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We evaluated the effects of the Gly-His-Lys-D-Ala peptide in a dose 0.5 μg/kg on skin wound regeneration in male Wistar rats (n=80) after initial surgical debridement when administered intracutaneously around the site of injury. Histological (severity of the inflammatory reaction, formation of granulation tissue, and epithelialization terms) and morphometric (number of fibroblastic cells, macrophages, granulocytes, and lymphocytes) studies were performed on autopsy specimens on days 3, 7, 10, and 30 of the experiment. Daily intracutaneous injection of the peptide resulted in an increase in the number of fibroblastic cells and macrophages, as well as in a decrease in the number of granulocytes against the background of active wound contraction on day 30 of the experiment. Thus, Gly-His-Lys-D-Ala alleviated the inflammatory reaction and promoted the regenerative processes., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

We studied the reparative and antioxidant effects of Thymogen and its new structural analogues obtained by binding amino acid D-Ala to the N- or C-end of the peptide molecule in acute toxic hepatopathy. Intragastric administration of carbon tetrachloride for 5 days caused the development of fat degeneration of hepatocytes, a decrease in catalase activity, and an increase in malondialdehyde concentration. Administration of peptides suppressed oxidative peroxidation and stimulated reparative regeneration of hepatocytes; Thymogen analogues produced more pronounced hepatotropic and antioxidant effects than Thymogen. Inclusion of D-Ala enhanced the effect of Thymogen on the processes of regeneration in hepatocytes and the antioxidant effect under conditions of acute carbon tetrachloride hepatopathy. The highest efficiency was achieved when the amino acid was added to the C-end of the molecule., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

We studied heart rate variability indexes in freely moving male Wistar rats at rest and under conditions of increased motor activity (treadmill exercise). Some regularities were revealed in the dynamics of HR, RRNN, Mo, indicator of the adequacy of regulation processes, VLF (msec2, %), HF, LF (%), LF/HF, and IC that characterize changes in the neurohumoral regulation and shifts in the level of cardiac rhythm control at the different stages of the experiment. It was found that changes in motor activity of male Wistar rats were accompanied by the transition of the functional state of the organism to a new level of regulation, which was confirmed by the dynamics of HR, RRNN, Mo, LF, VLF, LF/HF, and IC. These findings can be used as prognostic indicators for assessment of regulatory mechanisms in the body., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

We evaluated the effect of ACTH 6-9 -Pro-Gly-Pro (ACTH 6-9 -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 ACTH 6-9 -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, ACTH 6-9 -PGP administered in doses of 5 and 50 μg/kg prevented the stress-induced changes in the levels of pro- and inflammatory cytokines., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

The effects of the peptide ACTH(6-9)-Pro-Gly-Pro at doses of 5; 50; 500 μg/kg on the Wistar rats' behaviour and gut mucosal microbiota composition under conditions of chronic immobilization stress (CRS) were studied. CRS increased anxiety-like and depressive-like behaviour, disturbances in locomotor activity and gut dysbiosis. Administration of ACTH(6-9)-Pro-Gly-Pro showed many phenotypic results. Peptide demonstrated anti-depressant activity at doses of 5 and 500 μg/kg by a decrease in the total immobile time in the FST. ACTH(6-9)-Pro-Gly-Pro administered at a dose of 50 μg/kg resulted in an anxiolytic effect which is shown by an increase in the time in the open arms of EPM (p < 0.05) and a decrease in the time in the closed arms (p < 0.05). Moreover, the peptide led to a decrease in alpha- and beta-diversity of the gut microbiota (p < 0.01). Correlation and linear regression analysis demonstrated central mechanisms of ACTH(6-9)-Pro-Gly-Pro anxiolytic activity and both central and peripheral ones in an anti-depressant effect. In this way, peptide ACTH(6-9)-Pro-Gly-Pro could prevent the development of behavioural disturbances and gut dysbiosis caused by chronic restraint stress., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

