[Liver X receptors define the immune response during general adaptation syndrome (GAS)]. / Les récepteurs hépatiques X définissent la réaction immunitaire pendant le syndrome général d'adaptation (SGA).

The impact of stressful conditions on immunity seems mixed and at times counterbalanced. Such inconsistencies can often be attributed to the fact that the notion of stress has a very wide meaning and covers a large number of different situations. Research on liver X receptors using both natural and synthetic ligands may help to solve this conflict. When an infectious agent is present in a stressed body, LXR activation is likely to be a key element in the regulation of POMC, IFN-γ, and IL-18; moreover, it is a unique anti-inflammatory mode of action. They concurrently stimulate a non-specific immune reaction as they suppress inflammatory and autoimmune processes.

Chronic Stress in Children and Adolescents: A Review of Biomarkers for Use in Pediatric Research.

PROBLEM: Incorporating biomarkers of chronic stress into pediatric research studies may help to explicate the links between exposure to adversity and lifelong health, but there are currently very few parameters to guide nurse researchers in choosing appropriate biomarkers of chronic stress for use in research with children and adolescents. METHODS: Biomarkers of chronic stress are described, including primary mediators (glucocorticoids, catecholamines, and cytokines) and secondary outcomes (neurologic, immune, metabolic, cardiovascular, respiratory, and anthropometric) of the chronic stress response. RESULTS: Evidence of the use of each biomarker in pediatric research studies is reviewed. Recommendations for pediatric researchers, including selection of appropriate biomarkers, measurement considerations, potential moderators, and future directions for research, are presented. DISCUSSION: A wide range of biomarkers is available for use in research studies with children. While primary mediators of chronic stress have been frequently measured in studies of children, measurement of secondary outcomes, particularly immune and metabolic biomarkers, has been limited. With thoughtful and theoretically based approaches to selection and measurement, these biomarkers present an important opportunity to further explore the physiologic pathways linking exposure to chronic stress with later health and disease. CONCLUSION: The incorporation of chronic stress biomarkers into pediatric research studies may provide valuable insight into the mechanisms through which stressful environments "get under the skin" and ultimately inform efforts to promote health and reduce inequities among children exposed to adversity.

Objective assessment of the degree of improvement or deterioration with patients by means of Ipsative Trend Analysis of resting electroencephalograms.

We report on a new quantitative EEG-approach, called Ipsative Trend Assessment which is based on the spatio-temporally defined patterns which are generated by the global interaction of cortical neurons. METHODS: The data were acquired from EEGs being recorded under resting conditions. Target variables are not the usually employed absolute values of the spectral parameters but rather their change being calculated from successive recordings with a single subjects design. RATIONALE: Since the resting-EEG does not provide specific information, we had to decide what else might be addressed by that method. CONCLUSIONS: Our hypothesis according to which the SR-EEG indicates Selye's behaviorally non-specific General Adaptation Syndrome is based on good evidence. MAIN FINDINGS: Dynamic pattern comparison between subsequent EEGs on the single case level is a hitherto neglected method, which may be utilize, for instance, with regard to objective therapeutic outcome assessment. SIGNIFICANCE: In order to substantiate the clinical meaningfulness of our new approach we report two case vignettes of psychiatric impairments. Apart from that, our procedure should provide the desperately needed objective assessment of the therapeutic effect with any disease displaying a certain proportion of unspecific symptoms.

"Stress" is 80 Years Old: From Hans Selye Original Paper in 1936 to Recent Advances in GI Ulceration.

The first scientific publication on 'general adaption syndrome', or as we know today 'biologic stress' has been published in Nature in 1936 by the 29-year old Hans Selye. His results in that short publication that contained no references or illustrations, were based on experiments in rats that were exposed to severe insults/ stressors, but his idea about a 'nonspecific bodily response' originated from his observations of sick patients whom he had seen as a medical student and young clinician. Autopsy of stressed rats revealed three major, grossly visible changes: hyperemia and enlargement of the adrenals, atrophy of the thymus and lymph nodes as well as hemorrhagic gastric erosions/ulcers (the "stress triad"). Based on this and additional observations, he concluded that the key master organ in stress reactions is the adrenal cortex (although he also accepted the limited and short lasting effect of catecholamines released from the adrenal medulla) which stimulated by an increased secretion of ACTH, secreted by the anterior pituitary gland. He thus identified the first molecular mediators of the stress reaction, i.e., steroids released from the adrenal cortex that we call today glucocorticoids, based on his classification and naming of steroids. At the end of a very productive life in experimental medicine, Selye recognized that under both unpleasant and demanding stressors as well as positive, rewarding stimuli adrenal cortex releases the same glucocorticoids and only certain brain structures may distinguish the stimuli under distress and eustress - terms he introduced in 1974, that also contained his last definition of stress: the nonspecific response of the body on any demand on it. After brief description of the history of stress research, the rest of this review is focused on one element of stress triad, i.e., gastroduodenal ulceration, especially its pathogenesis, prevention and treatment. Following a short description of acute gastroprotection, discovered by one of Selye's students, we discuss new molecular mediators of gastroduodenal ulceration like dopamine and new drugs that either only heal (very potently, on molar basis) or prevent and heal ulcers like sucralfate derivatives and the relatively new peptide BPC-157. We conclude that despite the extensive and multidisciplinary research on stress during the last 80 years, a lot of basic and clinical research is needed to better understand the manifestations, central and peripheral molecular regulators of stress response, especially the modes of prevention/management of distress or its transformation into eustress and the treatment of stress-related diseases.

