Morphological Characteristics of Colon Tumors in Mice with Different Tolerance to Hypoxia.

In adult male C57BL/6 mice with high (HR) and low (LR) resistance to hypoxia, morphological features of colon tumors and blood parameters were evaluated 70 days after intraperitoneal injection of azoxymethane and subsequent consumption of 3 cycles of dextran sulfate sodium. On macroscopic analysis, tumors were found in the distal colon in 35% (7 of 20 animals) of HR and 31% (4 of 13 animals) of LR animals. Microscopic analysis of the distal colon revealed tumors in 75% (15 of 20 animals) of HR and 69% (9 of 13 animals) of LR mice. The tumors were presented by areas of glandular intraepithelial neoplasia and adenocarcinomas; the incidence and the area of the tumors did not differ in groups of HR and LR mice. The number of neuroendocrine and goblet cells in the distal colon mucosa in the areas of tumors was similar in the compared groups. However, in both HR and LR mice of the experimental groups, the content of goblet cells in tumors was lower and the content of endocrine cells was higher than in the corresponding control groups. In the peripheral blood, the erythrocyte count and hemoglobin content decreased in HR and LR mice of the experimental groups; the relative number of monocytes increased only in HR mice and the absolute number of lymphocytes and monocytes decreased in LR mice. Thus, 70 days after azoxymethane administration and dextran sulfate sodium consumption, the tumors in mice were presented by glandular intraepithelial neoplasia and adenocarcinomas, and their incidence and area did not differ between animals with different tolerance to hypoxia.

Comparative Molecular and Biological Characteristic of the Systemic Inflammatory Response in Adult and Old Male Wistar Rats with Different Resistance to Hypoxia.

Morphological, molecular, and biological features of the systemic inflammatory response induced by LPS administration were assessed in adult and old male Wistar rats with high and low resistance to hypoxia. In 6 h after LPS administration, mRNA expression levels of Hif1a, Vegf, Nfkb, and level of IL-1ß protein in old rats were higher than in adult rats regardless of hypoxia tolerance. The morphometric study showed that the number of neutrophils in the interalveolar septa of the lungs was significantly higher in low-resistant adult and old rats 6 h after LPS administration. Thus, in old male Wistar rats, systemic inflammatory response is more pronounced than in adult rats and depends on the initial tolerance to hypoxia, which should be considered when developing new approaches to the therapy of systemic inflammatory response in individuals of different ages.

Two Lineages of Oribatid Mites Morphologically Correspond to the Circumpolar Species Ameronothrus nigrofemoratus (Acari, Oribatida) but Differ Genetically as Distinct Species Are Revealed on the Kolguev Island.

Data reported from Northern Canada were until recently the only available data on the genetic characteristics of the oribatid mite Ameronothrus nigrofemoratus, which has a circumpolar distribution on the coasts of Arctic seas. A partial cytochrome oxidase I gene (COI) mtDNA sequence was examined in mites morphologically assigned to this species from the Kolguev Island. Two highly divergent phylogenetic lineages of A. nigrofemoratus (7% divergence) were revealed, neither of which was found on the Canadian coast. Four COI amino acid substitutions distinguished one of the lineages from North American A. nigrofemoratus, corresponding to the degree of difference between A. nigrofemoratus and its sister species A. lineatus.

Advantages and disadvantages of treatment of experimental ARDS by M2-polarized RAW 264.7 macrophages.

