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At least 19 recordsLinked to original sources

Recovery of the hypothalamic-pituitary-adrenal response to stress. Effect of stress intensity, stress duration and previous stress exposure.

Pathological consequences of stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis may be related to the duration rather than to the intensity of HPA axis activation after exposure to the stressor. Consequently a fine analysis of post-stress events is of importance. The present experiments were designed to study the importance of three key factors in HPA recovery: intensity of the stressor (experiment 1), duration of exposure to the stressor (experiment 2) and previous experience of the animals with the situation (experiments 3 and 4). In experiment 1, analysis of both the response to the stressor and the poststress period showed that the stronger the stressor, the greater the area under the curve of HPA activation. In experiment 2, different groups of rats were exposed to different periods of immobilization (IMO) (20 min, 1 h and 2 h) and sampled before, during and after exposure to IMO. The speed of recovery of plasma corticotropin (ACTH) levels was not related to the duration of exposure to the stressor. In experiments 3 and 4, the influence of previous experience with the stressor was studied in rats daily exposed to 20 min IMO or daily injected with hypertonic saline (HS) for 8 days and sampled on days 1, 2, 5 and 8. Whereas a significant decline in plasma ACTH levels was not observed immediately after IMO until day 8, a single previous exposure to IMO was enough to enhance recovery 90 min after the end of exposure to IMO. Corticosterone levels were related to the number of previous experiences with the stressor only in the post-IMO period. In response to a novel stressor (forced swimming), chronic IMO rats showed a slightly impaired recovery as compared to stress-naive rats, suggesting that enhanced recovery of the HPA axis was specific for the homotypic stressor. After daily HS injections, a pattern similar to that after IMO was observed, the delayed, but not the early response of the HPA axis being reduced as a function of the number of previous experiences with the situation. Taken together, the present results suggest that the speed of recovery of the HPA axis after its activation by stressors is sensitive to the intensity of the stressors but not to their duration, and that adaptation to a repeated stressor is more apparent during the delayed HPA response.

Adrenocorticotropic Hormone↗

[Stress assessment method for workers (Part 2)--The diagnostic analyses and judgements of stressful conditions of stress-dock examinees on the basis of the total score of numerical-valued stressors they have suffered for the past 1 year].

In order to evaluate the grade of reaction to stressors, especially those in the occupational life of workers, the following stress survey was conducted. This survey consisted of 65 stress questionnaires based on the social readjustment rating scale prepared by Holmes and Rahe, including 18 new questionnaires on the occupational environment. The method is as follows. That is, marriage is given a score of 50 in reference-standard for stress strength and these 65 items for 1,630 workers were evaluated by self-rating method ranging in score from 0 to 100. As for each item, we found the average value for the total sample and we called it the stress score. The subject group (1,426 employees who were examined for Stress-Dock) judged their experience during the past 1 year by their stress scores. The stress scores for the stressors experienced in a year were summed (total experienced stress score). We examined whether the total experienced stress score would be an index of the degree of stress, etc. We then analyzed the relationship between the total experienced stress score and stress conditions (i.e. "severe (hereafter, the assumed severe group)", "borderline (borderline group)" and "not severe (not severe group)"). In addition, the relationship between the total experienced stress score and mental disorders (stress related diseases were the majority) diagnosed by ICD-10 was examined. Our findings and conclusions are as follows: 1. We presented two typical cases. Next, the distribution of the total experienced stress score in all subjects was shown. 2. The average total experienced stress score increased from 135 to 219 points and 312 points in the order, not severe group, borderline group and severe group. It was paid noticeable that the severe group had scores 2.3 high times higher the not severe group. 3. The mental disorders group diagnosed with ICD-10 as mental disorders was large including 888 people, and the average total score for experienced stress score was a high 312 points. This was, as many as 94 points higher than in the normal group, and a significant difference was admitted by both. The difference of 1.1 point was admitted in the LCU numbers. Moreover, in statistical analysis, the score method showed a high significant difference according to F41 and F43 compared with the number of LCU items. We thought that the difference of the score method was more comprehensible than that of the number of LCU items as a result. 4. We took the possible total experienced stress score as 100 points, and examined the score for patients with mental disorders. It was 78.8% in the group with a high 400 points or more, but percentage for patients with mental disorders was only 39.3% in less than 100 points. The greater the point increases the higher the frequency of the appearance of disease. 5. We thought that we were able to measure the degree of worker's stress to obtain the total experienced stress score from life event in the above-mentioned way.

