Technology Transfer Innovative Solutions in Medicine

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Article
Aim: to develop a modern method to determine related impurities in bromide 1-(β-phenylethyl)-4-amino-1,2,4-triazole tablets by high performance liquid chromatography (HPLC). Methods: The development of a method to determine related impurities in bromide 1-(β-phenylethyl)-4-amino-1,2,4-triazole tablets involved an already developed method for the determination of 4-amino-1,2,4-triazole impurities in tablets by HPLC. The test solution and the comparison solution were prepared and chromatographed alternately according to the developed methods. At least three chromatograms were obtained for each solution for the purpose of the reliability of the study results. Results: Scientists of the Scientific-Production Association "Farmatron" jointly with the staff of the Pharmaceutical Chemistry Department of Zaporizhzhia State Medical University under the leadership of Professor Mazur I. A. obtained a new original compound – bromide 1-(β-phenylethyl)-4-amino-1,2,4-triazole (conditional name "Hypertril"), which exhibits antihypertensive, anti-ischemic and antioxidant properties. It is known that the quality of medicines largely depends on the degree of their purity. Therefore, in accordance with the regulatory documentation and quality control methods of medicines, it is mandatory to carry out tests for impurities. According to the results, the content of impurities of 4-amino-1,2,4-triazole in the tested tablets of bromide 1-(β-phenylethyl)-4-amino-1,2,4-triazole is in the range from 0.049 % to 0.195 % which meets the requirements of regulatory documentation. No peaks of unidentified impurities were detected on the chromatograms of the test solution. Conclusion: Therefore, a modern method to determine the related impurity of 4-amino-1,2,4-triazole in tablets of bromide 1-(β-phenylethyl)-4-amino-1,2,4-triazole has been developed. The methodology is reproducible, accurate and meets the requirements of regulatory documentation.
 
Article
Alzheimer's disease is a neurodegenerative disease characterized by pathological features of neurofibrillary tangles and β-amyloid plaques in the cerebral cortex. In Alzheimer's disease, tau protein undergoes excess phosphorylation, due to which its threads begin to merge and form neurofibrillary tangles within nerve cells. It has been shown that glycogen synthase kinase-3β is a key factor in the phosphorylation of tau protein, its increased activity leading to pathologies of neurofibrillary tangles and, consequently, to neurodegenerative changes in the brain. In this connection, the search for effective inhibitors of GSK-3β is a very important and urgent task, for their further use in the treatment of Alzheimer's disease.Aim of research.The aim of this study is to search new inhibitors of GSK-3β among N-amidoalkylated derivatives of 2-amino-1,3,4-oxadiazole by molecular docking methods.Materials and methods. We have carried out geometry optimization of analyzed structures within PM3 semi-empirical method, and GSK-3β molecular docking using software ArgusLab 4.0.1. The three-dimensional crystal structure of co-crystallizer GSK-3β and inhibitor has been loaded from the data bank of protein molecules (PDB ID: 3F7Z).Results. In this study it has been shown that the structures being studied mainly form stronger complexes with the enzyme compared to the known inhibitor. Based on the results of molecular docking, the compounds leaders N-(((5-(2-bromophenyl)-1,3,4-oxadiazol-2-yl)amino)methyl)benzamide and 2,4-dichloro-N-(2,2,2-trichloro-1-((5-(p-tolyl)-1,3,4-oxadiazol-2-yl)amino)ethyl)benzamide have been chosen. The structures of the compounds leaders have been tested for compliance with Lipinski criteria.Conclusions. Proposed compounds leaders can be recommended for further studies in the treatment of Alzheimer's disease. Despite the good results obtained in silico analysis, it is mandatory to perform biological tests in vitro and in vivo.
 
Correlation between general and local factors and delayed union of MF
Article
Delayed union of bone tissue in patients with mandibular fractures is observed in 2.4 – 26 % of clinical cases. Solution of this problem yet very much far from the final solutio and there is an urgent requirement in the comprehensive analysis of role of general and local factors of origin of delayed union MF.Methods. Modern clinical, laboratory and microbiological research methods were used in the work. Densitometry conducted on computed tomograph Planmeca Promax 3d (Finland) (85 kV 5–7 mA). The basal values of immunoglobulins of the main classes and interleukins IL-1β, FNT-α, IL-4, MDA, SOD and catalase activity, POL, β-Cross Laps and osteocalcin in peripheral blood were determined in 74 patients with delayed consolidation of the mandibular fractures. Correlation analysis of local and general (concomitant somatic pathology) factors, and clinic-laboratorial parameters in patients with delayed consolidation of the mandibular fractures is conducted.Results. There is a high correlation between β-Cross Laps (negative) and osteocalcin (positive) and bone mineral density. The mean inverse correlation relationship was established between the MDA and catalase activity and BMD (r=–0.57), and the high correlation of these indices with markers of bone remodeling (positive to β-Cross Laps (r=0.80 and r=0.87, respectively) and negative to osteocalcin (r=–0.80 and r=–0.84, respectively). High direct correlation between FNT-α indices and POL, MDA, and catalase indices, as well as very strong with β-Cross Laps (positive) and osteocalcin (negative), and also with high-correlation ligaments of sIgA and IL-1β.Discussion. Convincing clinical and laboratory data were obtained that the combined effect of local and general (concomitant somatic pathology) factors on the basis of the activation of inflammation processes, which increase the indirect influence on immune factors, processes of radical oxidation and bone metabolism, is resulted to delayed union. It was also found that clinical signs of the development of consolidation complications in patients with MF include increased signs of inflammation (oedema, exudation, etc.) up to the 3rd day and preservation of even moderate signs of inflammation (inflation, local hyperemia, and others) after the 7th day, BMD below 600 HU. Among the local factors that increase the infectious risk and inflammatory reaction, the following clinical situations should be distinguished: comminuted fracture; the presence of a tooth in the line of fractures; partially edentulous with loss of antagonist teeth (according to Eichner); complete adentia with mandible atrophy.
 
quantity and area of hyperplastic γ-glutamyl transpeptidase nodules in the rat liver
Article
Some studies have proven possible potentiating toxic effect of combined pesticides. The potentiating effect may be related to the impact of a certain substance on enzymatic activity of another one. Due to combined preparations popularity, the importance of evaluating probability of summation and synergetic or antagonizing action of the one-purpose substances becomes particularly important.Aim of the research is to study peculiarities of histomorphological liver changes associated with combined effect of active substances with one-purpose action.Methods. The authors have used toxicological, histochemical and statistical study methods. 45 rats have been used for the study. The liver specimens for histochemical analysis were selected immediately after dissection of the rats, from which the 5 micrometer sections were prepared, using freezing microtome. After leaving the sections in cold acetone, the histochemical reaction on determining the γ-glutamyl transpeptidase, a transformed hepatocyte marker, which forms nodules while proliferates, was conducted.Results. The authors have established that the above-mentioned characteristics in animals which were administered the drug (benthiavalicarb-isopropyl+folpet) do not differ from negative control group. General specific area of nodules per сm2 and specific quantity of nodules per сm2 haven’t reliably changed, the control group exceeding these data by 18 % and 12 %, respectively.Discussion. The study of the benthiavalicarb-isopropyl and folpet mixture effect on animals has not revealed liver tissue proliferation of the carcinogen-transformed cells and appearance of hyperplastic nodes, which express the γ-glutamyl transpeptidase, a histochemical marker of pre-tumor changes.So, the fungicide (benthiavalicarb-isopropyl+folpet) has not induced multiplication or size increase of glutamyl transpeptidase nodules, which evidences about loss of the modifying effect of folpet on the benthiavalicarb-isopropyl carcinogenicity in this preparation formula.The obtained results may be used when deciding on administration of combined fungicides with active substances of one-purpose action.
 