Stress in Gastrointestinal Tract and Stable Gastric Pentadecapeptide BPC 157. Finally, do we have a Solution?

Selye's syndrome produced by diverse nocuous agents and "response to damage as such" means Selye's stress triad in stress coping response to reestablish homeostasis. Logically, from the gastrointestinal tract viewpoint, such organoprotective/healing response implies the angiogenic growth factors that commonly signify the healing. Thereby, the gastric pentadecapeptide BPC 157-organoprotection (huge range of beneficial effects) signifies the Selye's stress concept/stress coping response implemented in and from gastrointestinal tract, and BPC 157 as an integrative mediator that integrates the adaptive bodily response to stress. In clinical trials without side effects, LD1 not achieved, BPC 157 healing in gastrointestinal tract, and particularly the healing of the extragastrointestinal tissues (i.e., skin/tendon/ligament/muscle/bone; nerve; cornea/ brain) were referred throughout its integrative capabilities (i.e., ulcerative colitis/multiple sclerosis model equally counteracted), native in gastrointestinal tract, stability in human gastric juice (and thereby, strong efficacy and applicability), its relevance for dopamine-system function (and thereby, counteracting effects of dopamine-system dysfunction and overfunction, centrally and peripherally (mucosa maintenance); interaction with serotonin- and GABA-system)), afforded cytoprotection/adaptive cytoprotection/organoprotection (and thereby, beneficial effects on gastric and whole intestinal tract lesions and adaptation, wounds and fistulas healing, blood vessels, somatosensory neurons, NSAIDs-side effects (including also pancreas, liver, brain lesions, and blood disturbances, prolonged bleeding, thrombocytopenia, thrombosis)). Further, we combine such gut-brain axis and the NO-system where BPC 157 counteracts complications of either L-NAME application (i.e., various lesions aggravation, hypertension) or Larginine application (i.e., hypotension, prolonged bleeding, thrombocytopenia). Also, BPC 157 particularly affects genes functions (i.e., Fos, c-Jun, Egr-1), all together suggestive for an indicative generalization. Thus, we could suggest gastric pentadecapeptide BPC 157 and BPC 157 induced-organoprotection as integrative mediator that integrates the adaptive bodily response to stress, and thereby practically applied in further therapy and in effective realization of Selye's stress response.

[A peculiar man - about Hans Selye, as reflected in his Hungarian connections]. / Egy "furcsa ember" - Selye Jánosról magyar kapcsolatainak tükrében.

Hans Selye made a great impact on the Hungarian medical, scientific and public life. His first Hungarian publication about the alarm-reaction appeared 1938 in the Orvosi Hetilap. His Hungarian relationship was quite extensive after the war as he published, gave lectures, and accepted Hungarian students for specialized training in his Canadian institute saw. The rich documents in archives about Selye are currently being processed and those will surely shed light on Selye's life in further details.

[Emotional stress as a clinical model to study the pathogenesis of the initial phase of the general adaptation syndrome].

