While neurostimulation technologies are rapidly approaching clinical applications for sensorimotor disorders, the impact of electrical stimulation on network dynamics is still unknown. Given the high degree of shared processing in neural structures, it is critical to understand if neurostimulation affects functions that are related to, but not targeted by, the intervention. Here, we approach this question by studying the effects of electrical stimulation of cutaneous afferents on unrelated processing of proprioceptive inputs. We recorded intraspinal neural activity in four monkeys while generating proprioceptive inputs from the radial nerve. We then applied continuous stimulation to the radial nerve cutaneous branch and quantified the impact of the stimulation on spinal processing of proprioceptive inputs via neural population dynamics. Proprioceptive pulses consistently produce neural trajectories that are disrupted by concurrent cutaneous stimulation. This disruption propagates to the somatosensory cortex, suggesting that electrical stimulation can perturb natural information processing across the neural axis.

Non-anthropoid primates cynomolgus monkeys (Macaca fascicularis), also known as crab-eating macaques, are increasingly used in biomedical and preclinical studies due to their evolutionary proximity to humans, sharing similar diets, infectious and senile diseases. Age-related changes and sexual dimorphism of the immune system of C. monkeys have not been sufficiently characterized in literature, though age and sex differences affect the course of diseases and sensitivity to medications. Aging in C. monkeys is accompanied by an increase in CD3+CD4+CD8+ (DP-T) cells, plasma B-cells, and a decrease in platelets. Erythromyeloid bias has also been noticed in older animals. There was an increase in eosinophils, haematocrit (HCT) and haemoglobin concentration (HGB). Senile decline in the function of the immune system had sex differences. An increase in the number of monocytes, cytotoxic lymphocytes (CTL) and a decrease in the T-helper population were more pronounced in older females. A significant reduction in the number of B-cells and activated T-cells was detected in males only. A moderate correlation with the regression model of aging was established for DP-T, HCT and HGB. The reduction in the B cells count in males and the increase in CTL level in females are moderately correlated with age. Other blood cell populations did not show significant correlations in the regression models due to their high sample variability. The novel cell population CD3-CD20loCD16/CD56+, presumably NK-cells subset, was revealed. This cell population demonstrated an increase trend with age in both sexes. Population-statistical age norms for different sexes for young and very old macaques were established. The blood population clusters associated with sex and immune status in older animals were also identified.

Introduction. Bronchial fistula often occurs after lung surgery. This is an extremely severe complication with high mortality. Despite the variety methods for the treatment of bronchial fistula, the results are not always effective. In our paper, we presented a method of preventing the development of bronchial fistula based on the cell therapy. The objective of the study was to evaluate the effects of the cell therapy on the regeneration of damaged bronchial tissue in an experiment on non-human primates. Methods and materials. The study was performed on 6 non-human primates. Laboratory animals were divided into 2 groups: experimental and control. The left pneumonectomy with the formation of a stump of the main bronchus was done in each primate. In the experimental group, a regenerative product was introduced into the stump; in the control group, 0.9 % NaCl solution was used. The regenerative product consisted of autologous platelet-rich plasma activated by thermal lysis and the suspension of the xenogeneic fibroblast’s culture. The primates were observed for 7, 14 and 21 days, the peripheral blood was taken to study the dynamics of biologically active substances. A histological examination of the autopsy material was performed at the end of the follow-up time. Results. On the early postoperative period, a typical inflammatory reaction was observed and resulted by the intraoperative tissue damage. Then the morphological changes were different in both group. The inflammatory were mild, the restoration of the natural function of the mucous membrane and the formation of scar tissue were earlier in the experimental group than in the control group. An analysis of the dynamics of plasma mediators in the postoperative period revealed an earlier dominance of regenerative processes in the experimental group. Conclusion. The results of the study showed that the cell therapy stimulates the tissue regeneration, thereby preventing the failure of the bronchial stump suture.