Article
In the overall structure of occupational diseases the large proportion is acute pesticide poisoning (mainly group cases). In recent decades in the structure of agricultural workers’ occupational diseases chemicals poisoning was 14,7-43,5 %.That is why the purpose of the work was to predict the possibility of acute toxic effects on agricultural workers when working with combined formulations.Methods. In order to assess the effects of the aforementioned substances on the workers’ organism the coefficient of possible inhalation poisoning (CIPP), the coefficient of pesticide effect selectivity at inhalation effect (CPESinhal.) and at dermal application (CPESderm.) were used.Results. According to the "Hygienic Classification of Pesticides by Degree of Danger", all studied compounds, as well as combined preparations based on them, are pertained to 4th hazard according to this criterion (CIPP <0,5). Calculated CPESinhal. (103,4-4701,2) and CPESderm. (237,4-12345,7) values for all investigated a.i. were more than 100, which indicates a rather high selectivity of their action.Discussion. Thus, the obtained results allow to predict the possible negative influence of pesticides of different classes on the initial stages of registration tests of pesticide formulations containing studied active substancesConclusion. The importance of observance of the established regulations for formulations application (norms and rates of application) and the obligatory use of the recommended individual protecting means for the respiratory and skin protection by agricultural workers during the application of studied pesticides are shown
 
Article
Aim: to evaluate the effectiveness of preventing the formation of microbial biofilms on the surfaces of implants made of titanium alloys VT5-1, VT6 with a transformed surface into anatase.Materials and methods. The study was carried out in the bacteriological laboratory of the Severodonetsk multidisciplinary city hospital from January 2019 to September 2019. The ability to prevent the formation of microbial biofilms of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa was evaluated. The static cell adhesion method and the disco diffuse method were used. The surface of the plates was examined on a XS 6220 UCMJS05100KPA microscope. The intensity of the formation of microbial biofilms on the plates was evaluated visually by the four-cross system.Results. On all coatings with anatase, in comparison with unmodified plates, the intensity of initial adhesion and the number of bacteria fixed on the surface of the colonies markedly decreased. On surfaces with silica crystals, biofilm formation was minimal. The altered surface of titanium alloys VT5-1 and VT6 anatase and anatase with silicon dioxide crystals does not inhibit microflora growth.Conclusions. The transformed surface of titanium implants into anatase and anatase with silicon dioxide crystals prevents the fixation of biofilms of microbial associations.
 
Article
The research estimates the state of liver detoxifying function and analyzes the changes in the levels of leptin, adiponectin and interleukin-6 in patients with arterial hypertension in combination with obesity and non-alcoholic fatty liver disease. Aim. The aim of the study is to evaluate levels of proto-hormones adipose tissue, interleukin-6 and indicators of detoxifying function of the liver in patients with hypertension and obesity combined with non-alcoholic fatty liver disease (NAFLD). Materials and methods. The study involved patients with arterial hypertension combined with obesity and NAFLD. All patients underwent anthropometric, general clinical, laboratory (blood lipid profile) and instrumental diagnostics (electrocardiography, echocardiography, ultrasonography, 13C-metacetin breath test, ELISA (adiponectin, leptin, IL-6). The patients’ height and weight were measured, the body mass index was calculated according to standard formulas. Results. Patients with arterial hypertension combined with obesity and NAFLD at the stage of steatohepatitis showed an increase in the levels of leptin and IL-6 and a decrease in the level of adiponectin. This group also revealed a moderate decrease in liver detoxifying function, as indicated by the results of 13C- MBT due to a 46.7 % decrease in the metabolic rate and a decrease in cumulative doses of CUM40 by 40 % and CUM120 by 46.8 %, respectively. Conclusions. The elevated levels of leptin and IL-6 and lowered adiponectin levels can be used to determine the degree of activity of non-alcoholic steatohepatitis and predict the course of NAFLD in combination with hypertension and obesity. An increased level of leptin and IL-6 and a low level of adiponectin in patients with such a comorbid pathology lead to an increase in the left ventricular myocardial mass index and aggravate the course of arterial hypertension.
 
Levels of collagen type IV and fibronectin in adolescents with obesity, depending on the presence of IR (M±σ)
The levels of N-terminal propeptides of type I collagen in children with obesity (M±σ)
Article
Non-alcoholic fatty liver disease occurs in most obese people, the main pathway of which is the process of fibrogenesis. This disorder is currently classified into two types: hepatic steatosis and nonalcoholic steatohepatitis. Hepatic steatosis is a reversible condition in which large vacuoles of triglyceride fat accumulate in the liver cells, causing nonspecific inflammation. Most people with this condition experience few, if any, symptoms, and it does not usually lead to scarring or serious liver damage. The majority of patients with nonalcoholic fatty liver disease have this type. Nonalcoholic steatohepatitis is the more severe, progressive form that involves not only fat accumulation (steatosis) in the liver but also inflammation. Steatohepatitis can lead to fibrosis and eventually to cirrhosis, which is severe scarring that can lead to liver failure.The real frequency of the prevalence of the disease is difficult to establish, due to the insufficient use of non-invasive screening diagnostic methods, through which it is possible to detect the initial forms of the disease.The aim: to study the diagnostic significance of the serum biomarkers of liver fibrogenesis in adolescents with obesity.Methods. On the base of the Department of Endocrinology, SI “Institute of children and adolescence health care of NAMS” (Kharkov) 226 patients with obesity aged 8–18 years were examined. Investigation of liver fibrosis consisted of measurement in blood the levels of fibronectin, collagen type IV, N-terminal propeptides and C-terminal telopeptides of type I collagen by IFA method.Results. The study of liver fibrogenesis revealed a significant increase in levels of type IV collagen and fibronectin in children with obesity (p<0.05). As diagnostic criteria for two physiologically diverse processes – fibrogenesis and fibrolysis, the levels of N-terminal propeptides and C-terminal telopeptides of type I collagen, respectively, were determined. The serum level of N-terminal propeptides of type I collagen significantly exceeds the normal values in all children with obesity, in contrast to the children of the control group (p<0.05).Conclusion. It has been established that a biochemical method for determining the level of type IV collagen, fibronectin, N-terminal propeptides and C-terminal telopeptides of type I collagen has a high sensitivity for the diagnosis of liver fibrogenesis.
 
Article
Metabolic changes in the body of dogs with atopic dermatitis and the causes of its occurrence still remain poorly understood. This study confirms the need for biochemical blood tests for the differential diagnosis of skin diseases in animals. The aim of the research. To identify metabolic changes in dogs with atopic dermatitis. Methods. Serum samples from five ill animals and five intact animals were tested. The diagnosis of the nosological form of skin lesions was established based on the results of anamnesis and clinical manifestations of the disease. Additionally, biochemical studies of the serum of sick animals were performed. Blood of dogs (n=5) was taken from the anterior subcutaneous vein of the forearm or the lateral subcutaneous vein of the tibia into blood tubes. Results. In the study of mineral metabolism, it was found that the concentration of inorganic phosphorus in the serum of sick animals is reduced by only 0.01 mmol/l, but the concentration of total calcium by 10.0 %. The concentration of cholesterol increases 1.3 times and exceeds the reference values by 0.16 mmol/l. In the blood of sick animals, the activity of alanine aminotransferase is significantly reduced by 21.0 % and aspartate aminotransferase – by 20.0 % compared to intact animals. The enzyme gamma-glutamyltransferase probably increases by 1.51 times (P
 
Article
The aim. The research was provided to obtain immunohistochemical changes in scalp biopsies of female patients with androgenetic alopecia (AGA) I-II stages according to the Ludwig scale and to detect possible changes after usage of platelet-rich plasma (PRP) injections in combination with topical minoxidil 2 % lotion. Materials and methods. Skin biopsies of 30 patients with AGA were examined by immunohistochemistry before and after treatment, which lasted for 3 months and included 3 PRP sessions (once per month) and topical application of minoxidil 2 % lotion twice daily. Results. It was found that AGA is accompanied by inflammatory perifollicular infiltration by T-lymphocytes CD3 +, CD4 + and CD8 +, macrophages (CD68 +); imbalance of growth polypeptides VEGF, TGF-β1, EGFR; accumulation of oxidative stress enzymes eNOS and iNOS; accumulation of pathological fraction of Collagen IV. The use of platelet-rich plasma in combination with topical 2 % minoxidil as AGA therapy leads to the normalization of immunohistochemical parameters of the skin, which indicates the possibility of its use for long-term therapeutic effect. Conclusions. This study supplemented the understanding of the pathogenesis of AGA and serves as the basis for improving treatment regimens for this pathology. But more research is required to further study the pathomorphology of androgenetic alopecia and to standardize the technique of using platelet-rich plasma in patients with this disease.
 
