Post-stress Changes Research Articles

Modulating effects of Ukrainian phytocomposition “Balm Truskavets’” on post stress changes in neuroendocrine-immune complex, metabolome, electrocardiogram, and gastric mucosa at rats

Introduction and aim. Earlier our group showed that the Ukrainian phytocomposition “Balm Truskavets’” (UPhCBT) exerts classical adaptogenic effects on parameters of neuro-endocrine-immune complex as well as biophotonics and acupuncture in humans with maladaptation. The list of important properties of adaptogens includes their stress-limiting effect, which is usually tested in an experiment. Therefore, the purpose of this study was to identify modulating effects of UPhCBT on post-stress changes in neuro-endocrine-immune complex, metabolome, electrocardiogram (ECG), and gastric mucosa at rats. Material and methods. The experiment is at 18 male and 20 female Wistar rats. 10 animals remained intact with free access to tap daily water. Rats of the control group for 7 days loaded through a tube with same tap daily water (2 mL once), while the animals of main groups received according to a similar scheme 0,1 mL of PhCBT dissolved in 2 mL of daily water or bottled table water “Truskavetska”™. Over the next 10 days, one animal remained intact and 3 other rats were exposed to acute (4 hours) water-immersion and restraint stress. The next day after stressing, EEG, endocrine, immune and metabolic parameters as well as gastric mucosa injuries was recorded. Results. Acute stress causes in control animals an increase in sympathetic tone, serum levels of catecholamines and corticosterone, combined with a decrease in vagal tone and serum testosterone levels. Such a neuro-endocrine reaction is accompanied by damage to the myocardium and gastric mucosa, an increase in the percentage of macrophages and fibroblasts in the thymus, entropy in the spleen, natural killer cells in the blood. Instead, the mass of the spleen and the percentage of lymphoblasts in it, theophylline-sensitive T-lymphocytes in the blood, the content of α-LP cholesterol in the serum, as well as the catalase and Na,K-ATPase activity of erythrocytes, decrease. Preventive use of phytocomposition, first of all, minimizes or even completely prevents damage to the myocardium and adverse post-stress deviations from the norm of listed parameters. Secondly, it initiates an increase in the level of PTH and the activity of serum acid phosphatase, the percentage of reticulocytes in the spleen and the intensity of phagocytosis of blood neutrophils, but at the same time a decrease in their bactericidal activity, as well as the percentage of monocytes and B-lymphocytes in the blood. Thirdly, it potentiates the post-stress increase in sympathetic tone and damage to the gastric mucosa, as well as natural killers, on the one hand, and the decrease in vagal tone, the level of testosterone in the serum, as well as the mass of the spleen - on the other hand. Fourthly, it reverses the activity of catalase of erythrocytes and the entropy of the splenocytogram. Conclusion. Ukrainian phytocomposition “Balm Truskavets” has a generally favorable adaptogenic effect on the post-stress state of the neuro-endocrine-immune complex and metabolome. However, there are certain adverse effects as the so-called adaptation fee.

Post-stress changes in il-6 and bdnf mRNA levels in the hippocampus and blood of rats with a genetically determined contrast level of nervous system excitability

Neuroinflammation is considered as one of the mechanisms by which stress can potentially lead to a disturbance of the functions of the central nervous system. The presence of neuroimmune dysfunction after stress, and what genetic factors increase the risk of post-stress neuroinflammation has not been sufficiently investigated. Genetically determined excitability of the nervous system is a promising marker of individual vulnerability to stress, manifested in post-stress disorders associated with the specifics of the formation of neuroinflammation.The aim of this work was to study post-stress changes in the expression of pro-inflammatory il-6 genes in the blood and hippocampus and anti-inflammatory cytokine bdnf in the blood of rats with genetically determined high and low levels of excitability of the nervous system. Breeding animals were used, males of two strains of rats aged 5 months: with a high threshold (HT) of excitability of the nervous system (low excitable) and a low threshold (LT) of excitability of the nervous system (high excitable) from the biological collection of the Pavlov Institute of Physiology of the Russian Academy of Sciences. The stress model is a long-term emotional and painful stress according to the scheme of K. Hecht. Experimental and control animals were decapitated 24 hours, 7 days and 24 days after the end of stress exposure. Changes in the mRNA level of the il-6 and bdnf genes were evaluated using real-time PCR.Chronic stress led to a significant increase in the level of il-6 mRNA in the hippocampus only in high excitable animals 24 days after the end of stress. In the blood, the mRNA level of this cytokine increased only in low-excitable rats. The expression of the bdnf gene in blood did not change in response to stress in any of the strains.

