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We studied interrelationships between behavioral parameters, metabolic processes, and cytokine content in the blood of male and female rats at different stages of postnatal ontogeny after intrauterine stress (mothers were forced to swim in cold water from the 10th to the 16th day of pregnancy). Correlations between behavioral and metabolic parameters in prenatally stressed rats were revealed at an earlier age (day 21 of life) than in controls. In comparison with intact rats, in males exposed to intrauterine stress no relationships between these parameters were revealed at older age, while in females, their direction and character change on day 60 of life. In prenatally stressed males, correlations of the blood levels of IL-6 were revealed: inverse relationships with behavioral parameters on the days 21 and 30 and direct relationships with metabolic parameters on day 60 of life. In prenatally stressed females on day 30 of life, we observed negative correlations between IL-4 levels and metabolic parameters that were absent under normal conditions. Thus, intrauterine stress leads to reorganization of the relationships between the parameters of metabolic and immune processes, which are essential for the purposeful behavior of mammals. The effects of stress seem to depend on the sex of the offspring and stage of postnatal development. [ABSTRACT FROM AUTHOR]

The new coronavirus infection spread around the world in a very short time and turned into a pandemic with a wave-like flow for more than two years. COVID-19infection affects selectively various organs and systems, including the nervous system; neurological manifestations have been reported, including anosmia, encephalopathy, stroke, epileptogenic disorders, which necessitates studies of the course of brain diseases, among which epilepsy occupies a significant place.

Objective: Clinical and psychophysiological assessment of the dynamics of the condition of patients with epilepsy in 4-6 months after the coronavirus infection., Material and Methods: An open controlled prospective comparative outpatient clinical and physiological study of patients diagnosed with epilepsy after suffering from COVID-19 (after 4-6 months) of moderate severity ( n =16), patients diagnosed with epilepsy who did not suffer from COVID-19 ( n =7), a control group ( n =11) after confirmed COVID-19 (after 4-6 months). All groups were in the age range 23 to 50 years. Clinical/neurological and somatic research included: anamnesis, neurological examination, questioning, ECG, EEG, clinical and psychometric tests., Results: There was an increase in the representation of epileptiform activity in the background EEG and more pronounced activity in provoking samples compared with background recording in 26.5% of patients who had suffered COVID-19 compared with the group of patients with epilepsy who had not suffered COVID-19. The detection of rare epileptic seizures in 18.8% of cases in the group of epilepsy patients, who underwent COVID-19, indicates an increase in epileptogenesis and a decrease in therapeutic control over seizures. At the same time, 87.5% of patients in this group showed a statistically significant increase in the influence of the sympathetic nervous system on the regulation of heart rhythm and an increase in anxiety and depression., Conclusion: The results can complement the understanding of the neuropsychiatric status of patients with epilepsy after COVID-19, which provides prerequisites for the development of optimal recovery directions in the rehabilitation period to maintain drug remission of epilepsy and reduce the possible progression of the disease.

A review of the current literature shows that the combined use of neurophysiological and structural-functional neuroimaging methods has significantly expanded the understanding of the mechanisms of migraine with vestibular dysfunction: functional and structural disorders were found in brain regions involved in multisensory vestibular control and Central vestibular processing. Analysis of numerous studies shows that epilepsy can also cause vestibular symptoms, they can occur both without epileptic markers, and in combination with epileptic paroxysms. In isolated epileptic vertigo, according to studies widely presented in the literature, epileptic activity was most often detected by EEG data in the temporal regions, to a lesser extent in the parietal regions. In these studies, neuroimaging findings of foci of reduced substance density were found, which could be a consequence of deafferentation, as well as violations of connections with the focus of neuronal activity. In the absence of structural abnormalities, numerous studies have shown using magnetic resonance spectroscopy, diffusion MRI, and PET that the physiological basis for impaired neuronal metabolism was a decrease in synaptic activity, a violation of maintaining the difference in membrane potentials on the surface of the hippocampus, or changes in neighboring tracts of the white matter of the brain.

