Materials and methods: Sixty patients aged 18 to 85 years who were ill with acute bacterial rhinosinusitis were examined. the average age of which was 36 ± 2 years. The research was carried out on the basis of the ENT Department of the City Clinical Emergency Hospital and the Municipal Medical Diagnostic Center of the city of Vinnitsya. All patients were divided into two groups. 30 patients with acute bacterial rhinosinusitis included in the baseline therapy group 1 (group of comparison), which included: systemic antibiotic therapy (selective drugs - cephalosporins II-III generation), anti-inflammatory (topical corticosteroids, non-steroidal anti-inflammatory drugs), irrigation therapy, local decongestants and drugs with mucolytic, secretomotor and secretory effect. Group 2 (main group) consisted of 30 patients with a diagnosis of acute bacterial rhinosinusitis, the bacteriophage (sta- phylococcal or piophage) was added to the baseline therapy. Patients undergoing bacteriophage (staphylococcus or piophage) were injected as drops in the nose, 3-4 drops in each nasal passage three times a day for 7-10 days or after catheterization of the nasal sinus was washed with sterile 0.9% sodium chloride solution, after which was injected through a catheter of 3-5 ml of a bacteriophage into the sinus cavity once a day for 7-10 days. The level of secretory immunoglobulin A (sIgA) was determined using an enzyme-linked immunosorbent assay in nasal secret. The statistical processing of the results was carried out using the statistical computer program Statistica for Windows, v.12 using parametric and nonparametric methods for evaluating the results. Results: Prior to the median treatment, the concentration of sIgA in nasal washes in group 1 was 0.92 mg / L, the interquartile interval of P25-P75 was in the range of 0.74; 1.15 mg / l, and in group 2 - median 0.94 mg / L, P25-P75 - 0.75-1.10 mg / l (p> 0.05). It was found that standard therapy was accompanied by a probable increase The concentration of sIgA in the nasal secret in 7-10 days from the beginning of treatment was 2.1 times (p <0.001), compared to the indicator before treatment, while the rates before treatment and after 12 weeks were not statistically significantly different (p = 0.051). Against the background of combination therapy, which included a bacteriophage, there was a more pronounced increase in the level of sIgA - after 7-10 days in 3 times (p <0,001), in 12 weeks in 2,5 times (p <0,001), compared with the indicator before treatment. A comparison of the mean values of sIgA concentration in the nasal secret between the study groups revealed that in 7-10 days and 12 weeks, the concentration of sIgA in patients receiving a bacteriophage was 21.3% and 43.9% higher, respectively, than in patients in the base group therapy (p = 0.048 and p <0.001). It was established that modified therapy with the use of bacteriophage contributes to the prevention of chronic acute bacterial rhinosinusitis, which was 36.6% less frequent than in the basic therapy group without bacteriophage (CS: 0.18; 95% CI: [0.05-0, 58]).

Experimental animal models of traumatic brain injury (TBI) were created to study themorpho-functional features of the disease and to fill the therapeutic window betweenpreclinical trials and the introduction of drugs into the clinical medical practice.The aim of the work – to study the morphological changes in the brain structures ofrats under conditions of model TBI.Material and methods. The experiments were performed on white male rats weighing160-190 g. The experimental model of TBI in rats under conditions of propofolanesthesia (60 mg/kg) was caused by the action of a stream of carbon dioxide underpressure, which was created using a gas cylinder air gun. For histological examination,the brain was fixed with 10% neutral formalin, dehydrated in alcohols in increasingconcentrations, and immersed in paraffin. Sections were stained with hematoxylinand eosin, toluidine blue. The microscopy of histological specimens was performedusing a light microscope OLIMPUS BX 41 using magnifications of 40, 100, 200 and400 times. The morphological research studied the structural changes of neurons inthe sensorimotor zone of the cerebral cortex, the hippocampal structures of the CA1zone and the condition of blood vessels in two groups of animals: Group II - rats withsimulated trauma.Results. In animals with model TBI, there was a predominance of the number ofdegenerating pyramidal neurons over those preserved in the sensorimotor zone ofthe cortex of the large hemispheres and in the CA1 zone of the hippocampus. In thesensorimotor zone of the cortex of the large hemispheres, the death of neurons wasmanifested by morphological signs of karyopyknosis, karyorexis and cytopicnosiswith the phenomena of cytolysis. Only single preserved neurons were visualized in thepyramidal layer; most cells are represented by pyknotic cells; 3) in the hippocampusof animals with TBI, the cytolytic type of nerve cell death was mainly observed. Themorphological signs of cytolysis indicate deep damage to all neurocyte structures.Conclusions. The morphological basis of the remodeling of brain structures in traumaticbrain injury is: reduction in the number of normochromic neurons in experimentalanimals, formation of a significant number of hypochromic neurons, formation ofhyperchromic neurons with pronounced signs of tigrolysis, hemodynamic disorderswith pericellular and perivascular edema.