Post-stress changes in the gut microbiome composition in rats with different levels of nervous system excitability.

The gut-brain axis is a critical communication system influencing the interactions between the gastrointestinal tract (GI) and the central nervous system (CNS). The gut microbiota plays a significant role in this axis, affecting the development and function of the nervous system. Stress-induced psychopathologies, such as depression and anxiety, have been linked to the gut microbiota, but underlying mechanisms and genetic susceptibility remain unclear. In this study, we examined stress-induced changes in the gut microbiome composition in two rat strains with different levels of nervous system excitability: high threshold (HT strain) and low threshold (LT strain). Rats were exposed to long-term emotional and painful stress using the Hecht protocol, and fecal samples were collected at multiple time points before and after stress exposure. Using 16S rRNA amplicon sequencing, we assessed the qualitative and quantitative changes in the gut microbiota. Our results revealed distinct microbial diversity between the two rat strains, with the HT strain displaying higher diversity compared to the LT strain. Notably, under prolonged stress, the HT strain showed an increase in relative abundance of microorganisms from the genera Faecalibacterium and Prevotella in fecal samples. Additionally, both strains exhibited a decrease in Lactobacillus abundance following stress exposure. Our findings provide valuable insights into the impact of hereditary nervous system excitability on the gut microbiome composition under stress conditions. Understanding the gut-brain interactions in response to stress may open new avenues for comprehending stress-related psychopathologies and developing potential therapeutic interventions targeted at the gut microbiota. However, further research is needed to elucidate the exact mechanisms underlying these changes and their implications for stress-induced disorders. Overall, this study contributes to the growing body of knowledge on the gut-brain axis and its significance in stress-related neurobiology.

The features of reactions to acute stress of neuro-endocrine-immune complex, metabolome, ECG and gastric mucosa in rats with various state of innate muscular endurance and resistance to hypoxia

Background. It is known about wide variety of individual reactions to stress explained by genetics factors. On the other hand, it is also known about aerobic fitness variability between individuals. From the above it follows the hypothesis that inter-individual differences in normal conditions determine the characteristics of the body's response to acute stress. The purpose of this study is to test the hypothesis. Material and methods. The experiment is at 58 rats (28 males) Wistar line. Animals were tested for resistance to hypoxic hypoxia and aerobic muscular performance by swimming test. On the basis of the received data two qualitatively equivalent groups in a ratio 10/48 were formed. After a week of recovery over the next 10 days, one animal remained intact and 5 other rats were exposed to water-immersion and restraint stress. The next day after stress, the ECG recorded and some endocrine, metabolic and immune parameters determined as well as erosive-ulcerative lesions of the gastric mucosa evaluated. Results. Four clusters by hypoxic and swimming tests were created retrospectively: normal resistance to hypoxia and muscular endurance (n=11); moderately reduced resistance to hypoxia and normal swimming test (n=25); drastic increased swimming test and normal hypoxic test (n=3); significantly increased resistance to hypoxia and normal swimming test (n=9). Each cluster is characterized by specific (correctness of classification 100%) post-stress changes in 6 neuro-endocrine, 12 immune, 10 metabolic and 2 ECGs parameters, as well as the index of damage to the gastric mucosa. The swimming test determines the post-stress state of the registered parameters by 63,8%, the hypoxic test - by 57,5%, and taken together - by 79,1%. Conclusion. The post-stress neuro-endocrine, immune and metabolic parameters as well as injuries of myocardium and gastric mucosa in rats are determined significantly by innate muscular endurance and resistance to hypoxia.