This work was designed to study the nonlinear dynamics of fluctuations in renal blood flow of rats under basal conditions and in the perturbed state. An intramuscular injection of aspirin in 0.9% physiological saline (0.5 mg per 100 g body weight) served as a perturbation factor. Capillary blood flow in the right kidney of a rat was measured by the method of laser Doppler flowmetry. The persistence of these time series was estimated by the Hurst method. Our study revealed the persistence of time series under basal conditions (Hurst index H = 0.817 ± 0.041). Statistical parameters of the perturbed series were shown to differ significantly from those observed in the initial state. However, the perturbed series remained persistent. The Hurst index for these series was H = 0.677 ± 0.057. A decrease in this index was insignificant (as compared to that for the baseline index).

This work was designed to study a change in cytokine content in the peripheral blood of behaviorally passive and active Wistar rats at various time intervals after acute stress on the model of night-time immobilization. A decrease in the concentration of most pro- and anti-inflammatory cytokines in passive animals was most pronounced immediately and, particularly, 3 days after stress exposure. Variations in the blood cytokine profile after experimental stress were lower in behaviorally active specimens. A statistically significant decrease was observed only in the amount of a proinflammatory cytokine IL-1α and anti-inflammatory cytokines IL-4 and IL-13. As differentiated from passive rats, these changes in active specimens were most pronounced 1 day after negative emotiogenic exposure. Our results illustrate a specific involvement of immunoactive substances in the systemic regulation of physiological functions and development of individual resistance to the negative consequences of stress.

A computer modeling revealed the following three regimens of heart rate dynamics: linear dynamics, "1st degree chaos", and "2nd degree chaos". This work was designed to study the persistence of these regimens by the method of Hurst. Our investigation showed that the Hurst index is highest for "2nd degree chaos" (H = 0,671 ± 0,028). The Hurst index for the "1st degree chaos" regimen was lower than that for "2nd degree chaos" (H = 0,473 ± 0,015). An increased persistence of cardiac rhythmogenesis in the "2nd degree chaos" regimen illustrates the non-stationarity and prognostic instability of these processes, which contributes to a high risk of heart diseases.

The basic somnological methodology, which is extensively used in the present time, focuses only on clinical practice. However, this approach is not appropriate for monitoring of physiological functions during natural sleep under home conditions. Our work was designed to develop a new information-and-equipment device for the reliable study of human physiological functions during sleep in the real everyday life. The information complex is a new portable microprocessor device and original software, which is constructed on the basis of PC and provides a control of vital physiological functions during sleep in the real everyday life. We developed a new methodology for the objective comprehensive study of sleep under real day-to-day conditions. This approach allows us to identify the phase structure of sleep and to control cardiovascular functions and breathing on the basis of a cross-correlation analysis of the heart rate and respiratory rate (that reflects the degree of emotional strain). The information system for control of sleep under living conditions is composed from interrelated units, which perform the following functions: registration, identification, and analysis of the phase structure of sleep; wake-up of a subject in a certain time during the pre-determined optimal phase of sleep (as regards the psychophysiological state of this subject); and interruption of a long-lasting hazardous phase of sleep. Due to a complex analysis of physiological functions, the information system provides monitoring of sleep under real living conditions and interruption of hazardous phases of sleep that can be accompanied by serious cardiovascular disorders (i.e., leading to cerebral stroke, myocardial infarction, and sudden death).