Изучено влияние иммуномодулирующего и противовоспалительного препарата «Тамерон» на старых обезьян. Показано, что 2-недельное введение тамерона в дозах, в 2,5 раза выше рекомендуемой дозы для человека, не приводит к изменению основных лабораторных показателей крови старых обезьян. Не найдены изменения в большинстве показателей после введения препарата, по сравнению с фоновыми значениями или показателями у обезьян экспериментальной и контрольной групп. В то же время, тамерон изменял число тромбоцитов, показатели гемостаза и уровень тестостерона, смещая их к значениям, характерным для более молодых животных. Изменения в этих параметрах коррелировали с возрастом обезьян. Сделан вывод о том, что тамерон безопасен и оказывал положительное действие на некоторые системы организма обезьян.

Idiopathic thrombocytopenic purpura is a chronic autoimmune hematological disease caused by an increased destruction of platelets and associated thrombocytopenia, for the treatment of which the imported drug romiplostim is used. Сreation of the drug biosimilar provides a reduction in the cost of therapy and an access for the treatment to more patients. The aim of the study was to compare the safety indicators of the reference drug and its biosimilar in vivo and in vitro. Materials and methods. In the in vitro study, a model of “complement-dependent cytotoxicity” induced by the complement was formed on the 32D hTPOR clone 63-cell line, followed by a cell viability measurement with the CellTitter Glo ® kit . An in vivo part of the study was carried out on Javanese macaque monkeys (Macaca fascicularis). During the experiment, the clinical condition, mortality, appetite of the animals, their body weight, body temperature, respiratory rate were assessed, the clinical parameters of blood and urine of the animals were also monitored, and the hemostasis indicators were additionally measured. Results. In the in vitro experiment, the original drug romiplostim and its biosimilar GP40141 were compared in terms of EC50 values. The indicatirs did not show complement-dependent cytotoxicity. According to the in vivo results, no deviations were recorded in the clinical status of the animals and their feed intake, and no lethality was fixed out in the groups either. For all the parameters studied (body weight and temperature, respiratory rate, clinical urinalysis, clinical and biochemical blood tests, coagulation hemostasis), GP40141 and romiplostim, when administered at the doses equivalent to 10 toxic doses (TDs), had comparable effects. Conclusion. In the comparison of safety performance both in vitro and in vivo , the original drug romiplostim and its biosimilar GP40141 showed similar results.

Correction of mitochondrial function is a promising direction for modulating aging processes. The effect of NAD+ (in the form of its precursor nicotinamide mononucleotide, NMN) and antioxidant MitoQ specifically affecting mitochondria was studied on male rhesus monkeys (Macaca mulatta). The first group of animals initially received only NMN, the second group received only MitoQ, and then both groups received both drugs simultaneously. The above treatment did not lead to changes in the body weight and body temperature, hemostasis, and ECG. The use of MitoQ, but not NMN improved some hematological and biochemical parameters, shifting them to the values of young animals. Changes in these parameters depended on animal age, so the use of MitoQ can only be effective until a certain age. Combined use of the two drugs had no clear advantages over MitoQ alone.

Introduction. Taking into account the particular importance of the assurance of the safety of antiviral vaccines containing, albeit attenuated, but live viruses, that can possibly retain the residual neurovirulence, it is important to develop additional tests to confirm the stability of attenuation using modern methods of laboratory diagnostics.The aim of the study was to assess the possibility of using the RT-PCR method as an additional test for monitoring the residual neurovirulence of attenuated rubella virus vaccine strains.Materials and methods. We used live attenuated vaccine strains of rubella virus "Orlov-V" and RA27/3. The study was carried out on 11 clinically healthy monkeys of the species Macaca mulatta weighing 3–5 kg, born and kept in the nursery of the Research Institute of Medical Primatology. The clinical material studied was tissue samples from various parts of the central nervous system (CNS), regional lymph nodes, parenchymal organs, plasma and cerebrospinal fluid of experimental animals. Control of extraneural dissemination of vaccine strains was carried out using virological (cytopathic action) and molecular biological methods (RT-PCR).Results. The absence of an infectious virus in the CNS, peripheral organs and blood plasma of monkeys infected with vaccine strains was demonstrated, which indicates a high level of attenuation of rubella virus strains "Orlov-B" and RA27/3. The analytical sensitivity of the RT-PCR method was found to exceed the analytical sensitivity of the cytopathic reaction by 1.7–3.3 lg when determining the content of rubella virus in the tissues of the CNS and peripheral organs of inoculated animals.Conclusion. Comparative analysis of experimental data showed that the detection of rubella virus by real-time PCR has a number of advantages due its specificity, sensitivity and a shorter turnaround time. In this connection, the RT-PCR method can be used as an additional test in the preclinical assessment of specific safety, namely, extraneural dissemination of attenuated vaccine strains, which is essential for quality and safety control of live rubella vaccines.