The effect of prolonged emotional and pain stress on the expression of the <i>bdnf</i> gene in the brain of rats with contrast excitability of the nervous system

BACKGROUND: The neurotrophic factor BDNF performs important functions in synaptic plasticity and functional activity of neurons, involve in the stress response and the pathogenesis of post-stress disorders. The specificity of post-stress changes in the bdnf mRNA level due to genetically determined features of excitability of the nervous system has not been studied.
 AIM: To study the level of bdnf mRNA in the prefrontal cortex, hippocampus and amygdala of rats of two strains with contrasting excitability of the nervous system in normal condition and at different times after prolonged emotional and painful stress exposure (after 24 hours, 7, 24, 60 days).
 MATERIALS AND METHODS: The study was carried out on adult male rats of two strains with a different level of excitability of the nervous system (HT high threshold and LT low threshold of excitability). As a model of chronic stress, a long-term emotional and painful exposure according to Hecht was used. The bdnf mRNA level was determined using quantitative real-time PCR. Changes in the level of bdnf mRNA in the prefrontal cortex, hippocampus and amygdala of control and experimental groups of rats of two strains were studied at different time points (24 hours, 7, 24 days, 2 months) after prolonged emotional and painful stress exposure.
 RESULTS: It was found that in highly excitable LT rats, a decrease in the expression of the bdnf gene in the prefrontal cortex occurs 24 hours and persists up to 7 days after exposure, in the hippocampus 2 months after exposure. In rats of the low-excitable HT strain, the decrease in bdnf mRNA was not detected.
 CONCLUSIONS: In highly excitable LT rats, prolonged emotional and painful stress causes a decrease in the expression of the bdnf gene in the prefrontal cortex and hippocampus. In low-excitable rats of the HT strain, no significant decrease in the mRNA level of this neurotrophin was found in any of the studied brain regions. The possible association of this specificity of changes in the level of bdnf mRNA with a greater severity of post-stress anxiety-like behavior disorders in highly excitable rats compared with low-excitable ones is discussed.

The Effect of Prolonged Emotional and Painful Stress on the Expression of Proinflammatory Cytokine Genes in Rats with High and Low Excitability of the Nervous System

Stress plays an important role in the pathogenesis of anxiety and depressive disorders. Neuroinflammation is considered as one of the mechanisms by which stress alters the molecular and cellular plasticity in the nervous tissue, which leads to a violation of the functions of the central nervous system. The contribution of genetically determined features of the nervous system to the development of post-stress neuroinflammation has not been sufficiently studied. In this study, the dynamics of poststress changes in the mRNA levels of the il1ß and tnf genes of proinflammatory cytokines interleukin-1-beta (IL-1ß) and tumor necrosis factor (TNF) in the blood and in the brain in two rat strains with high and low excitability thresholds of the nervous system (HT and LT) was evaluated. Changes in IL-1ß and TNF mRNA levels were assessed by real-time PCR 24 h, 7, 24 and 60 days after prolonged emotional and painful stress in the blood and three brain structures involved in the development of post-stress pathology (prefrontal cortex, hippocampus, amygdala). In highly excitable rats of the LT strain, the level of IL-1ß mRNA in the hippocampus and amygdala increased compared to the control 24 days after the end of stress, in low-excitable animals of the HT strain, an increase in the level of IL-1ß mRNA was detected only in the hippocampus at the same time. The TNF mRNA level did not change in any of the strains at any of the time points after stress. Genetically determined excitability of the nervous system is a promising marker of individual vulnerability to stress, manifested in post-stress disorders associated with the characteristics of the formation and dynamics of neuroinflammation.

The Effect of Long-Term Emotional and Painful Stress on the Expression of Proinflammatory Cytokine Genes in Rats with High and Low Excitability of the Nervous System.