We studied the effect of intraperitoneal administration ACTH (4-7) -PGP in doses of 5, 50, 150, and 450 μg/kg to Wistar male rats 12-15 min before modeling restraint stress on the morphofunctional state of the colon. In rats exposed to restraint stress, signs of atrophy and inflammatory reaction in the colon wall, changes in functional activity and number of mast cells, and increased serum level of corticosterone were observed. Administration of the peptide led to a decrease in corticosterone concentration, alleviated stress-induced pathomorphological changes, and promoted adaptation of the intestinal wall to stress. The positive effects of ACTH (4-7) -PGP can be determined by multifunctional nature of the physiological and pharmacological effects of the neuropeptide.

We studied the effect of Semax on the state of intestinal microbiota in rats subjected to restraint stress. Semax was injected to Wistar male rats intraperitoneally in doses of 5, 50, 150, 450 μg/kg 12-15 min before modelling chronic restraint stress. It was found that stress exposure reduced the number of obligate bacteria in the colon microbiota, but increased the content of opportunistic microorganisms. Semax in doses of 50 and 150 μg/kg prevented the stress-induced changes in the composition of colon microbiota. The observed effects of Semax might be mediated by the central neurotropic effects as well as by binding to peripheral melanocortin receptors of the intestine.

We studied the effects of Selank on the condition of the colon wall in Wistar male rats subjected to restraint stress. Selank was injected intraperitoneally in doses of 80, 250, and 750 μg/kg 15 min before stress exposure. In rats subjected to stress, signs of atrophy, inflammatory reaction, and changes in the number and functional activity of mast cells were observed against the background of increased corticosterone level. Selank administration led to a decrease in corticosterone levels, reduced pathomorphological manifestations of stress exposure, and accelerated adaptation. These effects were presumably realized due to multifunctional biological effects of Selank.

We studied the effects of Selank on morphological parameters of the liver in Wistar male rats subjected to chronic foot-shock stress. Selank was injected intraperitoneally in doses of 100, 300 and 1000 μg/kg 15 min before each stress session. Morphological and morphometrical analysis showed that chronic foot-shock stress induced hydropic degeneration of hepatocytes, an increase of the nucleus/cytoplasm ratio due to an increase in the area of nuclei and reduction of the cytoplasm area, the appearance of focal necroses, and lymphohistiocyte infiltration. Injection of Selank in all doses reduced the intensity of stress-induced degenerative changes. Administration of Selank in doses of 300 and 1000 μg/kg restored the nucleus/cytoplasm ratio in hepatocytes. The maximum stress-limiting effect was attained after administration of 300 μg/kg Selank.

We studied the effects of Selank on intestinal microbiota in Wistar male rats subjected to chronic restraint stress. Selank was injected intraperitoneally in doses of 80, 250 and 750 μg/kg 15 min before stress exposure. Chronic restraint stress led to a decrease in the content of obligate microflora, while the content of opportunistic microorganisms increased. Selank restored intestinal microbiota presumably via central (neurotropic) and peripheral (immunotropic) mechanisms.

We studied the effect of Selank administered intraperitoneally in doses of 100, 300, and 1000 μg/kg to male Wistar rats 15 min prior to restraint stress on the content of aminotransferases and total protein concentration in blood serum and intensity of free radical oxidation in the liver. Under conditions of acute restraint stress, Selank in doses of 100 and 300 μg/kg decreased catalase and superoxide dismutase activities and malondialdehyde concentration and increased total antioxidant activity in the liver homogenate. Administration of Selank in a dose of 1000 μg/kg reduced the content of aminotransferases in blood serum, decreased superoxide dismutase activity in the liver, and increased total antioxidant activity. Under conditions of chronic stress, Selank in all doses produced similar effects: reduced superoxide dismutase activity and malondialdehyde concentration in the liver tissue and AST activity in the serum. The other parameters remained unchanged.