New research on Methylene Blue (MB), carried out in 2020, shows that it can be an effective antiviral drug as part of COVID-19 treatment. According to the research findings, MB has potential as a direct antiviral drug for the prevention and treatment of COVID-19 in the first stages of the disease. However, the MB accumulation by various types of tissues, as well as by immune cells, has not been previously studied. Therefore, the objective of this study was to obtain spectral data on the interstitial distribution of the administered drug in endothelial tissues in primates. The data on interstitial MB distribution obtained by spectroscopic measurement at both macro- and microlevels during oral administration to Hamadryas baboon individuals demonstrate that MB accumulates in mucous membranes of gastrointestinal tract and the tissues of the respiratory, cardiovascular, immune, and nervous systems. Additionally, it was found that MB was present in lung and brain myeloid cells in significant concentrations, which makes it potentially useful for protection from autoimmune response (cytokine storm) and as a tool for the correction of immunocompetent cells’ functional state during laser irradiation. Since the cytokine storm starts from monocytic cells during SARS-CoV-2 cellular damage and since tumor-associated macrophages can significantly alter tumor metabolism, accumulation of MB in these cells provides a reason to conclude that the immune response correction in COVID-19 patients and change in macrophages phenotype can be achieved by deactivation of inflammatory macrophages in tissues with MB using laser radiation of red spectral range.

Primates represent a unique object for biomedical research, in particular in the field of physiology and pathology of the cardiovascular system. Echocardiography is the most important non‐invasive method for the intravital study of the heart structure and function, intracardiac and systemic haemodynamics. The available data on reference values of echocardiographic parameters in primates are limited.

We studied the localization and severity of morphological changes in CNS and internal organs of animals intacerebrally infected with a low-attenuated rubella virus strain "Orlov-14". The data obtained can be used as morphological criteria reflecting low level of attenuation of rubella virus strains to improve the control of the safety of attenuated strains of live rubella vaccines.

INTRODUCTION . High dietary sodium chloride intake has traditionally been considered an important factor in cardiovascular risk and an increase in blood pressure (BP). However, much remains unclear about the relationship between dietary sodium and cardiovascular health. In particular, it was shown that in rats a high content of salt in the diet can lead to miocardial remodeling/damage without increasing BP. It is possible whether this phenomenon in primates remains unknown. The AIM of the study was to trace the dynamics of BP and some echocardiographic (EchoCG) parameters in cynomolgus macaques ( Macaca fascicularis ), which have been on a high sodium chloride diet for a long time. MATERIAL AND METHODS . 12 male cynomolgus macaques 6-8 years with a body weight of 5,15-9,7 kg were studied. The animals were divided into two groups (six individuals each). The first (control) received a standard diet, the second – a diet high in sodium chloride (8 g NaCl/kg feed). After four and fourteen months, in the animals were measured blood pressure and conducted echocardiographic examination (EchoCG). RESULTS . During the follow-up period in the control group, no significant changes in the studied parameters were recorded. Increased salt intake at four months resulted in a significant decrease in left ventricular end-systolic dimension and an increase in ejection fraction values. After fourteen months, both of these indices returned, practically, to the initial level, but there was a significant increase in the thickness of the posterior wall of the left ventricle in systole and a decrease in systolic excursion of the tricuspid valve annulus compared with the basal data. BP in the salt group also did not change significantly. CONCLUSION . Cynomolgus macaques are able to resist an increase in blood pressure induced by a long stay on a high-salt diet, but in primates under such conditions, the initial manifestations of functional and structural rearrangement of the heart can be observed.