Stress plays an important role in the pathogenesis of anxiety and depressive disorders. Neuroinflammation is considered as one of the mechanisms by which stress alters the molecular and cellular plasticity in the nervous tissue and thus entails CNS dysfunction. The contribution of genetically determined features of the nervous system to the development of post-stress neuroinflammation has not been sufficiently studied. In this study, the dynamics of post-stress changes in mRNA levels of the il-1β and tnf genes encoding proinflammatory cytokines interleukin-1 beta (IL-1β) and tumor necrosis factor (TNF) were evaluated in the blood and brain of two rat strains with high and low excitability thresholds of the nervous system (HT and LT, respectively). Changes in IL-1β and TNF mRNA levels were assessed by real-time PCR 24 h, 7, 24 and 60 days after long-term long-term emotional and painful stress in the blood and three brain structures involved in the development of post-stress pathology (prefrontal cortex, hippocampus, amygdala). In highly excitable LT rats, IL-1β mRNA level in the hippocampus and amygdala increased compared to the control 24 days after stress termination, while in low-excitable HT animals, an increase in the level of IL-1β mRNA was only detected in the hippocampus at the same time point. TNF mRNA level did not change in any of the rat strains at any of the post-stress time points. Genetically determined excitability of the nervous system is a promising marker of individual stress vulnerability, as manifested in post-stress disorders associated with developmental and time-course features of neuroinflammation.

Prognostic value of absent left ventricular ejection fraction reserve with regadenoson SPECT MPI

BackgroundAn absent left ventricular ejection fraction (LVEF) reserve with vasodilator stress with PET cardiac imaging has been shown to provide significant independent and incremental value to the perfusion images for prediction of future cardiovascular adverse events. However, the prognostic value of LVEF reserve has not been well characterized with SPECT myocardial perfusion imaging (MPI). MethodsWe studied 858 consecutive patients with normal and abnormal perfusion pattern with regadenoson SPECT MPI. Change in LVEF was calculated as post-stress LVEF—rest LVEF. Absent LVEF reserve was defined as a drop in LVEF by 5% or more on the post-stress images. The primary outcome was a composite of cardiac death, non-fatal myocardial infarction and late coronary revascularization. ResultsAn absent LVEF reserve was more common in patients with abnormal vs normal MPI (31% vs 19%, P = .001). During a median follow-up of 32 months, the primary outcome was experienced by 31% of the study population. An absent LVEF reserve was not associated with an increased risk of the primary outcome in patients with normal (hazard ratio 1.1, 95% CI .4-2.7, P = .8) or abnormal (.75, .56-1.00, P = .05) MPI. There was no significant correlation between extent of ischemia and post-stress change in LVEF (Pearson r = − .072, P = .07). ConclusionsIn patients undergoing regadenoson SPECT MPI, absent LVEF reserve is not associated with worse cardiac outcomes. Thus, routine reporting of both post-stress and rest LVEF measurements in this setting may not be necessary.

Quantitation of Poststress Change in Ventricular Morphology Improves Risk Stratification.

Shape index and eccentricity index are measures of left ventricular morphology. Although both measures can be quantified with any stress imaging modality, they are not routinely evaluated during clinical interpretation. We assessed their independent associations with major adverse cardiovascular events (MACE), including measures of poststress change in shape index and eccentricity index. Methods: Patients undergoing SPECT myocardial perfusion imaging between 2009 and 2014 from the Registry of Fast Myocardial Perfusion Imaging with Next-Generation SPECT (REFINE SPECT) were studied. Shape index (ratio between the maximum left ventricular diameter in short axis and ventricular length) and eccentricity index (calculated from orthogonal diameters in short axis and length) were calculated in end-diastole at stress and rest. Multivariable analysis was performed to assess independent associations with MACE (death, nonfatal myocardial infarction, unstable angina, or late revascularization). Results: In total, 14,016 patients with a mean age of 64.3 ± 12.2 y (8,469 [60.4%] male were included. MACE occurred in 2,120 patients during a median follow-up of 4.3 y (interquartile range, 3.4-5.7). Rest, stress, and poststress change in shape and eccentricity indices were associated with MACE in unadjusted analyses (all P < 0.001). However, in multivariable models, only poststress change in shape index (adjusted hazard ratio, 1.38; P < 0.001) and eccentricity index (adjusted hazard ratio, 0.80; P = 0.033) remained associated with MACE. Conclusion: Two novel measures, poststress change in shape index and eccentricity index, were independently associated with MACE and improved risk estimation. Changes in ventricular morphology have important prognostic utility and should be included in patient risk estimation after SPECT myocardial perfusion imaging.

