Treatment Of Stress-related Diseases Research Articles

Relationships between neuro-endocrine, electrocardiogram, and gastric mucosal damage parameters in naїve and stressed rats

Introduction 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.1 Szabo et al2 in the anniversary review "Stress" is 80 Years Old” 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. In the vast majority of publications on stress, the HPA-, HPG- and autonomous systems are the objects of research, while the place in the general adaptation syndrome of such important hormones as calcitonin and PTH has been studied only in a few publications. Another methodological shortcoming of most studies is that the subjects of analysis are limited to a single neuro-endocrine system. Therefore, we set ourselves the goal: to analyze relationships between some adaptation hormones, HRV, calcitonin, and PTH as well as electrocardiogram and gastric mucosal damage in naїve and post stressed rats. Material and methods Ethics approval All animals were kept in room having temperature 22±2ºC, and relative humidity of 44-55% under 12/12 hours light and dark cycle with standard laboratory diet and water given ad libitum. Studies have been conducted in accordance with the rules and requirements of the “General Principles for the Work on Animals” approved by the I National Congress on Bioethics (Kyїv, Ukraine, 2001) and agreed with the provisions of the “European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes” (Council of Europe No 123, Strasbourg 1985), and the Law of Ukraine “On the Protection of Animals from Cruelty” of 26.02.2006. The removal of animals from the experiment was carried out under light inhalation (ether) anesthesia by decapitation. Participants The experiment is at 38 rats Wistar line: 18 males (Weight Mean=227 g; SD=25 g) and 20 females (Mean=214 g; SD=27 g). Study design and procedure Due to the purposeful formation of groups, the potential predictors of post-stress reactions of the neuro-endocrine-immune complex and the metabolome3,4,5 were almost identical both in mean values and, to a lesser extent, in variance (SD). In particular, the hypoxic test (sec) was: 136±59 and 133±81; swimming test (min): 19±11 and 19±17; HRV Stress index4 (units) as (AMo/2*Mo*MxDMn)1/3: 0,14±0,08 and 0,14±0,05 in intact animals and those exposed to acute stress. Results and discussion Adhering to the algorithm of the Truskavetsian Scientific School of Balneology, we recalculated the current values of the parameters in Z-scores. This approach makes it possible to adequately compare deviations from the norm of parameters expressed in different units and with different variability.10,11,12 This is all the more important in view of sexual dimorphism in endocrine parameters. In addition to drastically higher levels of testosterone (41.8±1.7 vs 3.53±0.24 nM/L), males have higher levels of calcitonin (36±6 vs 21±4 ng/L), but lower levels of parathyroid hormone (154±12 vs 185±3 ng/L), adrenals mass (44±5 vs 65±5 mg), corticosterone (340±45 vs 466±57 nM/L), and aldosterone (587±8 vs 639±24 pM/L). Conclusion The condition of the gastric mucosa and myocardium as essential targets of stressors is determined by the damaging and protective effects of adaptive hormones and the autonomic nervous system.

The Relationship between Stress, Inflammation, and Depression.

A narrative review about the relationship between stress, inflammation, and depression is made as follows: Chronic stress leads to various stress-related diseases such as depression. Although most human diseases are related to stress exposure, the common pathways between stress and pathophysiological processes of different disorders are still debatable. Chronic inflammation is a crucial component of chronic diseases, including depression. Both experimental and clinical studies have demonstrated that an increase in the levels of pro-inflammatory cytokines and stress hormones, such as glucocorticoids, substantially contributes to the behavioral alterations associated with depression. Evidence suggests that inflammation plays a key role in the pathology of stress-related diseases; however, this link has not yet been completely explored. In this study, we aimed to determine the role of inflammation in stress-induced diseases and whether a common pathway for depression exists. Recent studies support pharmacological and non-pharmacological treatment approaches significantly associated with ameliorating depression-related inflammation. In addition, major depression can be associated with an activated immune system, whereas antidepressants can exert immunomodulatory effects. Moreover, non-pharmacological treatments for major depression (i.e., exercise) may be mediated by anti-inflammatory actions. This narrative review highlights the mechanisms underlying inflammation and provides new insights into the prevention and treatment of stress-related diseases, particularly depression.

A Systematic Review and Meta-Analysis on the Effects of Exercise on the Endocannabinoid System.