Objective:to assess the potentials of using indocyanine green fluorescence angiography in evaluating revascularization of tissue-engineered construct that was obtained from the decellularized biological matrix of primate trachea, including using mesenchymal stem cells, after heterotopic tracheal allotransplantation.Material and methods.Tracheas were obtained from two male hamadryas baboons. After decellularization, 4 cm segments of tracheas were implanted under the lateral part of the latissimus dorsi in two healthy primates, one after recellularization with mesenchymal stem cells (animal 1), and the second without recellularization (animal 2). Immunosuppressive therapy was not performed. Blood flow in the transplanted segment of the trachea was evaluated 60 days after transplantation by surgical isolation of the flap of the latissimus dorsi with the transplanted segment of the trachea, while maintaining blood flow through the thoracodorsal artery. Indocyanine green near-infrared fluorescence angiography was visualized using a FLUM-808 multispectral fluorescence organoscope.Results.Sixty days after implantation, the tracheal cartilaginous framework macroscopically appeared to be intact in both animals, tightly integrated into the muscle tissue. The framework retained its natural color. After intravenous injection of indocyanine green, the tracheal vessels were visualized in both animals. Intercartilaginous vessels and portions of the cartilaginous semi-rings devoid of vessels were clearly distinguished. The entire implanted segment was almost uniformly vascularized. No local disruptions in blood supply were observed. The fluorescence brightness of the tracheal vessels was 193 ± 17 cu and 198 ± 10 cu in animals 1 and 2, respectively. The average muscle brightness in the implantation zone was 159 ± 9 cu and 116 ± 8 cu in animals 1 and 2, respectively.Conclusion. Indocyanine green fluorescence angiography is characterized by high-contrast images and high sensitivity. This facilitates vascular patency visualization and allows to assess the degree of neoangiogenesis after experimental transplantation of the tracheal segment, at different stages of experiment, without euthanizing the animal.

Abstract Background and Aims It is traditionally believed that high consumption of sodium chloride leads to the development of arterial hypertension, which, in turn, will cause heart remodeling. However, more and more evidence is accumulating that a high sodium chloride content in the diet can cause heart damage without increasing blood pressure (BP). This is confirmed in experiments on rats. In addition, in animals of this species, supplementing a high-salt diet with soy proteins can prevent cardiovascular damage. Whether such mechanisms operate in primates remains unclear. Method The study was performed on male Macacus fascicularis. Monkeys were included in the experiment at the age of 4.6 -7.0 years and had a body weight of 5,5-7,5kg. Animals were divided into 3 groups. The first (control) included 5 animals, received standard ration; the second – 5 animals, received diet with high sodium chloride content (8 g NaCl/1 kg of the feed); the third – 6 animals, who were on a diet with high salt contents supplemented by soya isolated proteins (200 g/kg of the feed). In anesthetized animals measured blood pressure and performed an echocardiographic investigation. Follow up period lasted four month. Results Initially, in all groups of animals, blood pressure levels (Mean(SEM)) and echocardiographic parameters did not significantly differ. During the observation period, the studied parameters did not change much. For example, in the first group, an ejection fraction (EF) increased from 61.7(1.67) to 71.6(4.74), %; P=0.045. In the same group, a tendency toward a decrease in the left ventricle end-systolic dimension (1.50(0.056)vs 1.29(0.118), mm; P=0.079) was noted. Whereas the level of systolic and diastolic blood pressures in this group (for example, systolic BP: 115.4(3.95)vs 126.0(5.39), mm Hg; P=0.134) as well as in other groups of monkeys did not change significantly. Nevertheless, after four months of observation, the level of systolic blood pressure in the second group (126.0(5.39) mm Hg) of animals was significantly higher than in the first (103.0(5.54), P=0.0118) and nonsignificantly - in the third (104.0(8.39), mm Hg; P=0.065). EF in the end of follow up period in second group (71.6(4.74%) was significantly higher than in control (58.1(2.72),%; P=0.039) but not in the third group (60.9(5.03),%; P=0.162). Tricuspid annular plane systolic excursion in second group (1.02(0.08), mm) had an insignificant tendency to increase in comparison to the first (0.782(0.096), mm; P=0.094) or third (0.818(0.049), mm; P=0.052) groups. Conclusion Our data do not exclude the possibility that a high salt content in the food of lower primates can contribute to an increase in blood pressure and a change in heart function. However, to resolve the issues of the relationship between changes in heart function and the level of blood pressure and the presence of the cardioprotective effect of soy proteins under these conditions, longer observations are needed.