Dynamics of blood pressure and pulse
Article
The aim of the article was to study of the influence of the apparatus “MOXI” as an alternative method for the correction of arterial hypertension and improving the quality of life of patients using acupuncture reflexotherapy.Materials and methods. The study was conducted in 36 patients with arterial hypertension of 1 stage, low risk, with the experience of the disease from 1 to 2.5 years, without taking antihypertensive therapy. The average age of patients was 41.3±2.6 years. The state of the psycho-emotional sphere was assessed by the SAN test. The determination of the general non-specific adaptation reaction according to Garkavi-Kvakina-Ukolova was carried out. Control of blood pressure and pulse, was carried out in the center, and by the diaries of self-control. We calculated the arithmetic mean of blood pressure for the day and week. Baseline blood pressure was 152/106 mmHg when measured at the center and 149/102 mmHg at home.Results. The obtained results indicate that the adaptogenic set of acupuncture points allows you to simultaneous selective regulation of the function of organs and systems according to the principle of segmental and vegetative innervation. After a course of preventive recovery, a statistically significant (p<0.05) normalization of well-being indicators according to the SAN test was noted from 4.0 to 4.6 points, activity from 3.9 to 4.4 points, mood from 3.9 to 4.7 points. All patients showed a pronounced reduction of complaints and autonomic disorders. In addition, we revealed improvement in the functional state of the cardiovascular system. So, systolic pressure decreased from 152±1.5 mmHg up to 134±2.4 mmHg, and diastolic from 106±0.7 mmHg to 82±1.8 mmHg.Conclusions. As a result of the prophylactic treatment, all patients registered a normal type of adaptive response, since the training reaction was detected in 44.4 % of cases, the calm activation reaction was 22.2 %, in the area of increased activation - 33.4 %. The use of the “MOXI” device in the treatment of patients with arterial hypertension of 1 type, with a low level of risk gives a positive therapeutic effect in the normalization of the psycho-emotional state of patients. It normalizes non-specific adaptation reactions of the body, and allows you to achieve a decrease in blood pressure to normal levels.
 
Article
Ambulatory blood pressure monitoring (ABPM) is a modern method of BP investigation. However, only some ABPM parameters, as diurnal systolic BP (SBP) and diastolic BP (DBP), are used now as the diagnostic guide according to international recommendations. It is pure knowledge in clinical practice about usage and calculation of mean blood pressure (MBP). Such parameter is the steady flow of blood through the aorta and its arteries and equals the cardiac output multiplied by vascular resistance [1], according to some clinical studies may have predictable value as SBP or DBP, however there is no clinical evidence about these parameters, as information how to calculate in ABPM.The aim of the study is to compare the mean blood pressure calculated by two methods using ABPM parameters.We selected 20 ambulatory blood pressure monitoring (ABPM) patients (median of age 60 [56; 64] years, 65 % women). ABPM was recorded using a bifunctional device (Incart, S.-P., RF). We calculated MBP as [[(2×DBP)+SBP]/3] [2] and as [DBP+[0.01×exp(4,14-40,74/HR)] ×PP] [3], Formula 1 and Formula 2, respectively. The analysis of difference between results of MBP measurements calculated by two methods was performed using the Bland and Altman method. The data show, that MBP calculated by Formula 1 and Formula 2 are as 87.7 [83.2−90.5] and 91.1 [85.4−93.5] mm Hg, respectively. The limits of agreements for the MBP were 0,49/5,91.In general, based on the findings of the current study, the measurements of MBP calculated using different formulas show good agreement. Further studies need to have more clinical evidence to analyze the result
 
Article
The chemical plant protection products application is an integral part of intensive crop production technologies. However, scientists have proven that the increase in chemical pollution of the environment in 2 times increases the general level of morbidity of the adult population by 25%. That is why the risk assessment of pesticide-contaminated products consumption is an important part of the regulatory process.Methods. The parameters of fungicides difenoconazole, tebuconazole, cyflufenamid, oxathiapiprolin, famoxadone persistence in agricultural crops were studied in the field experiments. For the integrated assessment of the potential risk of pesticide-contaminated products consumption for human (RPCPC), a methodology developed on the basis of the Institute of Hygiene and Ecology was used. The acceptable daily intake (ADI), the half-life period (τ50) in plants and the average daily consumption of the product have been evaluated using four-graded scale.Results. According to the persistency in tomatoes and potatoes, fungicides difenoconazole, cyflufenamid, famoxadone are pertained to 3 classes of hazard (5-14 days); tebuconazole - to 2 class (15-30 days); oxathiapiprolin - to 4 class (less than 5 days). After the addition of all the obtained points, the RPCPC value (tomatoes and potatoes) for difenoconazole, cyflufenamid, famoxadone amounted 8 points (2+2+2× 2 and 2+2+4, respectively); tebuconazole - 8 points (3+1+2×2 or 3+1+4, respectively); oxathiapiprolin - 6 points (1+1+2×2 or 1+1+4, respectively).Discussion. Thus, the studied compounds belong to the 3rd class of hazard according to pesticide-contaminated products consumption for human index value. The results obtained by us correlate with the studies carried out in the previous stage. The exception was only difenoconazole, which was classified as hazard class 2 due to its high toxicity for human.
 
Amino acid composition of Thalictrum foetidum L. herb
Article
Submitted article is concerned with the study of amino acid composition in a Thalictrum foetidum L. herb. Investigations have been performed by the high performance liquid chromatography method based on the extraction of free amino acids from the herbal raw material and on the acid hydrolysis of the herbal medicinal products followed by analysis of hydrolizates using the HPLC with precolumn derivatization with 9-fluorenylmethoxycarbonyl chloride (FMOC) and o-phthaldialdehyde (OPA) attended by the detection with fluorescence detector.Amino acid identification has been performed by the comparison of retention times with the mixture of standard amino acids (Agilent 5061-3334). The content of bound amino acids has been determined by the subtraction of free amino acids composition from their total composition.As a result of study 15 essential and non-essential amino acids have been found. It is important to note that L-Serine, L-Histidine, Glycine and L-Phenylalanine are not in a free state in Thalictrum foetidum L. herb. The quantity of L-Glutamic and L-Aspartic acids is 17.47 and 13.41 µg/mg, respectively (common amino acids). The content of abovementioned acids in a bound state is 15.66 and 9.84 µg/mg, respectively. As for content of other amino acids which were found in Thalictrum foetidum L. herb, it has to be said about their practically the same composition which is in the range from 4 to 5 µg/mg. Content of L-Histidine (1.80 µg/mg in general and bound state) and L-Tyrosine (1.76 µg/mg in general state and 0.08 µg/mg in bound state) is minimum in this herb.It has been established that amino acids are in a free and bound state in the investigated herbal raw material. Content of bound amino acids is higher than general content. Among the amino acids, which are in the overwhelming majority in the studied herb, it stands to mention L-Glutamic and L-Aspartic. These amino acids play an important role in supporting the physiological processes of the body, especially nervous system.In consideration of experimental data to be noticed is that Thalictrum foetidum L. is a promising plant for creation of phytotherapeutic medications with neurally mediated action.
 
