Effects of Combined Treatment with Compounds Affecting Mitochondria on Physiological Parameters in Old Monkey.

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.

[Comparative analysis of residual neurovirulence of vaccine and low attenuated rubella virus (Matonaviridae: Rubivirus: Rubella virus) strains in the experiments on the macaque rhesus (Macaca mulatta) monkeys].

INTRODUCTION: Rubella is currently an infection controlled by specific prophylaxis. Not only the right vaccine prophylaxis strategy and tactics, but also the use of effective and safe vaccine preparations is crucial for the elimination of this disease.The aim of the investigation was to study the morphological and pathogenetic patterns of changes developing in the central nervous system (CNS) and internal organs of monkeys (Haplorhini) during intracerebral inoculation with 2 strains of rubella virus (Matonaviridae: Rubivirus: Rubella virus) (RV): highly attenuated Orlov-B, and low attenuated Orlov-14. MATERIAL AND METHODS: In the experiments, seronegative rhesus macaque monkeys (Macaca mulatta) weighing 3.3-5.1 kg (n = 7) were used. Neurovirulence of the strains was determined by a complex of clinical, pathomorphological, and virological methods. RESULTS AND DISCUSSION: It was found that during attenuation, the Orlov-B strain lost the ability to replicate in CNS cells and induce moderate/expressed specific changes in them, as well as to overcome the blood-brain barrier and cause the damage of sensitive organs and tissues. This fact indicates a low level of residual neurovirulence of the vaccine strain. CONCLUSION: The results obtained in this study regarding the clinical symptoms of CNS lesions and the nature of the pathological process in its tissues in experimental animals can be significant for the improvement of safety control of live rubella vaccines. These data indicate that the Orlov-B strain can be considered as a candidate strain for further study on the development of a rubella vaccine based on the domestic vaccine strain.

Analysis of Morphological Changes in the CNS and Internal Organs of Macaca mulatta Monkeys after Intracerebral Injection of a Low-Attenuated Rubella Virus Strain.

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.

Study of the teratogenicity of the vaccine strain of the Rubella virus «Orlov-V¼ (Matonaviridae: Rubivirus: Rubella virus) in experience on rhesus macaques.

INTRODUCTION: Rubella virus has pronounced teratogenic properties that can cause generalized and persistent intrauterine infection of the fetus. As a result, the control of the loss of teratogenicity inherent in «wild-type¼ virus strains is a necessary stage of a preclinical study of the vaccine strain for a live attenuated rubella vaccine.The purpose of the study is to comprehensively study the teratogenic properties of the vaccine strain of rubella virus «Orlov-V¼ in the experiment on rhesus macaques. MATERIAL AND METHODS: Seronegative to rubella virus female rhesus macaques in early pregnancy at the age of 4-7 years (n = 13) were used in the experiment. Animals of the experimental group (n = 9) received single immunization intramuscularly with a preparation from the «Orlov-V¼ strain. The control group of the monkeys (n = 3) were immunized with a commercial vaccine containing Wistar RA27/3 strain. The female of the control group (n = 1) was injected with a solvent used in the rubella vaccine. Study of possible teratogenic properties of vaccine strains of rubella virus was carried out using a complex of clinical, immunological, pathomorphological and virological methods. Clinical observations were made within 3 months after the monkeys' birth. Determination of antibody titers in the blood serum of immunized monkeys was performed in HI test on the 28th-30th day after infection. The ELISA method was applied to determine IgM antibodies in the blood serum of newborns within the first month of life. Detection of rubella virus RNA was performed by PCR with electrophoretic detection of amplicons. RESULTS: No markers of congenital rubella infection were found in infants born from monkeys vaccinated during the pregnancy. It is shown that PCR can be an informative method to confirm the absence of teratogenic properties of vaccine strains of rubella virus. DISCUSSION: The obtained data demonstrated that vaccine strains of the «Orlov-V¼ rubella virus and Wistar RA27/3 have lost their teratogenic properties. The possibility of using an alternative strategy for preclinical assessment of specific safety of antiviral vaccines including a complex of clinical, immunological, pathologic and virological methods instead of the classical pathologic method is discussed. CONCLUSION: The results obtained in this study showed the absence of teratogenic properties and high immunogenic activity of the vaccine strain of rubella virus «Orlov-V¼.

Functional Parameters of Physiological Systems of Laboratory Primates after Administration of Doxorubicin and Transplantation of Mesenchymal Stem Cells.

We studied physiological parameters of rhesus monkeys after administration of anthracycline antibiotic doxorubicin. Intravenous administration of the drug caused intoxication manifested in in an abrupt body weight loss, baldness, vomiting, and exicosis. Intoxication in monkeys determined by the damaging effects of doxorubicin on organs and tissues is also characterized by significant changes in the blood: leukopenia, thrombocytopenia, neutropenia, monocytopenia, lymphocytosis, and a sharp drop of CD20+ B cell content. The total protein and albumin content in the blood significantly decreased. A sharp increase in C-reactive protein was also accompanied by an increase in activity of proinflammatory cytokine IL-6. Transplantation of mesenchymal stem cells in some cases can significantly alleviate doxorubicin-induced damage to organs and maintain normal clinical status of monkeys after two injections of the drug. Late transplantation of stem cells does not have a protective effect and does not protect the animals from the damaging effects of doxorubicin. We found that the protective effect of mesenchymal stem cells depends on the dose of the drug, total number of cells, and the time of their transplantation. It should be noted that human and monkey mesenchymal stem cells produce similar regenerative effects, at least in the doxorubicin toxicity model.

Use of Mesenchymal Stem Cells for Possible Repair of Doxorubicin-Damaged Organs and Tissues in Experimental Monkeys.

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.

Potential Contribution of Cytomegalovirus Infection to Prenatal and Early Neonatal Mortality of Monkeys in the Adler Breeding Center.

Scrapings from the cervical canals and uterine cavities of females with a history of miscarriages, pathological deliveries, and stillbirths were tested for the cytomegalovirus DNA. The incidence of the agent in the females with a history of gestosis and abnormal deliveries was significantly higher than in females without anamnesis of this kind. Parenchymatous organs of stillborn neonates and animals dead during the first month of life were studied. This analysis and studies of the umbilical cords and placentas showed generalized cytomegalovirus infection in 22% dead animals, which objectively proved intrauterine infection.