Hans Selye and his studies on the role of mast cells in calciphylaxis and calcergy.

Hans Selye was an endocrinologist, a pioneer of research on biological stress in human individuals and groups. His most important scientific contributions include in 1936 the evidence that the pituitary-adrenal-thymus axis was activated by various nocuous stimuli, which led to the involution of the thymus and of the lymphoid organs; in 1946, the theory of general adaptation syndrome (GAS), pointing out that this is a general reaction that leads to resistance of the organism to various insults. This review article is focused on the general interest of Selye on the important role played by mast cells in different pathological conditions and in particular in calciphylaxis and calcergy, summarized in a classic book, which is a lasting contribution on the subject.

"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.

[Naming and classification of steroids and human stress ulcers. Articles of historic significance published by Hans Selye 70 years ago]. / A szteroidok elnevezése, felosztása és az emberi stresszfekélyek. Selye János 70 éve megjelent történelmi jelentoségu cikkei.

The name of Hans Selye is mostly known worldwide as the discoverer of stress reaction. Yet, he made numerous other seminal and clinically relevant discoveries. Namely, since he had a focused research on steroid hormones originating from the adrenal cortex that play a crucial role in stress response, he was the first who introduced about 70 years ago the first classification of steroids that is still valid nowadays. This is based on three objective facts: (a) the names of steroid groups are identical with their organ of origin (e.g., corticoids from the adrenal cortex, testoids/androgens from the testis); (b) chemical structures of the steroids are identical within a group (e.g., all corticoids have pregnane nucleus with 21 carbon atoms); and (c) the biological effects are homogenous within a group (e.g., all glucocorticoids exert catabolic effect, while androgens are anabolic). It should be emphasized that Selye also discovered in animal models the pro-inflammmatory effect of mineralocorticoids and the anti-inflammatory properties of glucocorticoids, about 8-10 years before Nobel Prize was awarded to a physician for the first clinical use of adrenocorticotrop hormone and cortisone. Last, but not least, Selye was the first who recognized about 70 years ago the occurence of stress ulcers in humans, based on clinical reports on the huge increase in the number of perforated gastric anti-duodenal ulcers during bombings of London in World War II. The subsequent ulcer research by Selye`s former students and their contemporaries resulted in the recognition of anti-duodenal ulcer effect of dopamine, and the central gastroprotective actions of thyreotrop releasing hormone and endogenous opioids. Thus, Hans Selye made much more contributions to medical science and clinical practice than 'just' the discoverer of biologic 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.

SELYE'S CONCEPT OF PLURICAUSAL DISEASES AND ITS IMPACT ON REGULATORY SCIENCE.

Science assumed in recent decades an increasingly important role in the regulatory field. Regulatory science is now regarded as established specific brunch of science. A disturbing anomaly, the emergence of fraudulent data is of major concern both in the field of research and in the regulation. Hans Selye's work on stress, on several forms of pluricausal diseases and on other experimental models came into the focus of interest on the occasion of the Selye Symposium - 2013 held in May 2013 at the Hungarian Academy of Sciences in Budapest.

PERSONAL RECOLLECTIONS OF DR. HANS SELYE AND OF HIS INSTITUT DE MèDECINE ET DE CHIRURGIE EXPèRIMENTALES (IMCE).

This article is a short personal recollection of Dr. Hans Selye (HS) and of his institute in order to show, first, why and how he influenced us; second, who he was as a person, human being, physician, scientist, professor, mentor; third, what was the structure and functioning of the Institut de Mèdecine et Chirurgie Expèrimentales (IMCE) and fourth, what HS' contributions and accomplishments were.

HANS SELYE AND THE STRESS RESPONSE: FROM "THE FIRST MEDIATOR" TO THE IDENTIFICATION OF THE HYPOTHALAMIC CORTICOTROPIN-RELEASING FACTOR.

Selye pioneered the stress concept that is ingrained in the vocabulary of daily life. This was originally build on experimental observations that divers noxious agents can trigger a similar triad of endocrine (adrenal enlargement), immune (involution of thymus) and gut (gastric erosion formation) responses as reported in a letter to Nature in 1936. Subsequently, he articulated the underlying mechanisms and hypothesized the existence of a "first mediator" in the hypothalamus able to orchestrate this bodily changes. However he took two generations to identify this mediator. The Nobel Laureate, Roger Guillemin, a former Selye's PhD student, demonstrated in 1955 the existence of a hypothalamic factor that elicited adrenocorticotropic hormone release from the rat pituitary and named it corticotropin releasing factor (CRF). In 1981, Wylie Vale, a former Guillemin's Ph Student, characterized CRF as 41 amino acid and cloned the CRF1 and CRF2 receptors. This paves the way to experimental studies establishing that the activation of the CRF signaling pathways in the brain plays a key role in mediating the stress-related endocrine, behavioral, autonomic and visceral responses. The unraveling of the biochemical coding of stress is rooted in Selye legacy continues to have increasing impact on the scientific community.

[Stress, cortisone and homeostasis. Adrenal cortex hormones and physiological equilibrium, 1936-1960]. / Stress, Cortison und Homöostase. Kunstliche Nebennierenrindenhormone und physiologisches Gleichgewicht, 1936-1960.

This article investigates the emergence of the concept of stress in the 1930s and outlines its changing disciplinary and conceptual frames up until 1960. Originally stress was a physiological concept applied to the hormonal regulation of the body under stressful conditions. Correlated closely with chemical research into corticosteroids for more than a decade, the stress concept finally became a topic in cognitive psychology. One reason for this shift of the concept to another discipline was the fact that the hormones previously linked to the stress concept were successfully transferred from laboratory to medical practice and adopted by disciplines such as rheumatology and dermatology. Thus the stress concept was dissociated from its hormonal context and became a handy formula that allowed postindustrial society to conceive of stress as a matter of individual concern. From a physiological phenomenon stress turned into an object of psychological discourse and individual coping strategies.