Chronic Stress Conditions Research Articles

The condition of the oral fluid in patients under conditions of long-term chronic stress

Objective — to evaluate some qualitative and quantitative parameters of mixed saliva in patients at risk of metabolic‑associated diseases and military personnel under the conditions of the armed conflict in Ukraine.
 Materials and methods. The study involved patients who were included in three groups: the main group (27 individuals at risk of metabolic diseases), comparison group (19 military personnel) and control group (10 somatically healthy individuals). The survey has been performed with the use of questionnaire to assess dryness in the oral cavity, issues of changes in oral hygiene during the last year. To investigate some qualitative and quantitative parameters of unstimulated saliva, fasting oral fluid was collected in the morning. Salivation rate, oral fluid viscosity, and type of microcrystallization were studied using standard techniques.
 Results. Prevalence of persons, in whom the nature of nutrition and individual care of the oral cavity had changed, was established in all investigated groups. The study of the salivation rate revealed a significant decrease in salivation in patients of the main group and comparison groups vs the control group. The lowest secretion level was defined in patients with a risk of metabolic‑associated diseases, whose oral fluid viscosity had the highest values. The most favorable type I of crystallization prevailed only in patients of the control group, it was rare in the main group, whereas in the group of military personnel it was not found, and type II was defined in 26.3% of subjects. Negative changes in the normal life against the background of hostilities resulted in the deterioration in the physical indicators of salivation in both main and comparison groups.
 Conclusions. Long‑term chronic stress causes changes in the qualitative and quantitative composition of oral fluid. The study of microcrystallization of the mixed saliva can be used as a non‑invasive diagnostic method for detecting stress as one of the risk factors for premature aging in patients at risk of metabolic‑associated diseases.

Intranasal Monophosphoryl Lipid a Administration Ameliorates depression-like Behavior in Chronically Stressed Mice Through Stimulation of Microglia.

We and others have reported that systematic stimulation of the central innate immune system by a low dose of lipopolysaccharide (LPS) can improve depression-like behavior in chronically stressed animals. However, it is unclear whether similar stimulation by intranasal administration could improve depression-like behavior in animals. We investigated this question using monophosphoryl lipid A (MPL), a derivative of LPS that lacks the adverse effects of LPS but is still immuno-stimulatory. We found that a single intranasal administration of MPL at a dose of 10 or 20µg/mouse, but not at a dose of 5µg/mouse, ameliorated chronic unpredictable stress (CUS)-induced depression-like behavior in mice, as evidenced by the decrease in immobility time in tail suspension test and forced swimming test and the increase in sucrose intake in sucrose preference test. In the time-dependent analysis, the antidepressant-like effect of a single intranasal MPL administration (20µg/mouse) was observed 5 and 8h but not 3h after drug administration and persisted for at least 7 days. Fourteen days after the first intranasal MPL administration, a second intranasal MPL administration (20µg/mouse) still showed an antidepressant-like effect. The innate immune response mediated by microglia might mediate the antidepressant-like effect of intranasal MPL administration, because both inhibition of microglial activation by pretreatment with minocycline and depletion of microglia by pretreatment with PLX3397 prevented the antidepressant-like effect of intranasal MPL administration. These results suggest that intranasal administration of MPL can produce significant antidepressant-like effects in animals under chronic stress conditions via stimulation of microglia.

Amygdala subfield and prefrontal cortex abnormalities in patients with functional seizures

BackgroundFunctional seizures (FS) are paroxysmal episodes, resembling epileptic seizures, but without underlying epileptic abnormality. The aetiology and neuroanatomic associations are incompletely understood. Recent brain imaging data indicate cerebral changes, however, without clarifying possible pathophysiology. In the present study, we specifically investigated the neuroanatomic changes in subregions of the amygdala and hippocampus in FS. MethodsT1 MRI scans of 37 female patients with FS and 37 age-matched female seizure naïve controls (SNC) were analyzed retrospectively in FreeSurfer version 7.1. Seizure naïve controls included patients with depression and anxiety disorders. The analysis included whole-brain cortical thickness, subcortical volumes, and subfields of the amygdala and hippocampus. Group comparisons were carried out using multivariable linear models. ResultsThe FS and SNC groups did not differ in the whole hippocampus and amygdala volumes. However, patients had a significant reduction of the right lateral amygdala volume (p = 0.00041), an increase of the right central amygdala, (p = 0.037), and thinning of the left superior frontal gyrus (p = 0.024). Additional findings in patients were increased volumes of the right medial amygdala (p = 0.031), left anterior amygdala (p = 0.017), and left dentate gyrus of the hippocampus (p = 0.035). ConclusionsThe observations from the amygdala and hippocampus segmentation affirm that there are neuroanatomic associations of FS. The pattern of these changes aligned with some of the cerebral changes described in chronic stress conditions and depression. The pattern of detected changes further study, and may, after validation, provide biomarkers for diagnosis and treatment.

