is also clear that several other neuroendocrine mediators associated with stress responses can be immunomodulatory. Thus, correlation between glucocorticoid levels and immunosuppression does not conclusively demonstrate a cause-effect relationship. Demonstrating such relationships has been difficult, but it has been done in a few cases of drug-induced thymic hypoplasia by monitoring several parameters known to be affected by glucocorticoids and by measuring the ability of a glucocorticoid antagonist (RU 486) or adrenalectomy to block changes in these parameters. A similar strategy might be useful for evaluation of the role of glucocorticoids in drug- or chemical-induced suppression of a variety of immune functions, but the effects of RU 486 on neuroendocrine feedback circuits and the possibility of consequent immunological changes must be considered when the data are interpreted. This approach could also be applied to evaluation of the roles in chemical-induced immunosuppression of other neuroendocrine mediators for which antagonists or agents that block the synthesis or release of the mediator are available. However, it is likely that a comprehensive (and perhaps predictive) understanding of the relationship between chemically induced stress responses and immunosuppression will require more detailed and quantitative elucidation of the mechanisms and regulation of neuroendocrine-immune interactions.

Animals↗
PubMedDate not supplied

Nitrosative stress, cellular stress response, and thiol homeostasis in patients with Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder with cognitive and memory decline, personality changes, and synapse loss. Increasing evidence indicates that factors such as oxidative and nitrosative stress, glutathione depletion, and impaired protein metabolism can interact in a vicious cycle, which is central to AD pathogenesis. In the present study, we demonstrate that brains of AD patients undergo oxidative changes classically associated with a strong induction of the so-called vitagenes, including the heat shock proteins (HSPs) heme oxygenase-1 (HO-1), HSP60, and HSP72, as well as thioredoxin reductase (TRXr). In inferior parietal brain of AD patients, a significant increase in the expression of HO-1 and TRXr was observed, whereas HO-2 expression was decreased, compared with controls. TRHr was not increased in AD cerebellum. Plasma GSH was decreased in AD patients, compared with the control group, and was associated with a significant increase in oxidative stress markers (i.e., GSSG, hydroxynonenal, protein carbonyl content, and nitrotyrosine). In AD lymphocytes, we observed an increased expression of inducible nitric oxide synthase, HO-1, Hsp72, HSP60, and TRXr. Our data support a role for nitrative stress in the pathogenesis of AD and indicate that the stress-responsive genes, such as HO-1 and TRXr, may represent important targets for novel cytoprotective strategies.

Aged↗
PubMed1996

Stress and stress-related hormones during in-vitro fertilization treatment.

Whether stress and infertility are linked as cause or consequence is unclear, and there is no consensus on the most appropriate methods for measuring stress in infertile women. To address this question, we measured changes in biochemical and questionnaire-based assessments of stress in infertile women. Median baseline, follicular phase and pre-operative serum prolactin (229, 311 and 457 mIU/l) cortisol (278, 369 and 496 nmol/l) and state anxiety score (38, 40 and 49) respectively all increased during stimulated in-vitro fertilization (IVF) treatment. There was no such increase in a control group having similar laparoscopic surgery unrelated to infertility, or in women having unstimulated IVF without laparoscopy, suggesting that anxiety levels are greatest in stimulated IVF, increase as a result of the treatment, and are adequately reflected by state anxiety scores. Baseline serum prolactin in unstimulated IVF (384 mIU/l) was significantly higher than control (177 mIU/l), although this was not reflected in serum cortisol or state anxiety score. Trait anxiety was constant within and between groups, suggesting that stress is not contributing greatly to the infertility. Women who achieved a pregnancy had similar state anxiety scores to those who failed, suggesting that the degree of anxiety observed during IVF treatment is unlikely to influence the chance of pregnancy. There was a trend towards lower trait anxiety in women who became pregnant, but the numbers were small.

Anxiety↗
PubMed2001

Accumulation of plastid lipid-associated proteins (fibrillin/CDSP34) upon oxidative stress, ageing and biotic stress in Solanaceae and in response to drought in other species.

Plastid lipid-associated proteins, also termed fibrillin/CDSP34 proteins, are known to accumulate in fibrillar-type chromoplasts such as those of ripening pepper fruit, and in leaf chloroplasts from Solanaceae plants under abiotic stress conditions. It is shown here that treatments generating active oxygen species (high light combined with low temperature, gamma irradiation or methyl viologen treatment) result in potato CDSP34 gene induction and protein accumulation in leaves. Using transgenic tomato plants containing the pepper fibrillin promoter, a significant increase in promoter activity in leaves subjected to biotic stress, namely bacterial infections, was observed. In WT, a higher level of the endogenous fibrillin/CDSP34 protein is also observed after infection by E. chrysanthemi strain 3739. In addition to stress-related induction, a progressive increase in the fibrillin promoter activity is noticed during ageing in various tomato photosynthetic tissues and this increase correlates with a higher abundance of the endogenous protein in WT leaves. It is proposed that a mechanism related to oxidative events plays an essential role in the regulation of fibrillin/CDSP34 genes during stress and also during development. Using a biolistic transient expression assay, the pepper fibrillin promoter is found to be active in various dicot species, but not in monocots. Further, substantially increased levels of fibrillin/ CDSP34 proteins are shown in various dicotyledonous and monocotyledonous plants in response to water deficit.

Adaptation, Physiological↗