Major scientific achievements
1. Cellular technology
A bank of cryopreserved cultures of mesenchymal stem cells (MSC) of laboratory primates, hamadryas baboons and rhesus monkeys, has been created. MSC underwent from 5 to 40 passages of cultivation.
A model of experimental myocardial infarction confirmed by ECG and biochemical markers was produced in hamadryas baboons and rhesus monkeys. MSC has been used as a replacement therapy for experimental myocardial infarction.
Observations of animals in order to assess the effectiveness of replacement therapy are going on.
2. Endocrinology. Stress
For the first time, laboratory primates showed a decrease in the process of aging of the secretion of adrenal androgens - dehydroepiandrosterone, dehydroepiandrosterone sulfate, as well as precursors in the biosynthesis chain of steroid hormones - pregnenolone, 17-hydroxypregnenolone, 17-hydroxyprogesterone; a progressive increase in the ratio of molar concentrations of cortisol and adrenal androgens; decrease in transcortin binding ability and increase in biologically active free fraction of cortisol.
The absence or distortion of the circadian rhythm during aging of the reaction of the hypothalamic-pituitary-adrenal system (GGAS) to acute stress effects, as well as the decrease of the stress-reactivity of GGAS in the afternoon has been revealed. The leading role of age-related disorders of vasopressinergic and melatoninergic regulation of adenohypophysis in the mechanism of the age-related reduction of the GGAS reaction to acute stress effects has been established. The efficiency of using epitalon for the correction of age-related disorders of the stress-reactivity of GGAS has been proven. In joint studies with the Research Institute of Bioregulation and Gerontology of the North-Western Branch of the Russian Academy of Medical Sciences, St. Petersburg, as well as with the Institute of Gerontology, Academy of Medical Sciences of Ukraine, Kiev, the effectiveness of epitalon for the correction of age disorders in old people was shown.
Peculiarities of the circadian rhythm of melatonin secretion in lower monkeys and the nature of age-related impairments of the endocrine functions of the pineal and pancreas glands were revealed; the important role of age-related disorders of secretion of melatonin in the formation of age-related dysfunctions of the function of HGAS and pancreas and the effectiveness of pineal peptide preparations of epitalon and epithalamin in the correction of age-related endocrinopathy has been proved.
3. Immunology. Radiology
Normative indicators of the interferon status (IS) of monkeys - as one of the leading factors of nonspecific resistance have been established. It is shown that the levels of IFN-, IINF- and INF are as close as possible to those in humans. A significant difference in the production of interferon in monkeys of different ages was revealed, which does not depend on the sex of the animal. It is revealed that the regulatory indicators of cellular immunity in rhesus monkeys are most similar to those in humans.
As part of the implementation of the ‘Mars-500’ program (Gamma Breeze), it was shown that at low doses of radiation (250sGy), the number of B-lymphocytes in rhesus monkeys significantly decreases in comparison with T-lymphocytes, and the number of NK-cells practically does not change. With the same total dose of irradiation, the number of immunocompetent cells is restored earlier in monkeys after a single exposure than after fractional irradiation.
4. Behavior of primates
It was established that the behavior of the aggressor and the victim after the end of the conflict in monkeys depends on its nature and form. In green monkeys, post-conflict reconciliation is extremely rare and almost exclusively after the conflict of relatives. In anubis baboons, the values of the conciliatory tendency are several times higher than those of green monkeys. Cynomolgus macaques show intermediate values of a conciliatory tendency. It was established that the death of monkeys from the effects of intragroup aggression in the nursery amounts to 10% of the total death. It was found that there are significant interspecies differences in the structure of aggressive interactions in different species of monkeys, which are manifested in the ratio of the observed cases of dangerous and non-dangerous aggression. The highest level of dangerous aggression was observed in green monkeys, the lowest - in anubis baboons.
5.Medical and biological aspects of biosafety
It has been established that the normal intestinal micro flora of different species of lower Asian and African monkeys is represented by various taxonomic groups of microorganisms and, according to qualitative and quantitative indicators, approaches that of a healthy person.
