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A comparative experimental analysis of intensity of nitric oxide (NO) production and the copper content in the tissues of hippocampus of male Wistar rats after modeling of hemorrhagic stroke and brain injury was conducted using EPR spectroscopy. Modeling of hemorrhagic stroke was carried out by microinjection of 500 nl of autologous blood into the brain to a depth of 5.0 mm (hippocampus) on the left side. Brain injury was performed by removing a piece of nerve tissue from 5.0 mm depth on the left side of hippocampus. It was registered a significant decrease in the NO content in hippocampus by 36 ± 17% on the 3rd day after modeling of hemorrhagic stroke together with decrease by an average of 24 ± 14% of the copper content. There were no significant changes in the NO level in hippocampus found neither on the 3rd day nor on the 7th day after brain injury modeling. There was also no change in copper content. Thus, it was experimentally demonstrated that modeling of brain injury, in contrast to hypoxia induced by hemorrhagic stroke, was not accompanied with significant changes in NO production in hippocampus of rat.

In order to simulate apoptotic processes in the central nervous system and retina, one eyeball was enucleated in each of the male Wistar rats (n = 10) aged 10–12 weeks. Simultaneously, in one of the series of experiments (n = 5), 100 000 PKH67-labeled mesenchymal stem cells (MSCs) in 100 µL of buffer solution were injected parabulbarically on the side of an intact eye. In another series of experiments on rats (n = 5), immediately after enucleation, on one side of the eye, 100 000 PKH67-labeled MSCs in 100 µL of buffer solution were injected intranasally into the upper part of the nasal cavity. Three days after enucleation, brain and retinal slices were prepared on a cryostat. In both series of experiments, the distribution of fluorescent MSCs was determined in the mesencephalic quadruplet bodies, diencephalic lateral geniculate body, and intact eye’s retina. It was inferred that intranasal perineural implantation of MSCs, due to its simplicity and efficiency, is a promising alternative method of MSC delivery into the retina of patients with signs of dystrophic and degenerative processes.

Relevance. The problem of effective prevention and treatment of traumatic brain injuries (TBI) of various etiologies has not been resolved in all countries of the world. Primary brain damage from trauma initiates secondary damage to the nervous tissue. As a result, the interaction of brain neural networks is disrupted and the control of somatic and visceral functions of the body is weakened. The article is based on our own clinical observations and comparison of results with literature data and provides a discussion of the prospects for the use of cell technologies in the prevention of fatal disorders of vital functions control in traumatic brain injuries. Objective. To evaluate the effectiveness of intranasal perineural implantation of mesenchymal stem cells (MSCs) in the complex therapy of patients with TBI. Materials and methods. The technique intranasal perineural administration of MSCs was used in complex therapy of 15 patients with severe TBI. The patients were 19÷69 years old, 13 men and two women. A cell suspension was isolated from the adipose tissue of the patient's abdominal wall and centrifuged for 10 min at 1500 rpm. The cell pellet was washed in phosphate buffered saline and DMEM. Cells were cultured in plastic culture flasks in a humidified atmosphere with 5% CO2 content. The cell mass was trypsinized according to standard technique and resuspended in physiological saline on the day of implantation. Dynamics of culture growth, pluripotency, phenotyping of MSCs were monitored. MSCs were injected under general anesthesia into the submucosa of the nasal cavity 3-4 times with an interval of 3-7 days, depending on the growth rate of MSCs, in a single dose from 12.0×106 to 35.0×106 cells. Results. The use of allogeneic and predominantly autologous MSCs of adipose tissue in the complex treatment of patients with severe TBI by intranasal perineural delivery to the area of traumatic brain injury does not cause complications and is a safe technique. 8 patients with severe TBI showed from 4 to 7 points according to the Glasgow Outcome Scale Extended, with an average of 5.4±1.1 points after 6 months. The main result is that complex therapy, including intranasal implantation of MSCs in acute and subacute periods of severe TBI, contributes to the survival of patients and restoration of neurological – including cognitive – functions control. Conclusions. The effectiveness of intranasal perineural implantation of MSCs in the complex therapy of patients with TBI has been demonstrated. The mechanisms of the beneficial effects of perineural implantation of MSCs in patients with TBI require further research.

Chemotherapy is one of the main treatment options for cancer, but it is usually accompanied with negative side effects. The classical drugs combination with synergistic adjuvants can be the solution to this problem, allowing reducing therapeutic dose. Elucidating the mechanism of adjuvant action is of key importance for selection of the optimal agent. Here we examine the system drug-adjuvant to explain observed effect in practice. We used the first line drug – cisplatin. Morpholinium and 4-methylpiperazinium 4,5-dichloro isothiazol-3-carboxylates were selected as adjuvants. The study of cisplatin – adjuvant system was carried out by quantum chemical modeling with DFT method. It turned out that adjuvants form conjugates with cisplatin that leads to relocation of frontier molecular orbitals as well as increase of conjugate’s dipole moment. It results in change of the character of interaction with DNA and increase of bioactivity of system. The data obtained are the basis for expanding the studies to include other drugs and adjuvants. Oncologists will have opportunity to use “classical” chemotherapy drugs in combination with synergists for those patients who have not been previously recommended to such treatment because of pronounced toxic side effects.

Results of analysis of nitric oxide and copper content in rat liver and hippocampus after brain ischemia modeling are provided. The studies are carried out using the electron paramagnetic resonance spectroscopy method with spin traps. It was shown that, the day after brain ischemia modeling, nitric oxide content in hippocampus decreases on average by 50% and a tendency toward its decrease was observed in liver tissues. Two days after brain ischemia modeling, nitric oxide content in the brain recovered and a significant increase by 46% against control indices was observed in the liver. On the second day of the postischemic period, the copper content, which is associated with superoxide dismutase content, increased on average by 2.5-fold in the liver. No significant changes in copper content was found in the hippocampus.