Innate immunity reactions are core to any immunological process, including systemic inflammation and such extremes as acute respiratory distress syndrome (ARDS) and cytokine storm. Macrophages, the key cells of innate immunity, show high phenotypic plasticity: depending on microenvironmental cues, they can polarize into M1 (classically activated, pro-inflammatory) or M2 (alternatively activated, anti-inflammatory). The anti-inflammatory M2 macrophage polarization-based cell therapies constitute a novel prospective modality. Systemic administration of 'educated' macrophages is intended at their homing in lungs in order to mitigate the pro-inflammatory cytokine production and reduce the risks of 'cytokine storm' and related severe complications. Acute respiratory distress syndrome (ARDS) is the main mortality factor in pneumonia including SARS-CoV-associated cases. This study aimed to evaluate the influence of infusions of RAW 264.7 murine macrophage cell line polarized towards M2 phenotype on the development of LPS-induced ARDS in mouse model. The results indicate that the M2-polarized RAW 264.7 macrophage infusions in the studied model of ARDS promote relocation of lymphocytes from their depots in immune organs to the lungs. In addition, the treatment facilitates expression of M2-polarization markers Arg1, Vegfa and Tgfb and decreases of M1-polarization marker Cd38 in lung tissues, which can indicate the anti-inflammatory response activation. However, treatment of ARDS with M2-polarized macrophages didn't change the neutrophil numbers in the lungs. Moreover, the level of the Arg1 protein in lungs decreased throughtout the treatment with M2 macrophages, which is probably because of the pro-inflammatory microenvironment influence on the polarization of macrophages towards M1. Thus, the chemical polarization of macrophages is unstable and depends on the microenvironment. This adverse effect can be reduced through the use of primary autologous macrophages or some alternative methods of M2 polarization, notably siRNA-mediated.

[The contribution of the combined use of an electric toothbrush and specialized toothpaste for electric brushes to the dental health of young people aged 18-25 years]. / Vliyanie kombinirovannogo primeneniya otbelivayushchikh zubnykh past i elektricheskikh zubnykh shchetok na pokazateli stomatologicheskogo zdorov'ya molodykh lyudei 18­25 let.

THE AIM OF THE STUDY: Was to assess the impact of two toothpastes marked as «Whitening¼ and two electric toothbrushes on the dental health values of young adults aged 18-25 years. MATERIAL AND METHODS: The study comprised 139 young adults 18-25 years old participated to assess the improvement of dental index score in dynamic observation. The study groups were formed by random sampling. RESULTS: The effectiveness of two types of electric toothbrushes in combination with two different toothpastes has been studied. Significant improvement of oral health indices in 3 months of investigation was found in the study group with sonic electric brush and toothpaste specially designed for use with electric toothbrushes (p<0.01). CONCLUSION: The study showed the benefit of combined use of sonic electric brush and low abrasive toothpaste containing bromelain, xylite, calcium glycerophosphate and magnesium chloride for dental health of young adults aged 18-25 years.

Morphofunctional Characteristics of Lung Macrophages in Rats with Acute Respiratory Distress Syndrome.

A comprehensive morphofunctional study of the lungs and alveolar macrophages was carried out in Sprague-Dawley rats with acute respiratory distress syndrome (n=10) induced by intratracheal administration of E. coli LPS 0111:B4 in a dose of 15 mg/kg. On the first day after LPS administration, bronchopneumonia was observed in the lungs, the number of macrophages of the bone marrow origin and the number of M1 macrophages with the proinflammatory phenotype in the bronchoalveolar lavage increased, the expression of proinflammatory cytokines increased and the expression of anti-inflammatory cytokines decreased, which was accompanied by an increase in LPS and C-reactive protein in the blood serum. The revealed changes correspond to the development of acute respiratory distress syndrome in humans, and the decrease in the number of macrophages in the lungs and their predominant polarization to the M1-proinflammatory phenotype substantiate the use of cell therapy with reprogrammed M2 macrophages.

Morphological and Molecular Biological Features of the Systemic Inflammatory Response in Old Wistar Rats with High and Low Resistance to Hypoxia.

