RESUMEN
INTRODUCTION: Various human viruses have been identified in wild monkeys and in captive primates. Cases of transmission of viruses from wild monkeys to humans and vice versa are known. The aim of this study was to identify markers of anthroponotic viral infections in vervet monkeys (Chlorocebus pygerythrus) arrived from their natural habitat (Tanzania). MATERIALS AND METHODS: Fecal samples (n = 56) and blood serum samples (n = 75) obtained from 75 animals, respectively, on days 10 and 23 after admission to the primate center, were tested for the markers of anthroponotic viral infections (Ebola virus, Marburg virus, lymphocytic choriomeningitis, hepatitis C virus, herpes simplex virus (HSV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), parainfluenza types 1 and 3, intestinal adenoviruses, rotaviruses) by enzyme immunoassay (ELISA) and polymerase chain reaction (PCR). RESULTS AND DISCUSSION: Among the examined animals, markers of 6 out of 11 tested viral infections were identified. Detection rates of IgG antibodies to HSV-1,2 (15.9%) and CMV (15.9%) were two times as low as IgG antibodies to EBV (31.8%). Among the markers of respiratory viral infections, IgG antibodies to parainfluenza virus type 1 were found (6.8%). 14.3% of the animals had rotavirus antigen, and 94% had simian adenovirus DNA. Markers of hemorrhagic fevers Ebola, Marburg, LCM, hepatitis C, and type 3 parainfluenza were not detected. CONCLUSION: When importing monkeys from different regions of the world, an expanded screening for viral infections is needed considering the epidemiological situation both in the country of importation and in the country of destination.
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Infecciones por Citomegalovirus , Infecciones por Virus de Epstein-Barr , Fiebre Hemorrágica Ebola , Hepatitis C , Herpesvirus Humano 1 , Infecciones por Paramyxoviridae , Virosis , Virus , Chlorocebus aethiops , Humanos , Animales , Herpesvirus Humano 4 , Tanzanía , Virosis/epidemiología , Virosis/veterinaria , Citomegalovirus , ADN Viral , Inmunoglobulina GRESUMEN
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.
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NAD , Mononucleótido de Nicotinamida , Animales , Antioxidantes/farmacología , Masculino , Mitocondrias , NAD/farmacología , Mononucleótido de Nicotinamida/farmacologíaRESUMEN
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.
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Virus de la Rubéola , Rubéola (Sarampión Alemán) , Animales , Macaca mulatta , Vacuna contra la Rubéola , Rubivirus , Vacunas AtenuadasRESUMEN
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.
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Estructuras Animales/patología , Sistema Nervioso Central/patología , Sistema Nervioso Central/virología , Virus de la Rubéola/inmunología , Vacunas Atenuadas/administración & dosificación , Estructuras Animales/virología , Animales , Barrera Hematoencefálica/patología , Barrera Hematoencefálica/virología , Células Cultivadas , Niño , Humanos , Inyecciones Intraventriculares , Macaca mulatta , Conejos , Distribución Aleatoria , Rubéola (Sarampión Alemán)/líquido cefalorraquídeo , Rubéola (Sarampión Alemán)/patología , Rubéola (Sarampión Alemán)/virología , Virus de la Rubéola/fisiología , Vacunas Atenuadas/efectos adversos , Carga Viral , Activación Viral/fisiologíaRESUMEN
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.
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Vacuna contra la Rubéola/farmacología , Virus de la Rubéola/aislamiento & purificación , Rubéola (Sarampión Alemán)/sangre , Rubéola (Sarampión Alemán)/virología , Animales , Anticuerpos Antivirales/sangre , Modelos Animales de Enfermedad , Femenino , Pruebas de Inhibición de Hemaglutinación , Humanos , Recién Nacido , Macaca mulatta/virología , Embarazo , Rubéola (Sarampión Alemán)/inmunología , Rubéola (Sarampión Alemán)/prevención & control , Virus de la Rubéola/patogenicidad , Vacunación , Vacunas Atenuadas/farmacologíaRESUMEN
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.
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Agresión/fisiología , Temperatura Corporal/fisiología , Cognición/fisiología , Hipogravedad , Inmersión , Modelos Biológicos , Animales , Análisis Químico de la Sangre , Hematócrito , Macaca mulatta , Masculino , Vuelo Espacial , AguaRESUMEN
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.
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Antibióticos Antineoplásicos/toxicidad , Doxorrubicina/toxicidad , Trasplante de Células Madre Mesenquimatosas/efectos adversos , Alopecia/inducido químicamente , Animales , Peso Corporal/efectos de los fármacos , Proteína C-Reactiva/metabolismo , Humanos , Interleucina-6/metabolismo , Macaca mulatta , MasculinoRESUMEN
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.
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Doxorrubicina/efectos adversos , Células Madre Mesenquimatosas/fisiología , Animales , Linfocitos B/efectos de los fármacos , Linfocitos B/metabolismo , Citocinas/metabolismo , Interleucina-6/metabolismo , Macaca mulatta , Trasplante de Células Madre Mesenquimatosas , Células Madre/efectos de los fármacos , Células Madre/metabolismoRESUMEN
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.