The effect of the epiphyseal hormone melatonin on the activity of antioxidant enzymes, glutathione peroxidase (GPx), glutathione reductase (GR), and Cu/Zn-superoxide dismutase (Cu/Zn-SOD) was studied in peripheral blood erythrocytes of behaviorally passive and active Wistar rats. Acute emotional stress was modeled by immobilization of animals for1 h with simultaneous electrocutaneous stimulation. Basal activity of antioxidant glutathione enzymes in erythrocytes of behaviorally passive rats was higher than that in active animals. Administration of melatonin (2 mg/kg, intraperitoneally) was accompanied by a decrease in the activity of GPx and GR in erythrocytes from non-stressed passive animals. After experimental stress, passive rats demonstrated a significant increase in the activity of Cu/Zn-SOD and GPx in peripheral blood erythrocytes. The absence of stress-induced changes in functional activity of antioxidant defense enzymes in the blood of behaviorally active animals suggests a relatively constant oxidative status of tissues in these animals under stress conditions. Melatonin administration had little effect on stress-induced changes in functional activity of the erythrocyte antioxidant system in passive rats. Active specimens pretreated with melatonin before stress exposure were characterized by activation of study antioxidant enzymes. Quantitative parameters of the erythrocyte antioxidant defense enzymes did not differ in behaviorally active and passive rats subjected to experimental stress after melatonin injection. Thus, exogenous melatonin abolishes differences in the activity of study antioxidant enzymes in erythrocytes of animals with different behavioral parameters under basal conditions and after experimental stress. In passive rats melatonin mainly reduced the initial tension of oxidative processes. By contrast, administration of this hormone to active specimens is followed by an increase in functional activity of the antioxidant enzyme system under conditions of acute stress.

Taste perception is an important criterion for the state of the oral mucous membrane in patients with gastroesophageal reflux disease. The tongue, as an organ of taste, is characterized by serious changes in the functional state after injury with acid-containing substrates due to reflux. The specific features of taste perception and possibility for their correction were studied in 75 patients with this disorder. The type of changes in activity of tongue taste receptors and taste thresholds in patients before and after therapy were estimated by means of advanced gustometry and functional mobility technique. Specific changes in sensory function of the oral cavity were shown to be associated with acid aggression. Our results illustrate the possibility of taste correction in patients with gastroesophageal reflux disease. Taking into account some features of the general disease, it can be concluded that the introduction of Parodontax-F toothpaste and Emalan into combined therapy is accompanied by the improvement of taste perception. Correction of dysgeusia is an important criterion for the improvement of the quality of life of patients.

This work was designed to study the effect of melatonin on lipid peroxidation in the peripheral blood of behaviorally passive and active Wistar rats. Immobilization of rats with simultaneous electrocutaneous stimulation (1 h) served as a model of acute stress. After intraperitoneal injection of melatonin (2 mg/kg) the intensity of lipid peroxidation in the blood plasma remained practically unchanged in passive specimens, but increased in active animals. Stress exposure was followed by specific variations in free radical processes in the blood (passive rats, inhibition; active specimens, no changes). Administration of melatonin contributed to a decrease in the intensity of lipid peroxidation in the blood of stressed rats (as compared to control specimens receiving this neurohormone). Therefore, the effect of melatonin on free radical processes depends on the initial behavioral characteristics and physiological state of animals. These data illustrate the importance of an individual approach to studying the systemic mechanisms for organization of functions in mammals. Key words: melatonin, emotional stress, lipid peroxidation, blood plasma, rats with various behavioral characteristics.

At present biochemistry of nutrition involves the use of OMICs to investigate food quality, safety, bioactivity and nutrition mechanisms. In this context, nutrimetabolomics is one of the latest directions of nutrition development and provides a better understanding of the influence of nutritional factors on the metabolic pathways of the organism. Proteomic methods play an important role in nutrimetabolomics and allow to detect, identify and quantify proteins under different conditions. Variety of technical and methodological advances, improvements in bioinformatics and possibility of tandem use of different methods helps to solve a number of basic and applied science's problems. Currently huge amount of qualitative and quantitative data on the structure, functions and activities of proteins and their interactions is accumulated. Proteomics aims to establish and characterize a complete set of proteins of the organism. This review summarizes the basic applications of proteomics used in nutrimetabolomic researches. The advantages and disadvantages of the most common techniques of protein separation and sample ionization, types of mass analyzers, basic approaches to the identification of proteins and most widely used databases of known biological sequences are overviewed with a critical assessment of challenges and potential applications.

The work is devoted to the research of immune mechanisms in self-control of various functional systems of homeostatic and behavioral levels. Distinction of immune mechanisms in rats with different prognostic stress-resistance is established. Immunization of rats by conjugates of various neuromediators with bovine serum albumin selectively changes the animals stress-resistance. Participation cytokines in reactions of a brain's separate neurons and their interaction with a leading neuromediator - norepinephrine is established. Individual changes of pro- and anti-inflammatory cytokines in blood serum are shown in rats with different stress-resistance. There are revealed features of morphological distinctions of immunogenic structures small intestine fabrics in animals with various behavioral activity in the "Open field" test.