Ozone Environmental Pollution: Relationship between the Intestine and Neurodegenerative Diseases.

Repeated exposure to environmental ozone causes a chronic state of oxidative stress. This state is present in chronic degenerative diseases and induces a loss of control of the inflammatory response. Redox system dysfunction and failures in control of inflammatory responses are involved in a vicious circle that maintains and increases the degenerative process. The intestine also responds to secondary reactive species formed by exposure to ozone doses, generating noxious stimuli that increase degenerative damage. This review aims to elucidate how environmental pollution, mainly by ozone, induces a state of chronic oxidative stress with the loss of regulation of the inflammatory response, both in the intestine and in the brain, where the functionality of both structures is altered and plays a determining role in some neurodegenerative and chronic degenerative diseases. For this purpose, we searched for information on sites such as the Cochrane Library Database, PubMed, Scopus, and Medscape. Reviewing the data published, we can conclude that environmental pollutants are a severe health problem. Ozone pollution has different pathways of action, both molecular and systemic, and participates in neurodegenerative diseases such as Parkinson's and Alzheimer's disease as well in bowel diseases as Inflammatory Bowel Disease, Crohn's Disease, and Irritable Bowel Syndrome.

Activation of Type I Interferon and Complement component 3a receptor signaling mediates chronic stress-induced social behavior deficits

Inflammation is involved in the pathophysiology of many neuropsychiatric disorders. Chronic stress increases inflammation and alters protective immune responses. Type I interferons (IFN-I) are key players in the peripheral inflammatory response and are implicated in mood and behavior. In the present study, we investigated the roles of neuroinflammation and synapse loss in IFN-I signaling-mediated social behavior deficits under chronic stress conditions. Our findings show that chronic unpredictable stress (CUS) induces significant increases in serum IFNβ levels. Also, CUS induced microglial activation and synapse loss in the PFC of mice. Peripheral blockade of IFN-I signaling attenuated CUS-induced neuroimmune alterations and social behavioral deficits. Furthermore, complement component 3a receptor 1 (C3ar1) mediates systemic IFNβ-induced neuroinflammation and social behavior deficits. Together, these findings identify a key role of C3ar1 in IFN-I-mediated social behavior deficits under chronic stress conditions.

Stress, immune mechanisms, and mental illness: from etiology to treatment

It is now well-established that a strong relationship exists between psychiatric disorders and disturbances of immune mechanisms at different stages of life. Indeed, a derangement in the expression and function of specific immune elements may predispose and contribute to the development of different psychopathologic conditions and could also represent an important component that must be targeted by therapeutic intervention. The proposed symposium will summarize authoritatively the important recent advances on the immune mechanisms contributing to the etiology of psychiatric disorders, with a specific focus on the role of stress, and it will discuss if and how the effectiveness of therapeutic intervention may depend on the ability to regulate immune mechanisms that are altered under pathologic conditions. The symposium will unfold upon the discussion of preclinical and clinical studies addressing different aspects related to psychiatric disorders. Prof. A. Pillai (University of Texas, U.S.A.) will specifically discuss the roles of neuroinflammation and synapse loss in IFN-I signaling-mediated social deficits under chronic stress conditions. He will discuss how peripheral blockade of IFN-I signaling attenuated stress-induced neuroimmune alterations and social behavioral deficits and also the key role of complement component 3a receptor 1 (C3ar1) in these mechanisms. Along this line, Prof. M.A. Riva (University of Milan, Italy) will show how immune mechanisms and dysregulation of microglial function may contribute to the vulnerability to stress at different life stages, from adolescence to adulthood. Moreover, he will discuss how the normalization of some of these mechanisms following pharmacological intervention may contribute to therapeutic effectiveness in the treatment of different psychiatric disorders characterized, particularly in patients characterized by a higher inflammatory status. At the clinical level, Dr. G. Scaini (University of Texas, U.S.A.) will discuss the interplay between inflammation, stress, and mitochondria in bipolar disorder patients. She will highlight the significant correlation between alterations in mitochondrial proteins and inflammatory markers with a decrease in functional status and an increase in the severity of symptoms. Lastly, Prof. J. Felger (Emory Univ.) will discuss how depressed patients with increased inflammation show altered functional connectivity within the ventral striatum to ventromedial prefrontal cortex reward circuitry in relation to symptoms of anhedonia. These changes can be improved by pharmacological intervention aimed to increase dopamine levels suggesting that functional connectivity in reward circuitry may also serve as a modifiable imaging biomarker for the efficacy of pharmacological and/or behavioral interventions to reverse the impact of inflammation on the brain of depressed subjects.