Adult↗

Acute stress enhances while chronic stress suppresses skin immunity. The role of stress hormones and leukocyte trafficking.

Delayed-type hypersensitivity (DTH) reactions are antigen-specific, cell-mediated immune responses that, depending on the antigen, mediate beneficial (resistance to viruses, bacteria, fungi) or harmful (allergic dermatitis, autoimmunity) aspects of immunity. Contrary to the widely held notion that stress is immunosuppressive, we have shown that under certain conditions, stress can enhance immune function. DTH reactions can be studied in rats or mice by challenging the pinnae of previously sensitized animals with antigen. Studies have shown that acute stress administered immediately before antigen exposure significantly enhances skin DTH. In contrast, chronic stress significantly suppresses skin DTH. Stress-induced changes in leukocyte distribution may contribute to these bidirectional effects of stress, since acute stress induces a significant mobilization of leukocytes from the blood to the skin, whereas chronic stress suppresses leukocyte mobilization. In order to identify the hormonal mediators of the observed effects of stress, we first showed that adrenalectomy (ADX) eliminates the stress-induced enhancement of DTH. Acute administration (to ADX animals) of low doses of corticosterone and/or epinephrine significantly enhances skin DTH. In contrast, acute administration of high doses of corticosterone, low doses of dexamethasone, or chronic administration of moderate doses of corticosterone, suppress skin DTH. Thus, the timing and duration of stress may significantly affect the nature (enhancing versus suppressive) of the effects of stress on skin immune function. These results suggest that during acute stress, stress hormones may help enhance immune function by informing the immune system about impending challenges (e.g., wounding or infection) that may be imposed by a stressor (e.g., an aggressor). Thus, during acute stress, the brain may send a warning signal to the immune system, just as it does to other fight/flight systems in the body.

Acute Disease↗

Moderating factors explaining stress reactions: comparing chronic-without-acute-stress and chronic-with-acute-stress situations.

The author compared patterns of moderating factors explaining stress reactions during 2 states: chronic-without-acute-stress and chronic-with-acute-stress. She hypothesized that personal dispositions would contribute more to understanding stress reactions during a prolonged stress state than during an acute state. The participants were Israeli Jewish adolescents living in West Bank settlements during the prolonged (chronic-without-acute-stress) state of the intifada (the Palestinian uprising against Israeli occupation) and during the chronic-with-acute-stress state, immediately after the assassination of Prime Minister Rabin. The author examined 5 variables as moderating factors--trait anxiety, sense of coherence, cognitive appraisal of the political situation, family sense of coherence, and sense of community--and measured 2 stress reactions--state anxiety and psychological distress. Data were collected from 266 8th-grade students during the chronic-without-acute-stress state and 448 students at the same grade level at the chronic-with-acute-stress state. The overall magnitude of variance explanation was different at each state: The author found a relatively high explained variance of state anxiety and psychological distress in the chronic-without-acute-stress situation but not in the chronic-with-acute stress state. These data support the value of developing a model that would recognize the different types of stress situations for moderating the effects of stress.

Adolescent↗

Stress reactivity of the brain noradrenergic system in three rat strains differing in their neuroendocrine and behavioral responses to stress: implications for susceptibility to stress-related neuropsychiatric disorders.

The brain noradrenergic system is activated by stress, modulating the activity of forebrain regions involved in behavioral and neuroendocrine responses to stress. In this study, we characterized brain noradrenergic reactivity to acute immobilization stress in three rat strains that differ in their neuroendocrine stress response: the inbred Lewis (Lew) and Wistar-Kyoto (WKY) rats, and outbred Sprague-Dawley (SD) rats. Noradrenergic reactivity was assessed by measuring tyrosine hydroxylase mRNA expression in locus coeruleus, and norepinephrine release in the lateral bed nucleus of the stria terminalis. Behavioral measures of arousal and acute stress responsivity included locomotion in a novel environment, fear-potentiated startle, and stress-induced reductions in social interaction and open-arm exploration on the elevated-plus maze. Neuroendocrine responses were assessed by plasma adrenocorticotropic hormone. Compared to SD, adrenocorticotropic hormone responses of Lew rats were blunted, whereas those of WKY were enhanced. The behavioral effects of stress were similar in Lew and SD rats, despite baseline differences. Lew had similar elevations of tyrosine hydroxylase mRNA, and initially greater norepinephrine release in the lateral bed nucleus of the stria terminalis during stress, although both noradrenergic responses returned toward baseline more rapidly than in SD rats. WKY rats showed depressed baseline startle and lower baseline exploratory and social behavior than SD. However, unlike the Lew or SD rats, WKY exhibited a lack both of fear potentiation of the startle response and of stress-induced reductions in exploratory and social behavior, indicating attenuated stress responsivity. Acute noradrenergic reactivity to stress, measured by either tyrosine hydroxylase mRNA levels or norepinephrine release, was also attenuated in WKY rats. Thus, reduced arousal and behavioral responsivity in WKY rats may be related to deficient brain noradrenergic reactivity. This deficit may alter their ability to cope with stress, resulting in the exaggerated neuroendocrine responses and increased susceptibility to stress-related pathology exhibited by this strain.