Morphological and molecular biological features of LPS-induced systemic inflammatory response were assessed in old male Wistar rats with high (HR) and low (LR) resistance to hypoxia. The systemic inflammatory response was modeled by intraperitoneal injection of E. coli O26:B6 LPS; the animals were sacrificed after 6 h. In histological sections, the number of neutrophils in the interalveolar septa and the area of necrosis in the liver were determined. The expression levels of Hif1a, Hif2a, Nfkb, Vegf, Il1b, Il6, Il10, and Tgfb mRNA in the liver and serum concentrations of HIF-1α and IL-1ß were determined. In 4-6 h after LPS injection, 3 (43%) of 7 HR rats died, whereas no deaths were observed among LR rats. At 6 h after LPS injection, the number of neutrophils in the interalveolar septa of the lungs in LR rats was significantly higher than in HR rats, while the area of necrosis in the liver did not differ. At the same time, the mRNA expression levels of the proinflammatory cytokine genes Il1b and Il6 increased in the liver of both HR and LR rats, whereas the expression of Il10 increased only in HR rats. The expression of the Hif1a gene in the liver was higher in LR rats, but the content of HIF-1α protein in blood serum was higher in HR animals. These data should be taken into account when developing new approaches to the therapy of systemic inflammatory response in infectious and inflammatory diseases in the elderly.

[Assessing of iodine consumption with iodized salt in organized nutrition of children of preschool and school age in the Tyumen region].

The territory of the Tyumen region is an endemic region with insufficient iodine content in the environment, in which, since the early 1990s, active preventive measures have been taken to increase the use of iodized salt (IS) in households, catering and the food industry. The purpose of the research was to assess the consumption of iodine with IS used in the organized nutrition of children in the Tyumen region. Material and methods. The assessment of iodine intake was carried out in preschool institutions and schools randomly selected the city of Tyumen and rural areas (village of Isetskoye). Modeling of iodine consumption in organized groups was carried out for children aged 1-3, 3-7, 7-11 and 12 years and older in urban and rural areas, respectively, using a standard menu and a technological map of dishes. Iodine intake was estimated based on the content of 40 µg of iodine in 1 g of salt and its 30% loss during cooking. Model 1 assumed the mandatory use of IS in the preparation of all salt-containing meals for preschoolers and schoolchildren. Model 2, in addition to the mandatory use of IS in school and preschool meals accounted the consumption of iodine with bakery products (BP) produced with IS. Results. The modeling showed that the average intake of iodine with meals (model 1) in preschool institutions in Tyumen was 89±16 µg/day for children aged 1-3 years. When BP with IS were included in the menu (model 2), iodine intake increased to 101±14 µg/day. In children aged 4-7 years iodine intake was 115±18 and 126±18 µg/day, respectively. In rural areas, iodine intake was lower: in children aged 1-3 years, under model 1, iodine intake was 66±3 µg/day, under model 2 - 76±4 µg/day. In children aged 4-7 years, these figures were 83±3 and 92±4 µg/day, respectively. Iodine consumption in a school in Tyumen under model 1 in children 7-11 years old was 24±5 µg/day, and in children 12 years and older - 27±6 µg/day. When BP with IS were included in the menu (model 2), iodine intake increased to 32±5 µg/day in children 7-11 years old and to 39±6 µg/day in children 12 years of age and older. In rural areas, when using model 1, iodine intake in children aged 7-11 years was 37±15 µg/day, in children aged 12 and over 40±21 µg/day. When BP with IS were included in the menu (model 2), iodine intake increased to 44±15 µg/day in children aged 7-11 years and to 50±21 µg/day in children 12 years of age and older. Conclusion. The use of IS in the preparation of salt-containing meals in preschool educational institutions of the Tyumen region fully covered the iodine requirements of preschool children, which confirms the effectiveness of the chosen strategy for the prevention of iodine deficiency and can be considered as an important part of the concept of universal salt iodization. The use of IS in preparation of school breakfast meals provides 23.5-36.9% of the recommended nutrient intake for iodine in rural schools and 15.4-26.4% of the recommended nutrient intake in urban schools, which can be a significant contribution to the total intake of this micronutrient.

Morphological and molecular-biological features of glioblastoma progression in tolerant and susceptible to hypoxia Wistar rats.