Article
Amlodipine besylate belongs to a group of blockers of calcium channels, derivatives of 1,4-dihydropyridine, is used to treatment of arterial hypertension and vasospastic forms of angina pectoris. According to the literature sources, amlodipine in case of overdose can provoke the development of breast cancer, cause ischemia of the optic nerve. Deadly poisoning with amlodipine may accompany drug overdoses or suicidal cases. The development of highly sensitive and selective methods for the study of amlodipine during forensic toxicological examination of biological material is an actual task. One of the important stages of forensic toxicological examination is the choice of organs of corpses for investigation of them for the presence of poisons, which requires the analysis of amlodipine in the organs of poisoned animals.The aim of the investigation is the study of the distribution of amlodipine in organs of poisoned animals, using developed highly sensitive and selective techniques for the analysis of amlodipine in biological objects.Materials and methods. To study the distribution of amlodipine in organs of poisoned animals, rats weighing 200-250 g were used. Amlodipine besylate solution was administered to rats using a probe in the stomach from the calculation of70,0 mg / kg, after 3 hours rats were decapitated. For the study blood, urine, heart, liver, kidneys, lungs, stomach and intestine with contents and spleen were taken. Control experiments were delivered with the appropriate organs in parallel. Extraction of the substance was carried out with a mixture of methanol and acetonitrile (2: 3), purification was carried out by extraction of impurities with diethyl ether at pH 2,0-3,0 and TLC-method. Amlodipine was identified in biogenic extracts by the TLC-method in three systems of mobile solvents. The substance content was determined by spectrophotometry methods in the UV region of the spectrum.Results and discussion. It is established that the highest amount of amlodipine was found in the stomach and intestine with the content, which is typical for acute poisoning. Less amount of amlodipine is found in the liver, kidneys and urine - organs and liquids that provide active detoxification of the body. According to the results of the research, it was found that in case of lethal poisoning, amlodipine for forensic toxicological studies should be carried out in urine, stomach with contents, intestine with contents, liver, spleen and kidneys.Conclusions. The distribution of amlodipine in organs of poisoned animals with oral administration was studied. It is established that in case of lethal poisoning with amlodipine, for forensic-toxicological research it is necessary to be conducted in urine, stomach with contents, intestine with contents, spleen and kidneys. The developed methods can be proposed for introduction into the practice of the Bureau of Forensic Medical Examination, toxicological centers
 
Article
Spinal anaesthesia is commonly used for elective caesarean section. But it has some disadvantages and complications in intra- and postoperative period. The aim of this study was to explore the efficacy of intrathecal or intravenous dexamethasone to prevent some early complications of spinal anaesthesia such as arterial hypotonia, nausea, vomiting, bradycardia, shivering etc. Material and methods: there were examined 154 healthy, not obese women, ASA I–II, 18–36 years old, 36–40 weeks of gestation, undergoing elective caesarean section under spinal anaesthesia. All patients were divided into three equal groups for randomized, prospective, double-blinded, placebo-controlled clinical trial. The women of each group received intrathecal hyperbaric bupivacaine 0.5 % 10 mg. Group B (n=51) additionally received intrathecal 1 ml of normal saline=placebo; Group BD (n=52) additionally received 4 mg (1 ml) intrathecal dexamethasone, and Group D (n=51) received 8 mg intravenous dexamethasone directly after spinal puncture. The patients were evaluated for blood pressure, heart rate, nausea, vomiting, shivering or other complications during intra- or postoperative period (24 h). The complications that required medicines correction were recorded and cured. Results: the addition of intrathecal dexamethasone in Group BD vs Group B significantly decreased frequency and manifestations of arterial hypotonia and nausea (Pearson's χ2 =0.486 and χ2=0.479, p<0.05) in intra- and postoperative period after the spinal anaesthesia in elective caesarean section. Intrathecal dexamethasone in Group BD vs Group B significantly reduced shivering (Pearson's χ2=0.316, p<0.05) in intra- and postoperative period, and significantly didn`t impact on vomiting and bradycardia. Conclusions: the addition of 4 mg intrathecal dexamethasone as an adjuvant for spinal anaesthesia can significantly decrease frequency and manifestations of arterial hypotonia and nausea, reduce shivering during perioperative period. The addition of 8 mg intravenous dexamethasone has not the same quality.
 
Article
According to the Princeton Consensus, female sexual dysfunction can be a sign of androgen deficiency (AD) in women of reproductive age, which necessitates the inclusion of appropriate therapy in fertility rehabilitation protocols for patients with biochemically confirmed AD. Most often, AD is associated with ovarian dysfunction. With ovarian hypofunction of autoimmune origin, an increase in inhibin B production occurs, in contrast to ovarian insufficiency of another etiology, which is due to selective damage to theca interna cells, while granulosa cells synthesizing inhibin B remain intact.Aim of the research. The study of the value of inhibin B as a prognostic marker of fertility recovery in women with androgen deficiency and sexual dysfunction.Materials and methods. The study design included 77 women of reproductive age of the main group with sexual dysfunction and androgen deficiency: 45 women with sexual dysfunction and the presence of thyroperoxidase Ak (I-a group), I-b group of 32 women with sexual dysfunction without antibodies to any organism tissues. Control group – 31 healthy women of reproductive age. Diagnostic laparoscopy was performed on anOLYMPUS device using a standard technique. Hormone testing was performed using a Johnson & Johnson Vitros automated system. Blood samples for the study were taken in the morning (8–11) on an empty stomach with venipuncture of the ulnar vein in the 1st phase of the menstrual cycle. Ultrasound test was performed on an Aloka Hitachi apparatus (Japan) with a sensor frequency of 7 MHz. Sexual dysfunction was determined by the Skindex-16V questionnaire. The diagnosis of the examined “Violation of female sexual desire / arousal” was done according to the classification DSM-5. Clinical manifestation of sexual dysfunction was >6 months.Results. The average age of the examined main group was 32.3±1.7 years, in the control group – 33.9±1.6 years. The average age of menarche for women of both groups was 13–14 years (in the main 13.3±0.34, in the control – 13.0±0.23 (p>0.05). The study of the hormonal background showed a pronounced, statistically significant in compare with healthy women, a decrease in the concentrations of not only estradiol, but also androgens, total testosterone, free testosterone, as well as dehydroepiandrosterone sulfate. Concentrations of sex steroids directly and statistically significantly correlated with the I-a group with concentrations of gonadotropins (luteinizing hormone (LH) and estradiol r=0.67; follicle-stimulating hormone (FSH) and estradiol r=0.64; LH and total testosterone r=0.47; FSH and total testosterone r=0.42; for all p <0.001). LH and DHEA-S p=0 <33 (p=0 <02), FSH and DHEA-S p=0<27 (p=0 <03). In group I-b, LH correlation and total testosterone r=0.58 p<0.001 were noted.Diagnostic laparoscopy with ovarian biopsy was performed in 12 women of group I-a and group 23 of group I-b. At the same time, the presence of lymphoid infiltration, autoantibodies and complement on growing follicles was established, with primordial and primary follicles intact. Tissue fibrosis, the presence of activated B and T lymphocytes: CD8+, CD4+, natural killer cells (NK), polyclonal plasmocytes, macrophages of primordial and primary follicles were characteristic for group I-b.Conclusions. The level of inhibin B can serve as an early marker of autoimmune ovarian damage in women of reproductive age with female sexual dysfunction. Therapy of androgen deficiency should be carried out taking into account the pathogenesis of the disease.
 