INTRODUCTION: General adaptation syndrome (GAS), the basis of the development of which is stress phenomenon, is an essential component of the pathogenesis of many diseases and syndromes. However, the patho genesis of GAS hitherto is considered exclusively from the endocrinological viewpoint. This relates primarily to the initial phase of the GAS, a clinical model for the study of which may be psycho-emotional stress (PES), which we studied using three groups of volunteers. METHODS: The first one consists of 25 students who were waiting for unaccustomed physical activity (17 men) and play debut on the stage (8 women). The second group consists of 48 children (2-14 years) who expected for "planned" surgery. The third group of volunteers is made up of 80 students (41 women and 39 men) during the first exam. The concentration of cortisol, endotoxin (ET), the activity of antiendotoxin immunity (AEI) and the haemostatic system parameters were determined in the blood serum of volunteers in various combinations. RESULTS: We found laboratory evidence for PES at 92% of students of the first group, 58% of children of the second one and in 21% of students of the third group of volunteers (mostly women). The concentration of ET increased at 13 (52%) volunteers of the first group with a significant increase of average indicators in the whole group (from 0.84 ± 0.06 to 1.19 ± 0.04 EU/ml). At children of the second group, the average concentration of ET increased even more significantly (from 0.42 ± 0.02 to 1.63 ± 0.11 EU/ml), which was accompanied by the activation of the hemostasis system. A degree of the activation was directly dependent on the level of ET in the general circulation and on an activity of AEI. Examination stress in the third group of volunteers is accompanied by activation of plasma hemostasis (increased initial thrombosis rate and reduced the time it starts, lag-period) in 26% of female students and 15% of male students. CONCLUSION: We suggest that it is possible to use the PES as a clinical model for studying the initial phase of the GAS, examine the role of excess of intestinal ET in the general blood circulation (endotoxin aggression) in the induction of systemic inflammation, which is very likely participated in the initiation of the GAS.

Adult cyclical vomiting syndrome: a disorder of allostatic regulation?

Cyclic vomiting syndrome (CVS) is an idiopathic illness characterized by stereotypic and sudden-onset episodes of intense retching and repetitive vomiting that are often accompanied by severe abdominal pain. Many associated factors that predict CVS attacks, such as prolonged periods of fasting, sleep deprivation, physical and emotional stress, or acute anxiety, implicate sympathetic nervous system activation as a mechanism that may contribute to CVS pathogenesis. Furthermore, adult patients with CVS tend to have a history of early adverse life events, mood disorders, chronic stress, and drug abuse-all associations that may potentiate sympathetic neural activity. In this review, we set forth a conceptual model in which CVS is viewed as a brain disorder involving maladaptive plasticity within central neural circuits important for allostatic regulation of the sympathetic nervous system. This model not only can account for the varied clinical observations that are linked with CVS, but also has implications for potential therapeutic interventions. Thus, it is likely that cognitive behavioral therapy, stress management ("mind-body") interventions, regular exercise, improved sleep, and avoidance of cannabis and opiate use could have positive influences on the clinical course for patients with CVS.

El concepto de allostasis en la Biomedicina actual / Allostasis's concept in the current Biomedicine

Los comportamientos que realizan los mamíferos en momentos de peligro son adaptaciones muy importantes para su supervivencia. Fueron denunciados por Hans Selye en 1936 quien lo llamó "síndrome general de adaptación". El acuñó el vocablo estrés que ha sido adoptado en todos los idiomas. Ello estimuló una cantidad enorme de investigación que nos han llevado en los años 2000 al replanteamiento de muchas cuestiones y al establecimiento del concepto de allostasis –mantenimiento de la estabilidad a través del cambio- y también de carga y sobrecarga allostática. Estos procesos se realizan bajo estricto control cerebral. Sus conclusiones nos están llevando a la revisión de muchas cuestiones e incluso a una nueva concepción de la salud y la enfermedad (AU)

Mammal behaviour in response to danger is a critical adaptation for surviving. This idea was first enunciated by Hans Selye in 1936 who named the process: "general adaptation syndrome". Selye himself coined the word stress, which was included in all languages. From that moment to the present century, the huge amount of research on the subject has changed our view of the process and has guided to the current concept of allostasis - maintaining stability through change - and also to allostatic load and overload. All these processes are brain regulated. The conclusions from that research are leading to the reconsideration of many notions and to a new concept of health and disease (AU)

Stress reactivity and corticolimbic response to emotional faces in adolescents.