As part of the study of natural Helicobacter pylori infection, it was established that in the mucous membrane of the stomach and duodenum of monkeys a rather high percentage of H. pylori infection is determined by PCR method. The presence of ure genes (36.9%), vac A (21.9%), cag A (6.2%), as well as various combinations of them, was found in the H. pylori DNA. Despite the high percentage of H. pylori DNA detection, unlike in humans, monkeys practically do not have ulcerative lesions of the stomach and duodenum, as well as stomach tumors. The process is limited to inflammatory changes of varying severity. This is probably due to the fact that the marker genes for pathogenicity of H. pylori are 10 times less frequent in monkeys than in human strains.
Studies of urogenital infections (UGI) of different species of monkeys have been conducted.
A wide spread of spontaneous infection by chlamydia and representatives of the Mollicutes family (mycoplasmas, ureaplasmas) among different species and age groups, lower African and Asian monkeys, has been established by PCR. UTI pathogens (C.trachomatis, M.hominis, U.urealyticum) are found in clinically healthy monkeys with normal reproductive function and in animals with various pathologies of the urogenital tract. In the pathology of pregnancy and childbirth and inflammation of the urogenital tract the detection of infectious agents increases dramatically.
In all cases of pathology, the predominant pathogen is found to be C.trachomatis (71.4%).
PCR test systems for species multiplex detection and identification of Chlamydiatrachomatis and Chlamidophilapneumoniae have been developed.
Species composition of the parasitic fauna of 6 monkey species and the degree of infection of each species with various parasites was established. Monkeys are characterized by both mono- and polyinvasion. Numerous combinations of intestinal protozoa with worms and enterobacteria are found.
A museum of pathogenic and conditionally pathogenic bacteria cultures isolated from monkeys has been created.
Together with the Virus Research Center of the Ministry of Defense of the Russian Federation, a model of avian influenza A H5N1 on cynomolgus monkeys with the endotracheal introduction of the virus was developed. At the same time, there was a serious disease of monkeys with fever for 6-7 days, with pneumonic and necrotic changes in the lungs.
Together with the Research Institute of Influenza, Russian Academy of Medical Sciences, preclinical tests have been carried out on cynomolgus monkeys of the live intranasal GHB04VN vaccine with the defective NS1 gene. This vaccine was developed by AVIR GreenHills Biotechnology, Austria. The vaccine was tested in liquid form in the form of drops and in powder form. Of all the forms of the live intranasal vaccine GHB04VN, the liquid form of the vaccine in the form of drops had the greatest immunogenicity and the powder form had a lower immune activity. All forms of the intranasal vaccine were completely areactogenic. After immunization, the virus from nasal washes was secreted in low titers for no more than 72 hours in 16% of monkeys.
A new hepatitis C-like (HCV-like) infection in rhesus monkeys has been characterized. The peculiarities of the indicators of the humoral response to the virus were revealed in a comparative aspect with a human being, which were expressed in a wide variety of antibody spectrum variants for the main HCV diagnostic proteins, the prevalence of antibodies to non-structural proteins of the virus, as well as their low reactivity. Markers of HCV-like monkey infection have been detected for several years. The infection is almost asymptomatic. Work has been done to determine SV-40 virus infection in a healthy population in various regions of Russia. During the examination of fifty donor blood samples from Moscow using a PCR method, 8 positive samples (16%) were detected. During the examination of 310 blood samples from healthy people from Siberia (Krasnoyarsk Territory and the Novosibirsk Region), 86 infected people were found (28%).
Investigation of 100 donor blood samples from the Krasnodar Territory revealed 49 positive samples (49%).
Studies on the possible connection of the SV-40 virus with certain types of human tumors showed that of 48 samples of brain tumor tissue (astrocytomas, glioblastomas, oligodendromes, ependiomas), SV-40 DNA is present in 19 samples (39%). Of the 12 mesothelioma samples, 3 were positive (25%). During the examination of 58 tissue samples of non-Hodgkin's lymphoma the DNA of the SV-40 virus was detected in 15 cases (26%).
A universal PCR test system was developed to determine the cytomegalovirus virus (subfamily Betaherpesvirinae) of primates, and their phylogenetic analysis was performed. The test system allows differentiating cytomegalovirus of lower primates and humans.