Animals↗

Brief psychological interventions ("debriefing") for trauma-related symptoms and the prevention of post traumatic stress disorder.

OBJECTIVES: To assess the effectiveness of brief psychological debriefing for the management of psychological distress after trauma, and the prevention of post traumatic stress disorder. SEARCH STRATEGY: Electronic searching of MEDLINE, EMBASE, PsychLit, PILOTS, Biosis, Pascal, Occ.Safety and Health, CDSR and the Trials Register of the Depression, Anxiety and Neurosis group. Hand search of Journal of Traumatic Stress. Contact with leading researchers. SELECTION CRITERIA: The inclusion criteria for all randomized studies was that they should focus on persons recently (one month or less) exposed to a traumatic event, should consist of a single session only, and that the intervention involve some form of emotional processing/ventilation by encouraging recollection/reworking of the traumatic event accompanied by normalisation of emotional reaction to the event. DATA COLLECTION AND ANALYSIS: 8 trials fulfilled the inclusion criteria. Quality was generally poor. Data from two trials could not be synthesised. MAIN RESULTS: Single session individual debriefing did not reduce psychological distress nor prevent the onset of post traumatic stress disorder (PTSD). Those who received the intervention showed no significant short term (3-5 months) in the risk of PTSD (pooled odds ratio 1.0, 95% ci 0.6-1.8). At one year one trial reported that there was a significantly increased risk of PTSD in those receiving debriefing (odds ratio 2.9, 95% ci 1.1-7.5). The pooled odds ratio for the two trials with follow ups just included unity (odds ratio 2.0, 95% ci 0.9-4.5). There was also no evidence that debriefing reduced general psychological morbidity, depression or anxiety. REVIEWER'S CONCLUSIONS: There is no current evidence that psychological debriefing is a useful treatment for the prevention of post traumatic stress disorder after traumatic incidents. Compulsory debriefing of victims of trauma should cease.

Crisis Intervention↗

Residual stresses in oscillating thoracic arteries reduce circumferential stresses and stress gradients.

The purpose of this paper is to examine the effects of residual stresses and strains in the oscillating arteries on the stress distribution in the vascular wall. We employ a static theory of large elastic deformations for orthotropic material (Chuong and Fung, 1986, J. biomech. Engng 108, 189-192) with the acceleration term added to make the theory dynamic. We use the static elastic parameters of residual stresses in our analysis because the dynamic parameters are not available in the literature. Our analysis reveals that the effect of considering the residual stresses is to decrease the very large circumferential stresses at the inner wall by 62% and reduces the stress gradient through the arterial wall by 94% compared to the case when residual stresses are ignored. Thus, because the arteries do contain residual stresses, the consequent lower stresses at the inner wall and the reduced stress gradient may reduce the progression of atheroma. Our computations show that the stress gradients do not depend on the heart rate.

Animals↗

Influence of exogenous glucagon on gastric acid secretion, mucosal blood flow, and stress ulcers in the rat: dose-response results under non-stress conditions and immobilization stress.