We studied the effect of intraperitoneal administration of peptide ACTG 4-7 -PGP to male Wistar rats in doses of 5, 50, 150, and 450 μg/kg on the morphofunctional state of hepatocytes in chronic emotional and painful stress. A dose-dependent stress-limiting effect of the peptide was observed: it normalized the protein synthesis function of the liver and serum activity of ALT. The anticytolytic effect of the peptide increased with increasing its dose against the background of the increase in the relative number of multinucleated and multinucleolated cells and deceleration of the recovery of serum protein concentration. The decrease of hepatocyte cytolysis against the background of more intense morphological signs of protein synthesis processes attests to activation of reparative processes in the liver parenchyma via enhanced constitutional synthesis of protein.

We studied the effect of delta sleep-inducing peptide (40, 120, and 360 μg/kg intraperitoneally, 1 h before the experiment) on free radical oxidation in the liver, aminotransferase activity, and total serum protein content in male Wistar rats during restraint stress. Treatment with the peptide in a dose of 40 μg/kg increased catalase and superoxide dismutase (SOD) activities and malonic dialdehyde (MDA) concentration in the liver homogenate of animals subjected to acute stress. No significant changes were found after administration of this peptide in other doses. Under conditions of chronic stress, the peptide in a dose of 40 μg/kg caused the most pronounced effect. Catalase and SOD activities and MDA concentration decreased, while aminotransferase activity and protein content remained unchanged under these conditions. Administration of the peptide in a dose of 120 μg/kg was accompanied by a decrease in SOD activity and MDA concentration, increase in total protein content, and reduction of AST activity. Increasing the peptide dose to 360 μg/kg abolished its effects.

The effect of delta sleep-inducing peptide (DSIP) intraperitoneal injection in the doses of 40, 120, 360, and 1080 mcg/kg b. w. on lipid peroxidation and functional hepatocyte state in Wistar male rats subjected to acute and chronic electrical foot-shock stress was investigated. It was observed that 120 mcg/kg peptide normalized the elevation of malondialdehyde (MDA) level in the liver homogenate caused by acute foot-shock stress and also significantly decreased catalase activity in all investigated doses. In serum the injection of DSIP up to 40 mcg/kg increased aminotransferase activity. Peptide in all doses provided the normalization of protein synthetic hepatocyte function, increased catalase and superoxide dismutase activity in chronic stress. In addition malondialdehyde content in the liver homogenate was significantly decreased in the dose of 40 mcg/kg and in other cases it was significantly increased against the background of the common antioxidative activity reduction. The stress-induced increase in serum alanine aminotransferase activity was normalized by peptide administration in the doses of 120, 360, and 1080 mcg/kg.

Stable correlations between the amplitude parameters of stimulation myography of forearm muscles and parameters of bimanual coordination of complex voluntary purposeful movements during performance of tasks of different complexity were studied in men and women. We found that men are characterized by higher coordination of hand movements and selective involvement of motor units of flexor and extensor muscles innervated by stimulated nerves during motor task performance with minimum number of errors. In women characterized by relatively low level of bimanual coordination, generalized involvement of neuromuscular units of the right and left forearms into realization of motor programs, potentiation of interactions with increasing the task complexity, and correction after errors were observed.

Intraperitoneal administration of tripeptide Gly-His-Lys to male rats in doses of 0.5, 5, and 50 μg/kg 12 min before the start of the experiment produced an anxiolytic effect in the elevated plus maze test manifested in an increase in the time spent in open arms and shortened time spent in the closed arms. The anxiolytic effect was most pronounced after injection of 0.5 μg/kg peptide and decreased with increasing the dose of the peptide. Replacement of L-lysine with D-lysine in the tripeptide molecule was accompanied by a significant weakening of the neurotropic effects in all studied doses. Attachment of D-alanine to N- or C-terminus of Gly-His-Lys peptide leveled its anxiolytic action in all doses; significant changes in some measures of increased anxiety after administration at 50 μg/kg were found.

