Vol 24, No 3 (2024)

The previous part of the review examined the role of the intestinal microbiota as a susceptibility factor to multiple sclerosis. This part of the review provides facts that confirm the trigger role of intestinal microbiota. The main attention is paid to the initial stages of pathogenesis, which, according to the modern concept of multiple sclerosis, occur in the gastrointestinal tract.

BACKGROUND: Criteria for stenosis of the celiac artery in duplex ultrasound diagnostics based on measurements of peak systolic velocity of blood flow are still a discussed topic for the diagnosis of blood flow disorders in the branches of the abdominal aorta.

AIM: To clarify the calculation formulas for determining the degree of emergency stenosis based on the literature speed indicators, compare the results obtained with each other and with angiographic data.

MATERIALS AND METHODS: When calculating the dependence of the degree of stenosis on the speed of blood flow, the theoretical prerequisites of the mechanics of incompressible fluids, one of which is whole blood, were used. The Mathcad 15.0 algebraic computing software package was used. Data correlation was evaluated using the corr functional using the Pearson correlation coefficient. The value of the correlation coefficient was interpreted using the Cheddock scale. The relationship between the results of ultrasound and angiographic data was also considered using the concepts of evidence-based medicine for diagnostic tests (sensitivity, specificity, predictive value and accuracy).

RESULTS: Statistical indicators of the “discrepancy” of the data obtained from the above calculation formulas and clinical angiographic observations were: standard deviation SD 25.90%, maximum absolute deviation Δ 93.71% and reduced error δ 93.71%. The correlation of the average strength between the Doppler and the corresponding angiographic data was established (R = 0.467). The indicators of ultrasound tests generally correspond to angiographic data and are characterized on average by the following parameters: sensitivity Se = 100%, specificity Sp = 75.02, prognostic values PPV = 50.00%, NPV = 100% and overall accuracy P = 78.79%.

CONCLUSIONS: It is concluded that the ultrasonographic duplex scanning data can be considered as satisfactorily determining the percentage of stenosis, which corresponds to the literature data on the ultimate sensitivity, specificity and prognostic value of detecting abdominal artery stenosis based on peak systolic velocity. At the same time, the given calculation formulas for the degree of stenosis, depending on the velocity parameters of blood flow, generally correctly reflect the degree of circulatory disorders in the abdominal trunk. Finally, the issue of the hemodynamic significance of disorders and the pathogenetic basis of the disease should be resolved on the basis of angiographic indicators.

BACKGROUND: Modeling intrusive memories of psychologically traumatic event in post-traumatic stress disorder and assessing the development of mental disorders in the long-term period is relevant in order to understand the mechanisms of vital stress caused. Pathological anxiety may reflect the experienced feeling of fear and helplessness and intrusive traumatic memories in post-traumatic stress disorder.

AIM: The purpose of the study was to assess the level of anxiety and exploratory activity of male rats in the Elevated Plus Maze test after experiencing vital stress in association with twice repeated trauma reminders in a delayed period.

MATERIALS AND METHODS: The study was performed on mature male Wistar rats weighing 300–350 g (n = 34). Mental trauma was modeled by the circumstances of experiencing the situation of partner’s death from the action of a predator and the threat to their own life when placing rats in a terrarium with a tiger python. In rats, the behavior in the Elevated Plus Maze test was analyzed two months after an exposure to stress.

RESULTS: In the delayed period after vital stress, the Elevated Plus Maze test showed an increase in anxiety and a decrease in exploratory activity of male rats. When placed twice in a traumatic environment, male rats with previously received psychogenic trauma maintained an increased level of anxiety and suppression of exploratory activity in the long-term period.

CONCLUSIONS: Two months after vital stress, male rats show increased anxiety and reduced exploratory activity. The traumatic event reminder leads to worsening of behavioral disorders caused by psychogenic trauma, indicating a stable, long-lasting development of post-traumatic stress disorder.

BACKGROUND: Searching for substances with high analgesic activity is one of the main problems of modern medicine. N-methyl-D-aspartate receptors present in all areas of the central nervous system responsible for reaction on pain stimulation. Moreover, peripheral glutamate receptors may be directly involved in the genesis of pain reactions. Therefore, it is of interest to search for new analgesics among N-methyl-D-aspartate receptor ligands.

AIM: To develop a preparative method of synthesis and to investigate the antinociceptive activity of 1,2-dialkylimidazole-4,5-dicarboxylic acids bis-methylamides on the example of 2-propyl-1-ethylimidazole-4,5-dicarboxylic acid bis-methylamide.

MATHERIALS AND METHODS: 1-Ethyl-2-propylimidazole-4,5-dicarboxylic acids bis-methylamide was obtained using methods of organic synthesis. The Gaffner test of mechanical irritation of the base of the tail and the hot water tail-flick test in mice were selected to study the antinociceptive activity.

RESULTS: It was shown that the amidation of 2-substituted imidazole-4,5-dicarboxylic acids dimethyl ether followed by the alkylation of the resulting 2-substituted imidazole-4,5-dicarboxylic acids bis-amide is а preferable method of the two alternative for obtaining of 1,2-dialkylimidazole-4,5-dicarboxylic acids bis-amides. It was shown that 1-ethyl-2-propylimidazole-4,5-dicarboxylic acids bis-methylamide exhibits pronounced antinociceptive activity exceeding the activity of the comparative drugs analgin and ketorolac.

CONCLUSIONS: A preparative method for the synthesis of 1,2-dialkylimidazole-4,5-dicarboxylic acids bis-amides is proposed. The dose-dependent antinociceptive activity of 1-ethyl-2-propylimidazole-4,5-dicarboxylic acids bis-methylamide was shown. 1-Ethyl-2-propylimidazole-4,5-dicarboxylic acids bis-methylamide exhibits antinociceptive activity exceeding the activity of analgin and ketorolac.