#4277 EGF, GDF-15 AND NEOPTERIN AS PREDICTORS OF CHRONIC KIDNEY DISEASE PROGRESSION IN CHILDREN BY MEANS OF ARTIFICIAL NEURAL NETWORK MODELS

Abstract Background and Aims Progression of chronic kidney disease (CKD) is a compound process, where activation of immunocompetent cells and subclinical inflammation play pivotal role. Enhanced atrophy of the tubular cells, and finally, gradual fibrosis of tubulointerstitial tissue, are responsible for irreversible character of the disease. Multiple molecules influence above-mentioned processes. Growth differentiation factor (GDF)15, a member of TGF-β cytokine superfamily, is a marker of inflammation and an integrative signal in both acute and chronic stress conditions. Elevated serum concentrations of GDF15 were associated with increased risk of development and progression of CKD in adults, as well as with mortality in this group of patients. Our previous investigation revealed increased serum GDF15 concentrations in children on chronic dialysis. Epidermal growth factor (EGF), a tubule-specific protein, promotes proliferation, differentiation and migration of epithelial cells, and therefore, modulates regeneration of injured renal tubules. Decreased concentrations of EGF in urine were observed in variety of kidney diseases, including diabetic nephropathy, lupus nephritis or CKD. Our previous analysis of EGF serum concentrations in CKD children confirmed their decreased values on chronic dialysis. Neopterin is a product of activated monocytes and macrophages and serves as a marker of cell-mediated immunity. Elevated serum concentrations of neopterin were observed in CKD adult patients, our investigation revealed its increased values in children on chronic dialysis. None of the above mentioned markers was analyzed in the population of CKD children treated conservatively. Therefore, the aim of study was to assess the serum concentrations of EGF, GDF-15 and neopterin in children with CKD on conservative treatment and verify the usefulness of these markers in predicting CKD progression by means of artificial intelligence tools. Method The study group consisted of 153 children with pre-dialysis CKD stages 1-5 (stage 1 – 27 patients, stage 2 – 26 patients, stage 3 – 51 patients, stage 4 - 28 patients, stage 5 – 21 patients). EGF, GDF-15 and neopterin serum concentrations were assessed by ELISA. The patient database was implemented into the artificial neural network. In detail, the recursively selected subsets of input variables constituted the input layer of an artificial neural network built of perceptrons (multi-layer perceptron). Anthropometric data, biochemical parameters, EGF, GDF15 and neopterin were included into the model, serum creatinine and eGFR, as direct classifiers of CKD stage, were excluded. Various models were tested, regarding their accuracy, AUROC and Matthews correlation coefficient (MCC) values. Results EGF serum concentrations decreased gradually, whereas GDF15 and neopterin values rose systematically with CKD progression, keeping statistically significant inter-stage differences. Moreover, the most precise ANN model, among the tested artificial neural networks, contained EGF, GDF15 and neopterin as input parameters and classified patients into either CKD 1-3 or CKD 4-5 groups. This model has put new patients into appropriate classes with excellent Accuracy of 96.77%, AUROC 0.9169 and Matthews correlation coefficient (MCC) of 0.9157. Conclusion The presented model of an artificial neural network, with serum concentrations of EGF, GDF15 and neopterin as input parameters, may serve as a useful predictor of CKD progression in the pediatric population. It suggests the essential role of inflammatory processes, defined by newly discovered markers, in the renal function decline towards advanced stages of CKD in children.