Article
According to the consensus of An Endocrine Society Clinical Practice in Princeton, USA, worsening well-being and dystrophic mood, permanent weakness and altered sexual function, including libido decline and lack of orgasm, were considered as typical signs of androgen deficiency syndrome. Particular attention is required to study the state of the genitourinary system, which is hormone dependent, so it is obvious that age-associated symptoms of pathological processes of the lower urinary tract are likely to be considered as a "urological mask" of the deficiency of sex hormones.Aim of the work. Identify and describe the most common urogenital disorders in women of reproductive age with androgen deficiency.Materials and methods. The study was conducted at the Ukrainian Scientific and Practical Center of Endocrine Surgery, Endocrine organs and tissues transplantation of the Ministry of Health of Ukraine during 2017–2018 years. A survey was conducted on 80 women of reproductive age who had major complaints of sexual disturbances (decreased libido and lack of orgasm, as well as dyspareunia as the main manifestations of androgen deficiency in women) and 30 healthy reproductive women without complaints of sexual dysfunction. General clinical methods were used (questionnaire of patients with a detailed study of socio-economic status, somatic, gynecological, obstetric and sexual history). The condition of external and internal genital organs was evaluated in the study of cervix and vagina in mirrors and gynecological bimanual study. At the same time, batches of analyzes for bacteriological research and colpocytology studies were conducted. The “HAWK 2102 EXL” (Germany) apparatus was used for ultrasound examination of pelvic organs using transabdominal and transvaginal convection sensors with frequencies of 3.5 and 5 MHz, respectively. Consultation of the urologist in order to exclude organic urological pathology and, if necessary, cystoscopy was also done.In the plasma of venous blood, the following hormonal indices were also determined by solid phase IFA, namely, content: free testosterone, DHEA, androstenedione, prolactin, ACTH, cortisol, FSH, LH, estradiol, progesterone.Results. It was revealed after exclusion of the urologist of the organic pathology of the urinary tract, in 49 % (39) of the main group, there were disturbances of urination associated with atrophic changes in the distal sections of the urinary tract. The revealed signs of vulvovaginal atrophy: pH 6.1±0.7 in women of the main group and pH 4.3±0.5 in women of the control group, in addition reduction of the karyopyknotic index and increase of the ripening index as signs of atrophic changes in the vaginal mucosa and cervical canal, was detected in 70 % (56) women in the main group and not found in the control group. At the same time, the prolapse of the genitalia of mild degree in women of the main group was detected in 32 % (27), and in the control group, this pathology was not found.Conclusions. Detection of these changes, which was considered characteristic of women in perimenopause and postmenopausal, makes it important and valid for the continuation of the study of patients with androgen deficiency, the discovery of clinical and laboratory criteria for diagnosis and the development of methods for correcting androgen deficiency in women of all ages.
 
Classification of common nematodes that cause disease in humans 
Results of antimicrobial activity research (n=5) 
Article
Parasitic infections are one of the most acute problems of the modern society as this group of diseases is met in all countries of the world. According to the World Health Organization around 1.2 billion people are infected with diverse parasitic infections each year. Helminthiases of digestive system, primarily nematodosis, constitute a group of special risk, since a particularly sensitive audience for them are children of younger and middle age.Phytotherapy, which is based on the centuries-old experience of folk medicine, promises to be a solution to this problem, enabling to create effective complex medicines for nematodosis prevention and treatment. Thus, the herbal mixture was prepared on the basis of the offered composition of medicinal plant raw material.The research of antimicrobial activity of the studied herbal mixture was conducted in vitro by the method of diffusion into agar at the Biotechnology Department of the National Pharmaceutical University under the direction of Doctor of Pharmaceutical Sciences, prof. Strelets O.P.The obtained results of the carried out research of the antimicrobial properties of the herbal mixture samples allowed examining the level of antimicrobial activity.The further research of the investigated herbal mixture and the offered phytocomposition is promising for creation of new effective medicines with the complex action including anthelminthic (specific to nematodes), antiparasitic, anti-inflammatory, antibacterial, antiseptic, hepatoprotective, nephroprotective, laxative, antiallergic, antispasmodic, analgesic, sedative activities
 
Article
Among the current problems of medicine and pharmacy, attracting the attention of researchers around the world, allergic diseases are on an important place; for example, bronchial asthma, allergic rhinitis, atopic dermatitis, and others. These pathologies affect their abundance not only among adults, but also among children [1]. According to statistics, almost every child had allergic reactions to drugs, food, clothing, hygiene products, etc. at least once [2]. In this regard, we have developed a new anti-allergic drug for children in the form of suppositories under the conditional name "Loravit".The purpose of this work was to conduct microbiological research of new anti-allergic drug "Loravit" for children in the rectal dosage form.During researches, the correlation of the growth properties of nutrients was analyzed and the microbiological purity of the drug "Loravit" was studied. A thioglyсol semi-liquid substratum, Saburo’s substratum, solid nutrient substrata: nutrient agar, Saburo’s substratum, Chistovich's substratum, nutrient agar based on blood agar, Endo’s substratum, and also test microorganisms - Staphylococcus aureus ATCC 6538, Esherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 9027, Bacillus subtilis ATCC 6633, Candida albicans ATCC 885/653 were used for carrying out these studies.In the study of microbiological purity, the method of direct seeding on liquid nutrient substrata and the method of deep sowing were applied.As a result of the conducted studies it was established that a new medicinal product for children in the form of suppositories for the treatment of allergic diseases meets the requirements of the State Pharmacopoeia of Ukraine and European Pharmacopeia for the indicator "Microbiological purity". The norms of microbiological purity of suppositories "Loravit" are also established. The test results were included in the draft quality control methods for the developed drug.
 
Article
The results of the study of antimicrobial and fungicidal properties of the experimental preparation “Sukhodez” against microorganisms E. coli, Salmonella enteritidis, Staphylococcus aureus and fungi Candida albicans in the laboratory are presented. The aim of the research. To study the antimicrobial and fungicidal properties of powdered disinfectant and analyze the prospects for its further use in a set of anti-epizootic measures in particular in poultry farms. Materials and methods. The research was conducted during 2021 at the Department of Veterinary Examination, Microbiology, Zoohygiene and Safety and Quality of Animal Products of the Faculty of Veterinary Medicine of Sumy National Agrarian University. Evaluation of bactericidal properties of the experimental agent “Sukhodez” was determined on museum strains of E. coli ATCC 25922, Salmonella enteritidis ATCC 13076 and Staphylococcus aureus ATCC 6538, fungicidal properties were studied on fungi Candida albicans. All cultures were standardized to 109 CFU / cm3. Results. It is established that as a result of the conducted researches at studying preparation “Sukhodez” antimicrobic properties, it had high efficiency concerning action on strains of both gram-positive and gram-negative bacteria. It had a detrimental effect on bacteria when applied to concrete at an exposure of 1 hour with a rate of 75 mg per 1 m2, and had the same effect as when applied to a wooden surface, where it expressed antimicrobial action at a rate of 50 mg/m2 after 4 hours. When determining the fungicidal properties, it was found that when exposed to 5 hours, the preparation “Sukhodez” had an effect on study contaminated objects with a rate of 50 mg/m2, and with a rate of 75 mg/m2 inhibited the growth of fungi for 1 hour. Conclusions. It was found that the most sensitive to the preparation “Sukhodez” were the culture of Salmonella enteritidis – at a rate of 25 g / m2 and action on concrete and wooden surfaces, the disinfectant inhibited the growth of the culture when exposed to 5 hours, and at a rate of 50 g / m2 – for 2 years. Staphylococcus aureus was the most stable bacterial culture, so at a rate of 50 g / m2 on concrete and wood surfaces, bacterial growth was inhibited for 4 and 5 hours, respectively. At the same time, in the study of fungicidal properties, “Sukhodez” showed a fungicidal effect on Candida albicans when applied to a concrete surface at a rate of 50 mg / m2 for 3 hours, when applied to a wooden surface – for 4 hours. In general, at a rate of 75 g / m2, “Sukhodez” has an instant bactericidal and fungicidal effect on bacteria and fungi applied to concrete and wooden surfaces
 
Article
The aim of the study. Analysis of tactics of antiviral therapy for chronic viral hepatitis b in pregnant women. Methods. Theoretical analysis of scientific literature; analysis and generalization. Statistics and comparisons. Classification of theoretical material and development of recommendations. Research results. Today, there are about 2 billion people in the world ill with a chronic infection caused by the hepatitis B virus, 350 million of whom suffer from chronic hepatitis B, and most are asymptomatic carriers of the Australian antigen (HBsAg). Up to 50 % of all new cases of hepatitis B virus infection are due to vertical infection. Despite the lack of increase in viral load during pregnancy, alanine aminotransferase tends to increase in late pregnancy and in the postpartum period. A sharp drop in postpartum corticosteroids may create favourable conditions for hepatitis B virus activation. It is emphasized that the current treatment of hepatitis B virus includes the use of antiviral drugs, where Peg-IFN is absolutely contraindicated in pregnancy, lamivudine and entecavir are classified by the FDA as category C, and tenofovir and telbivudine are classified as category B. During pregnancy, it is recommended to use mainly category B drugs. Conclusions. The use of antiviral therapy in combination with immunoprophylaxis of new-borns is the optimal strategy for implementation as a universal program, as the success of such an intervention can make a significant contribution to achieving the ultimate goal of global elimination of hepatitis B virus.
 
