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Previous studies investigating the effects of blocking the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis in prostate cancer found no effects of the growth hormone receptor (GHR) antagonist, pegvisomant, on the growth of grafted human prostate cancer cells in vivo. However, human GHR is not activated by mouse GH, so direct actions of GH on prostate cancer cells were not evaluated in this context. The present study addresses the species specificity of GH-GHR activity by investigating GH actions in prostate cancer cell lines derived from a mouse Pten-deletion model. In vitro cell growth was stimulated by GH and reduced by pegvisomant. These in vitro GH effects were mediated at least in part by the activation of JAK2 and STAT5. When Pten-mutant cells were grown as xenografts in mice, pegvisomant treatment dramatically reduced xenograft size, and this was accompanied by decreased proliferation and increased apoptosis. RNA sequencing of xenografts identified 1765 genes upregulated and 953 genes downregulated in response to pegvisomant, including many genes previously implicated as cancer drivers. Further evaluation of a selected subset of these genes via quantitative reverse transcription–polymerase chain reaction determined that some genes exhibited similar regulation by pegvisomant in prostate cancer cells whether treatment was in vivo or in vitro, indicating direct regulation by GH via GHR activation in prostate cancer cells, whereas other genes responded to pegvisomant only in vivo, suggesting indirect regulation by pegvisomant effects on the host endocrine environment. Similar results were observed for a prostate cancer cell line derived from the mouse transgenic adenocarcinoma of the mouse prostate (TRAMP) model.

The effect of allogenic combined transplantation of placental multipotent mesenchymal stromal and hemopoietic stem cells on regeneration of the myeloid tissue and spleen after acute blood loss was studied in laboratory mice. Combined transplantation of these cells did not change the content of cytogenetically modified cells in the bone marrow under normal conditions, but reduced their levels after acute blood loss. Combined transplantation of multipotent mesenchymal stromal and hemopoietic stem cells promoted activation of erythropoiesis and granulocytopoiesis. The major morphometric and cytological parameters of the white pulp of the spleen decreased, presumably due to immunosuppressive effect of multipotent mesenchymal stromal cells.

Development of radiation mucositis in patients with oropharingeal cancer who are treated by radiation therapy leads to constrains breaks, decreases of the quality of life and makes the radiation dose in target insufficient. All above mentioned increases recurrence risk. Since 2010 there was developed and introduced the method of prophylaxis and treatment of radiation injuries of oral cavity in patients with oropharingeal cancer which gives an ability to improve radiation treatment outcomes and the quality of life of patients.

The purpose of this work was to study the effect of combined transplantation of multipotent mesenchymal stromal (MSCS) and hematopoietic stem cells (HSCs) isolated from the placenta, on the regeneration of white and red pulp of the spleen under physiological conditions and in conditions of exposure to ionizing radiation. Methods. The experiments were performed with laboratory mice-males. We studied the influence of ionizing radiation dose of 4.0 Gy. Animals of the experimental group were intravenously infused into MMSC and GSK respectively at a dose of 6 million cells/kg and 330 thousand cells/kg, suspended in 0.2 ml of 0.9% NaCl solution. The selection of hematopoietic stem cells was carried out using the direct technique of immune magnetic separation. Were studied the following morphometric parameters of the spleen: the average area of lymphoid follicles, the average area of zone of lymphoid follicles, average size of germinal center of lymphoid follicles, average size T-zones of lymphoid follicles, the average distance between the centers of the follicles, the average cellularity of the red pulp. Results. As a result, of research obtained that after exposure to ionizing radiation on the background of combined transplantation of HSC and MSCS there is an increase in size of lymphoid follicle at the expense of area B-zone of the follicle, the area germinative center of the follicle, restoring the content of lymphoblasts and lymphoblasts and lymphocytes to normal values. On the background of transplantation MMSC and GSK in terms of radiation exposure changes and the red pulp of the spleen. The increase in the density of cells in the red pulp of the spleen and, as a consequence, of the increase of the distance between the centers of lymphoid follicles. The increase in the density of cells in the red pulp occurs due to the increase in the content of erythroid cells and by increasing granulocytes. Key words: ionizing radiation, multipotent mesenchymal stromal cells, hematopoietic stem cells, spleen, regeneration. Conclusion. Studies have shown the effectiveness of combined transplantation MSC and GSK in respect of the main morphometric parameters of the spleen after exposure to ionizing radiation.