Hypoxia is a major pathogenetic factor in many cancers. Individual resistance to suboptimal oxygen availability is subject to broad variation and its possible role in tumorigenesis remains underexplored. This study aimed at specific characterization of glioblastoma progression in male tolerant and susceptible to hypoxia Wistar rats. Hypoxia resistance was assessed by gasping time measurement in an 11,500 m altitude-equivalent hypobaric decompression chamber. Based on the outcome, the animals were assigned to three groups termed 'tolerant to hypoxia' (n = 13), 'normal', and 'susceptible to hypoxia' (n = 24). The 'normal' group was excluded from subsequent experiments. One month later, the animals underwent inoculation with rat glioblastoma 101.8 followed by monitoring of survival, body weight dynamics and neurological symptoms. The animals were sacrificed on post-inoculation days 11 (subgroup 1) and 15 (subgroup 2). Relative vessels number, necrosis areas and Ki-67 index were assessed microscopically; tumor volumes were determined by 3D reconstruction from histological images; serum levels of HIF-1α, IL-1ß, and TNFα were determined by ELISA. None of the tolerant to hypoxia animals died of the disease during observation period, cf. 85% survival on day 11 and 55% survival on day 15 in the susceptible group. On day 11, proliferative activity of the tumors in the tolerant animals was higher compared with the susceptible group. On day 15, proliferative activity, necrosis area and volume of the tumors in the tolerant to hypoxia animals were higher compared with the susceptible group. ELISA revealed no dynamics in TNFα levels, elevated levels of IL-1ß in the susceptible animals on day 15 in comparison with day 11 and tolerant ones. Moreover, there were elevated levels of HIF-1α in the tolerant animals on day 15 in comparison with day 11. Thus, the proliferative activity of glioblastoma cells and the content of HIF-1α were higher in tolerant to hypoxia rats, but the mortality associated with the tumor process and IL-1ß level in them were lower than in susceptible animals. Specific features of glioblastoma 101.8 progression in tolerant and susceptible to hypoxia rats, including survival, tumor growth rates and IL-1ß level, can become the basis of new personalized approaches for cancer diseases treatment in accordance to individual hypoxia resistance.

Effect of Carnosine on the Activity of Matrix Metalloproteinase-2 and Oxidative Stress in the Kidneys in Experimental Urate Nephrolithiasis.

The effect of carnosine on MMP-2 activity and oxidative stress in the kidneys in experimental urate nephrolithiasis was studied. Urate nephrolithiasis was modeled in Wistar rats by intragastric administration of a mixture of oxonic and uric acids. Carnosine was administered intragastrically through a tube in a dose of 15 mg/kg. In rats treated with carnosine, the concentration of MMP-2 in the urine decreased by 3.7 times, and the excretion of MMP-2 with urine decreased by 4.3 times. In the homogenate of the kidneys from rats treated with carnosine, the concentration of TBA-reactive substances decreased by 5 times and the concentration of MMP-2 decreased by 12.7%. After treatment with carnosine, the number of histologically confirmed cases of urate nephrolithiasis decreased by 2 times, while the mean size of urate deposits decreased by 2.7 times. Thus, carnosine inhibits MMP-2 and reduces the intensity of oxidative stress in the kidneys, which prevents the development of urate nephrolithiasis.

Morphofunctional Changes in the Thymus in Prepubertal Male Wistar Rats in LPS-Induced Systemic Inflammatory Response in Relation to Hypoxia Tolerance.