The effect of ACTH4-7-PGP (Semax) intraperitoneal injection at the doses of 5, 50, 150 and 450 μg/kg b. w. on lipid peroxidation and functional hepatocytes state in Wistar male rats subjected to acute and chronic electrical foot-shock stress was investigated. It was observed that peptide at the doses of 50 and 450 μg/kg normalized malondialdehyde (MDA) level elevation in the liver homogenate caused by acute foot-shock stress. On the contrary, at the doses of 5 and 150 μg/kg Semax significantly increased MDA content without essential changes of antioxidant defense activity (catalase, superoxide dismutase, common antioxidative activity). In serum peptide at the all doses decreased stress-induced asparate aminotransferase activity elevation. In chronic stress peptide provided the normalization of protein synthetic hepatocytes function and the serum alanine aminotransferase activity with less effect on lipid peroxidation.

The intraperitoneal administration of Gly-His-Lys tripeptide to male BALB/c mice 12 min before the beginning of the study at doses 0.5, 1.5, 5, 15, and 50 mg/kg produced analgesic effect in the hot-plate test, which was manifested by an increase in the duration of the latent period of the paw-licking reaction. The replacement of L-lysine by D-lysine in the tripeptide molecule was accompanied by significant weakening of the analgesic effect after administration in the same doses. The attachment of D-alanine to N- or C-end of Gly-His-Lys peptide led to leveling of the analgesic effect. On the contrary, after the administration of these analogs, the duration of the latent period of the paw-licking reaction was increased in almost all experimental groups of animals and reached in some cases significant differences that were indicative of the manifestation of algic effects of the modified peptides.

The authors studied relationships of intentional attention features in individuals with styles of accentuated accuracy of self-regulation in information perception. Findings are that the best adaptational possibilities are associated with the styles with more volume and distributability. High attention switchability is also very important. The data obtained, with consideration of age range of the studied group, is recommended for optimization of work and for rehabilitation measures.

Stable correlations between correction task characteristics and components of visual evoked potentials in response to light flash have been revealed. Faster task performance in males in comparison with females was established to be attained due to effective tuning and attuning of visual-motor system at the levels of specific and nonspecific systems related to visual analyzer. This determines potential for monotonous activity requiring constant visual attention.

Analysis of the stable correlation of asymmetry of the acoustic stem evoked potentials intervals with parameters of bimanual coordination was performed. Different mechanisms of the auditory asymmetry at the stem level were found in men and women. Optimum bimanual performance in men is provided by adequate co-adjustment of sensor-motor system elements, and is connected with sensory input and the feature of its bilateral irradiation through the right input. The left channel input and its sensory asymmetry is much more important in women. Bilateral irradiation in this case does not lead to adequate integration of the systems elements in performance of the motor task, that indicates the lower level of bimanual coordination.

The intrasensory and sensor-effector interactions between inter-spike intervals of acoustic stem-evoked potentials with parameters of hands coordination was found with the help of correlation analysis. Role of excitation of ascending fibres of rostral part of the pons and lateral loop in mechanisms of the auditory-motor coordination was determined. Sex-dependent differences in integration of elements of the sensor-motor system because of lateralization of incoming auditory information and complication of the motor task performed were revealed. In men, mechanisms of auditory-motor coordination have less determined character than in women. That probably determines higher level of bi-manual coordination in men. Optimal correct realization of motor program in men is performed prognostically, while in women--after a mistake has been done.

In experiments on Wistar rats L-lysine (0.15, 0.5, 1.5, 5.0, 15.0, and 50.0 microg/kg intraperitoneally) exhibited a dose-dependent algic effect during electrocutaneous stimulation of the tail and dose-dependent effects in aggressive defense behavior caused by electrical painful stimulation of paws. It was found that the effect of L-lysine depended on situation determining the predominance of defense or aggression, rather than on the intensity of painful stimulation.