We studied the effects of pro-inflammatory cytokine interleukin-1beta and antiinflammatory cytokine interleukin-4 on serum albumin parameters in rats with various behavioural characteristics in the open-field test. Under control conditions, the total concentration of serum albumin in active animals was higher than in passive those. However, the ratio of the effective-to-total concentration of albumin (i.e., binding capacity of this protein) was greater in passive rats. Administration of interleukins was accompanied by a decrease in the total content and effective concentration of albumin in passive and, particularly, in active rats. The initial intergroup differences in the ratio of the effective-to-total concentration of albumin were not found after injection of immunomodulating agents. It was mainly related to a more significant increase in this parameter in active animals. An increase in the binding capacity of albumin after cytokine treatment could be associated with conformational changes in the protein molecule. We believe that interleukin-1b and interleukin-4 exert similar effects on the properties of binding sites of serum albumin in rats with various behavioural characteristics.

We studied the effect of shift in the natural light/dark regimen (desynchronosis) and treatment with melatonin on behavioral characteristics of rats with different activity in the open-field test. Experiments were performed on 172 Wistar rats kept under conditions of the natural or shifted light/dark regimen. Some animals were intraperitoneally treated with 1 ml physiological saline or melatonin in doses of 1 and 2 mg/kg, while others did not receive the injections. Desynchronosis altered the normal rhythm of locomotor activity and abolished the differences between daytime and nighttime activity rats not receiving the injections. The influence of melatonin on locomotor activity of rats maintained under normal or shifted light/dark conditions depended on its dose, time of treatment, and initial behavioral characteristics of animals. Our results indicate that the use of melatonin for treatment of disturbances produced by a shift in the light/dark conditions should be performed taking into account individual behavioral characteristics of the organism.

Effects of phase shifts in circadian rhythms and of melatonin administration on rectal temperature in rats with different activity were studied in the open-field test on 176 Wistar rats kept under conditions of natural or shifted light-darkness period. Under normal light-darkness conditions, the amplitude of diurnal variation in rectal temperature was higher in active rats as compared with passive ones. A shift in the light-darkness conditions inverted the circadian rhythm of rectal temperature and augmented the difference between daytime and night time temperatures in passive and, particularly, in active rats. Melatonin effect depended on dose and time of administration. 1 mg/kg Melatonin enhanced the amplitude of diurnal rhythms of energy metabolism in behaviourally active rats. These changes seem to contribute to adaptive reconstruction in the organism during desynchronosis.

Microionophoretic administration of melatonin into the perineuronal space of lateral hypothalamic neurons in WAG and Fischer-344 rats decreased the firing rate and regularized activity of the cells. Moreover, the effects of melatonin completely blocked the activation of neurons and changes in their pulse activity produced by norepinephrine. The effects of melatonin on neuronal activity in behaviorally active stress-resistant WAG rats were more pronounced than in behaviorally passive stress-predisposed Fischer-344 rats. These data suggest that stress-protective activity of melatonin is associated with inhibition of the pulse activity of neurons in emotiogenic structures of the brain and changes in neuronal sensitivity to norepinephrine.

Effects of synthetic thymomimetic vilon on open field behaviour, immediate early gene c-Fos expression in paraventricular hypothalamus properties of organs sensitive to emotional stress, and characteristics of albumin in the blood plasma in male Wistar rats, were investigated and are discussed in the article. It is shown that intraperitoneal vilon injection rises the resistance against emotional stress according to prognostic indexes open field behaviour. Vilon administration also inhibits hypertrophy of the adrenals, involution of the thymus, and elevates concentration of albumin in the blood plasma. The number of Fos-immunoreactive neurons in the paraventricular hypothalamus was lower after vilon administration especially in rats resistant against emotional stress.