Protectoral action of molsidomin ATP combination in chronic stress in young and old rats

Adaptive reactions to chronic stress, reaching a certain intensity, can become harmful and be involved in any pathological process. Therefore, the search for new ways to increase the adaptive capacity reduced with age and the body's resistance to the negative effects of chronic stress remains relevant. The aim of the study was to experimentally study the age-related protective properties of the combination of molsidomine and ATP in chronic mild stress. The experiments were performed on young (6 months) and old (26 months) Wistar rats exposed to stressors that changed periodically at random for 8 weeks. During the 6-8th week of the experiment, against the background of stress, the animals were sublingually administered a pharmacological combination based on molsidomine - 2 mg / kg, ATP - 10 mg / kg. It was found that the adaptive reactions of young and old animals to chronic stress have qualitative and quantitative differences. Chronic stress in old rats caused changes in behavior and psycho-emotional state, deterioration of cognitive function, changes in lipoperoxidation. On the part of the immune system in old rats, against the background of a pronounced age involution of lymphoid organs, no significant changes in thymus mass and cellularity were observed during chronic stress, while the mass and cellularity of the spleen increased. The combination of molsidomine and ATP prevented post-stress changes in animal behavior, reduced anxiety, normalized social activity, restored the lost ability to recognize, improved cognitive function. The drug contributed to the preservation of the function of immunocompetent organs in young animals and to a lesser extent showed a protective effect in older animals against the background of involutional changes caused by both aging and chronic stress. The combination of molsidomine and ATP had an antioxidant effect. Thus, in chronic mild stress, older animals showed a different response from young animals to both stress and the administration of molsidomine with ATP. The applied pharmacological combination can be considered as a promising stress-protective agent that has a complex effect on various pathogenetic links of chronic stress due to its neuro- and immunomodulatory, energy-saving, antioxidant properties. Keywords: aging, chronic stress, anxiety, social activity, cellularity of the thymus and spleen, lipid peroxidation, combination of molsidomine and ATP, pharmacological action.

Біомоніторинг постстресових адаптивних змін органів травлення стерляді в умовах замкненого водозабезпечення

Біомоніторинг постстресових адаптивних змін органів травлення стерляді в умовах замкненого водозабезпечення

Early post-stress decrease in cardiac performance by impedance cardiography and its relationship to the severity and extent of ischemia by myocardial perfusion imaging

BackgroundWhile single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is a well-established noninvasive procedure for the evaluation of patients with coronary artery disease (CAD), it is unable to detect the presence of, or underestimates the extent of CAD in certain patients. We aimed to show that a bio-impedance device can detect early post-stress changes in several hemodynamic parameters, thereby serving as a potential marker for the presence of significant ischemia.MethodsProspectively enrolled patients, referred to our Medical Center for clinically-indicated MPI, underwent testing using a Non-Invasive Cardiac System (NICaS) before and immediately after exercise. The differences between rest and stress hemodynamic parameters were compared with the severity and extent of myocardial ischemia by MPI. The study included 198 patients; mean age was 62 years, 26% were women, 54% had hypertension, and 29% diabetes mellitus. Of them, 188 patients had ≤10%, and 10 had > 10% of myocardial ischemia.ResultsIn the first group, there was a significantly greater increase in post-exercise stroke index, stroke work index, cardiac index and cardiac power index (19.2, 29.1, 90.5 and 107%, respectively) compared with the second group (− 2.7, 3.8, 43.7 and 53.5%, respectively), as well as a significantly greater decrease in total peripheral resistance index (− 38.7% compared with − 16.3%), with corresponding p values of 0.015, 0.017, 0.040, 0.016, and < 0.001, respectively.ConclusionsOur data suggest that immediate post-stress changes in several hemodynamic parameters, detected by the NICaS, can be used as an important adjunct to SPECT MPI for the early detection of myocardial ischemia.