1. Cellular technology
A bank of cryopreserved cultures of mesenchymal stem cells (MSC) of laboratory primates, hamadryas baboons and rhesus monkeys, has been created. MSC underwent from 5 to 40 passages of cultivation.
A model of experimental myocardial infarction confirmed by ECG and biochemical markers was produced in hamadryas baboons and rhesus monkeys. MSC has been used as a replacement therapy for experimental myocardial infarction.
Observations of animals in order to assess the effectiveness of replacement therapy are going on.
2. Endocrinology. Stress
For the first time, laboratory primates showed a decrease in the process of aging of the secretion of adrenal androgens - dehydroepiandrosterone, dehydroepiandrosterone sulfate, as well as precursors in the biosynthesis chain of steroid hormones - pregnenolone, 17-hydroxypregnenolone, 17-hydroxyprogesterone; a progressive increase in the ratio of molar concentrations of cortisol and adrenal androgens; decrease in transcortin binding ability and increase in biologically active free fraction of cortisol.
The absence or distortion of the circadian rhythm during aging of the reaction of the hypothalamic-pituitary-adrenal system (GGAS) to acute stress effects, as well as the decrease of the stress-reactivity of GGAS in the afternoon has been revealed. The leading role of age-related disorders of vasopressinergic and melatoninergic regulation of adenohypophysis in the mechanism of the age-related reduction of the GGAS reaction to acute stress effects has been established. The efficiency of using epitalon for the correction of age-related disorders of the stress-reactivity of GGAS has been proven. In joint studies with the Research Institute of Bioregulation and Gerontology of the North-Western Branch of the Russian Academy of Medical Sciences, St. Petersburg, as well as with the Institute of Gerontology, Academy of Medical Sciences of Ukraine, Kiev, the effectiveness of epitalon for the correction of age disorders in old people was shown.
Peculiarities of the circadian rhythm of melatonin secretion in lower monkeys and the nature of age-related impairments of the endocrine functions of the pineal and pancreas glands were revealed; the important role of age-related disorders of secretion of melatonin in the formation of age-related dysfunctions of the function of HGAS and pancreas and the effectiveness of pineal peptide preparations of epitalon and epithalamin in the correction of age-related endocrinopathy has been proved.
3. Immunology. Radiology
Normative indicators of the interferon status (IS) of monkeys - as one of the leading factors of nonspecific resistance have been established. It is shown that the levels of IFN-, IINF- and INF are as close as possible to those in humans. A significant difference in the production of interferon in monkeys of different ages was revealed, which does not depend on the sex of the animal. It is revealed that the regulatory indicators of cellular immunity in rhesus monkeys are most similar to those in humans.
As part of the implementation of the ‘Mars-500’ program (Gamma Breeze), it was shown that at low doses of radiation (250sGy), the number of B-lymphocytes in rhesus monkeys significantly decreases in comparison with T-lymphocytes, and the number of NK-cells practically does not change. With the same total dose of irradiation, the number of immunocompetent cells is restored earlier in monkeys after a single exposure than after fractional irradiation.
4. Behavior of primates
It was established that the behavior of the aggressor and the victim after the end of the conflict in monkeys depends on its nature and form. In green monkeys, post-conflict reconciliation is extremely rare and almost exclusively after the conflict of relatives. In anubis baboons, the values of the conciliatory tendency are several times higher than those of green monkeys. Cynomolgus macaques show intermediate values of a conciliatory tendency. It was established that the death of monkeys from the effects of intragroup aggression in the nursery amounts to 10% of the total death. It was found that there are significant interspecies differences in the structure of aggressive interactions in different species of monkeys, which are manifested in the ratio of the observed cases of dangerous and non-dangerous aggression. The highest level of dangerous aggression was observed in green monkeys, the lowest - in anubis baboons.
5.Medical and biological aspects of biosafety
It has been established that the normal intestinal micro flora of different species of lower Asian and African monkeys is represented by various taxonomic groups of microorganisms and, according to qualitative and quantitative indicators, approaches that of a healthy person.