In non-stressed rats and rats stressed by immobilization, gastric secretion (acid, pepsin), mucosal blood flow (MBF), stress ulcers as well as glucose, insulin, and glucagon in blood were studied during 8 h, with and without additional infusion of exogenous glucagon (0.2, 1.4, 9.8 micrograms/kg/h). Metabolic clearance of glucagon and the disappearance half-time of exogenous glucagon from blood do not differ during zero stress and stress, a fact that favors the assumption of hypersecretion of glucagon as the cause of stress hyperglucagonemia. During stress alone acid secretion (volume, acidity) and MBF are lower than during zero stress; pepsin remains unchanged. Under zero stress condition additionally administered glucagon inhibits pepsin and MBF, but not acid secretion, in a dose-dependent manner. The ulcer index increased without changing the severity of ulcers. During stress the intermediate and highest glucagon doses stimulate MBF and pepsin secretion, other variables remaining unchanged. It is concluded that glucagon effects on functions of the gastric mucosa in the rat vary fundamentally, depending upon the environmental conditions.

Animals↗

Exploration of stress-induced immunosuppression in chickens reveals both stress-resistant and stress-susceptible antigen responses.

In the present study, depriving chickens of foraging material was shown to induce stress. The impact of this type of stress on the immune response was compared with feeding of corticosterone (1.5 mg per bird per day), a hormone known to be immunosuppressive and to be the major stress hormone of chickens. Corticosterone feeding induced stress as revealed by higher heterophil/lymphocyte (H/L) ratios, longer tonic immobility (TI) reaction, reduced body weight gain and reduced egg production. Blood corticosterone levels were increased. Corticosterone feeding decreased the antibody response to tetanus toxoid and SRBC, DTH to PPD from Mycobacterium tuberculosis and the inflammatory response to PHA. Housing chickens on slats also induced chronic stress, as evidenced by increased H/L ratios, prolonged TI duration and decreased egg production. Corticosterone levels were slightly but not significantly enhanced. This novel form of chronic stress strongly suppressed humoral and cellular immune responses as evidenced by lower antibody titers to sheep red blood cells (SRBC) and tetanus toxoid (TT) decreased DTH reaction to PPD and inflammatory reaction to PHA in the skin. In contrast, the antibody response to human serum albumin (HSA) was neither influenced by corticosterone feeding nor by keeping the birds on slats. Even the combination of corticosterone feeding and housing the birds on slats did not significantly impair antibody responses to HSA. In conclusion, the present study showed that chronic stress induced by depriving the birds of foraging material led to a similar impairment of humoral and cell-mediated immunity as did feeding with corticosterone. More importantly, it showed for the first time that depending on the antigen tested, there are stress-resistant and stress-susceptible antigen responses.

Animals↗

[Recognition of stress in workers (report 1)--relationship between recognitions of causes of stress and stress reaction].

Three aspects of the recognition of stress in 665 workers were investigated; namely, causes of stress, stress reactions and modifying factors. We examined the relationship among these aspects, in order to determine some different types of recognition. Several characteristics of the different recognition groups were also examined. 1) The workers who recognized that the causes of their stress were mainly "daily hassles" or "minor events which happened occasionally" accounted for 82.5% of all subjects, and the workers who recognized that their stress was caused mainly by "major life events" accounted for the remaining 17.5%. 2) The subjective stress of the workers in the "major life events" group was significantly larger than that of the workers in "daily hassles". 3) The group with stress due to "daily hassles or minor events" recognized the stress reaction mainly as "irritability", and their actual stressor was "busyness in work". In contrast, the recognition of a stress reaction due to a "major life event" group was represented by "depression/anxiety", and their actual stressors were not only major events such as "promotion or transfer" but also psychological factors such as "low emotional support of family members". 4) The mean age and rank of the "major life event" group were significantly higher than those of the other group.

Adult↗

Energy metabolism in largemouth bass (Micropterus floridanus salmoides) from stressed and non-stressed environments: adaptations in the secondary stress response.

White muscle proteins, carbohydrates, lipids, adenylates, phosphagen and the AEC, (adenylate energy charge) were measured in bass inhabiting stressful and non-stressful environments. Within an environment, in June stressed bass had higher carbohydrates, while non-stressed bass had lower ATP, total adenylates and AEC. Comparisons between environments revealed: non-stressed bass had higher ATP/ADP and AEC's in May, CrP/ATP in June, and protein in July; while stressed bass had higher carbohydrate in June and lipid in July. Other metabolites varied insignificantly. AEC's of both groups were within the optimal range indicating physiological compensation (adaptation) of energy metabolism (secondary stress response) occurred in bass inhabiting the stressful environment.

Acclimatization↗

The effect of stress inoculation training on self-reported stress, observer's rating of stress, heart rate and gymnastics performance.