Anxiety and neurometabolite levels in the hippocampus and amygdala after prolonged exposure to predator-scent stress

Here, to study the relationship between anxiety levels with changes in the neurometabolic profile in the hippocampus and amygdala, an experimental predator stress model was reproduced in which Sprague-Dawley rats were exposed to cat urine for 10 minutes on a daily basis for 10 days. At the time of presentation of the stimulus, an online survey of behavioral reactions was conducted. Fear, aggressiveness, avoidance of stimulus and grooming were recorded. Fourteen days after the completion of the last stress exposure, the total level of anxiety was determined in the test of the“cross maze”. Using the method of in vivo NMR spectroscopy, the content of neurometabolites was determined in the hippocampus and in the amygdala. According to the peculiarities of behavioral reactions to a stressor, animals were retrospectively divided into two phenotypes. The first phenotype used a passive behavioral strategy, and the second phenotype was active. In animals of the first phenotype, the indicators of anxiety behavior remained at the control level. In animals of the second phenotype, a decrease in anxiety was observed. Animals of the second phenotype showed elevated levels of lactate in the hippocampus compared to animals of the first phenotype, and the lowest N-acetylaspartate levels significantly differed from those in the control and the first phenotype animals. In the amygdala, in animals of the second phenotype, the content of taurine is sharply reduced in comparison with those in the control and the animals of the first phenotype. Thus, the results obtained indicate a relationship of post-stress changes in anxiety, with the peculiarities of the behavioral reactions presented at the moment of the immediate action of the stressor. Among the hippocampal and amygdala neurometabolites, the most informative for the characterization of the anxiolytic action of the predator stress are identified.

Cellular Composition of the B- and T-Cell-Dependent Areas in the Small Intestine during the Post-Stress Period (Experimental Study).

A quantitative study of lymphoid cells in the B- and T-cell-dependent areas of intestinal lymphoid nodules and mesenteric lymph nodes in behaviorally passive and active rats was performed at various periods after acute stress on the model of 1-h immobilization with simultaneous electrocutaneous stimulation. Stress exposure is accompanied by a decrease in the number of lymphoid cells in immunogenic structures of the gastrointestinal tract. Post-stress changes in the cytoarchitectonics of B- and T-cell-dependent areas in mesenteric lymph nodes of animals are less pronounced than in lymphoid nodules. Quantitative changes in lymphoid cells of B-cell-dependent areas in the small intestine of rats are greater than in T-cell-dependent areas. Changes in the cellular composition of immunogenic structures in the digestive system are most significant at the early stages of the post-stress period (1st week). Passive rats are characterized by significant changes in the cytoarchitectonics of B- and Tcell-dependent areas in the small intestine after extreme exposure, which illustrates functional exhaustion of the lymphoid tissue in stress-predisposed specimens.

Социально-психологические последствия современного терроризма

One of the serious social and psychological aftermaths of the terrorist threat is the formation of various mental disorders in the population of countries been exposed to terrorist attacks. The variety of mental impacts of the terrorist threat aftermath is extremely wide - from frustration and mental responses to some serious mental disorders. Long-term emotional tension, uncertainty, fear of death often lead to a decrease in the social functioning of individuals, and as a result, the whole society. At the same time, specific symptoms occur not only in the early stages of experiencing the terrorist threat, but also, often, progress in the delayed period, mainly in the form of affective disorders, psychosomatic pathology, chronic post-stress changes in the personality. The article reviews and analyzes the nature of the response of society as a whole and its individual groups, the impact of professional and national factors on the perception of the terrorist threat in various countries of the world over the past twenty years.

Incremental Diagnostic Performance of Combined Parameters in the Detection of Severe Coronary Artery Disease Using Exercise Gated Myocardial Perfusion Imaging.

