Selye's Stress Research Articles

Stable Gastric Pentadecapeptide BPC 157, Robert's Stomach Cytoprotection/Adaptive Cytoprotection/Organoprotection, and Selye's Stress Coping Response: Progress, Achievements, and the Future.

We reviewed again the significance of the stable gastric pentadecapeptide BPC 157 as a likely mediator of Robert’s stomach cytoprotection/adaptive cytoprotection and organoprotection and as novel mediator of Selye’s stress coping response to reestablish homeostasis. Specific points of BPC 157 therapy and the original concept of Robert’s cytoprotection/adaptive cytoprotection/organoprotection are discussed, including the beneficial effects of BPC 157. First, BPC 157 protects stomach cells and maintains gastric integrity against various noxious agents (Robert’s killing cell by contact) and is continuously present in the gastric mucosa and gastric juice. Additionally, BPC 157 protects against the adverse effects of alcohol and nonsteroidal anti-inflammatory drugs on the gastric epithelium and other epithelia, that is, skin, liver, pancreas, heart (organoprotection), and brain, thereby suggesting its use in wound healing. Additionally, BPC 157 counteracts gastric endothelial injury that precedes and induces damage to the gastric epithelium and generalizes “gastric endothelial protection” to protection of the endothelium of other vessels (thrombosis, prolonged bleeding, and thrombocytopenia). BPC 157 also has an effect on blood vessels, resulting in vessel recruitment that circumvents vessel occlusion and the development of additional shunting and rapid bypass loops to rapidly reestablish the integrity of blood flow (ischemic/reperfusion colitis, duodenal lesions, cecal perforation, and inferior vena caval occlusion). Lastly, BPC 157 counteracts tumor cachexia, muscle wasting, and increases in pro-inflammatory/procachectic cytokines, such as interleukin-6 and tumor necrosis factor-α, and significantly corrects deranged muscle proliferation and myogenesis through changes in the expression of FoxO3a, p-AKT, p-mTOR, and p-GSK-3β (mitigating cancer cachexia).

Biomarkers for classification and class prediction of stress in a murine model of chronic subordination stress.

Selye defined stress as the nonspecific response of the body to any demand and thus an inherent element of all diseases. He reported that rats show adrenal hypertrophy, thymicolymphatic atrophy, and gastrointestinal ulceration, referred to as the stress triad, upon repeated exposure to nocuous agents. However, Selye’s stress triad as well as its extended version including reduced body weight gain, increased plasma glucocorticoid (GC) concentrations, and GC resistance of target cells do not represent reliable discriminatory biomarkers for chronic stress. To address this, we collected multivariate biological data from male mice exposed either to the preclinically validated chronic subordinate colony housing (CSC) paradigm or to single-housed control (SHC) condition. We then used principal component analysis (PCA), top scoring pairs (tsp) and support vector machines (SVM) analyses to identify markers that discriminate between chronically stressed and non-stressed mice. PCA segregated stressed and non-stressed mice, with high loading for some of Selye’s stress triad parameters. The tsp analysis, a simple and highly interpretable statistical approach, identified left adrenal weight and relative thymus weight as the pair with the highest discrimination score and prediction accuracy validated by a blinded dataset (92% p-value < 0.0001; SVM model = 83% accuracy and p-value < 0.0001). This finding clearly shows that simultaneous consideration of these two parameters can be used as a reliable biomarker of chronic stress status. Furthermore, our analysis highlights that the tsp approach is a very powerful method whose application extends beyond what has previously been reported.

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.

Ian Miller, A Modern History of the Stomach: Gastric Illness, Medicine and British Society, 1800-1950