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Cuerpos Extraños/cirugía , Trasplante de Células Madre Mesenquimatosas , Tereftalatos Polietilenos/farmacología , Ingeniería de Tejidos/métodos , Andamios del Tejido , Tráquea/trasplante , Animales , Biomarcadores/metabolismo , Adhesión Celular/efectos de los fármacos , Expresión Génica , Queratinas/genética , Queratinas/metabolismo , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Masculino , Receptor de Manosa , Lectinas de Unión a Manosa/genética , Lectinas de Unión a Manosa/metabolismo , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Papio hamadryas , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Tejido Subcutáneo/cirugía , Trasplante Autólogo , Vimentina/genética , Vimentina/metabolismoRESUMEN
The effect of decellularization on the biomechanical properties of macaque lungs was studied. The quality of the biological scaffold was additionally assessed by morphological methods, and the contents of extracellular matrix (ECM) fibers were determined both qualitatively and quantitatively. Histological analysis revealed no damage of structural integrity of ECM components, but the scaffold elasticity significantly decreased, which was confirmed by the changes in the hysteresis loop without a concomitant decrease in peak loads, with the mechanical strength of the samples being retained. These changes require taking additional measures to prevent a decrease in the effective lung volume.
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Matriz Extracelular/metabolismo , Pulmón/fisiología , Ingeniería de Tejidos , Animales , Fenómenos Biomecánicos , Elasticidad , Macaca mulatta , Masculino , Ingeniería de Tejidos/métodos , Andamios del TejidoRESUMEN
Culture of mesenchymal stem cells isolated from the bone marrow of primates by their characteristics met the requirements of stem cells. It was shown that transplantation of allogeneic mesenchymal stem cells (2 million cells per 1 kg body weight) immediately after ligation of the left anterior descending coronary artery between the middle and upper thirds led to neovascularization and capillarization of the ischemic myocardium.
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Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Infarto del Miocardio/terapia , Neovascularización Fisiológica/fisiología , Animales , Células de la Médula Ósea/citología , Vasos Coronarios/cirugía , Masculino , PapioRESUMEN
Cellular immunity of clinically healthy Macaca fascicularis was studied by fl ow cytometry with monoclonal antibodies. Parameters of cellular immunity in Macaca fascicularis and Macaca rhesus virtually coincided and were maximally close to those in humans.
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Inmunidad Celular/fisiología , Animales , Citometría de Flujo , Linfocitos/inmunología , Macaca fascicularisRESUMEN
Clinical status, hematological and biochemical parameters, and allergenic activity of organogermanium compounds used as adjuvants in complex with preparation from Orlov rubella virus vaccine strain and reference commercial anti-rubella vaccine based on Wistar RA 27/3 strain were studied on Macaca fascilcularis of both genders. Physiological parameters of monkeys immunized with the Russian and foreign rubella virus vaccine strains with and without adjuvants did not differ. The adjuvants were inessential for the safety of vaccines (absence of toxicity, reactogenic activity, or allergenic activity) in preclinical studies on lower primates.
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Adyuvantes Inmunológicos/química , Anticuerpos Antivirales/sangre , Compuestos Organometálicos/inmunología , Vacuna contra la Rubéola/inmunología , Virus de la Rubéola/inmunología , Rubéola (Sarampión Alemán)/prevención & control , Adyuvantes Inmunológicos/administración & dosificación , Animales , Recuento de Células Sanguíneas , Evaluación Preclínica de Medicamentos , Femenino , Germanio/química , Germanio/inmunología , Inmunización , Inmunoglobulina E/sangre , Macaca fascicularis , Masculino , Compuestos Organometálicos/administración & dosificación , Compuestos Organometálicos/química , Ratas , Rubéola (Sarampión Alemán)/sangre , Rubéola (Sarampión Alemán)/inmunología , Rubéola (Sarampión Alemán)/virología , Vacuna contra la Rubéola/administración & dosificación , Vacuna contra la Rubéola/biosíntesis , Vacunas AtenuadasRESUMEN
Cytomegalovirus (CMV) infection is a wide-spread disease throw humans and monkeys, which and associated with various diseases. The development of this infection in human organism is much like that in rhesus macaque, which makes CMV-infected monkeys adequate model for studying and elaborating prophylactic and therapeutic measures against this disease in humans. This article presents data on the efficiency of cycloferon action on animals with the M. mulatta CMV infection. Cycloferon stimulated an increase in the IFN-alpha production and promoted the period of remission in CMV-infected animals.