Introduction: The endocannabinoid (eCB) system plays a key role in maintaining homeostasis, including the regulation of metabolism and stress responses. Chronic stress may blunt eCB signaling, and disruptions in eCB signaling have been linked to stress-related psychiatric disorders and physical health conditions, including anxiety, depression, post-traumatic stress disorder (PTSD), diabetes, and obesity. Pharmacological and nonpharmacological behavioral interventions (e.g., exercise) that target the eCB system may be promising therapeutic approaches for the prevention and treatment of stress-related diseases. In this study, we perform a systematic review and the first meta-analysis to examine the impact of exercise on circulating eCB concentrations. Materials and Methods: We performed a review of the MEDLINE (PubMed) database for original articles examining the impact of exercise on eCBs in humans and animal models. A total of 262 articles were screened for initial inclusion. Results: Thirty-three articles (reporting on 57 samples) were included in the systematic review and 10 were included in the meta-analysis. The majority of samples that measured anandamide (AEA) showed a significant increase in AEA concentrations following acute exercise (74.4%), whereas effects on 2-arachidonoylglycerol (2-AG) were inconsistent. The meta-analysis, however, revealed a consistent increase in both AEA and 2-AG following acute exercise across modalities (e.g., running, cycling), species (e.g., humans, mice), and in those with and without pre-existing health conditions (e.g., PTSD, depression). There was substantial heterogeneity in the magnitude of the effect across studies, which may relate to exercise intensity, physical fitness, timing of measurement, and/or fasted state. Effects of chronic exercise were inconsistent. Conclusions: Potential interpretations and implications of exercise-induced mobilization of eCBs are discussed, including refilling of energy stores and mediating analgesic and mood elevating effects of exercise. We also offer recommendations for future work and discuss therapeutic implications for exercise in the prevention and treatment of stress-related psychopathology.

Pleiotropic actions of allopregnanolone underlie therapeutic benefits in stress-related disease

For several years, research from around the world has suggested that the neuroactive steroid (3α,5α)-3-hydroxypregnan-20-one (allopregnanolone) may have therapeutic potential for treatment of various stress-related diseases including post-traumatic stress disorder (PTSD), depression, alcohol use disorders (AUDs), as well as neurological and psychiatric conditions that are worsened in the presence of stress, such as multiple sclerosis, schizophrenia, and seizure disorders. In this review, we make the argument that the pleiotropic actions of allopregnanolone account for its ability to promote recovery in such a wide variety of illnesses. Likewise, the allopregnanolone precursors, pregnenolone and progesterone, share many actions of allopregnanolone. Of course, pregnenolone and progesterone lack direct effects on GABAA receptors, but these compounds are converted to allopregnanolone in vivo. This review presents a theoretical framework for understanding how endogenous neurosteroids that regulate 1) γ-aminobutyric acid (GABA)A receptors, 2) corticotropin releasing factor (CRF) and 3) pro-inflammatory signaling in the innate immune system and brain could play a key role in both the prevention and treatment of stress-related disease. We further discuss cautions and limitations of allopregnanolone or precursor therapy as well as the need for more clinical studies.

"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.

Inflammation: The Common Pathway of Stress-Related Diseases

While modernization has dramatically increased lifespan, it has also witnessed that the nature of stress has changed dramatically. Chronic stress result failures of homeostasis thus lead to various diseases such as atherosclerosis, non-alcoholic fatty liver disease (NAFLD) and depression. However, while 75%–90% of human diseases is related to the activation of stress system, the common pathways between stress exposure and pathophysiological processes underlying disease is still debatable. Chronic inflammation is an essential component of chronic diseases. Additionally, accumulating evidence suggested that excessive inflammation plays critical roles in the pathophysiology of the stress-related diseases, yet the basis for this connection is not fully understood. Here we discuss the role of inflammation in stress-induced diseases and suggest a common pathway for stress-related diseases that is based on chronic mild inflammation. This framework highlights the fundamental impact of inflammation mechanisms and provides a new perspective on the prevention and treatment of stress-related diseases.