Administration of Surfagon, a gonadotropin-releasing hormone analogue, in doses of 0.1 and 5.0 microg/kg before emotional nociceptive stress increased lymphocyte migration from the thymus, decreased the volume of lymphoid tissue in the spleen and thymus, reduced the width of the zona fasciculata and increased the width of the zona glomerulosa in the adrenal cortex of male CBA mice. These effects of the peptide persisted in castrated animals. Surfagon prevented stress-induced activation of the adrenal glands and accidental transformation of the thymus and spleen in castrated animals.

Intraperitoneal injection of L-arginine to male Wistar rats 12 min before the start of the experiment produced a nociceptive effect on models of electrocutaneous stimulation of the tail or hot-plate test and increased nociceptive behavior due to high sensitivity of supraspinal nociceptive structures to this compound. The nociceptive effect of this amino acid was more pronounced and persistent under conditions of electrocutaneous stimulation.

Intraperitoneal treatment with an analogue of gonadotropin-releasing hormone in doses of 0.004-450 microg/kg produced an analgesic effect on male mice in the hot plate test. Castration significantly elevated the nociceptive thresholds. In castrated mice the effects of the test peptide were less pronounced and had an algesic nature. Our results indicate that these effects depend on functional activity of the hypothalamic-pituitary-gonadal axis.

Intraventricular administration of the synthetic analogue of gonadotropin-releasing hormone (surfagon) results in increased humoral immune response and neutrophile activation including phagocytic and special functional indices in rats. Since testosterone blood level is not changed it may be concluded that the surfagon effect is mediated by nervous mechanisms. The conclusion is also confirmed by the obtained data of the brain stress-limiting system activation manifested by the decrease of oxidative stress.

Infection of surfagon (gonadotropin-releasing hormone analog) in a dose of 0.1 microg/kg to male CBA mice stimulated lymphocyte migration from splenic B zones, caused moderate thinning of the thymic cortex, thickening of the zona fasciculata of the adrenal cortex with signs of corticocyte activation. After administration of 5 microg/kg surfagon we observed alteration of the splenic T zone, drastic thinning of the thymic cortex, and extension of the zona glomeruloza in the adrenal cortex. These effects were retained after castration, which attests to their steroid-independent nature.

Gonadotropin-releasing hormone's synthetic analogue (surfagon) injected intraperitoneally exerted a dose-dependent influence on humoral immune response values in rats and on phagocytic and functional activity of neutrophiles in mice. Castration induced a reliable decrease of the immune response and character. It may be concluded that the surfagon effect is not mediated by steroids.

Surfagon, a synthetic analog of gonadotropin-releasing hormone injected before emotional painful stress dose-dependently changed the number of antibody-producing cells in rats and phagocytic and functional activities of neutrophils in mice. In castrated animals this peptide increased all studied parameters. This suggests that sex steroids are not involved in the realization of these effects.

Food conditioning worsened following a luliberine analogue surfagon administration in short-sleeping (SS) rats. Castration mostly inhibited the peptide effect. The findings suggest a possibility of the peptide effect occurring even without steroids.

The synthetic luliberin analogue-agonist surfagon exerted a dose-dependent activating effect on formation of alcoholic motivation in white male rats. No such effect occurred in castrated rats, even though the rate of alcohol consumption was higher in the latters. The data obtained suggest a steroid-dependent mechanism of surfagon.

Luliberin's analogue (surfagon) has been established to activate shock-induced aggression of short-sleeping (SS) and long-sleeping (LS) rats in painful stress. The using of the castration and hypophysectomy has proved this effect to result from the direct neurotropic action of peptide. It has been shown, that SS rats differ from LS ones by more expressed reducing of painful aggressive and reference reactions after castration and hypophysectomy as well as by definitive peculiarities of peptidergic effects of surfagon.

Leu-enkephalin and its analogue N 171 increased the pain thresholds and reduced the affective aggression in unrestrained male rats. The N 171 manifested a greater analgesic and antiaggresiogenic effect, particularly in i.p. administration. Preliminary administration of peptides manifested a more obvious effect in alcohol-preferring rats under painful stress.