Eighteen volunteer female subjects received preliminary instruction in a simple gymnastics bench sequence. They were then given a pre-intervention test on a bench at ground level. Self-reported distress, an independent observer's ratings of distress and heart rates were monitored immediately prior to performance of the sequence. Performances were also videotaped and formally scored by a qualified gymnastics judge. Subjects were then randomly assigned to a stress inoculation training group or a 'no stress management' training control group. Stress inoculation group subjects then received seven sessions of training in relaxation, imagery and making self-statements in order to develop a set of coping skills. Control group subjects also received seven training sessions during which they practised a series of coordination exercises, but no psychological stress management training was given to this group. All subjects were then re-tested on the bench sequence but this time at a height of 1.52 m. Self-reported stress, observer's ratings of distress and heart rate were recorded as before. Performance was again videotaped for scoring. The stress inoculation group reported significantly less stress prior to the test on the elevated beam than the control group. However, the groups did not differ in terms of heart rate. Further, the stress inoculation group performed reliably better than the control group on the elevated bench.

Adult↗

A comprehensive model of stress. the roles of experienced stress and neuroticism in explaining the stress-distress relationship.

BACKGROUND: In this study, a complex theoretical model regarding the stress-distress relationship was evaluated. The various components in the model included experienced stress (daily hassles), psychological distress, neuroticism, problem-focused coping, avoidant coping, satisfaction with received social support and unassertiveness. On the basis of various previous findings, experienced stress was assumed to have a direct effect on psychological distress. In addition, neuroticism was assumed to have a direct effect on psychological distress as well as an indirect effect through its association with experienced stress, problem-focused coping, avoidant coping, satisfaction with social support and unassertiveness. Further, both problem-focused and avoidant coping were assumed to affect the level of psychological distress directly as well as indirectly through their influence on experienced stress. Similarly, satisfaction with social support was assumed to have a direct beneficial effect on psychological distress in addition to an indirect effect through its association with coping and experienced stress. Finally, unassertiveness was assumed to have a direct effect on psychological distress as well as an indirect effect through its influence on experienced stress and coping. METHODS: A covariance path analysis technique (LISREL) was used. RESULTS: A considerable predictive power of the model could be demonstrated. Experienced stress and neuroticism turned out to be most predictive of psychological distress. The effects of social support, coping and unassertiveness on psychological distress were seriously attenuated by their common association with neuroticism. CONCLUSION: Above all, the present findings underscore the need to investigate all variables that are expected to play a role simultaneously so as to be able to take their interdependency into account. It is argued that although such comprehensive models may be more difficult to interpret as of yet, they are likely to more closely resemble reality.

Adaptation, Psychological↗

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

Stress-controlled transcription factors, stress-induced genes and stress tolerance in budding yeast.

The transcriptional response to environmental changes is a major topic in both basic and applied research. From a basic point of view, to understand this response includes unravelling how the stress signal is sensed and transduced to the nucleus, to identify which genes are induced under each stress condition and, finally, to establish the phenotypic consequences of this induction in stress tolerance. The possibility of using genetic approaches has made the yeast Saccharomyces cerevisiae a compelling model to study stress response at a molecular level. Moreover, this information can be used to isolate and characterise stress-related proteins in higher eukaryotes and to design strategies to increase stress resistance in organisms of industrial interest. In this review the progress made in recent years is discussed.

Genes, Fungal↗

Stress integration after acute and chronic predator stress: differential activation of central stress circuitry and sensitization of the hypothalamo-pituitary-adrenocortical axis.

Predator exposure is a naturalistic stressor of high ethological relevance. In the current study, our group examined central and peripheral integration of stress responses in rats after acute or repeated exposure to a natural predator (cat). Acute cat exposure rapidly induced hypothalamo-pituitary-adrenocortical (HPA) axis activation and paraventricular nucleus (PVN) CRH mRNA production. Repeated daily cat exposure (7 and 14 d) also up-regulated PVN mRNA CRH expression, but did not result in frank adrenocortical hyperactivity. Unlike other chronic homotypic stress regimens, repeated cat exposure facilitated corticosterone secretion after the 6th or 13th day of exposure. Notably, ACTH secretion and central amygdaloid nucleus CRH mRNA expression were enhanced in animals that were preexposed to the holding chamber relative to chamber-naive rats, suggesting that contextual cues can sensitize subsequent responses to a fearful stimulus. Analysis of c-fos activation was then used to identify brain circuits activated by acute predator stress. Cat exposure elicited a pattern of central c-fos activation that differed substantially from that after either restraint or hypoxia. Predator-specific c-fos mRNA induction was observed in several brain regions comprising the hypothetical brain defense circuit (bed nucleus of the stria terminalis, medial region of the ventromedial nucleus, and dorsal premammillary nucleus). Surprisingly, acute cat exposure did not induce c-fos expression in the PVN. In summary, the data indicate that 1) predation stress invokes a unique stress circuitry that promotes homotypic sensitization of the HPA axis, and 2) familiarization of animals to testing environments can prime central stress pathways to respond robustly to novel threats.