Intranasal administration of lipopolysaccharide reverses chronic stress-induced depression-like behavior in mice by microglial stimulation

We recently reported that intraperitoneal injection of a low dose of lipopolysaccharide (LPS) reversed depression-like behavior in mice induced by chronic stress by stimulating microglia in the hippocampus. In this study, we found that a single intranasal administration of LPS at a dose of 5 or 10 μg/mouse, but not at a dose of 1 μg/mouse, rapidly reversed depression-like behavior in mice stimulated with chronic unpredictable stress (CUS). In the time-dependent experiment, a single intranasal administration of LPS (10 μg/mouse) reversed CUS-induced depression-like behavior in mice 5 and 8 h but not 3 h after drug administration. The antidepressant effect of a single intranasal LPS administration (10 μg/mouse) lasted at least 10 days and disappeared 14 days after administration. Fourteen days after the first intranasal LPS administration, a second intranasal LPS administration (10 μg/mouse) still reversed the increased immobility time in TST and FST and the decreased sucrose uptake in SPT in CUS mice, which again exhibited depression-like behaviors 5 h after LPS administration. The antidepressant effect of intranasal LPS administration was dependent on microglial activation, because inhibition of microglia by pretreatment with minocycline (40 mg/kg) or depletion of microglia by pretreatment with PLX3397 (290 mg/kg) prevented the antidepressant effect of intranasal LPS administration in CUS mice. These results suggest that stimulation of the microglia-mediated innate immune response by intranasal administration of LPS can produce rapid and sustained antidepressant effects in animals under chronic stress conditions.

Affecting burden and cost of care for the caregiver of dependent patients with advanced stage of cancer who had an arrangement for expected death at home.

e24000 Background: The terminal stage cancer patients suffer from disease and related therapeutic processes, lead to increasing need for caring from their caregivers. This affects the quality of life(QOL) of caregivers. Currently, there is no data on burden of caregivers who caring for cancer patients who are choose to die at their home. Objective: This study examined burden of caregivers, impact on QOL and satisfaction of caregivers for patients with terminal cancer, comparing in the group of patients who die at home versus at hospital, comparing in regular care group(RC) versus palliative care group(PC). Methods: The semi-qualitative-quantitative study enrolled caregivers of advance cancer patients who had PPS < 60 at Ramathibodi Hospital from Dec 2021-Nov 2022. We assessed participants on 3-time-points (enrolment, 1, 2 months) for QOL and burden via telephone interviews, questionnaires by EQ5D5L and Zarit Burden. If the patients passed away, we interviewed caregivers in qualitative study. Analysis responses were recorded, transcribed and organized thematically analyzed. Analysis stratified on care with palliative care or not, and place of death. Results: We enrolled 108 participants, child (56%) and spouses (29%). They spent carring time average of 16.56 hr/day. 52 patients have passed away: home death(34) and hospital death(18). No significant difference in burden score and QOL between RC and PC. Burden score significantly increasing when time of death approach in both groups. However, significantly higher satisfaction score in caregivers of patients who died at home(P < 0.001). In patient who died in hospital, early integrated palliative showed significantly higher satisfaction score(P = 0.046). Qualitative analysis revealed 3 primary themes, 1) caregiver burden is increasing and chronic stress condition until the death of their loves and still continue post their death 2) need more help in coping and nursing strategies, more early palliative care can relieve their distresses 3) opinion of the caregivers in group of hospital death, If they could turn back time, they would have promised to look after their lovers better in changing the pass away at their home. Conclusions: Caregivers for terminal cancer patients have a high burden. However, caregiver of patients who died at their home rather have more satisfaction. Early integrated palliative care improves satisfaction in caregiver of patients who died at hospital. [Table: see text]

Catechins and Proanthocyanidins Involvement in Metabolic Syndrome.