OBJECTIVE: Adolescence is a critical period in the development of lifelong patterns of responding to stress. Understanding underpinnings of variations in stress reactivity in adolescents is important, as adolescents with altered stress reactivity are vulnerable to negative risk-taking behaviors including substance use, and have increased lifelong risk for psychopathology. Although both endocrinological and corticolimbic neural system mechanisms are implicated in the development of stress reactivity patterns, the roles of these systems and interactions between the systems in reactivity to social stimuli in adolescents are not clear. We investigated the relationship between cortisol response to a laboratory-based social stressor and regional brain responses to emotional face stimuli in adolescents. METHOD: Changes in cortisol levels following the Trier Social Stress Test-Child version (TSST-C) were measured in 23 disadvantaged and chronically stressed adolescents who also participated in functional magnetic resonance imaging during processing of emotional faces and structural magnetic resonance imaging. The relationships between changes in cortisol following the TSST-C with regional brain activation during face processing, as well as with regional brain morphology, were assessed. RESULTS: Cortisol change on the TSST-C showed a significant inverse relationship with left hippocampus response to fearful faces (p < .05, corrected); significant associations with volume were not observed. CONCLUSIONS: Increased cortisol response to the Trier social stressor was associated with diminished response of the left hippocampus to faces depicting fear. This suggests that HPA-corticolimbic system mechanisms may underlie vulnerability to maladaptive responses to stress in adolescents that may contribute to development of stress-related disorders.

[Neurobiological consequences of child sexual abuse: a systematic review]. / Revisión sistemática de las consecuencias neurobiológicas del abuso sexual infantil.

OBJECTIVE: The results of several studies suggest that there is a critical timeframe during development in which experiences of maltreatment and sexual abuse may lead to permanent or long-lasting neurobiological changes that particularly affect the hypothalamus-pituitary-adrenal axis response. The aim of the present study was to provide an updated review on the main neurobiological consequences of child sexual abuse. METHODS: We selected articles published between January 1999 and January 2010 in English or Spanish that focused on the neurobiological consequences of child sexual abuse available through Medline, Scopus and Web of Science. We also examined the references in published articles on the consequences of sexual victimization in childhood. RESULTS: In this review we included 34 studies on neurobiological consequences, indicating different kinds of effects, namely: neuroendocrine, structural, functional and neuropsychological consequences, which affect a large number of victims. CONCLUSIONS: The existing body of work on the neurobiological consequences of maltreatment shows the need to consider maltreatment and child sexual abuse as health problems that affect different areas of victims' lives, which would in turn favor the development of intervention and treatment programs that take these multiple effects into account.

[Immunity and health: the accelerated aging of immune system in veterans of extra risk divisions].

This article presents the data about state of health and immunity in veterans of extra risk divisions. The increased morbidity and immunity infringement in the remote terms after nuclear tests, and also while liquidation of consequences of radiating failures on nuclear submarines are shown. Changes of humoral factors of nonspecific protection, concentration of immunoglobulinums, in blood whey, a sensitization of lymphocytes to respiratory viruses, humoral and cellular autoimmune shifts are registered. Some of the revealed changes (complement, lysozyme, concentration of immunoglobulinums) are a consequence of advanced age and accompanying diseases in the people surveyed, and others (autoimmune shifts, a sensitization to respiratory viruses) can be connected with carrying out of tests of the nuclear weapon. Some of immunological changes are apparently a consequence of joined actions of radiating and not radiating factors. Among the last ones stress plays the essential role. For the characteristic of a state of health in 20-40 years after carrying out nuclear tests and possible radiating influence the estimation of autoimmune changes has a great value. The important role of such changes in morbidity of veterans of extra risk divisions is shown.

[Effects of phenibut on parameters of cerebral hemodynamics in swimmers with dysadaptation syndrome and various types of systemic hemodynamics].

Administration of phenibut (0.25 g) during 4 weeks as a means of rehabilitation promoted optimization of the biochemical status and cerebral blood circulation in swimmers with various types of systemic hemodynamics, which were examined 20 minutes after warm-up.

Pulmón y altitud. Recomendaciones para el viaje en altitud / No disponible

No disponible

[Effect of adrenocorticotropic hormone (ACTH4-10) on information network of the cardiovascular systems].

The polyparametric description of adaptation syndromes in students using a uniform set of parameters of cardiovascular system and their relationships is presented. An analog of adrenocorticotropic hormone (ACTH4-10) is shown to exert varying effects on the development of different adaptation syndromes. Adaptation syndromes characterized by moderately active physiological processes (as judged by EGG, rheovasogram, respiration rate) and lowered vascular tonus were associated with marked improvement of the health status.

[Application of balneotherapeutic factors in the system of rehabilitative treatment of children with environmental dysadaptation syndrome].

Combined balneotherapy including intake and external application of Zheleznovodsk-type mineral water was given to 60 children at the age from 7 to 14 years presenting with environmental dysadaptation syndrome. This treatment ensured favourable dynamics of clinical signs of asthenovegetative, dyspeptic, and pain syndromes. Moreover, it exerted beneficial influence on the mechanisms of vegetative regulation, improved the psychoemotional status of the patients and functional capacity of their immune system.