The study examined the effect of combined transplantation of multipotent mesenchymal stromal and hematopoietic stem cells on the regeneration of the intestinal epithelium in the conditions of influence of extreme factors. Obtained in physiological conditions and in the conditions of influence of extreme factors combined transplantation of multipotent mesenchymal stromal and hematopoietic stem cells derived from mature and old animals is accompanied by increased content of epithelial cells of the crypts of the jejunum. In physiological conditions in mature animals, this effect is realized through the increase of proliferative activity of epithelial cells, while the old - through the inhibition of apoptosis. In the conditions of influence of extreme factors of the increase in the content of the cell population of the crypts in mature animals is achieved by increasing the proliferative activity and the inhibition of apoptosis of epithelial cells in the old organism through inhibition of apoptosis.Изучали влияние сочетанной трансплантации мультипотентных мезенхимальных стромальных и гемопоэтических стволовых клеток на регенерацию эпителия кишечника в условиях воздействия экстремальных факторов. Получено, что в физиологических условиях и в условиях воздействия экстремальных факторов сочетанная трансплантация плацентарных мультипотентных мезенхимальных стромальных и гемопоэтических стволовых клеток у зрелых и старых животных сопровождается увеличением содержания эпителиоцитов крипт тощей кишки. В физиологических условиях у зрелых животных этот эффект реализуется через повышение пролиферативной активности эпителиоцитов, у старых животных — через ингибирование апоптоза. В условиях воздействия экстремальных факторов увеличение содержания клеточной популяции крипт у зрелых животных достигается за счет повышения пролиферативной активности и угнетения апоптоза эпителиоцитов, а в старом организме — за счет ингибирования апоптоза.

We studied the effects of the anorexigenic peptide obestatin on the coagulation system and blood rheology (by the parameters of platelet aggregation and osmotic resistance of erythrocytes) in vitro and in vivo. Obestatin inhibited in vitro platelet aggregation in the entire dose range and reduced osmotic resistance of erythrocytes in all doses except 300 nmol/kg (obestatin in a dose of 300 nmol/kg had no effect on this parameter). Similar to the results of in vitro experiments, intranasal, intraperitoneal, and subcutaneous administration of obestatin in a dose of 300 nmol/kg inhibited platelet aggregation and had no effect on the osmotic resistance of erythrocytes.

The effects of chronic intranasal administration of 300 nmol/kg obestatin and its fragment FNAP-NH

In this study, we studied homing multipotent mesenchymal stromal cells under influence of extreme factors: after radiation exposure, acute blood loss. Absorbed dose ionizing radiation amounted to 4.0 C (causes acute radiation sickness in mice), acute blood loss was caused by bleeding from the tail vein of the mouse in the amount of 2% of the body weight of the animal. Label MMSC used fluorochrome DAPI, ready to use. The experiments were performed on 60 Mature mice (males) age 6-8 months, weighing 20-25 g. Experiments on the culture of multipotent mesenchymal stromal cells from the placenta (chorion) performed on laboratory mice female at the age of 3-4 months in the gestation period of 14 days. Introduction suspensions of MMSC was carried out at a dose of 6 million cells/mouse, suspended in 0.2 ml 0.9% NaCl solution. The control group of laboratory animals MMSC transplantation was carried out also in the amount of 6 million cells/mouse. The assessment was made of tissue chimerism in the peripheral blood, bone marrow, spleen, small intestine, liver, lung, kidney, heart after 1 and 24 hours after transplantation of labeled cells. It was found a significant decrease in the content of labeled MMSC in the peripheral blood at extreme impact, indicating a migration of the transplanted cells in the damaged tissue. Homing transplanted MMSC is realized mainly in those tissues that underwent the most damage.

The objective of the work was to study morphometric and cytological indexes of the spleen in mature and old laboratory animals after acute blood loss on the background of allogenic transplantation of placenta MMSC and GSC. The study proved that 5 days after acute blood loss on the background of stem cells transplantations to the mature animals there was a reduction of lymphoid follicles area due to reduction in thymus independent area. There were no immunosuppressive effects to the white pulp of the spleen in old animals. The increase of leucocytes' and erythrocytes' elements in red pulp in the mature animals was noted. In old animals, the increase of cells' density in red pulp is mainly due to increased number of erythroid cells.