Recent studies on natural antioxidant compounds have highlighted their potentiality against various pathological conditions. The present review aims to selectively evaluate the benefits of catechins and their polymeric structure on metabolic syndrome, a common disorder characterized by a cluster of three main risk factors: obesity, hypertension, and hyperglycemia. Patients with metabolic syndrome suffer chronic low inflammation state and oxidative stress both conditions effectively countered by flavanols and their polymers. The mechanism behind the activity of these molecules has been highlighted and correlated with the characteristic features present on their basic flavonoidic skelethon, as well as the efficient doses needed to perform their activity in both in vitro and in vivo studies. The amount of evidence provided in this review offers a starting point for flavanol dietary supplementation as a potential strategy to counteract several metabolic targets associated with metabolic syndrome and suggests a key role of albumin as flavanol-delivery system to the different target of action inside the organism.

Effects of ACTH6-9-Pro-Gly-Pro Peptide on the Levels of Pro- and Anti-Inflammatory Cytokines in Wistar Rats under Conditions of Chronic Restraint Stress.

We evaluated the effect of ACTH6-9-Pro-Gly-Pro (ACTH6-9-PGP) peptide on the serum levels of pro- and anti-inflammatory cytokines in experimental animals under conditions of chronic restraint stress. Stress exposure over 2 weeks led to an increase in the levels of IL-1β, IL-6, and IFNγ in rats. Daily intraperitoneal injection of ACTH6-9-PGP in a dose of 5 μg/kg before stress exposure significantly decreased the levels of IL-6 and IFNγ by 4.8 and 49.3% respectively. Administration of the peptide in a dose of 50 μg/kg decreased the levels of IL-1β and IFNγ by 51.2 and 39.7%, respectively. However, no changes in the cytokine levels were observed after injection of the peptide in a dose of 500 μg/kg. Thus, ACTH6-9-PGP administered in doses of 5 and 50 μg/kg prevented the stress-induced changes in the levels of pro- and inflammatory cytokines.

126 Time-budget and welfare indicators of stabled horses in three different stall architectures: A cross-sectional study

Keeping horses in single stalls can prevent them from performing natural behaviors leading to the development of abnormal behaviors (AB) and stereotypic behaviors (SB). Time-budget (TB) is the daily amount of time an animal engages in behavioral activities. Differences in the TB of domesticated horses compared with feral conspecifics in their natural environment can be used to reveal welfare impairment. Other measurements indicative of stress levels in horses are the cortisol circadian rhythm (CCR), and the leucocyte numbers (LN). The current study aimed to identify how 3 different stall architectures can influence the TB and physiological parameters in full-time stabled horses fed at 1.45% DMI/BW twice a day with a 34:66 grain: forage ratio. Stall types included: 1) 3.2 × 3.7m stalls with tactile contact (TC) between horses, B1; 2) 2.6 × 3.5m stalls with only visual contact (VC) between horses with outside view, B2; 3) 2.3 × 3.4m stalls with VC and outside view, B3. The horses were used for light exercise, 4 d a week. Surveillance cameras were installed in one stall per barn. Twenty-nine mixed breed horses (10 horses from B1 and B3, and 9 from B2) were randomly selected and filmed for one period of 24 h per horse. The video was analyzed with continuous sampling and the time spent in SB, AB and other activities was measured second-by-second and inserted into a spreadsheet. Blood collection wasperformed one day after de recording period at 8:00 a.m. and at 5:00 p.m. The samples were used to determine the cortisol levels, and CCR. The effects of the different stall architectures were analyzed by ANOVA and significant results compared by post hoc Tukey test. B1 had higher social interaction time (2.77% of the TB) compared with B2 (0%) and B3 (0.01%) (P = 0.020), with no other differences among barns. Restricted availability of food had a direct impact on all the horses’ TB, creating long periods of idleness (41% of the TB observing the exterior, 18% of the TB standing attentively) and fasting. The low time spent eating (204 ± 13 min) may have led horses to develop AB like bed-eating (176 ± 19 min), coprophagy (18 ± 9 min) and wood-chewing (42 ± 19 min). All horses presented SB and AB, 25% of the horses low LN, 38% of the horses had cortisol above the reference range, and 29% of the horses an altered CCR. The physiological and TB alterations along with high prevalence of SB and AB indicate that horses were in a state of chronic stress and the stalls’ architecture did not affect the horses’ capability to cope with such housing conditions. Feed restriction likely led to AB and SB.