Article
The article presents the new method of art-therapeutic psychodiagnostics of anxious disorders in children. There are separated formal elements that have a diagnostic importance in differentiation of anxiety and depression in children in the age aspect. There are presented the features of the course of anxious disorders in the age aspect: in children – comorbidity of anxiety with cognitive disorders (neurocognition) and phobias, in teenagers – anxiety with emotional (depression) and behavior disorders (avoiding behavior). It was established, that the constitutional-neuropathic variant of an anxious disorder prevails in children of 7 – 11 years old, and in teenagers – the thymopatic variant of it. There are the separated informative signs of phobic formations that provide the reliable psychopathological differentiation of anxious disorders: dominating type, determining a clinical picture, accessory type, participating in pathoplasty of complicated syndrome complexes and isolated type. There are separated the psychological predictors of the anxiety disorder development in children: infantilism, personal anxiety, poly-accentuation of a character. It was established, that the formation of anxious disorders, regardless of age, is influenced by the pathological type of family relations (disconnected, separated and rigid). In a projective figure of a family a disorder of emotional family connections was diagnosed in most children with anxious disorders. There are established the factors of prediction of an anxious-phobic disorders in children: genetic predisposition and external conditions of this state residual-organic, family (disorders of a family interaction with forming symbiotic relations between a child and an anxious parent) and environmental)). The analysis of the information, obtained in projective figural tests, allowed to differentiate and to systematize graphic signs of anxiety, phobias and depression. It was shown, that the method of art-diagnostics widens possibilities of early detection of disorders of social and cognitive functioning of children with anxious disorders
 
Article
In the structure of regional and planetary pollutants, pesticides are in the top ten, and among food contaminants along with heavy metals – they occupy first place in the world. It is known that pesticides and agrochemicals, which belong to the group of biologically active compounds, are one of the important factors affecting the human body. The aim: comparative hygienic assessment of working conditions and occupational risk when using pesticides by different methods of application (knapsack, rod, ventilator, unmanned and aviation) on the example of the fungicide Amistar Extra 280 SC. Materials and methods. Field studies were conducted in 2018–2021. When applying the formulation knapsack sprayer SOLO-10, trailed boom sprayer AMAZON 1201 UF combined with a tractor MTZ 82.1 Belarus, unmanned aerial vehicle (UAV) for spraying fields Agras T16, AN-2 aircraft combined with OZh-2 were used. Results. As a result of field researches of working conditions of employees during the performance of production operations on the pesticides application, it was found that in the air treatment areas and in areas of possible drift the levels of studied active ingredients were below the limit of quantification of the method. The difference between azoxystrobin (0,04±0,003) and cyproconazole (12,4±0,5) for the tank refueler and the UAV external pilot in the field studies is significant according to Student's criterion (p >0,05). For the operator who applied the pesticide with a knapsack sprayer, the values of inhalation risks were significantly higher than for the tankers of the sprayer tank at p >0,05. The values of the combined risk when using a fan sprayer (0,46±0,02) significantly exceeded the data obtained when using a rod sprayer (0,14±0,006) Conclusions. Analysis of the obtained results showed that the values of the combined risk are significantly higher for the operator / tractor driver, signalman than for their refuelers (at p
 
Article
One of the pressing problems of modern cardiology is the study of the etiological and risk factors for sudden cardiac death (SCD). Arrhythmias, which in most cases correlate with signs of myocardial hypertrophy, are important for its occurrence. The most common cause of left ventricular hypertrophy (LVH) is hypertension. However, an equally important trigger mechanism for malignant arrhythmias is coronary heart disease (CHD). It is known that LVH is considered as an independent risk factor for cardiovascular complications.Methods. The study design included an assessment of the effect of cardiac remodelling, the degree of LVH, and the degree of dilatation of left atrium (LA) on the development of malignant disorders of rhythm and conduction of the heart (DRCH). 78 patients with II degree of hypertension were examined. Patients were divided into two groups depending on the presence of CHD. In each group, there were malignant rhythm and conduction disorders. The control group consisted of 20 healthy people.Results and discussion. The stages of LVH were equally represented in both groups, but the concentric LVH, the initial degree of LVH, and the dilatation of LA predominated. In patients with malignant DRCH, a moderate degree of LVH predominated. Significantly, more likely malignant DRCH occurred in the second group and presented with high-grade ventricular extrasystoles, prolonged QT interval, and sinus node weakness syndrome.
 
Article
The relationship of visceral obesity and excess body weight (EBW) with the development of cardiovascular diseases, type 2 diabetes mellitus (DM) and effect on quality and duration of life determine the relevance of studying this problem. The aim: to assess omentin-1 metabolism and pathophysiological relationship between its level and the severity of lesions in the intima-media thickness (IMT) of the carotid arteries in type 2 DM in combination with EBW and obesity. Materials and methods. We examined 98 people with DM, the first group consisted of 64 people with EBW and obesity, second group consisted of 34 people with normal body weight, control group – 28 healthy individuals. The concentration of omentin-1 was investigated by ELISA by solid-phase enzyme-linked immunosorbent assay in vitro. Ultrasound of the carotid arteries was performed in the lying position of the patient on the device MyLab50X with a linear sensor of 7 MHz with a slight deviation of the patient's head in the opposite direction. Results. Evaluation of the correlation matrix showed the presence of a positive rather strong negative connection between IMT, especially the right carotid artery and the level of omentin-1 in the blood (Rs = –0.55; p = 0.002). The largest number of individuals with omentin-1 levels from 5–10 ng / ml had significant disorders of the vascular wall (IMT from 1.0 to 1.2 mm). Conclusion. Obtained data indicate a statistically significant associative relationship between the dynamics of the predictor of cardiovascular risk – IMT with the degree of impaired expression of omentin-1.
 
Article
The activity of the juvenile idiopathic arthritis evaluates the speed of the process progression, intense of its clinical manifestation, effect of the carried treatment.The aim of our study was to estimate changes of the inflammatory response signs as well as content of NF-kB due to basic therapy of the JIA.Materials and methods. At our study, we had checked 68 children with JIA, who passed their treatment at Vinnytsya regional children’s hospital within the period from 2011 to 2014 years.Results. At the patients we studied currency of the JIA was characterized with articular variant of the disease, mainly in monoarthritis type. Laboratory activity of the inflammatory response characterized with increased content of the C-reactive protein (71.2±3.7 %), inflammatory cytokines – ІL-1β (54.8±4.1 %) and ІL-6 (56.2±2.4 %), as well high quantity of the nuclear factor-kB (70.5±3.1 %). Currency of the JIA in children characterized with high increasing of the inflammatory response signs especially C-reactive protein (6.55(4.2;9.8)), ІL-1β (7.3(3.5;11.9)), ІL-6 (6.8(4.5;10.6)) and NF-kB (6.76 (4.8; 9.1)), that are in correlative connections with clinical signs (number of the injured and swelled joints, evaluation of the general condition of the child according to doctors and own response) of the disease activity (rxy = +0.34 up to 0.62, p< 0.01).Conclusion. During the managing of the basic therapy in children with JIA we estimated decreasing of the IL-1β content in patients at the background of methotrexate administration (38.7±3.7 %), at the second group with use of sulfasalazine (28.5±3.5 %) and the third with leflunomide prescription (29.1±5.1 %), but significant decreasing of the ІL-6 content, that is one of the main inflammatory mediators and as well NF-kB was found just in group of the patients with methotrexate administration (on 36.3±3.8 % and 32.4±2.4 % for NF-kB).
 