Single administration of the obestatin fragment 1-4 (300 nmol/kg) to male Wistar rats produced a significant weight loss in male rats on observation days 5-8, while in female rats only on day 8. In addition, males demonstrated decreased risk factor in the elevated plus-maze test, but no effect of the preparation on behavior of female rats was revealed. Obestatin fragment 1-4 had no effect on corticosterone level 1 week after single administration in both females and male rats.

The development of the program of group preventive consultation of visitors of the centers of health concerning nutrition and assessment of its efficiency was the purpose of the work. The analysis of the results of inspection of 2569 visitors of the Health сenter at the age of 18–78 years and randomized, open, cross research of 242 women (27–72 years old) who passed group preventive consultation in the Center of health at «School of a balanced nutrition » were carried out. Anthropometrical data and the actual nutrition with use of the computer program «Analysis of the Person Nutrition» were studied. The study of nutritional status of 242 women with different body mass revealed an excess consumption of fats and carbohydrates, dietary energy supply in obese. Basing on the structural features of patient’s nutrition the School nutrition program was developed. Сomparing of laboratory, diagnostic and resource capabilities of Health сenter with algorithm of overweight and obesity patients treatment has shown wide opportunities of Health сenter, not only in the diagnosis (the study of nutrient, metabolic status), but also in the complex treatment of patients with different body mass. Due to group preventive counseling in the School of a balanced nutrition the efficiency of such an approach contributed 1-month weight loss (2.18±1.28 kg) in 64.4% of the participants.

Obestatin is an endogenous regulator of appetite with anorexigenic action. In this study, we analyzed the effects of single and chronic intranasal administra� tions of obestatin or its fragment (1–4) at a dose of 300 nmol/kg on the glucose content of blood and food and water motivation under the conditions of depriva�

303 children with the diagnosis "Hepatobiliary disorders of cystic duct or gall bladder" and "Sphincter Oddu's spasm" have been examined. After a profound children's examination, the data of objective survey, and also laboratory, biochemical, immune, functional rates (such as ultrasound survey, cardiointervalography) and findings of chemical-analytical survey of the toxics rate (such as aroma carbons, phenol, aldehydes, aliphatic alcohols) in biospheres of children's organisms were a nalysed. The evaluation of the effectiveness of children's hepatobilliary disorders'treatment in conditions of the environmentae negative factors' influence.

The aim of the present study was to investigate the effects of acute hypobaric hypoxia in early organogenesis on three following generations including pregnant females (FO) and two generations of their posterity (F1 and F2). Animals of all generations mentioned above demonstrated marked changes in motor and exploratory activity as well as in anxiety level while the litter of F1 and F2 generations showed also changes in learning ability. Besides, acute hypobaric hypoxia interfered in maternal behavior of females of the FO and F1 generations. The revealed changes kept till pubertal period. Possible mechanisms of gestational stress influence are discussed.

This study analyses the spontaneous behavior and anxiety-phobic status of mature rats that were subjected to antenatal intermittent hypoxia during the early stages of organogenesis. Antenatal intermittent hypoxia caused a decrease of motor activity as well as an enhanced anxiety level in rats of both sexes, while males appeared to be more sensitive to hypoxic influence. The effects of single antenatal intermittent hypoxia were more expressed than those of double exposure.

We studied the effect of acute hypobaric hypoxia in early organogenesis on physiological and behavioral parameters of second-generation albino rats. Antenatal acute hypoxia was followed by physical and sexual retardation, increase in the mortality rate, and behavioral changes in second-generation animals (hypoactivity of males and females on day 22 of life and hyperactivity of males on day 57 of life). Second-generation animals exhibited no gender differences in body weight and horizontal and vertical locomotor activity.

The influence of antenatal intermittent normobaric hypoxia during early organogenesis (days 9-10 of intrauterine development) on the physical development, vegetative balance, and antioxidant defense system of 60-day-old rats was studied. Antenatal exposure to intermittent hypoxia resulted in the impaired physical development of all offspring during the early 15-day postnatal period and caused changes in the vegetative balance of heart regulation, which were differently directed in males and females. Moreover, females that survived antenatal hypoxia had a decreased superoxide dismutase activity in the brain, compared to that in the control rats.