PurposeMyocardial perfusion imaging (MPI) using gated single-photon emission tomography (gSPECT) may underestimate the severity of coronary artery disease (CAD). This study aimed to evaluate the significance of combined parameters derived from gSPECT, as well as treadmill stress test parameters, in the detection of severe CAD.MethodsA total of 211 consecutive patients referred for exercise MPI between June 2011 and June 2013 (who received invasive coronary angiography within six months after MPI) were retrospectively reviewed. Exercise MPI was performed with Bruce protocol and 201Tl injected at peak exercise. Gated SPECT was performed using a cadmium-zinc-telluride camera and processed by QPS/QGS software. Perfusion defect abnormalities such as sum stress score (SSS); sum difference score, algorithm-derived total perfusion deficits, transient ischemic dilatation ratios of end-diastolic volumes and end-systolic volumes, post-stress changes in ejection fraction, and lung/heart ratio (LHR) were calculated. Treadmill parameters, including ST depression (STD) at the 1st and 3rd minutes of recovery stage (1’STD and 3’STD), maximal STD corrected by heart rate increment (ST/HR), heart rate decline in 1st and 3rd minutes of recovery stage, recovery heart rate ratio (HR ratio), systolic and mean blood pressure ratios (SBP ratio and MAP ratio) during recovery phase were recorded. Diagnostic performances of these parameters were analyzed with receiver operating characteristic (ROC) analysis and logistic regression for detection of left main (≥ 50%) or 3-vessel disease (all ≥ 70% luminal stenosis) on invasive angiography.ResultsAmong various MPI and treadmill parameters used for detection of severe CAD, SSS and ST/HR had the highest AUC (0.78, 0.73, p = NS) and best cut-off values (SSS > 6, ST/HR > 17.39 10-2mV/bpm), respectively. By univariate logistic regression, all parameters except 1’HRR, 3’HRR, SBP and MAP ratios increased the odds ratio of severe CAD. Only increased L/H ratio, 3’STD, and HR ratio remained significant after multivariate regression. The predicted values of combined MPI and treadmill parameters (LHR, 3’STD, and HR ratio) gave the best ROC (AUC: 0.91) than any individual parameter or parameter combination.ConclusionsOf all treadmill and gSPECT parameters, the combination of MPI and treadmill parameters can offer better diagnostic performance for severe CAD.

Melatonin effects on serum cytokine profiles of rats with different behavioral parameters in acute emotional stress.

The effects of melatonin (epiphyseal neurohormone) on the serum cytokine profiles of rats with different behavioral characteristics were studied after acute emotional stress. One-hour immobilization of animals with simultaneous electrocutaneous stimulation of subthreshold intensity served as the stress model. Acute stress exposure of animals with active behavior led to reduction of the peripheral blood concentrations of pro-inflammatory (IL-1α, IL-1β, IL-2, IFN-γ, granulomonocytic CSF) and anti-inflammatory (IL-4, IL-10) cytokines. Passive rats exposed to emotional stress developed a pronounced increase of pro-inflammatory IL-1β concentration. Reduction of pro-inflammatory cytokine levels in active rats exposed to stress was less pronounced after intraperitoneal preinjection of melatonin (2 mg/kg). In passive animals, exogenous melatonin inverted the poststress changes in the serum levels of pro-inflammatory IL-2 cytokine and of anti-inflammatory IL-4 and IL-10 cytokines. The modulatory effect of melatonin on the cytokine profiles of rats with different behavioral parameters seemed to contribute to adaptation of animals to emotional stress exposure.

The impact of acute mental stress on brachial artery flow-mediated dilation differs when shear stress is elevated by reactive hyperemia versus handgrip exercise