Ian Miller's book aims to fill a gap in the literature, since, he argues, we lack accounts of the modern constructions of gastric disorders. It also aims to show that the stomach has been imbued with high emotional and cultural significance, acting as a rhetorical site of professional identity, rather than being ‘just’ a medical artefact. The first chapter explores nineteenth-century holism, nervous theory and concepts of sympathetic relationship rendering the stomach a site of anxiety about modernity and industrialisation in a rapidly shifting British society. Further chapters explore the isolation, mid-nineteenth century, of gastric ulcer disease from a more all-encompassing terminology, (in particular, dyspepsia) a process related to the rise of pathological anatomy and of physiological investigation. Such modes sought to overturn traditional dietetic interventions, but met with controversy due to their perceived affinity with animal experimentation, increasingly framed as a form of torture. Miller then charts the rise of surgical interventions, with operations touted as diagnostic and therapeutic techniques—a ‘pathology of the living’—improving on clinical management that often came too late. There is a chapter on re-emerging psychosomatic and holistic understandings in relation to World War Two, in particular regarding apparently common wartime ulcers, and concluding remarks on recent bacterial understandings of ulcer aetiology. Miller sometimes fascinatingly relates professional debates to wider social and cultural phenomena: for example, through concerns in the 1840s that symptoms of poisoning might be confused with those of a perforating ulcer, leading to false murder accusations and miscarriages of justice; or in resistance to physiological experimentation and investigative tools such as the stomach tube and the ‘stomach bucket’. Resistance was based on perceptions that clinicians were normalising deviant physiological processes rather than caring for a sick person, but also on the similarity of techniques with vivisection, opposition to which inhibited the adoption of technologies of physiological exploration, more so in the British clinic than elsewhere. These anxieties evoked familiar tensions between the laboratory and the clinic, but were also embedded within powerfully gendered dynamics, as in the force-feeding, with stomach tubes, of hunger-striking Suffragettes. Such material could, however, do with further exploration. The book's key rubric is the competing professional ambitions of physicians, physiologists and surgeons, and Miller is strong on professional rhetoric about technologies. However, the material occasionally veers into a technological determinism, and the wider social and cultural context of professional wranglings remains unevenly conveyed. For example, Miller argues that surgery was less problematically associated with the brutality of physiological experiments, on the grounds that surgery was more easily justified by the prospect of cure, but his account is a little threadbare. Just how were such strong anxieties assuaged, given the sometimes brutal and dangerous nature of intervention? In his focus on professional competition, Miller also takes somewhat at face value key terms and concepts (such as ‘scientific’ methods, or the distinction between ‘functional’ and ‘organic’ disorders) that are in fact at stake in the very processes of the professional claim-making he describes. He ascribes disciplinary orientations—such as ‘reductionistic’ or ‘holistic’—to individuals without exploring whether and how his protagonists used and understood these terms. Similarly, he writes about ‘psychiatric ideas’ and ‘psychological theories’ being incorporated into clinical management of gastric problems, when the identities of ‘medicine’ and ‘psychiatry’—not to mention Selye's stress research, or Cannon's physiology—are precisely what was being repeatedly reshaped in debates about mind, emotions, environment, and body during the twentieth century. By failing to engage with the historical emergence and contestation of the very disciplines that have coalesced under the terms ‘psychiatry’, ‘psychosomatic medicine’, or ‘physiology’, Miller's account remains in thrall either to the disciplinary self-identification of protagonists, or to a wearily familiar pitting against one another of the categories of medical ‘reductionistism’ and ‘holism.’ There is much fascinating material in this well-written book. But in his more historioraphically engaged conclusion, Miller argues—against a retired surgeon prominent in debates about ulcer aetiology—that shifts in aetiological and diagnostic trends come out of changes in professional activity; that diagnostic categories, in other words, are not stable. This is convincing enough, but historians of medicine need, I think, more robust—and more nuanced—historiographical hypotheses to get their teeth into.

Chronic stress and epigenetics. Relation between academic sciences and theology

The author gives a short account on the principles of Selye's stress theory, and discusses similarities and dissimilarities of acute and chronic stress. Both the external, and the internal environment, as well as the psycho-mental status are involved in the notion of the environment. Basic principles of epigenetics are reviewed: interaction between environment and genes, neuroendocrine and enzymatic mechanisms involved in silencing and activation of genes, notions of phenotypic plasticity, and epigenetic reprogramming are discussed. Epigenetic mechanisms of interrelation between pathological clinical states (diseases) and the characteristic phenotypes, causative role of psycho-mental status in evoking pathological somatic alterations, and the potential therapeutic consequences are briefly discussed. The etiological role of chronic, civilization stress in producing the worldwide increment of cardiovascular morbidity is cited, argumentation and criticism of the current therapeutical practice is discussed. The author concludes that recent advances in epigenetic knowledge seem to solve the controversy between the academic and theological sciences.

Change of Biotransformation Steps of Formaldehyde Cycle in Water-Melon Plants after Infection with Fusarium Oxysporum

Recent experiments indicate that the measurable formaldehyde (HCHO) level is considerably elevated in the parts of water-melon plants immediately after a nonlethal infection with Fusarium oxysporum f. sp. niveum. At the same time the level of some quaternary ammonium compounds (N(epsilon)-trimethyl-L-lysine, choline) as potential HCHO generators (gene products) is considerably decreased. That is probably due to the fact that the alarm reaction phase of this biotic stress syndrome includes an intensive demethylation process. It has been proved that HCHO may play a role in dynamic methylation-demethylation processes that also may include the methylation of biotic stress proteins. In this paper we report on qualitative and quantitative changes in the biotransformation steps of the formaldehyde cycle in different parts of the water-melon plant after nonlethal infection (biotic stress) with Fusarium. In consequence of the infection identical quantitative changes, but to a different degree, of the compounds examined are observable in both varieties. The connections resulting from the depiction of the time-dependent quantitative changes of the measured methylated compounds due to infection show a picture similar to that of Selye's stress syndrome model.