Physical development, spontaneous behavior, and training capacity were evaluated in adult progeny of albino rats exposed to acute hypobaric hypoxia on days 9–10 of gestation, corresponding to the early organogenesis period. Prenatal hypoxia caused delayed behavioral disorders, which were more pronounced in females born from mothers with low resistance to hypoxia. Therapeutic intranasal administration of Pro-Gly-Pro peptide in a dose of 1 mg/kg to rat pups on days 13–15 of life completely prevented the negative consequences of acute prenatal hypoxia in adult females and leveled virtually all negative consequences, except delayed physical development, in males.

The aim of the present study was to compare the survival, physical development and spontaneous behavior of rat pups born from white rats subjected to acute hypobaric hypoxia on the 3rd-5th days of gestation (progestation) period or on the 9-10th day of gestation (period of early organogenesis). It was shown that the delayed effects of progestation hypoxia were less expressed than those following acute hypoxia modeled in the early organogenesis. In latter case, hypoxia led to the increased mortality among rat pups of both sexes while hypoxia-induced delay in physical development and changes in spontaneous behavior and anxiety level were registered up to the 57th day of postnatal period.

The survival rate, physical development, and spontaneous behavior has been evaluated in pups of albino rats exposed to acute hypobaric hypoxia on the 9-10th day of gestation corresponding to the onset of organogenesis. Prenatal hypoxia increased the mortality among the offspring, delayed their physical development, and affected their spontaneous behavior up to the age of 2 months. The females exposed to intrauterine hypoxia proved to be more sensitive to hypoxia than males.

The effects of acute hypobaric hypoxia on the stages of progestation or beginning of organogenesis on biogenic amines levels in brain stem and cerebral cortex of their mature offspring as well as on their behavior, were investigated. It was shown that acute hypoxia applied in the period of embryonic organogenesis resulted in severe delayed changes in offspring spontaneous behavior and led to marked changes of biogenic amine levels, particularly expressed for dopaminergic system. Females subjected to antenatal hypoxia happened to be more sensitive to its influences than males.

Influenza A virus M-proteins can cause depression in experimental animals 1 day after administration. HA and NA, on the contrary, activate motor activity in animals under the similar conditions. The effect of viral proteins is dose-dependent.

The paper analyses several risk factors of cardiac postoperative complications in 284 patients with atherosclerosis of terminal aorta or lower limb arteries and correlation between preoperative management and intervention outcomes. Results of preoperative functional examination (transesophageal electric stimulation, echocardiography) and intraoperative monitoring of central hemodynamics were highly prognostic for cardiac complications. Causative analysis of cardiac complications enabled to develop a preventive strategy that has decreased the complication rate in 1.8 times.

There were three medical examinations (in March, June and October) of oilers on shift days 5-6 in a field medical post in the Polar region. The survey protocol included analysis of morning (before breakfast) biochemical and cell indices, physiological examination, testing reactions to standard stimuli (color, tone), psychological testing, assessment of factual nutrition, analysis of the cardiorespiratory function at rest and during physical tests. It was stated that recovery of physical performance varied with the seasons. In March, the shift workers were significantly less reactive to the color stimulus. At low ambient temperature (-38 degrees C) blood content of alpha 1- and alpha 2-globulins went up, and there were atypical proteins and considerable amounts of total cholesterol, pre-beta-lipoproteins and alpha-lipoproteins in blood.

Acute hypobaric hypoxia of pregnant rats led to a significant delay in body weight gain, growth and time of eye opening in newborn rat pups which was paralleled by behavioral changes. Preventive intranasal instillations of peptide mixture (semax and beta-casomorphine-7) to pregnant females prevented the effect of hypoxia on the progeny.

The effects of intraperitoneal administration of the heptapeptide beta-casomorphin-7 (beta-K-7) and its des-Tyr analogues (beta-K-6 and beta-K-4) on spontaneous locomotor activity were investigated in rats using "Opto-Varimax", "RODEO-2" and "open field" tests. At 20 mg/kg 5 minutes prior to the beginning of measurements beta-K-7 produced a significant decrease in linear locomotion and rearing. As for beta-K-6 and beta-K-4, their influence on locomotion of the experimental animals was less evident. In contrast to beta-K-7, its des-Tyr analogues (20 mg/kg) produced a marked decrease in nose-poking behavior. Beta-K-7 in doses that had no effect on spontaneous behaviour (1 and 5 mg/kg) attenuated extreme behavioural displays under stress conditions. The experimental results suggest the advisability of further investigations of neurotropic properties of beta-K-7 and related peptides.