Currently: the problem of choosing an effective drug approach for cerebroprotection, in case of traumatic brain injury (TBI), remains to be poorly understood. Clinical studies of cerebroprotectors - antagonists of NMDA-receptors indicate the feasibility of their use in practice. In our opinion, for further research, it would be correct to choose a compound that has neuroprotective properties and synthesized under the guidance of Academician M.O. Lozynsky at the Institute of Organic Chemistry of the National Academy of Sciences of Ukraine, a derivative of 1-adamantylethyloxy-3-morpholoin-2-propanol hydroxide (Ademol). Materials and Methods: The pharmacological action of Ademol was investigated on the example of a simulated TBI at a dose of 2 mg/kg intravenously every 12 hours for 8 days. The control group and pseudooperated animals received NaCl 0,9% at a dose of 2 mg/kg intravenously (i/v), the comparison group received Amantadine sulfate 5 mg/kg. To determine the efficiency and activity of these molecules the activity of the protein S 100 was used. Results: The dynamics of S 100 protein levels in groups of rats with Ademol and Amantadine sulfate with traumatic brain injury on the 8th day of observation indicates that on the background of the above therapy, the content of the studied marker decreased by an average of 50,8 and 39.9%. Treatment of rats with severe traumatic brain injury with Ademol at a dose of 2 mg/kg (i/v), was probably better than treatment of rats in the control group with saline and amantadine sulfate and better helped to reduce the growth of protein S 100 level, while Ademol exceeded the reference drug at 18,2% (p <0.05).

The choice of drugs in traumatic injuries of the head is one of the most complex problems in the complex treatment of such patients. The aim was to estimate the cerebroprotective action of Ademol on the indicator of lethality of rats against the background of an experimental traumatic brain injury (TBI). The experimental model of the TBI of severe severity was caused by the action of the flow of carbon dioxide under pressure that was created using a gas cylinder pneumatic gun. The therapeutic effect of Ademol on the model TBI was evaluated at doses of 1, 2 and 4 mg/kg intravenously. Pseudo-operative animals and control group received a 0.9% NaCl solution at a dose of 2 ml/kg. The results were processed using the statistical program StatPlus 2009. Used Fisher angular transformation when accounting for results in an alternative form. In the course of the experiment, it was found that in the control group at the end of the experiment, 8 days after the TBI model, death of 90% of the rats was recorded p<0.05. Ademol showed the highest protective effect on the brain at a dose of 2 mg/kg where the death of rats was 30% on the 8th day of the experiment. The obtained data indicate that among the studied doses 1; 2 and 4 mg/kg is conventionally effective at just 2 mg/kg, in which Ademol exhibited the highest neuroprotective activity (p<0.05).