We studied the effects of hypogravity modeled by water immersion on cognitive functions and physiological parameters of monkeys. Cognitive capacities of monkeys were evaluated using computer-controlled joystick task with food reward in case of target hit. Water immersion (3 days for 3 h) affected in cognitive functions, body temperature, and blood parameters. The intensity of changes depended on the type of monkey behavior. In animals with non-aggressive behavior, the number of target hits did not decrease after water immersion, and even slightly increased. On the contrary, aggressive monkeys showed poorer test performance. Body temperature after each cycle of water immersion was decreased slightly in non-aggressive monkeys, while in aggressive animals, the changes were significant. At the same time, changes in the erythrocyte count, hemoglobin concentration, and hematocrit were significant in non-aggressive monkeys. Our results are in line with previous data performed on BION biosatellites and correspond to changes of physiological parameters in astronauts during space flights.

BACKGROUND. Increased salt intake is associated with a number of cardiovascular events, including increased blood pressure (BP) and the development of left ventricular hypertrophy (LVH). However, there is much evidence that a high content of sodium chloride in the diet does not always lead to an increase in BP, but almost inevitably causes cardiac remodeling, in particular, LVH. Many aspects of myocardial remodeling induced by high sodium content in the food have not been studied enough. THE AIM of the study was to trace the echocardiographic changes in Wistar rats fed the high salt ration and the high salt ration supplemented with soy proteins.MATERIAL AND METHODS. Echocardiography and BP measurements were performed on male Wistar rats, divided into three groups. The first (control; n = 8) included rats that received standard laboratory feed (20.16 % animal protein and 0.34 % NaCl); the second (n = 10) – animals that received standard feed and 8 % NaCl (high salt ration). The third group (n = 10) consisted of rats who consumed a low-protein diet containing 10 % soy protein isolate (SUPRO 760) and 8 % NaCl. The follow-up period was 2 and 4 months.THE RESULTS of the study showed that: (1) the intake of a large amount of salt with a diet does not necessarily lead to the formation of arterial hypertension; (2) despite the absence of a distinct increase in BP, under these conditions signs of cardiac remodeling, in particular, LVH, appear rather quickly; (3) supplementing a high-salt diet with soy isolates counteracts the development of LVH.CONCLUSION. High salt intake with food can cause heart remodeling, regardless of blood pressure, while soy proteins can counteract this process.

Three injections of doxorubicin to rhesus macaques cause severe intoxication, characterized by anemia, cachexia, and degeneration of the viscera. The life span of monkeys injected with the drug and receiving after 24 h mesenchymal stem cell transplantation varied from 96 to 120 days in comparison with 50-74 days in animals receiving stem cells before doxorubicin. Controls received doxorubicin and saline; the lifespan of one monkey was 24 days, of the other - 1 year and 8 months. The increase in activity of proinflammatory cytokine IL-6 was paralleled by an increase in the level of C-reactive protein.

Biological compatibility of a tissue engineered construct of the trachea (synthetic scaffold) and allogenic mesenchymal stem cells was studied on laboratory Papio hamadryas primates. Subcutaneous implantation and orthotopic transplantations of tissue engineered constructs were carried out. Histological studies of the construct showed chaotically located filaments and mononuclear cells fixed to them. Development of a fine connective tissue capsule was found at the site of subcutaneous implantation of the tissue engineered construct. The intact structure of the scaffold populated by various cell types in orthotopic specimens was confirmed by expression of specific proteins. The results indicated biological compatibility of the tissue engineered construct with the mesenchymal stem cells; no tissue rejection reactions were recorded; simulation of respiratory disease therapy on Papio hamadryas proved to be an adequate model.