Impact of Yoga and Meditation on Stress Levels of Industrial Employees

Stress is Sudden Biological Change. It has become the curse of 21st century and is silent killer in the modem world. Stress is the greatest danger the information era. Stress is the priceless poison for human life in the universe. It can disturb any one's physical, mental, emotional and behavioral balance. Stress can damage different parts of human body from muscles from tissues organs and blood vessels. It can speed up pulse rate and respiration. It can raise blood pressure and body temperature. It can also interfere with the body metabolism, digestion, appetite, sleep, sexuality and even fertilityIndian scholars viewed the phenomenon of stress from various perspectives ranging from stimulus oriented responses and psychodynamic point of view. A comprehensive description of certain concepts which relate closely the modem concepts of stress can be found in traditional texts like Charak Sumlita..Yoga sutrar and Bhagavat Gita. Some of these, for example, are Dukha (pain / misery) Klrsu (afflictions) Kumu or trisna (desires) Atman and Ahumkara (self & ego). It is interesting note that the body - mind relationship, characteristic of modem stress studies, The holistic ancient Indian view of stress and management of stress are obtaining currency at international levels.Yoga is an ancient art that is defined as the union of the soul with God (Anand, 2000). It is a path of personal spiritual development that utilizes meditation bring enlightenment, self-realization, and, ultimately, the attainment of God and bliss (p. 109). Originally, the ultimate goal of yoga was called Samadhi, or self-realization (Iyengar, 2001).The word meditate comes from the Latin word meditari, which means, to think or reflect upon (Bonadonna, 2003). It is defined as simple mind-body technique that allows you gain unique state of restful awareness or alertness. Mindfulness meditation is the more difficult of the two (Bonadonna, 2003). It is defined as attempting awareness of the whole perceptual field. More than 2 million Americans have learned meditation over the past years (Bonadonna, 2003). Recent studies and evidence have demonstrated that such yoga practices are effective in reducing stress.Smith et al.,(2007) reported that Yoga was found be as effective as relaxation in reducing stress, anxiety and improving health status on seven domains of the SF-36. Yoga was more effective than relaxation in improving mental health.James et al. (2010) reported that improved mood and significantly Meditation training has become popular intervention for the prevention and treatment of stress-related diseases and for the management of stress. Manocha et al. (2011) Conduct study on A Randomized, Controlled Trial of Meditation for Work Stress, Anxiety and Depressed Mood in Full-Time Workers. Results show that There was significant improvement for the meditation group compared both the relaxation control and the wait-list groups.Hartfiel et al. (2011) results show that even short program of yoga is effective for enhancing emotional well-being and resilience stress in the workplace.Mohan et al. (2011) Report that significant increase in physiologic galvanic skin response (GSR), heart rate (HR), electromyography (EMG), sympathetic reactivity(GSR, EMG, HR, QTc/QS2) and psycho logic (acute stress questionnaire scores) maikers of stress. Meditation was associated with relaxation (significant decrease in GSR, EMG, QTc/QS2, and acute stress questionnaire scores). Meditation, if practiced before the stressful event, reduced the adverse effects of stress. Memoiy quotient significantly increased, whereas cortisol level decreased after both stress and meditatioa visual-choice reaction time (VCRT).showed no significant change.Cutshall et al. (2011)report that self-directed, computer-guided meditation training program is useful for stress reduction in hospital nurses, this pilot study suggest the feasibility and efficacy of biofeedback-assisted, self-directed, meditation training program help hospital nurses reduce their stress and anxiety. …

Disruption of Poly(ADP-ribose) Polymerase (PARP) Protects Against Stress-Evoked Immunocompromise

Chronic stress, mediated by adrenal hormones, is a major risk factor in the progression and outcome of human disease. While the secretion of adrenal hormones is known to be the primary endocrine mediator of stress-induced immunocompromise, the molecular mechanisms underlying the immunocompromise remain unspecified. Overproduction of the nuclear enzyme, poly (ADP-ribose) polymerase (PARP) has been implicated in the molecular pathway that leads to cell death by energy depletion following stress. Wild-type (WT) mice and mice with targeted disruption of the gene encoding PARP-1 (PARP-1 -/-) were subjected to 2 wk daily cold-water swim; splenocyte proliferation, anti-KLH IgG, and serum corticosterone concentrations were assessed. Additional mice of each genotype received daily i.p. injections of dexamethasone (DEX) (0.75 mg/kg) for 2 wk, and splenocyte proliferation and anti-KLH IgG were assessed. Splenocyte proliferation and specific antibody concentrations of stressed WT mice were reduced by ~20% of their pre-stress levels. In contrast, PARP-1 -/- mice maintained normal cell-mediated and humoral immune function following enforced cold-water swim stress. PARP-1 -/- mice also failed to compromise immune function following DEX treatment, whereas WT mice displayed significant reductions of immune function following this treatment. These results provide support for the involvement of PARP activation in immunological damage following physical stress. These results suggest that glucocorticoid-induced immunosuppression may require the activation of PARP in order for apoptosis of immune cells to take place. Taken together, these results suggest that therapies designed to inhibit PARP may prove valuable in the treatment of stress-related diseases.

JOURNALS IN BEHAVIORAL MEDICINE

The field of behavioral medicine has developed out of a convergence of several antecedent disciplines, most noticeably psychosomatic medicine, and behavioral psychology. Definitions of the field vary, but it is generally agreed to involve the formal application of behavioral principles to problems of clinical medicine. This application may take the form of behavioral techniques which (a) facilitate biomedical treatment, (b) assist in the modification of habits with undesirable health consequences, (c) assist in the treatment of stress-related diseases, or (d) produce direct alterations in pathological states. This article defines and traces the field of behavioral medicine. Relevant journal literature is discussed.