As part of the study of natural Helicobacter pylori infection, it was established that in the mucous membrane of the stomach and duodenum of monkeys a rather high percentage of H. pylori infection is determined by PCR method. The presence of ure genes (36.9%), vac A (21.9%), cag A (6.2%), as well as various combinations of them, was found in the H. pylori DNA. Despite the high percentage of H. pylori DNA detection, unlike in humans, monkeys practically do not have ulcerative lesions of the stomach and duodenum, as well as stomach tumors. The process is limited to inflammatory changes of varying severity. This is probably due to the fact that the marker genes for pathogenicity of H. pylori are 10 times less frequent in monkeys than in human strains.
Studies of urogenital infections (UGI) of different species of monkeys have been conducted.
A wide spread of spontaneous infection by chlamydia and representatives of the Mollicutes family (mycoplasmas, ureaplasmas) among different species and age groups, lower African and Asian monkeys, has been established by PCR. UTI pathogens (C.trachomatis, M.hominis, U.urealyticum) are found in clinically healthy monkeys with normal reproductive function and in animals with various pathologies of the urogenital tract. In the pathology of pregnancy and childbirth and inflammation of the urogenital tract the detection of infectious agents increases dramatically.
In all cases of pathology, the predominant pathogen is found to be C.trachomatis (71.4%).
PCR test systems for species multiplex detection and identification of Chlamydiatrachomatis and Chlamidophilapneumoniae have been developed.
Species composition of the parasitic fauna of 6 monkey species and the degree of infection of each species with various parasites was established. Monkeys are characterized by both mono- and polyinvasion. Numerous combinations of intestinal protozoa with worms and enterobacteria are found.
A museum of pathogenic and conditionally pathogenic bacteria cultures isolated from monkeys has been created.
Together with the Virus Research Center of the Ministry of Defense of the Russian Federation, a model of avian influenza A H5N1 on cynomolgus monkeys with the endotracheal introduction of the virus was developed. At the same time, there was a serious disease of monkeys with fever for 6-7 days, with pneumonic and necrotic changes in the lungs.
Together with the Research Institute of Influenza, Russian Academy of Medical Sciences, preclinical tests have been carried out on cynomolgus monkeys of the live intranasal GHB04VN vaccine with the defective NS1 gene. This vaccine was developed by AVIR GreenHills Biotechnology, Austria. The vaccine was tested in liquid form in the form of drops and in powder form. Of all the forms of the live intranasal vaccine GHB04VN, the liquid form of the vaccine in the form of drops had the greatest immunogenicity and the powder form had a lower immune activity. All forms of the intranasal vaccine were completely areactogenic. After immunization, the virus from nasal washes was secreted in low titers for no more than 72 hours in 16% of monkeys.
A new hepatitis C-like (HCV-like) infection in rhesus monkeys has been characterized. The peculiarities of the indicators of the humoral response to the virus were revealed in a comparative aspect with a human being, which were expressed in a wide variety of antibody spectrum variants for the main HCV diagnostic proteins, the prevalence of antibodies to non-structural proteins of the virus, as well as their low reactivity. Markers of HCV-like monkey infection have been detected for several years. The infection is almost asymptomatic. Work has been done to determine SV-40 virus infection in a healthy population in various regions of Russia. During the examination of fifty donor blood samples from Moscow using a PCR method, 8 positive samples (16%) were detected. During the examination of 310 blood samples from healthy people from Siberia (Krasnoyarsk Territory and the Novosibirsk Region), 86 infected people were found (28%).
Investigation of 100 donor blood samples from the Krasnodar Territory revealed 49 positive samples (49%).
Studies on the possible connection of the SV-40 virus with certain types of human tumors showed that of 48 samples of brain tumor tissue (astrocytomas, glioblastomas, oligodendromes, ependiomas), SV-40 DNA is present in 19 samples (39%). Of the 12 mesothelioma samples, 3 were positive (25%). During the examination of 58 tissue samples of non-Hodgkin's lymphoma the DNA of the SV-40 virus was detected in 15 cases (26%).
A universal PCR test system was developed to determine the cytomegalovirus virus (subfamily Betaherpesvirinae) of primates, and their phylogenetic analysis was performed. The test system allows differentiating cytomegalovirus of lower primates and humans.