Intact GR dimerization is critical for restraining plasma ACTH levels during chronic psychosocial stress

Male C57BL/6N mice exposed to the chronic subordinate colony housing (CSC; 19 days) paradigm, a preclinically validated model of chronic psychosocial stress, are characterized by unaffected basal morning plasma corticosterone (CORT) concentrations despite adrenal and pituitary hyperplasia and increased adrenocorticotropic hormone (ACTH) plasma concentrations, compared with single-housed control (SHC) mice. However, as CSC mice are still able to show an increased CORT secretion towards novel heterotypic stressors, these effects might reflect an adaptation rather than a functional breakdown of general hypothalamus-pituitary-adrenal (HPA) axis functionality. In the present study we used male mice of a genetically modified mouse line, to investigate whether genetically-driven ACTH overexpression compromises adaptational processes occurring at the level of the adrenals during CSC exposure. Experimental mice carried a point mutation in the DNA binding domain of the glucocorticoid (GC) receptor (GR), attenuating dimerization of GR (GRdim), resulting in a congenially compromised negative feedback inhibition at the level of the pituitary.In line with previous studies, CSC mice in both the wild type (WT; GR+/+) and GRdim group developed adrenal enlargement. Moreover, compared with respective SHC and WT mice, CSC GRdim mice show increased basal morning plasma ACTH and CORT concentrations. Quantitative polymerase chain reaction (qPCR) analysis revealed neither a genotype effect, nor a CSC effect on pituitary mRNA expression of the ACTH precursor proopiomelanocortin (POMC). Finally, CSC increased anxiety-related behavior, active coping and splenocyte in vitro (re)activity in both WT and GRdim mice, while a CSC-induced increase in adrenal lipid vesicles and splenic GC resistance was detectable only in WT mice. Of note, lipopolysaccharide (LPS)-stimulated splenocytes of GRdim mice were resistant to the inhibitory effects of CORT.Together our findings support the hypothesis that pituitary ACTH protein concentration is negatively controlled by GR dimerization under conditions of chronic psychosocial stress, while POMC gene transcription is not dependent on intact GR dimerization under both basal and chronic stress conditions. Finally, our data suggest that adrenal adaptations during chronic psychosocial stress (i.e., ACTH desensitization), aiming at the prevention of prolonged hypercorticism, are protective only to a certain threshold of plasma ACTH levels.

Gastroesophageal reflux disease in conditions of chronic stress. Review with own observation

It is known that 20 to 42% of patients receiving a proton pump inhibitor for the treatment of gastroesophageal reflux disease do not respond satisfactorily to it. This condition is called refractory gastroesophageal reflux disease. To achieve a therapeutic effect, it is advised to use H2‑receptor antagonists, alginates, baclofen or antidepressant therapy in complex treatment. Recent years, solutions containing sodium alginate have been widely used. These drugs reduce the severity and frequency of heartburn when used postprandially as adjunctive therapy to proton pump inhibitors in patients with gastroesophageal reflux disease. The alginates, available in the US and European markets, differ, with the latter containing higher concentrations of alginate, possibly contributing to higher efficiency. This is supported by some researchers reporting rapid efficacy for both postprandial and nocturnal symptoms in patients with refractory gastroesophageal reflux disease. Given the absence of significant side effects, it is advised to use alginates as an addition to proton pump inhibitors, taking into account the availability, as well as the preferences of the doctor and patient.
 The article presents modern scientific data on a widespread Gastroenterological disease — GERD in the context of the impact of stress factor on its course. The analysis was performed of the recent investigations, aimed at the study of the mechanisms of traumatic effect of psychosocial and psychoemotional stress on the functional activity of the upper gastrointestinal tract. The results of the study of the role of anxiety‑phobic and depressive disorders because of prolonged exposure to stressors were analyzed. The author presented data of his own research, which clearly demonstrated a significant increase of frequency and level of anxiety and depression under wartime stress. It has been established that combination of gastroesophageal reflux disease with anxiety and depression exacerbates the clinical manifestations of the disease and reduces the effectiveness of treatment, which requires an individual approach to the choice of therapeutic measures. It is advisable to use antacids and alginic acid preparations, as well as methods of psychological correction, along with proton pump inhibitors or instead of them.