A comparative experimental analysis by EPR spectroscopy of the intensity of nitric oxide (NO) production and the content of the copper in the tissues of olfactory bulb of the brain of male Wistar rats were performed after modeling of ischemic stroke and treatment with immediate intranasal injection of mesenchymal stem cells (MSCs). Brain ischemia was simulated by ligation at the level of bifurcation of the common carotid arteries. It was found a significant reduction of NO content in the olfactory bulb of the brain of rats on the 1st and 2nd days after modeling of ischemia. The level of NO production was also reduced on the 1st and 2nd days after ischemia with MSCs’ administration as compared to intact animals. It was not found the significant difference of the NO content in rats after ischemia with MSCs’ administration relative to ischemic rats. The copper content in the olfactory bulb of the rat, which corresponds to the level of superoxide dismutase 1 and 3, tended to increase after modeling ischemia and remained for 2 days. The MSCs’ administration was accompanied by a significant increase in copper content on the 1st day after modeling of ischemia and by decrease of its content on 2nd day after ischemia. The experiments showed that MSCs’ administration did not affect the intensity of NO production on the 1st and 2nd days after the modeling of brain ischemia, but was accompanied by an increase in the antioxidant protection of the nervous tissue 1 day after ischemia.

It was shown by electron paramagnetic resonance (EPR) spectroscopy that one day after bilateral occlusion of the common carotid arteries (to simulate ischemia) in Wistar rats (group 1, n = 15) under ketamine-xylazine-acepromazine anesthesia (55.6, 5.5, 1.1 mg/kg, respectively, intraperitoneally), the content of nitric monoxide (NO) in the olfactory bulbs decreased, and recovered after two days. A similar trend was observed in Wistar rats (group 2, n = 15), which, simultaneously with ischemia modeling, were implanted intranasally with mesenchymal stem cells (MSCs). An intact group of rats (group 3, n = 15) was kept in the usual conditions of the vivarium and did not undergo surgical interventions. The content of copper in the olfactory bulbs of rats (for assessing the activity of superoxide dismutases 1 and 3) after ischemia modeling (group 1) tended to increase and maintain the increase for two days of observation. Intranasal administration of MSCs during the ischemia modeling was accompanied by a more significant increase in copper content on the first day after brain ischemia modeling, but after two days, a tendency towards restoration of the initial copper level was noted.

Non-small cell lung cancer (NSCLC) cells of a specific patient N have been analyzed to determine sensitivity to cisplatin. Intraoperative material was examined under sterile conditions in a culture box after pre-treatment of tissue pieces from the primary NSCLC tumor and from metastases to the lymph nodes of lung root. NSCLC tumor cells were cultivated in vials for four days and then in 24 well plates with and without cisplatin at different dosages (150.0 μg, 15.0 μg, 1.5 μg per well). High resistance of NSCLC tumor cells of patient N from the lymph nodes of lung root to cisplatin was established using an automatic enzyme immunoassay analyzer in 24 hours. In comparison with this fact, NSCLC tumor cells from the tissue of primary were killed by cisplatin. Obtained facts are the basis for considering the use of one of chemotherapy drugs recommended by international protocols (atezolizumab, ceritinib, osimertinib, and pembrolizumab) instead of cisplatin in patient N.

Experiments were performed on 28 sexually mature Wistar rats divided into two equal groups. Rats were fixed in stereotactic apparatus and received 2.8×105 C6 glioma cells in 20 μl of F10 medium locally into frontal region of brain under ketamine-xylazine-acepromazine anesthesia. One group of rats (n=14) was implanted with 40×104 MSCs in 40 μl of low glucose DMEM medium into submucosa of nasal cavity. Further, only rats from this group received 40×104 mesenchymal stem cells (MSCs) intranasally in the form of a spray on a weekly basis. All 14 rats from the second group died within two months. Rats with implanted MSCs started to die in two and a half months. Two rats lived up to 8.5 months. One of these rats was decapitated, brain slices stained with hematoxylin-eosin and Nissl – and no tumor cells were found. A connective tissue scar was found at the site of injection.

Medical devices are used for diagnosis and prevention [1,2], therapy [2,3], rehabilitation of patients, and depending on the purpose, require sterilization in accordance with related regulations...

Electron paramagnetic resonance (EPR) was used as a method to record nitric oxide (NO) production in the tissues of the brain, heart and liver of healthy rats, and rats after modeling of ischemic stroke. Direct measurement of the dynamics of NO production by EPR spectroscopy in our experiments showed that after the emergence of signs of ischemic stroke, 5 h after the start of ischemia, the content of NO in the hippocampus decreased two- to threefold and this decrease was maintained at 24 and 72 h. Deserving special attention is the data demonstrating that there is a greater decrease of NO production in the tissues of the heart and liver than in the brain. Consequently, the change in intensity of NO production in the modeling of ischemic events in the brain has a systemic, not a local character.

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Methyl 5-hydroxy-4-oxo-4 H-pyran-2-carboxylate was synthesized by esterification of methanol with comenic acid under acidic catalysis. The obtained ester was alkylated with 3-(chloromethyl)-5-phenylisoxazole and 4,5-dichloro-3-(chloromethyl)isothiazole to afford corresponding conjugates containing isoxazole and isothiazole moieties which then were transformed into water-soluble Li-salts. During the bioassays of synthesized isoxazole and isothiazole derivatives of comenic acid in mixtures with first-line antitumor drug Temobel (Temozolomid) used in brain tumors chemotherapy, a synergetic effect was observed.