Amygdala↗

T lymphocyte stress response. II. Protection of translation and DNA replication against some forms of stress by prior hyperthermic stress.

We have compared the effects of a mild heat shock and febrile temperatures on heat-shock protein (hsp) synthesis and development of stress tolerance in T lymphocytes. Our previous studies demonstrated that febrile temperatures (less than or equal to 41 degrees C) induced the synthesis of hsp110, hsp90, and the constitutive or cognate form of hsp70 (hscp70; a weak induction of the strongly stress-induced hsp70 was also observed. In the studies reported herein, we demonstrate that a mild heat shock (42.5 degrees C) reverses this ratio; that is, hsp70 and not hscp70 is the predominate member of this family synthesized at this temperature. Modest heat shock also enhanced the synthesis of hsp110 and hsp90. In order to assess the relationship between hsp synthesis and the acquisition of thermotolerance, purified T cells were first incubated at 42.5 degrees C (induction temperature) and then subsequently subjected to a severe heat-shock challenge (45 degrees C, 30 min). T cells first incubated at a mild heat-shock temperature were capable of total protein synthesis at a more rapid rate following a severe heat shock than control cells (induction temperature 37 degrees C). This phenomenon, which has been previously termed translational tolerance, did not develop in cells incubated at the febrile temperature (induction temperature 41 degrees C). Protection of translation also extended to immunologically relevant proteins such as interleukin-2 and the interleukin-2 receptor. Because clonal expansion is a critical event during an immune response, the effects of hyperthermic stress on DNA replication (mitogen-induced T cell proliferation) was also evaluated in thermotolerant T cells. DNA synthesis in control cells (induction temperature 37 degrees C) was severely inhibited following heat-shock challenge at 44 degrees C or 45 degrees C; in contrast, T cells preincubated at 42.5 degrees C rapidly recovered their DNA synthetic capacity. T cells preincubated at a febrile temperature were moderately protected against hyperthermic stress. The acquisition of thermotolerance was also associated with enhanced resistance to chemical (ethanol)-induced stress but not to heavy metal toxicity (cadmium) or dexamethasone-induced immunosuppression. These studies suggest that prior hsp synthesis may protect immune function against some forms of stress (e.g., febrile episode) but would be ineffective against others such as elevated glucocorticoid levels which normally occur during an immune response.

Animals↗

Nicotine increases oxidative stress, activates NF-kappaB and GRP78, induces apoptosis and sensitizes cells to genotoxic/xenobiotic stresses by a multiple stress inducer, deoxycholate: relevance to colon carcinogenesis.

Epidemiologic studies indicate that environmental (smoking) and dietary factors (high fat) contribute to carcinogenesis in many organ systems. The aim of our study was to test the hypothesis that nicotine, a component of cigarette smoke, and sodium deoxycholate (NaDOC), a cytotoxic bile salt that increases in concentration in the gastrointestinal tract after a high fat meal, induce similar cellular stresses and that nicotine may enhance some of the NaDOC-induced stresses. We found that nicotine, at 0.8 microM, the very low sub-micromolar level occurring in the tissues of smokers: (1). increases oxidative stress; (2). activates NF-kappaB, a redox-sensitive transcription factor; (3). activates the 78 kD glucose regulated protein promoter, an indication of endoplasmic reticulum stress; (4). induces apoptosis; (5). enhances the ability of NaDOC to activate the 153 kD growth arrest and DNA damage promoter, an indication of increased genotoxic stress; and (6). enhances the ability of NaDOC to activate the xenobiotic response element. Our findings have applicability to G.I. cancer, in general, since smoking is a risk factor in the development of esophageal, pancreatic, gastric and colon cancer, and these cancers are also promoted by bile acids.

Apoptosis↗