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Acridinas/farmacología , Infecciones por Citomegalovirus/tratamiento farmacológico , Citomegalovirus , Inductores de Interferón/farmacología , Interferón-alfa/sangre , Animales , Infecciones por Citomegalovirus/sangre , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/virología , Interferón-alfa/biosíntesis , Interferón-alfa/inmunología , Macaca mulattaRESUMEN
We describe the methods of isolation and culturing of mesenchymal stem cells from 3 monkey species Macaca mulatta, Papio hamadryas, and Macaca fascicularis. Flow cytofluorometry showed that the cells do not express CD34, CD45, and HLA-DR, but most of them (78-98%) express CD90 marker. The cardioprotective effects of cultured mesenchymal stem cells in cardiomyopathy induced by administration of antitumor anthracycline drugs (doxorubicin).
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Cardiomiopatías/prevención & control , Cardiomiopatías/terapia , Macaca , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Papio hamadryas , Animales , Antígenos CD34/metabolismo , Azacitidina , Cardiomiopatías/inducido químicamente , Técnicas de Cultivo de Célula , Diferenciación Celular , Separación Celular , Células Cultivadas , Doxorrubicina , Antígenos HLA-DR/metabolismo , Antígenos Comunes de Leucocito/metabolismo , Macaca fascicularis , Macaca mulatta , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Antígenos Thy-1/metabolismoRESUMEN
The blood picture and interferon status of rhesus macaques infected with one or two simian latent viruses do not differ from those of clinically healthy seronegative monkeys.
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Herpesviridae/patogenicidad , Interferones/sangre , Animales , Latencia del VirusRESUMEN
The cytokine status (IFN, IL, etc.) of different monkey species (M. mulatta, P. hamadryas, C. aethiops) was studied. The interferon status is determined by the following parameters: IFN content in circulating blood and production of IFN-alpha and IFN-gamma by lymphocytes after appropriate in vitro induction. The interferon status of monkeys is similar to that of humans. The capacity to produce IFN reduces with age. It was found that genes of virtually all studied cytokines are expressed in blood cells and hence, in immune system cells.
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Citocinas/sangre , Primates/sangre , Animales , Chlorocebus aethiops/sangre , Interferón-alfa/sangre , Interferón gamma/sangre , Macaca mulatta/sangre , Papio/sangreRESUMEN
The aim of the study was to define the comparative immunophenotypic characteristics ofwidely spread lymphoid cell cultures, derived from Burkett's lymphoma named as Raji and P3HR-1 in comparison with analogous monkey cultures. It has been shown that P3HR-1 culture consists of similar type cells - activated B-lymphocytes CD23 with k phenotype, which demonstrates its monoclonality. Raji culture includes cells with markers of immature B-lymphocytes CD10 and CD24, as well as elements expressing CD10 antigens. T-cell markers were found in none of the cultures. In contrast to human cells, monkey lymphoid culture expressed both B- and T-cell markers. Moreover, in one of them, obtained from a green monkey, T-cells of suppressor type (CD8) prevailed. The immunophenotypic characteristics of primate lymphoid cell cultures, revealed by the study, are of great importance for their proper application to medical and biological studies.
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Inmunofenotipificación/métodos , Linfocitos/inmunología , Animales , Antígenos CD/análisis , Linfocitos B/inmunología , Antígeno CD24/análisis , Antígenos CD8/análisis , Células Cultivadas , Citometría de Flujo , Técnica del Anticuerpo Fluorescente Indirecta , Haplorrinos , Humanos , Activación de Linfocitos , Neprilisina/análisis , Receptores de IgE/análisis , Linfocitos T/inmunología , Células Tumorales CultivadasRESUMEN
Immunophenotyping of cultured continuous simian lymphoid cultures using a panel containing monoclonal antibodies to human B- and T-cell antigens has been carried out, by employing enzyme immunoassay and flow cytofluorometry. The test cultures showed a wide variety of cells containing B- and T-cell antigens with their varying expression. The cultures were also found to comprise lymphoblasts simultaneously containing B- and T-cell markers. Simian lymphotropic viruses, such as EBV-like and STLV-1 retrovirus, detected apart or simultaneously, have been verified by polymerase chain reaction. Whether there is a possible relationship between the type of cells in the culture and the type of their replicating virus(es) is discussed in the paper.
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Herpesvirus Humano 4/aislamiento & purificación , Linfoma/inmunología , Linfoma/virología , Virus Linfotrópico T Tipo 1 de los Simios/aislamiento & purificación , Animales , Antígenos de Diferenciación de Linfocitos B/análisis , Antígenos de Diferenciación de Linfocitos T/análisis , Línea Celular Tumoral , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Genes Virales/genética , Herpesvirus Humano 4/genética , Inmunofenotipificación , Reacción en Cadena de la Polimerasa , Primates , Virus Linfotrópico T Tipo 1 de los Simios/genéticaRESUMEN
The authors of the article have first determined standards of interferon (IFN) status of healthy primates (M. mullatta) belonging to different age groups, such as serum IFN, spontaneous IFN production, IFN-a and IFN-y production. They showed that old healthy primates have low ability of IFN-a and IFN-y production and high serum IFN level. The parameters of IFN status were compared to the number of B- and T-lymphocytes and their subpopulations; qualitative evaluation of protective properties of young and old healthy primates' immunity was carried out.