The aim of the investigation is to assess the quantity of brain-derived neurotrophic factor (BDNf), glial cell line-derived neurotrophic factor (GDNf) and neuron specific enolase (NSE) in plasma of newborns with perinatal hypoxic damage of CNS.Materials and Methods. Neurotrophic factors and NSE enzyme concentrations in plasma of newborns (gestation age 31-42 weeks) was studied. The main groups consisted of newborns with the symptoms of perinatal CNS damage (group 1 -with convulsive states, group 2 -with the signs of severe perinatal CNS damage), diagnosed according to physical examination, evaluation of the neurological status dynamics and neurosonographic studies. Control group included healthy neonates. Concentration of BDNf, GDNf (R&D Systems, uSA) and NSE enzyme (Vector Best, Russia) was determined by ElISA kit during hospitalization and on day 10-14 after the rehabilitation therapy.Results. Carried out experiments revealed the significant increase of NSE concentration in plasma of newborns with convulsive states. The higher levels of this enzyme were detected in infants with severe perinatal CNS damage. Moreover, BDNf concentration significantly increases in plasma of patients with the symptoms of severe CNS damage in the period following rehabilitation therapy. These experiments also demonstrate the inverse correlation between BDNf and GDNf levels. It was shown the important prognostic value of BDNf and NSE determination in plasma of newborns with CNS injury.Conclusion. The most diagnostic value for assessing the severity of brain damage in early neonatal period is associated with measurements of NSE and BDNf concentrations in plasma, which allows to use these markers immediately after birth and before the development of neurological symptoms.

The aim of the investigation was to study in experiment total toxicity and immunological safety of a novel domestic therapeutic vaccine against recurrent respiratory papillomatosis and anogenital condylomatosis, the vaccine injected intramuscularly.Materials and Methods. we studied acute toxicity of the vaccine by the following parameters: clinical presentation of intoxication, median lethal dose size, the change of body weight of the surviving animals; chronic toxicity -by dynamics of general condition of the animals, body weight, hematological and biochemical indices of peripheral blood, functional status of central nervous system, cardiovascular system, kidneys, as well as pathomorphological changes of viscera.Allergenicity was studied by systemic and active cutaneous anaphylactic tests. we assessed immunotoxicity by direct a hemagglutination assay and a delayed-type hypersensitivity test, as well as by neutrophilic activity using luminal-dependent chemiluminescence. Proliferative activity of В-and Т-lymphocytes to lipopolysaccharides and concanavalin А (ConА) was estimated in a direct immunofluorescence test using immunocytochemical assay with anti-Ki-67 monoclonal antibodies.Results. Mean lethal doses (lD 50 ) were not reached in white outbread rats injected intramuscularly by the tested vaccine at a maximum possible single dose (25 ml/kg). Multi-dose administration to white outbread rats and chinchilla rabbits at doses of 0.043; 0.43; 0.86 ml/kg and 0.023; 0.23; 0.4 ml/kg respectively, did not cause significant damage of functional status of basal organs and systems of experimental animals.The findings of systemic anaphylaxis and active cutaneous anaphylactic response to the vaccine in albino guinea pigs at the doses of 0.033 and 0.33 ml/kg intramuscularly indicated the vaccine to exhibit no allergenic properties.Intramuscular vaccine injected to first filial hybrid mice (СВА×С57Bl/6)f 1 at the doses of 0.084; 2.5 and 25 ml/kg showed neither significant increase or decrease of inflammatory response intensity relating to reference values. The vaccine at the doses of 0.084 and 2.5 ml/kg did not cause any changes of vaccination titer (IgG), phagocytic activity, spontaneous or induced blastic transformation of lymphocytes compared to the control group. The vaccine administered at the dose of 25 ml/kg significantly reduced the antibody formation level relating to the controls, as well as produced a suppressive effect on spontaneous and induced phagocytic activity resulting in the significant reduction of ConА-induced proliferative activity of Т-lymphocytes by the number of Ki-67 positive cells compared to the control group.Conclusion. The animal study of different types of general toxicity of the vaccine against recurrent respiratory papillomatosis and anogenital condylomatosis, the vaccine injected intramuscularly, showed the vaccine to be low toxic and immunologically safe in the dose range from 0.033 to 2.5 ml/kg.

The aim of the investigation was to study the effect of glial cell line-derived neurotrophic factor (GDNF) on animals' resistance to cerebral-ischemia-induced damage.Materials and Methods. In vivo studies were carried out on C3H male mice weighing 18-40 g. Ischemia modeling was performed by bilateral irreversible occlusion of both carotid arteries. A neurological status as well as an orientative-exploratory behavior of experimental animals and their learning capability in the post-ischemic period were analyzed by using "Open field" and "Passive avoidance" tests. In addition, high-resolution respirometer Oxygraph-2k (Oroboros, Austria) was applied to study an oxygen uptake rate of brain mitochondria in ischemic conditions.Results. GDNF application in bilateral occlusion of carotid arteries was found to contribute to the neurological status recovery. Moreover, it normalizes oxygen uptake rate of mitochondria in the post-ischemic period.Conclusion. GDNF has a marked neuroprotective and antihypoxic effect under ischemia modeling in vivo.Key words: glial cell line-derived neurotrophic factor; GDNF; neuroprotection; cerebral ischemia. During several years the number of ischemic brain injury incidents has been dramatically increased, that determines topical and socially important issue for modern neurology and neuroscience. The consequences of cerebral ischemia are directly related to memory and neurological status deteriorations as well as to impairment of learning capabilities and cognitive functions. Therefore, the development of modern techniques to effectively protect the nervous system from those damaging effects is urgently needed. A promising approach to improve adaptive capabilities of nervous system supposed to the activation of endogenous systems promoting the survival of nervous cells under stress factors and maintenance their functional activity. The use of neurotrophic factors such as glial cell linederived neurotrophic factor (GDNF) is of special interest. These proteins are attracted of scientists' attention because of their possibilities to regulate neurogenesis and the functioning of the nervous cells not only in early ontogenesis, but also in an adult brain. Moreover, they are involved in the processes of synapses formation, and have a pronounced effect on growth Biomedical investigations

This research was aimed at investigating the features of free radical activity and the parameters of glutathione metabolism in tumor tissues and the peritumoral zone at different degrees of glial tumor anaplasia. We analyzed postoperative material from 20 patients with gliomas of different degrees of anaplasia. The greatest differences compared to adjacent noncancerous tissues were found in the tumor tissue: an increased amount of glutathione and glutathione-related enzymes at Grades I and II, and a decrease of these parameters at Grades III and IV. For the peritumoral zone of Grades I and II, the indices changed in different directions, while for Grades III and IV, they occurred synchronously with the tumor tissue changes. For Low Grade and High Grade gliomas, opposite trends were revealed regarding changes in the level of glutathione and the enzymes involved in its metabolism and in the free radical activity in the peritumoral zone. The content of glutathione and the enzymes involved in its metabolism decreased with the increasing degree of glioma anaplasia. In contrast, free radical activity increased. The glutathione system is an active participant in the antioxidant defense of the body and can be used to characterize the cell condition of gliomas at different stages of tumor development.

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