Article
The aim – to study the effectiveness of zinc salts in the treatment of patients with neurological forms of Wilson's disease (WD).Materials and methods. The analysis of the treatment results of 128 patients with hepatocerebral degeneration (71 men and 57 women) in the State Institution “Institute of Neurology, Psychiatry and Narcology of the National Academy of Medical Sciences of Ukraine” was carried out. At the time of hospitalization, the age of patients ranged from 5 to 55 years, an average of 27.3 years, and at the time of debut of the disease - from 1 year to 40 years, an average of 21.3 years. 33 patients underwent monotherapy with zinc salts, 63 – combined therapy with small doses of penicillamine and zinc salts, 32 – monotherapy with penicillamine.Results. Because of the treatment, 67.1 % of patients showed an improvement in neuropsychiatric status: speech improved significantly, tremor of the extremities and the amplitude of hyperkinesis decreased, muscle tone decreased, and cognitive functions improved. According to the international two-level rating scale (UWDRS), the total pathology index decreased by 21 points. Zinc salts are effective and low-toxic and can be the drug of choice in the treatment of patients with hepatocerebral degeneration in the pre-symptomatic stage of the disease, as well as at the stage of maintenance treatment, both as monotherapy and in combination with penicillamine. However, zinc salts and penicillamine are not enough for the treatment and rehabilitation of patients with hepatocerebral degeneration. Therefore, taking into account the clinical picture and the data of additional research methods, it is necessary to conduct courses of symptomatic treatment at least 1-2 times a year.Conclusions. Thus, it can be noted that zinc salts are very effective and low toxic, and, therefore, can be the drug of choice in the treatment of patients with HCD in the pre-symptomatic stage of the disease, as well as at the stage of maintenance therapy as a single drug, and in combination with penicillamine or other chelate drugs.
 
Some quality indicators of children's suppositories with licorice root extract
Metrological characteristics of quantitative determination of glycyrrhizin acid in one suppository in terms of glycyram
Article
The aim of this work was the development of technology of rectal suppositories of immunomodulatory action for children and their standardization.To obtain suppositories, a licorice root extract, chamomile and tea tree essential oils were used. Given that the introduction of ingredients in a dissolved form is preferable, we studied the possibility of using emulsion suppository bases. To evaluate the compositions, the homogeneity and colloidal stability of the suppositories obtained were studied. Estimation of homogeneity, melting temperature, decay time, average mass was carried out according to the State Pharmacopoeia. To confirm the authenticity of the active ingredients, a chromatography method was used. The quantitative determination of glycyrrhizin acid was carried out by spectrophotometric method. Suppositories were prepared by the pouring method. The licorice root extract was added to the suppository when dissolved in the hydrophilic phase of the base. Essential oils of chamomile and tea tree were introduced when a solid fat of type A dissolved in a melt, at a temperature of (42.0±2.0) ºC. Optimum indices for the criteria of “homogeneity” and “colloidal stability” were noted for the samples of the composition: purified water, polysorbate-80, lecithin, solid fat type A. To prove the authenticity of the licorice root extract in suppositories, the chloroform-methanol-water system was optimal (26:14:3). Identification of essential oils on a gas chromatograph showed that on the chromatogram the peaks and retention times of the solution under study coincide with the peaks and retention times of the reference solutions. The conducted studies of quantitative determination of glycyrrhizin acid have shown that its content in one suppository is not less than 0.035 g in terms of glycyram.
 
Sagittal section of the corpus callosum of a man: upper snapshot-after epoxy plastination; lower snapshot-its slice when stained with methylene blue: 1-the splenium; 2-the trunk; 3-the genu; 4-the rostrum; 5-venous vessels of the transparent septum; 6-pillars of the fornix 
The place of the spike of the fornix body and the corpus callosum. Epoxy slice, stained methylene blue. ×7: 1-substance of the corpus callosum; 2-matter of the fornix body; 3-interfunicular connective tissue septum of the corpus callosum 
The place of consolidation of the fornix body with the corpus callosum. Paraffin section, Van Gieson's stain. ×10: 1-substance of the corpus callosum; 2-substance of the fornix body 
Article
It is commonly known that the body of the fornix belonging to the limbic brain is fused with the corpus callosum. Therefore, the question arises about the existence of commutation interactions between the limbic brain and the new pallium through the collector system of the corpus callosum, which is probably the mediating link between the subconscious and conscious spheres of a person's mental activity. However, in the literature this question is not discussed in this way.Aim of research. The aim of this study is to establish whether the fornix has an organic connection with the myeloarchitectonics of the corpus callosum.Materials and methods. The median whole mounts (about4 mm thick) of the corpus callosum (including the transparent septum and the structures of the fornix) of 10 men aged 36 to 60 years were used in the course of the study. Some of the mounts underwent a complete plastination in epoxy resin. After this they were used to make polished slices, stained with a 1% solution of methylene blue in a 1% borax solution. The remaining mounts of corpus callosum were used to make serial paraffin sections with further hematoxylin and eosin and Van Gieson’s stain.Results. It has been established that the pillars of the fornix enter the body of the corpus callosum on the border between its trunk and splenium. In the area of contact between the fornix body and the corpus callosum there is a loosened scissura, which gradually narrows toward the splenium and then disappears leading to the complete consolidation of the fornix and corpus callosum. This consolidation is expressed in the fact that the interfunculary connective tissue septa of the latter penetrate into the body of the fornix and as a result it is divided into the cabled-like assemblies of myelinated nerve fibers. However, unlike the corpus callosum, this division is not complete: it concerns only the layer of the fornix that is directly attached to the corpus callosum.Conclusions. On the boundary between the corpus callosum trunk and its splenium, that is, in the area of its isthmus, the commutation interconnection between the conducting system of the limbic brain and the commissural pathways of the neopallium is structurally fixed
 
The composition of the studied combined fungicides (Formulations No. 1-8) 
Article
Toxicological assessment of combined fungicides proposed for application on cereal spiked crops in Ukraine was performed according approved State Sanitary Norms and Rules. Statistics, bibliographical methods were used in the study. The classes of hazard were established after evaluation of toxicometry parameters, which included assessment of acute oral toxicity, acute dermal toxicity, acute inhalation toxicity, irritation potential to eyes (mucous membranes) and skin, and sensitizing properties. Integral hazard class of the studied formulations was established. Formulations No.1, 2, 3, 5 and 7 can be pertained to integral hazard class 2 by acute inhalation toxicity as limiting criterion of hazard (formulation No.1 also has additional point of concern – its irritation of the skin and eyes). Formulation No.4, 6 and 8 were classified as integral hazard class 3 by the same limiting criterion of hazard, but the danger of formulation No.4 possibility to cause sensitization and irritation of the eyes was taken into account. Recommendations for the studied combined fungicides application in agricultural sector of Ukraine were given. Maximum daily time of contact with formulations for workers engaged in its application on cereal spiked crops was suggested. 4 hours per day were approved for formulations No.1,2,3,5 and 7, and 6 hours per day for No. 6 and 8, respectively
 