Experiments were performed on 24 male Wistar rats weighing 210 +/- 14 g. Depending on the activity in the open field test, all rats were divided into behaviorally active and passive subgroups. Water-immersion stress (2 hrs) followed by 2-hrs rest period was used as the model of acute emotional stress. Tissue samples from aortic ascending arch were taken from control and stressed rats immediately after decapitation and used for further electron microscopy. The number of micropinocytosis vesicles along the free and basal layers of the cytoplasm and the area of mitochondria were determined. Emotional stress was shown to intensify metabolic processes involving micropinocytosis vesicles between the aortic lumen and its wall. Passive rats display the most severe alterations induced by stress (damages of aortic endotheliocytes, partial regeneration of the plasmalemma by membranes of micropinocytosis vesicles, and decrease in the average area of mitochondria). Morphological equivalents of the initial stages of emotional stress-induced formation of fibrous changes in the aortic arch intima are believed to be found. Such changes can lead to the appearance of atherosclerotic patches.

The study was made on Wistar rats. A shift in endogenous biological rhythms was simulated by that in the light phase by 12 hours and evaluated by the shift in the rhythm of rectal temperature. Experiments revealed that desynchronization potentiated ulcerative processes in the rat stomach. The study demonstrated the protective effect of intraperitoneally injected melatonin to prevent the formation of ulcerative defects in the rat stomach during artificially simulated desynchronization.

The influence of short-form water immersion stress of rats on lipids in the skin, the cerebellum and the medulla oblongata was studied. The level of total lipids and absolute and relative contents of the main lipid fractions (phospholipids, nonesterified cholesterol, free fatty acids, triglycerides, and cholesterol esters) were measured. Stress induced delayed changes of the lipid component of the skin. The first significant changes of lipid fractions were only observed 20 h later after the stress procedure. These changes were retained (being at nearly constant levels) till the end of the second day. The decrease in contents of total lipids and esterified cholesterol was revealed in the cerebellum of stressed rats (in comparison to these levels in control rats). These results suggest the involvement of cholesterol metabolic system in the stress reaction. The content of total lipids decreased also in the medulla oblongata. However, levels of the main lipid fractions changed differently. The content of diglycerides increased and the content of cholesterol decreased. The data obtained suggest that degradation of triglycerides is the principle pathway of metabolic conversions of lipids. Free fatty acids formed during these processes are probably involved in the synthesis of phospholipids and cholesterol esters. The data indicate absolutely different mechanisms of interrelations between individual lipid fractions in the brain regions studied. Various roles of the brain structures in the stress response of the body may account for the differences revealed.

Blood serum melatonin concentrations were measured in male Wistar rats exposed to acute water-immersion emotional stress (ES) during intraperitoneal injections of physiological saline or different doses of melatonin. ES increased blood melatonin levels in rats receiving physiological saline 1 hour before or just after ES. When physiological saline was administered just ES, blood melatonin concentrations remained unchanged. The blood levels of melatonin both in control and stressed animals injected with exogenous melatonin were higher than those in rats given physiological saline alone. Immersion ES decreased blood melatonin concentrations in rats receiving different exogenous melatonin doses just before ES. However, in rats given melatonin, 1.0 mg/kg, after ES, its blood levels after ES was higher than those in the animals unexposed to stress. The findings suggest that it is just exogenous rather than endogenous melatonin that is consumed in rats injected with its different doses just prior to immersion ES.

Superoxide dismutase, glutathione peroxidase, and glutathione reductase activities were measured in 15-to 30-mg specimens of the cerebral cortex, amygdala, hypothalamus, and midbrain of adult male August rats subjected to 1-h immobilization stress. Of all these brain regions, the hypothalamus and amygdala had the strongest baseline total antioxidant defenses. However, immobilization inhibited the antioxidant enzymes in hypothalamus to much greater extent (an average of 30%) than in any other brain region (10% to 18%). After immobilization, the activities of glutathione reductase in the four brain regions were strongly and positively correlated. These data are consistent with our earlier findings of rapid accumulation of thiobarbituric acid-reactive material in the rat hypothalamus after a brief immobilization and suggest that hypothalamus is subject to strong pro-oxidant impacts arising at the early stages of immobilization stress.