Effects of various stressors on in vivo norepinephrine release in the hypothalamic paraventricular nucleus and on the pituitary-adrenocortical axis.

The hypothalamic-pituitary adrenocortical (HPA) system and sympathoneural and adrenomedullary systems are major effector systems that serve to maintain homeostasis during stress. Corticotropin-releasing hormone (CRH) in the paraventricular nucleus (PVN) of the hypothalamus, a determinant of both HPA and autonomic responses to stress, is under the control of many neurotransmitters and neuropeptides. Norepinephrine (NE) potently stimulates CRH neurons in the PVN; however, the physiologic role of NE in stress-induced activation of the HPA is unknown. In the present study we exposed animals to various stressors (immobilization (IMMO), cold (COLD), hemorrhage (HEM), hypoglycemia elicited by insulin administration (INS), pain and tissue damage caused by formalin injection (FORM) and sc injection of physiological saline (SAL), all of which are known to activate the HPA axis. Injection of physiological saline iv was used as a control. In vivo microdialysis was used to assess stressor- and intensity-specific activation of the PVN noradrenergic system, based on measurements of NE, its intraneuronal metabolite dihydroxyphenylglycol (DHPG), and the dopamine metabolite, dihydroxyphenylacetic acid (DOPAC). Simultaneously with microdialysate collections, blood samples were obtained via catheters in the femoral artery to measure plasma ACTH and corticosterone (CORT) levels as dependent measures, to assess stress-induced activation of the HPA axis. At their highest intensities, all the stressors significantly increased levels of PVN microdialysate NE, DHPG, and DOPAC, and plasma ACTH and CORT. PVN NE levels varied across stressors, with IMMO and FORM more potent than INS, COLD, or HEM. INS and HEM evoked proportionately larger plasma ACTH responses than did IMMO, FORM, and COLD. Plasma CORT responses were largest during IMMO, FORM, and HEM. Except for COLD and HEM, there was a strong correlation of plasma ACTH levels with levels of NE, DHPG, and DOPAC in PVN microdialysate. The data suggest that, except for COLD or HEM, there is a strong positive correlation of PVN noradrenergic activation and activity of the HPA axis. With stressors such as IMMO and FORM, NE synthesis, reflected by DOPAC changes, is strongly positively correlated with activity of the HPA axis. Furthermore, the results indicate substantial stressor specificity of PVN catecholaminergic and of HPA responses to different stressors and are inconsistent with a founding tenet of Selye's stress theory, the doctrine of nonspecificity, which defines stress as the nonspecific response of the body to any demand.

Perceived sources of stress among pediatric oncology nurses.

This study examined the stressors most commonly experienced by pediatric oncology nurses. A descriptive, correlational design was used, and Selye's stress theory served as the theoretical framework. The final sample consisted of 155 members of the Association of Pediatric Oncology Nurses who completed and returned the Spielberger State-Trait Anxiety Inventory, and the Pediatric Oncology Nurse Stressor Questionnaire (PONSQ). The participants reported that relapse or sudden death of a favorite patient was their greatest source of stress. The second most common stressor was a workload perceived as too great to give quality patient care. The participants reported no more state or trait anxiety than the reference group. Statistics for white-collar working women were used as the reference group by Spielberger. The PONSQ shows that pediatric oncology nursing is a stressful profession. Additional research is needed to identify positive strategies for reducing this stress.

Workload, stress, and strain among police officers.

Data relevant to stress and strain were analyzed separately for police officers with high and low workloads. Although these groups of officers were not found to differ in demographic characteristics or on overall levels of stress and strain, the sources of stress and strain were remarkably different. For the low workload officer, the sources of stress and strain appear to be difficulties in interpersonal relations with peers, community, and especially with supervisors. These difficulties appear to be mediated by effects on self-evaluation. The sources of stress and strain among high workload officers appear to be stress-producing events in their lives in general, as well as in performing the job of patrol officer and in dealing with crime and related matters. The differences between high and low workload officers can be explained by social comparison theory, by identity theory, or by Selye's stress theory.

Rem-sleep deprivation, stress and emotional behavior in rats

Eighty-eight adult white rats were divided into 9 groups. Groups 1 and 2 served as controls. The rats of Group 3 were repeatedly aroused during 4 days at the very onset of each REM-sleep period by direct midbrain reticular formation stimulation. This deprivation decreased the daily amount of REM-sleep by 70%, while slow-wave sleep was reduced by 10% only. In Group 4, the animals were given food and water for 1 h a day only. Groups 5 and 6 were subjected to immobilization and cold stress, respectively. Groups 7, 8 and 9 were deprived of REM-sleep on platforms of 15, 11 and 6.5 cm in diameter, respectively. Stress was estimated by the classical Selye's triad: weight of adrenals and thymus and gastric ulceration. Emotionality was measured in the open-field and also by self-stimulation of the lateral hypothalamus. Neither emotional behavior disturbances nor Selye's stress features were found after REM-deprivation in Group 3. Moreover, arousal deprivation induced a slight, though significant, reduction in adrenal weight. Also, no changes in emotional behavior were noted in stress-exposed groups (5 and 6). Only the interplay between REM-sleep deprivation and stress on the platforms (Groups 7, 8 and especially 9) led to a considerable shift in emotionality.