The dynamics of morphofunctional changes in the thymus during the LPS-induced systemic inflammatory response was assessed in prepubertal male Wistar rats in relationship with the resistance to hypoxia. The systemic inflammatory response was modeled by intraperitoneal administration of E. coli O26:B6 LPS. In histological sections of the thymus, the relative number of thymic bodies and proliferative activity of cells were evaluated. The relative number of CD3+CD4+, CD3+CD8+, and CD4+CD8+ cells in the thymus was determined by flow cytometry. The content of HIF-1α and endotoxin was determined in the blood serum. The expression level of Nfkb mRNA was assessed in the liver. The most pronounced changes in the indicators of the functional state of the thymus were detected 3 and 6 h after LPS administration following the increase in the content of HIF-1α and endotoxin in blood serum and Nfkb mRNA expression in the liver. In the thymus, a decrease in the number of thymic bodies consisting of 3-5 epithelial cells and an increase in the number of bodies consisting of 5 or more cells was observed. In 24 h after LPS administration, the relative number of CD3+CD4+ and CD3+CD8+ cells in the thymus decreased. At the same time, the number of Ki-67+ cells in the subcapsular zone of the thymus increased 6 and 24 h after LPS administration. These data should be taken into account in the development of approaches to the treatment of infectious and inflammatory diseases in prepubertal children.

Ex Vivo Production of IL-1ß and IL-10 by Activated Blood Cells of Wistar Rats with Different Resistance to Hypoxia after Systemic Inflammatory Response Syndrome.

We studied spontaneous and ex vivo activated cytokine production by blood cells of male Wistar rats with different resistance to hypoxia against the background of an LPS-induced systemic inflammatory response. In rats with low (LR) and high resistance (HR) to hypoxia, the number of leukocytes, granulocytes, and peripheral blood lymphocytes was determined, the levels of spontaneous and stimulated production of IL-1ß and IL-10 and their ratio were assessed ex vivo. Against the background of a systemic inflammatory response, only HR animals showed a decrease in spontaneous and stimulated production of IL-1ß and spontaneous production of IL-10. The IL-1ß/IL-10 ratio decreased only in LR rats during the development of a systemic inflammatory response, while in HR animals, no changes in this indicator were observed. The obtained data suggest a high proinflammatory potential of blood cells in LR rats, which apparently determines the development of a more severe course of the systemic inflammatory response.

Age-Specific Features of the Levels of Reference Proteins Actin, Tubulin, and GAPDH in Different Organs of Male Wistar Rats.

Western blot analysis is used for evaluation of the level of proteins production in organs and tissues, and housekeeping proteins GAPDH, actin, and tubulin are usually used as the reference proteins. The signal of the target protein is normalized to the corresponding signal of the reference protein. The data on the intensity of actin, tubulin, and GAPDH synthesis are fragmentary: their expression differs in different organs and can vary depending on age, which is often not taken into account in experimental studies. We studied the features of the production of reference proteins in the liver, heart, brain, and lungs of newborn, prepubertal, and adult male Wistar rats. Age-related differences in the expression of ß-actin, ß-tubulin, and GAPDH in the myocardium and dorsal prefrontal cortex were revealed. GAPDH expression in the dorsal prefrontal cortex in adult rats was significantly higher than in prepubertal rats; GAPDH expression in the myocardium of adult rats was significantly higher than in newborns. The level of actin in the dorsal prefrontal cortex in newborn rats was significantly higher than in prepubertal and adult rats. In the liver and lungs, the expression of actin, tubulin, and GAPDH did not differ in newborn, prepubertal, and adult rats. When choosing the reference protein for Western blotting, animals age and the studied organ should be taken into account.

Nephroprotective Effect of Leu-Ile-Lys Tripeptide in Experimental Diabetes Mellitus.

We studied the effect of tripeptide Leu-Ile-Lys on kidney function in rats with experimental diabetes mellitus modeled by single intraperitoneal administration of streptozotocin (65 mg/kg). The tripeptide was intragastrically administrated in a dose of 11.5 mg/kg from week 5 to week 8 of the pathological process. The concentrations of glucose, protein, and creatinine in the urine were measured before and then weekly throughout the experiment. In 8 weeks, the markers of activity of the free radical oxidation process (concentration of TBA-reactive substances, total prooxidant activity, and total antioxidant activity, as well as activities of catalase, superoxide dismutase, and glutathione peroxidase) were assayed and a morphological study was conducted. After administration of the tripeptide Leu-Ile-Lys for 4 weeks, glucose concentration in the urine decreases by 3-44 times (p<0.001) and protein concentration by 2.3-3.7 times (p=0.007). The concentration of TBA-reactive substances decreased by 1.3 times (p<0.001), and the total antioxidant activity increased by 2.3 times (p<0.001). Administration of the tripeptide Leu-Ile-Lys to animals with experimental diabetes mellitus led to significant improvement of the renal function against the background of significant alleviation of oxidative damage and an increase in the antioxidant protection of the renal tissues. Improvement of the morphofunctional state of tissues and cells of the renal glomerulus was confirmed histologically, in particular, an increase in the number of podocytes by 1.5 times was observed.