Objective. To evaluate the effectiveness and safety of ademol for oxidative stress in the brain of rats with traumatic brain injury (TBI). Materials and methods. In 260 male-rats weighing 160-180 g, the preclinical efficacy of ademol was studied against the background of the actual developed TBI model. Several groups of animals were formed: pseudo-operated (TBI + 0.9 % NaCl intravenously), control pathology (TBI + 0.9 % NaCl intravenously), TBI + ademol 2 mg/kg intravenously, comparison drug (TBI + amantadine sulfate). The experimental model was induced by the action of a stream of carbon dioxide under pressure using a gas-balloon air pistol “Baikal MR-654K”, evaluated only severe trauma (the air pistol hole is close to the center of the trepanation hole in rats). Ademol (Ademol-Darnytsia, Ukraine) was administered in several doses to determine the conditionally effective dose, and the reference drug amantadine sulfate (PC-Merz, Switzerland) was administered slowly with infusomate for 2 h after 12 h for 8 days, 60 min after injury. Biochemical processes in traumatically damaged brain (in homogenates and postnuclear supernatant) were studied on the 8th day, oxidative stress parameters were evaluated by the content of malonic dialdehyde (MDA) by reaction with thiobarbituric acid, carbonyl groups of proteins (CGP) – by reaction with dinitrophenylhydrazine, activity of antioxidant enzymes – by reaction with superoxide dismutase (SOD), glutathione peroxidase (GPO) and catalase. Statistical processing was performed according to StatPlus programs, by parametric and nonparametric criteria, the differences were considered significant at p<0.05. Results and discussion. Hyperactivation of free radical oxidation of biomembrane lipids is registered in the brain structures of injured rats. In the group of pseudooperated animals, the median content of the secondary metabolite of lipoperoxidation MDA in the brain was 13.2 (95 % confidence interval (CI) 12.8-14.2) μmol/g of dry tissue. In the control pathology group, the MDA index is 2.28 times (p<0.05) higher than in pseudooperated animals, the median is 30.8 (95 % CI 28.6-33.3) μmol/g of dry tissue. The use of the studied drugs reduces the activation of lipid peroxidation processes in brain tissues. Ademol had the most active influence. In the group of animals treated with this drug, the content of MDA in the brain was lower by 58.3 % (p<0.05) than in the control pathology group, the median was 14.6 (95 % CI 12.6-15.5) μmol/g of dry tissue. Amantadine sulfate was inferior to ademol: the content of MDA in the brain was lower by 48.4 % (p<0.05), the median was 16.1 (95 % CI 14.9-16.7) μmol/g of dry tissue. The development of TBI was associated with the activation of oxidative modification of CGP. In pseudooperated animals, the median content of CGP in the brain was 4.73 (95 % CI 4.29-5.01) μmol/g of dry tissue, the level of CGP is 1.77 times higher (p<0.05) in control pathology group. The active preventive drug was ademol: the content of CGP in the brain decreased by 40.1 % (p<0,05) than in animals of the control pathology group, the median was 4.90 (95 % CI 4.62-5.54) μmol/g of dry cloth. Amantadine was slightly inferior to ademol in this effect: the content of CGP in the brain was lower by 39.1 % (p<0.05), against control pathology, the median was 4.99 (95 % CI 4.65-5.59) μmol/g of dry cloth. Oxidative stress occurred against the background of decreasing the rate of inactivation of the superoxide anion radical: the median activity with the participation of SOD in the brains of pseudooperated animals was 2.68 (95 % CI 2.23-3.05) um. od/mg protein; there was also a decrease in the activity of SOD in the brain by 51.7 % (p<0.05) in the control pathology group, the median activity of the enzyme was 1.31 (95 % CI 0.97-1.57) um. od/mg protein. Pharmacotherapy prevented a drop in the reaction rate of SOD: on the background of ademol, it was 105 % higher than the control pathology group, the median of its activity was 2.69 (95 % CI 2.17-3.16) um. od/mg protein. Amantadine sulfate was slightly inferior to ademol: the activity of SOD in the brain was less by 101 %, the median of its activity was 2.53 (95 % CI 2.09-3.11) um. od/mg of protein. TBI is also accompanied by inhibition of hydrogen peroxide inactivation by the enzymes GPO and catalase: a decrease in brain tissues activity of GPO by 55.3 % and catalase by 53.0 %. When corrected with ademol, the activity of GPO in brain was higher by 70.9 %, as well as the activity of catalase – by 89.5 % (ranged from 6.39 to 7.45 μcatal/mg protein), against levels in the control pathology group. Amantadine sulfate contributed to an increase in the activity of GPO by 44.5 % (from 55.5 to 61.2 μmol/min per 1 mg of protein), an increase in catalase – by 79.0 % (from 6.21 to 6.75 μcatal/mg of protein) than indicators in the control pathology group. Conclusions. The use of ademol in rats with TBI contributes to the probable restraint of oxidative stress: reducing the prooxidative effect of trauma and activation of antioxidant enzymes.