BACKGROUND: Data on the potential for mast cell activation and degranulation under these IgG-containing immune complexes indicate the presence of another innovative pathway for mast cell activation and help explain the severe infection following vaccination.

AIM: The aim of the study was to evaluate the possibility of activation and degranulation of mast cells of peritoneal exudate in mice by binding Fcγ receptors.

MATERIALS AND METHODS: Influenza viruses A/Vietnam/1194/2004(H5N1) NIBRG-14 and A/New York/61/ 2015(H1N1)pdm09 were used in the work. Cells of the peritoneal exudate of CBA mice, containing an average of 7–10% mast cells, were used as a source of mast cells. The degranulation of mast cells 40 min after the introduction of IgG-containing immune complexes into cultures was assessed by the release of histamine into culture attachments. The histamine level was determined fluorimetrically after the formation of its complexes with orthophthalic aldehyde, and the histamine concentration was expressed in ng/ml.

RESULTS: In response to the binding of Fcγ receptors, a dose-dependent release of histamine from the mast cells occurs. Histamine production was noted both during the introduction of model immune complexes formed by thermally aggregated IgG, and during the formation of complexes including IgG and influenza viruses of different strains. A higher level of histamine secretion was noted during the formation of IgG complexes with the H5N1 influenza virus. The level of histamine mast cells production during Fcγ receptor binding was comparable to the response to Fcε receptor binding.

CONCLUSIONS: Binding of immune complexes containing IgG class immunoglobulins to receptors on the surface of peritoneal exudate mast cells leads to their activation and degranulation, which is accompanied by dose-dependent histamine secretion, the level of which also depends on the strain of influenza virus in the complex.

BACKGROUND: Kisspeptin 1 plays a significant role in regulating the activity of the hypothalamic-pituitary-gonadal axis. It is known it interacts directly with gonadotropin-releasing hormone by stimulating its secretion in the hypothalamus and thus affecting downstream sex hormones via gonadotropins, but the exact mechanism of kisspeptin 1 effects on follicle-stimulating and luteinizing hormones is poorly understood.

AIM: To investigate the effects of a synthetic kisspeptin 1 analog on follicle-stimulating and luteinizing hormone levels in the gonads of Danio rerio.

MATERIALS AND METHODS: The study involved 84 sexually mature Danio rerio females after spawning. The model animals were anesthetized with lidocaine and synthetic analog of kisspeptin 1, 0.9% sodium chloride solution were administered intracerebrally in doses of 2, 8 µg/kg. After 1 or 4 hours, follicle-stimulating and luteinizing hormone’s levels were measured using enzyme immunoassay.

RESULTS: A statistically significant increase in follicle-stimulating hormone levels occurs at a dose of 8 µg/kg after 1 and 4 hours and at a dose of 2 µg/kg 4 hours after injection relative to the corresponding control groups. An increase in luteinizing hormone’s production was also recorded at a dose of 8 μg/kg after 1 and 4 hours of exposure compared with the control. Elevated follicle-stimulating and luteinizing hormone’s levels were also recorded at a dose of 8 μg/mg and exposure for 1 hour relative to a dose of 2 μg/kg at the same resting time. Without taking into account the time exposure, the administration of synthetic analog of kisspeptin 1 at a dose of 8 µg/kg leads to an increased level of both hormones, and a dose of 2 µg/kg contributes to an increase in luteinizing hormone’s level.

CONCLUSIONS: The obtained results contribute to the study of pharmacological functions of synthetic analog of kisspeptin 1 and in the future can be used for therapeutic purposes in the treatment of diseases of the gonadal system.

BACKGROUND: Glucocorticoids play an important role in the development of the stress response in the organism. Synthetic glucocorticoids such as dexamethasone are widely used in medicine due to their anti-inflammatory effects. However, there is evidence that glucocorticoid-based drugs used in sufficiently high doses can induce pro-inflammatory effects by affecting predominantly the hippocampus in the central nervous system as the most plastic brain structure. It is important to note that the dose, route and timing of administration can affect the effects of glucocorticoids, and it is therefore an important biomedical task to choose the optimal parameters of glucocorticoid administration in order to achieve the most effective treatment results.

AIM: The aim of our study was to investigate the effect of peripheral administration of a synthetic glucocorticoid, dexamethasone, at a dose of 8 mg/kg on the development of neuroinflammation in the rat hippocampus at different periods after administration.

MATERIALS AND METHODS: Thirty-two sexually mature male Wistar rats distributed into 8 groups of 4 animals each were used in the experiment. The animals were injected with dexamethasone at a dose of 8 mg/kg and decapitated for different periods (1, 3, 9, 12, 18, 24, 48 hours — time of decapitation after administration), group К — control group with saline injection). Further, the cytokine profile expression was analyzed by real-time reverse transcription polymerase chain reaction method.

RESULTS: In this study, we found an increase in the expression of proinflammatory cytokines AIF1 (IBA-1) and IL-1β after 12 and TNF-α after 24 hours after dexamethasone administration at a dose of 8 mg/kg, which may indicate a neuroinflammatory effect of dexamethasone at this dose. It should be noted that the level of NF-êB gene, a marker of inflammation, remained unchanged, possibly due to the activation of compensatory mechanisms to control inflammation or stress.

CONCLUSIONS: The increase in mRNA of inflammatory markers IL-1β, TNF-α and AIF1, in the hippocampus after 12 hours after single dexamethasone administration to rats at a dose of 8 mg/kg may indicate a switch of the effect of this drug from antiinflammatory to proinflammatory, which should be taken into account when dexamethasone is used such a treatment during several diseases.