ROLE OF NO IN SOFT PERIODONTAL TISSUES OF RATS DURING STRESS AND INFLAMMATION

Aim. To evaluate the activity of NO-synthase isoforms, the concentration of peroxynitrites and nitrosothiols in the soft tissues of the periodontium of rats under the conditions of modeling chronic stress against the background of lipopolysaccharide-induced inflammation. Methods. Experimental studies were performed on 24 male Wistar rats weighing 190–240 g. The animals were divided into 4 groups: 1 — control, 2 — chronic stress (ChrStr group), animals were kept above water for 1 hour every day for 30 days, 3 — animals that were intraperitoneally injected with 0.4 μg/kg of bacterial LPS of S. typhi (pyrogenal) (LPS group); 4 — animals that were simultaneously simulated chronic stress as in group 2 and administered LPS as in group 3 (ChrStr+LPS). The activity of inducible NO-synthase (iNOS), constitutive NO-synthase (cNOS), the concentration of nitrosothiols (S-NO), and concentration of peroxynitrites of alkali and alkaline earth metals (ONOO) were studied in the homogenate of the periodontal soft tissues of rats. Results. The activity of NOS in the soft periodontal tissues of rats under chronic stress simulation conditions, LPS administration, combined exposure to chronic stress and LPS was increased compared to control group. The concentration of ONOO- in the soft periodontal tissues of rats under chronic stress simulation conditions, LPS administration, combined exposure to chronic stress and LPS was increased compared to the control group. The concentration of nitrosothiols in the soft periodontal tissues of rats under the conditions of chronic stress simulation, LPS administration, combined exposure to chronic stress and LPS was decreased compared to the control group. Conclusions. The combined effect of bacterial lipopolysaccharide and chronic stress leads to increased production of nitrogen monoxide from inducible NO-synthase and elevates concentration of reactive forms of nitrogen, which creates possibility for development of nitrosative stress in the soft periodontal tissues.

New opportunities for the pharmacotherapy of insomnia in the practice of a family doctor

The article discusses modern problems of etiology, pathogenesis, clinic and treatment of various forms of sleep disorders – insomnia. Special attention is paid to situational insomnia in connection with the relevance of chronic stress states as a leading factor in the mentioned form of sleep disorders. An analysis of the advantages and disadvantages of various drugs used today for the pharmacotherapy of insomnia in domestic clinical practice was carried out. The mechanisms and clinical possibilities of the new domestic combined remedy Gammavital as an innovative and promising tool for the treatment of sleep disorders, first of all, situational insomnia, are considered in detail. Reasoned expediency of combining individual components of Gammavital in the specified combination with the aim of synergism of their effect on the main pathogenetic ways of formation of sleep disorders. The combination of effectiveness and safety of the clinical and pharmacological action of Gammavital allows to recommend it as a tool of choice in the treatment of stress-dependent forms of sleep disorders in the practice of a family doctor.

Nerve Growth Factor in Psychiatric Disorders: A Scoping Review.

Neurotrophins have been implicated in multiple psychiatric disorders. Nerve Growth Factor (NGF) is one of the major neurotrophins that has attracted much research interest. Therefore, we undertook, to the best of our knowledge, the first scoping review encompassing all major psychiatric disorders and their relation to NGF. This review aimed to identify the current position of NGF in psychiatric research and to outline present gaps in knowledge, which can be answered with a more detailed systematic review in the future. Suitable studies were identified using PubMed. A total of 20 studies were included in the review: two on bipolar affective disorder (BPAD), three on schizophrenia, seven on depression, and eight on alcohol use disorder. NGF levels are definitively reduced in BPAD and depression, while NGF levels in schizophrenia decreased further after treatment than in the drug-naïve state. The effect of treatment on NGF levels in depression varied based on treatment modalities and severity of depression. In patients with depression, raised NGF was a predictor of conversion to bipolar disorder (BD). NGF levels were raised in acute alcohol intoxication and withdrawal but normalized slowly as abstinence was maintained. NGF may play a protective role in preventing the toxic ill effect of acute alcohol intoxication on the central nervous system. Based on current knowledge, NGF levels may be a useful biomarker of a chronic mental stress condition. However, further research is needed before it can be used to identify a specific psychiatric illness or predict treatment response.