The »Stockholm Stressone» and Coronary Heart Disease

A model is presented which links social change, stress and disease as a series of interacting variables. The mechanisms underlying Cannon and Selye stress are discussed and it is suggested that neither response properly meets the coping needs induced by current stressful experiences. Evidence from this Symposium and elsewhere suggests that coronary heart disease (CHD) has psychosocial stress as one of its major predisposing factors. Two key hypotheses are developed: that all psychosocial stresses may be reduced to a small number of categories, and that pathology arises when the stress responses are inappropriate to the problem in hand. Both of these hypotheses, if validated, could have practical value in assessing an individual's risk of contracting stress induced disease, and in demonstrating at a very early stage whether interventions were improving the situation or making it worse.

A historical view of the stress field.

Abstract An analysis is presented of selected aspects of stress theory and research in biology and medicine, both before and after the introduction of Selye's stress formulations, which have been of major importance in the development and popularity of this research area. An attempt is made to explore some possible sources of present confusion and controversy in the stress field, with a view to the development of new research strategies that may enable us to clarify, update, and revise stress concepts and to facilitate future progress. In particular, it is suggested that an experimental re-evaluation of the concept of the non-specificity of pituitary-adrenal cortical response is a matter of particular strategic importance, if we are to move out of the present prolonged period of stalemate and confusion over stress theory and terminology. Recent experimental studies which suggest that the nonspecificity concept may have been applied erroneously to lower level physiological mechanisms, rather than to higher level psychological processes, are reviewed. The possible implications of this development are discussed in terms of clarifying current concepts and providing guidelines for future lines of approach in stress research.

A Historical View of the Stress Field

An analysis is presented of selected aspects of stress theory and research in biology and medicine, both before and after the introduction of Selye's stress formulations, which have been of major importance in the development and popularity of this research area. An attempt is made to explore some possible sources of present confusion and controversy in the stress field, with a view to the development of new research strategies that may enable us to clarify, update, and revise stress concepts and to facilitate future progress. In particular, it is suggested that an experimental reevaluation of the concept of the non-specificity of pituitary-adrenal cortical response is a matter of particular strategic importance, if we are to move out of the present prolonged period of stalemate and confusion over stress theory and terminology. Recent experimental studies which suggest that the nonspecificity concept may have been applied erroneously to lower level physiological mechanisms, rather than to higher level psychological processes, are reviewed. The possible implications of this development are discussed in terms of clarifying current concepts and providing guidelines for future lines of approach in stress research.

Hematological and histological changes induced by adrenocorticotropic hormone and formaldehyde stressor in the domestic fowl.

In the present experiment, changes of percentage of leucocytes in the adult chicken blood induced by ACTIH injection and histological changes of lymphoid tissues and adrenals in the young chick induced by formaldehyde stressor, were examined.Hematological changes: Relative heterophilia and lymphopenia were observed in the treated chicks which were injected with 10mg of ACTH intravenously or intraperitoneally, and were not observed in the chickens injected with the same dose of ACTH intramuscularly or subcutaneously. It was found that pricking of comb has some stressor agentical effect upon blood in the fowl, and also it was suggested that Selye's stress concept should be applicable to the chicken.Histological changes: Single comb white leghorn cockerels 3-4 weeks old were used. They were injected with 1 cc of 4% formaldehyde intramuscularly 3times during 36hours. They were sacri ficed at the end of the period of 12hours after the last injection. The decrease in weights of thymus, spleen and bursa Fabricii and hypertrophy of adrenal gland were observed. Histologically, in the thymus of the treated chicks, the thymocytes of the thymus cortex drained into medulla, so that the demarcation between cortex and medulla became unvisible, and naked reticular cells appeared in the thymus cortex. The number of Hassal-body increased relatively, and the PAS positive degenerating intercellular granules also seemed to increase in their number. In the speen, severe involution of the lymph follicle in the white pulp, and heteropoiede in the red pulp were observed.Hyperplasia, hypertrophy, mitotic figures of the interrenal cells and loss of chromaffin substances in the chromaffiiin cells were observed in the adrenal gland. In the bursa Fabricii, though involutic change of the follicles was observed, other striking changes could not be confirmed histologically or cytologically. From these facts, it could not be decided whether the bursa Fabricii is a true lymphoid organ or not.These changes were comparable to those in mammals, and function of bursa Fabricii were discussed in the present parper.