Acute mental stress can impair brachial artery (BA) flow-mediated dilation (FMD) in response to reactive hyperemia (RH) induced increases in shear stress. Handgrip exercise (HGEX) is emerging as a useful tool to increase shear stress for FMD assessment; however, the impact of acute mental stress on HGEX-FMD is unknown. The purpose of this study was to determine whether acute mental stress attenuates RH- and HGEX-induced BA-FMD to a similar extent. In 2 counterbalanced visits, 16 healthy males (19-27 years of age) performed RH-FMD or HGEX-FMD tests after a counting control task (prestress FMD) and a speech and arithmetic stress task (poststress FMD). BA diameter and mean blood velocity were assessed with echo and Doppler ultrasound, respectively. Shear stress was estimated using shear rate (SR = BA blood velocity/BA diameter). Mean arterial pressure (MAP), heart rate (HR), and salivary cortisol were used to assess stress reactivity. Results are expressed as mean ± SE. The stress task elevated MAP (Δ24.0 ± 2.6 mm Hg) and HR (Δ15.5 ± 1.9 beats·min(-1)), but not cortisol (prestress vs. poststress: 4.4 ± 0.7 nmol·L(-1) vs. 4.7 ± 0.7 nmol·L(-1); p = 0.625). There was no difference between the pre- and poststress SR stimulus for RH (p = 0.115) or HGEX (p = 0.664). RH-FMD decreased from 5.2% ± 0.6% prestress to 4.1% ± 0.5% poststress (p = 0.071); however, stress did not attenuate HGEX-FMD (prestress vs. poststress: 4.1% ± 0.6% vs. 5.3% ± 0.6%; p = 0.154). The pre- to poststress change in FMD was significantly different in the RH-FMD vs. the HGEX-FMD test (-1.1% ± 0.6% vs. +1.1% ± 0.8%; p = 0.015). In conclusion, acute mental stress appears to have a disparate impact on FMD stimulated by RH vs. HGEX induced increases in shear stress.

Antioxidant Protection of the Brain in Rats during Acute Stress and Administration of Interleukin-1β

We studied the effect of IL-1β on antioxidant enzyme activity in emotiogenic structures of the brain (hypothalamus, sensorimotor cortex, and amygdala) in behaviorally passive and active rats with different sensitivity to stress. One-hour immobilization of animals with simultaneous electrocutaneous stimulation was used as a model of stress. An intraperitoneal injection of IL-1β (5 μg/kg) was followed by the decrease in glutathione reductase activity in the hypothalamus of rats. Behaviorally active animals of the IL-1β group were characterized by an increase in the activities of Cu/Zn superoxide dismutase and glutathione peroxidase in the sensorimotor cortex and amygdala, respectively. IL-1β administration was accompanied by activation of Cu/Zn superoxide dismutase and glutathione peroxidase in the amygdala of passive rats. Pretreatment with IL-1β abolished the poststress changes in enzyme activity in the hypothalamus and sensorimotor cortex of active and passive rats, respectively. These data illustrate the specific effects of IL-1β on antioxidant protection of CNS tissues in rats with various behavioral characteristics.

Exposure of Wistar rats to 24-h psycho-social stress alters gene expression in the inferior colliculus

Recently, we have demonstrated that the exposure of Wistar rats to psycho-social stress results in a transient auditory hypersensitivity. Here, to learn more about modifications occurring in auditory brainstem, we have analyzed gene expression pattern in inferior colliculus using quantitative RT-PCR. As targets, we have chosen genes associated with: neural activity (FBJ osteosarcoma viral oncogene, cFos), hypoxia (nitric oxide synthase inducible, iNos; superoxide dismutase 2, Sod2), neuroprotection (nerve growth factor beta, Ngfb; heat shock factor 1, Hsf1; heat shock protein 70, Hsp70) and inflammation (tumor necrosis factor alpha, Tnfa; tumor necrosis factor alpha receptor, Tnfar; substance P, Sp; cyclooxygenase 2, Cox2). We found that the expression of all genes was modified following stress, as compared to the controls. Immediately after stress, the number of transcripts encoding iNos, Sod2, Hsf1, Ngfb, Tnfa, Tnfar and Sp was significantly increased, suggesting possible modulation during exposure to stressor. Interestingly, we found that expression of Hsf1 and Ngfb at this particular time was left–right asymmetrical: there were more transcripts of both genes found in the left colliculi, as compared to the right colliculi. Three hours post-stress, iNos, Hsf1, Tnfa and Tnfar were still upregulated, Sod2, Ngfb and Sp went back to baseline and Cox2 was upregulated. Six hours post-stress, cFos mRNA became downregulated. The number of Hsp70 mRNA increased 24h post-stress. Except for the reduced number of cFos transcripts, expression of all other genes tested reached the baseline seven days post-stress. Presented results corroborate the concept of auditory system responding to the psycho-social stress. Post-stress changes in the IC gene expression could likely indicate shift from allostasis to homeostasis in the auditory brainstem.