Simple and effective solutions in the correction of anxiety and stress

Acute and chronic stress conditions have an adverse effect on human health at any age and are related to the psychosocial risk factors for chronic non-communicable diseases, increasing the risk of occurrence and development of not only cardiovascular, but also other common diseases such as diabetes mellitus, obesity, broncho-obstructive diseases, ulcerative lesions of gastrointestinal tract, etc. The negative effect of stress on the human health is effectuated both through endogenous pathophysiological changes and through behavioural disorders such as physical inactivity, malnutrition, smoking, alcohol intake, etc. It has also been shown that psychosocial risk factors significantly aggravate the clinical course of existing diseases, significantly reduce adherence to treatment, worsen quality of life, increase the risk of disability and expenditures paid in the healthcare system in patients with chronic non-communicable diseases. Thus, acute and chronic stress have a negative effect on the physical, mental and emotional health, that's why the right choice of both preventive measures and timely management is very important. The combination of non-pharmaceutical effect, including training in stress resistance skills, proper response and emergency self-help in a stressful situation, with the prescription of effective pharmacological therapy can be considered as the optimal strategy. Valocordin® available in the form of drops or tablets represents a combination of low doses of phenobarbital with ethyl bromisovalerianate and plant components, which enhances the positive effects of the combination due to functional.

Chronic Stress Alters Hippocampal Renin-Angiotensin-Aldosterone System Component Expression in an Aged Rat Model of Wolfram Syndrome.

Biallelic mutations in the gene encoding WFS1 underlie the development of Wolfram syndrome (WS), a rare neurodegenerative disorder with no available cure. We have previously shown that Wfs1 deficiency can impair the functioning of the renin-angiotensin-aldosterone system (RAAS). The expression of two key receptors, angiotensin II receptor type 2 (Agtr2) and bradykinin receptor B1 (Bdkrb1), was downregulated both in vitro and in vivo across multiple organs in a rat model of WS. Here, we show that the expression of key RAAS components is also dysregulated in neural tissue from aged WS rats and that these alterations are not normalized by pharmacological treatments (liraglutide (LIR), 7,8-dihydroxyflavone (7,8-DHF) or their combination). We found that the expression of angiotensin II receptor type 1a (Agtr1a), angiotensin II receptor type 1b (Agtr1b), Agtr2 and Bdkrb1 was significantly downregulated in the hippocampus of WS animals that experienced chronic experimental stress. Treatment-naïve WS rats displayed different gene expression patterns, underscoring the effect of prolonged experiment-induced stress. Altogether, we posit that Wfs1 deficiency disturbs RAAS functioning under chronic stressful conditions, thereby exacerbating neurodegeneration in WS.

Work addiction, work engagement, job burnout, and perceived stress: A network analysis.

Recently, the network theory of mental disorders has been used to conceptualize work addiction as a dynamic system of symptoms in direct relationships. This study aimed to extend previous work by investigating the direct relationships of work addiction symptoms with dimensions of work engagement, job burnout, and perceived stress. These phenomena were measured with the Bergen Work Addiction Scale, the Utrecht Work Engagement Scale, the Maslach Burnout Inventory-General Survey, and the Perceived Stress Scale. The sample comprised 676 working Poles with a mean age of 36.12 years (SD = 11.23). The network analysis followed the guidelines for estimating psychological networks from cross-sectional data. Work engagement and job burnout were more closely associated with each other than with work addiction which supports the notion that engagement and burnout represent polar opposites of the same construct and that work addiction is a separate phenomenon, related to both work engagement and job burnout via specific pathways. The symptoms of work addiction were connected with other phenomena through four direct relationships: (1) mood modification-absorption, (2) mood modification-stress, (3) withdrawal-absorption, and (4) problems-exhaustion. These findings narrow down and specify hypotheses regarding potential mechanisms leading from engagement to addiction and from addiction to burnout. The possible mechanisms focus on the absorption component and mood modification related to efforts focused on alleviating chronic stress and negative emotional states. In turn, problems arising from work addiction may lead to exhaustion. Future studies investigating these mechanisms in detail may enable proper prevention programs and therapeutic interventions.