[Neonatal thyrotropin - indicatior of monitoring of iodine deficiency severity. What's level is considered a «cutoff point¼?]

BACKGROUND: The issues of monitoring the effectiveness of iodine deficiency prevention programs are an important component in the process of iodine elimination. Neonatal thyrotropin (TSH) has been used as a criterion for the severity of iodine deficiency since 1994, however, the question of the "cut-off point" of the neonatal TSH level has been widely discussed in the recent literature. AIM: Evaluate the criterion for neonatal hyperthyroidism above 5 mIU/l from the perspective of monitoring iodine deficiency and establish a «cut-off point¼ on the model of healthy pregnant women with adequate iodine status. MATERIALS AND METHODS: A prospective study was conducted in a population of pregnant women in the city of Tyumen, with the formation of observation groups according to the level of iodine excretion in the urine - the main group (with adequate iodine status throughout the entire gestation period) and the comparison group (women with iodine levels less than 150 µg/l). The results of neonatal screening for congenital hypothyroidism in children of women participating in the study were evaluated. The frequency of neonatal TSH above 5mIU/l was assessed in the observation groups. ROC-analysis was performed and a «cut-off point¼ of the level of neonatal TSH was established as an indicator of iodine deficiency. RESULTS: The median urinary iodine concentration in the population of pregnant women in Tyumen was 159.05 µg/l, the incidence of goiter was 0.38%, the incidence of neonatal hyperthyroidism above 5 mIU/l was 2.88%, which characterizes adequate iodine intake in the pregnant population women. The frequency of neonatal TSH above 5 mIU/l in newborns from women from the main group was 1.47%, and in the comparison group - 9.3% (p = 0.076). ROC analysis revealed a threshold value of neonatal TSH of 2.77 mIU/l at the cut-off point, which corresponded to the highest value of the Youden index. Urinary iodine concentrations greater than 150 µg/l were predicted for nTSH values below this value. CONCLUSION: Analysis of databases of neonatal screening for congenital hypothyroidism makes it possible to effectively, quickly and at minimal cost annually assess the iodine status in the population. The established «cut-off point¼ of neonatal TSH in the model of healthy pregnant women with adequate iodine intake in our work is 2.77 mIU/l, the absence of statistically significant differences in the incidence of neonatal hyperthyroidism above 5 mIU/l from women with different iodine status during pregnancy indicate the need to revise the existing threshold of 5 mIU/l and may be an incentive to conduct large-scale studies in regions with different iodine supply.

Infradian 4-Day Rhythm of Proliferative Activity of L-929 Mouse Fibroblast Culture in the Logarithmic Growth Phase Is Exogenous.

We studied the dynamic of proliferative activity of cultured mouse transformed fibroblast-like L-929 cells in the logarithmic growth phase. During a long period (December 5-23, 2020), we revealed a 4-day rhythm of daily increase in the number of L-929 cells with an amplitude not lower than in a culture of embryonic fibroblast-like cells. Hence, the formation of the 4-day rhythm is not associated with the molecular mechanisms of inhibition of proliferation, which are absent in transformed cells. Daily thawing of samples of one culture over 17 days showed the presence of a 4-day rhythm synchronous between all thawed samples and the control cell culture. As deep freezing leads to the cessation of all life processes in cells, the formation of a 4-day rhythm of proliferative activity of cell culture is determined by an exogenous mechanism.

Morphofunctional Changes in Colon after Cold Stress in Male C57BL/6 Mice Susceptible and Tolerant to Hypoxia.

There are individual differences in the tolerance to hypoxia and stress. Stress can contribute to the development of various diseases, including inflammatory bowel disease. It was found that inflammatory bowel diseases in animals susceptible to hypoxia runs more severe course than in tolerant animals. We studied morphofunctional changes in the colon under conditions of modeled cold stress in male C57BL/6 mice susceptible and tolerant to hypoxia. The animals were daily subjected to cold stress (20 min at -20°C) for 2 weeks. Cold stress was followed by an increase in the volume fraction of goblet cells in the colon and production of mucins by these cells in mice tolerant to hypoxia and an increase in cell content in the lamina propria of the colon mucous membrane in animals susceptible to hypoxia. The number of serotoninproducing endocrine cells increased in both groups, but these changes were more pronounced in mice susceptible to hypoxia.

Effect of Carnosine on the Course of Experimental Urate Nephrolithiasis.

The prospect of using the antioxidant dipeptide carnosine for the treatment of urate nephrolithiasis was evaluated. Urate nephrolithiasis was modeled in rats by intragastric administration of a mixture of oxonic and uric acids. Carnosine was administered intragastrically through a tube in a dose of 15 mg/kg. In rats treated with carnosine, the concentration of TBA-reactive products decreased by 1.4 times, the total antioxidant activity increased by 1.4 times, and catalase activity increased by 1.3 times. By the end of the experiment, the lactate dehydrogenate level in experimental rats was 2-fold lower than in the control, and the number of urate deposits decreased by 1.6 times with a concomitant alleviation of the inflammatory processes. Thus, the use of direct peptide antioxidant carnosine attenuated the manifestations of urate nephrolithiasis.

Morphological and Functional Peculiarities of the Immune System of Male and Female Rats with Different Hypoxic Resistance.

The morphological and functional peculiarities of the immune system are studied in adult male and female Wistar rats with high and low hypoxic resistance. Sex-specific differences in the subpopulation composition of the peripheral blood lymphocytes, not depending on the hypoxic resistance of animals, are detected: the males have lower absolute counts of T helpers and higher percentage of regulatory T cells than the females in the diestrus phase. Comparison of the morphofunctional status of the immune system in male and female (diestrus) rats with high resistance to hypoxia has shown a better developed subcapsular zone of the thymus, higher levels of anti-inflammatory cytokine TGF-ß, and lower absolute counts of cytotoxic T lymphocytes in the peripheral blood in the males. Males with low hypoxic resistance have higher counts of phase II thymic bodies in comparison with low-resistant females. Hence, morphofunctional differences in the immune system of male and female rats with different hypoxic resistance are detected, which can determine the course of inflammatory diseases.

Experience of Using Tripeptide Leu-Ile-Lys for Experimental Therapy of Chronic 16-Week Oxalate Nephrolithiasis in Rats.

We studied the effect of tripeptide Leu-Ile-Lys on the course of chronic 16-week oxalate nephrolithiasis in rats modeled by administration of 1% ethylene glycol solution in drinking water for 16 weeks. The tripeptide Leu-Ile-Lys obtained by chemical synthesis (sample purity ≥98%) was administered intragastrically through a probe in a dose of 11.5 mg/kg in 1 ml saline. It was found that during tripeptide Leu-Ile-Lys significantly alleviated the course of experimental pathology, which was confirmed by characteristic biochemical and morphological indicators. We observed a decrease in the concentration of calcium ions by 4.4 times, weakening of oxidative stress in the renal tissue due to a decrease in the total prooxidant activity by 1.2 times, normalization of increased catalase activity, and reduction of superoxide dismutase activity by 2.4 times relative to disease control. Histological signs of nephrolithiasis were recorded in 9% cases (vs. 75% cases in disease control).