ROC-curve for prediction of AF in STEMI patients using NT proBNP level
ROC-curve for prediction of MACEs in STEMI patients using NT proBNP level
Clinical characteristics of examined patients
Article
Our aim was to study the predictive value of NT proBNP regarding the risk of AF and clinical features in acute phase of ST-segment elevation MI (STEMI).Methods. We examined 56 patients with STEMI and AF who did undergo the primary PCI. 35 (62.5 %) of patients had the new-onset AF (group 1), 21 (37.5 %) had pre-existing AF (group 2). Control group consisted of 60 patients with STEMI without AF (group 3).Results. Group 3 patients were more likely to be smokers than patients in group 2. They had lower admission heart rate and glycemia, lower NT proBNP, higher hemoglobin and ejection fraction. Patients in group 1 were more likely to have anterior MI, left anterior descending artery as an infarction-related artery (IRA) and adverse cardiac events (MACEs). Patients in group 2 had higher left atrium end-systolic diameter and were more likely to have three-vessel injury. NT proBNP correlated positively with age, admission glycemia, mean PA pressure and negatively – with GFR.ROC analysis had shown the cut-off point of NT proBNP level for prediction of AF was >1050 pg/ml. Cut-off point for prediction of the risk of MACE in STEMI complicated with AF was >2189 pg/ml.Discussion. It was shown that NT proBNP is higher in STEMI patients who have AF. Increased NT proBNP is associated with the risk of adverse events in acute STEMI phase. NT proBNP level can be utilized as AF predictor in STEMI patients and as predictor of MACEs in patients with STEMI and AF.
 
Article
The most common articular pathology is osteoarthrosis of the knee joints. More than 10 % of the world's population suffers from this disease. The development of osteoarthrosis (OA) is also affected by metabolic syndrome (MS), which is characterized by abdominal obesity, dyslipidemia, arterial hypertension and disturbance of carbohydrate metabolism. The combination of MS and osteoarthrosis creates conditions of overload for the functioning of axial joints, which is one of the main causes of premature disability and invalidization of the population.Treatment of OA of the knee joints in women in the menopausal period with concomitant metabolic syndrome presents great difficulties. To achieve a stable result of treatment, therapy with chondroprotectors and nonsteroidal anti-inflammatory drugs (NSAIDs) is used. Treatment was carried out in 60 women in the menopausal period with MS, suffering from OA of knee joints. In the group of women in the menopausal period with OA of knee joints and MS who took therapy with the inclusion of the soybean and avocado drug alongside with NSAIDs, a significant effect was obtained with regard to arresting the pain syndrome, improving the quality of life, reducing the degree of inflammation as well as increased joint mobility compared with the group of patients, who took only chondroprotectors and NSAIDs
 
Article
Aim of the work. The focus of this study was to analyze the frequency of fetal intrauterine symptomatic realization as a result of B19 parvovirus infection of pregnant women during I and II gestation periods, with the combination of determination the levels of alpha-fetoprotein in maternal serum blood and histopathological investigation of placenta in cases of negative effects for infected fetuses.Materials and methods. A total of 478 pregnant women were at risk of infection and screened for parvovirus B19. The study was based on serological, morphological and virological testing of fetuses from mothers with confirmed parvovirus B19 infection. Infection of pregnant women was detected by serological diagnosis of specific antibodies IgM and IgG to parvovirus B19. Intrauterine fetal infection was confirmed by polymerase chain reaction method. Levels of alpha-fetoprotein in meternal venous blood were detected using an immunochemical test method. An antenatal diagnosis of hydrops fetalis was confirmed by ultrasound scanning. Placenta from the 8 infected fetuses was studied histologically with hematoxylin and eosin staining using electron microscope during gestational periods of 12-22 weeks. Statistical analysis of the obtained data was carried out using nonparametric statistics with the definition of Fisher's criterion.Results and discussion. The average gestational period of symptomatic manifestations of intrauterine fetal infection was 19.9±0.5 weeks of gestation. It was established that in 33 of cases were confirmed the intrauterine infection due to parvovirus B19 by using the morphological placenta tissue analysis. The research found that the levels of maternal serum alpha-fetoprotein was significantly higher (in 2.17 times) in group of fetuses who suffered from fetal hydrops and in cases of intrauterine fetal death before detecting the general echographic sings of fetal failure (p˂0.05). It will be very important to compare this indicator with the Doppler ultrasound measurements of the human fetal middle cerebral artery peak systolic velocity (MCA PSV) and blood flow parameters in the fetal ductus venosus and to predict the possibility of poor perinatal outcomes. It was identified a cytopathic effect in placental cells viral origin and detected in cells of the cytotrophoblast, syncytiotrophoblast, endothelial cells, and blood cells.Conclusions. Parvovirus B19 fractions were visualized in 100 % of cases of miscarriages with fetal hydrops and placental edema during 12-22 weeks of gestation, while acute maternal parvovirus infection (with the detection of IgM against to parvovirus B19) was diagnosed by immunoassay only in 62.5 % of cases.Detection of B19 particles in placental tissue from fetuses with non-immune origin hydrops is an auxiliary method in the diagnosis of vertical transmission of parvovirus during pregnancy. It is more preferable to estimate the levels of alpha-fetoprotein in maternal serum blood in case of parvovirus B19 affected pregnancies as raising rates of this marker may be an early prediction hallmark for adverse fetal outcome.
 
Article
The problem of treatment of subclinical mastitis often arises after calving, especially in cows of the first lactation. The paper presents the results of the therapeutic effect of Bacillus megaterium in subclinical mastitis in cows. The aim of the research. To determine the effect of Bacillus megaterium on the microflora of the gastrointestinal tract and colonies of microorganisms isolated from subclinical mastitis in cows. Materials and methods. The research was conducted in a dairy farm growing Holstein. Cows with subclinical mastitis of the experimental groups were given concentrated feed with the addition of Bacillus megaterium (1 × 109 CFU/g) at a dose of 15–35 g per animal. The control group of cows was given the usual diet for dairy cows. The experiment lasted 30 days. Results. The use of Bacillus megaterium (1 × 109 CFU/g) at a dose of 35 g per animal had a pronounced effect on the microflora of the gastrointestinal tract of cows. The amount of Lactobacillus sp. was 67 % higher and Bifidobacterium 58 % higher than the control. In addition, the level of opportunistic pathogens on Escherichia coli decreased by 45 %, Clostridium by 27 %, Enterobacteriaceae and Staphylococcus by 75 %, and Candida by 80 % compared to controls. The amount of microflora in milk decreased by 40.2 % and the number of somatic cells by 87.9 %. Conclusions. The therapeutic efficacy of Bacillus megaterium (1 × 109 CFU/g) at a dose of 35 g per animal for 30 days in subclinical mastitis has been proven. After treatment, the amount of microflora in cow's milk decreased by 40.2 % and the number of somatic cells by 87.9 %. A positive effect on the microflora of the gastrointestinal tract of cows, where the number of Lactobacillus sp. increased by 67 % and Bifidobacterium by 58 %. The level of opportunistic pathogenic microflora decreased by Escherichia coli – by 45 %, Clostridium – by 27 %, Enterobacteriaceae and Staphylococcus – by 75 %, Candida – by 80 %, compared to the control.
 
Article
The aim of the study was to clarify obstetric and perinatal risk in women born with low or overweight. Materials and methods. 343 women with birth weight abnormalities were examined. From them 3 groups are made, according to criterion “weight of the woman at a birth”: I – 107 women with low weight at a birth, II – 126 with excess, III – 110 people with normal weight. The anamnesis, in particular, family and own perinatal, as well as nutritional support, anthropometric data, the structure of pregnancy complications, the rate of growth and development of the fetus, perinatal results were determined. Levels of eicosapentaenoic and docosahexaenoic acids were determined as markers of nutritional support of the organism, as indicators of angiogenesis were determined – concentration of vascular endothelial growth factor and placental growth factor in blood, morpho-functional studies of placenta were performed. Results. Women born underweight are more likely to have menstrual disorders (every 4), infertility (every 10), miscarriage (every 5) and gynecological diseases. The pathology of gestation in such women and their mothers is similar in spectrum, which is an example of intrauterine programming. The implementation of this program is facilitated by negative factors of nutritional provision: inadequate breastfeeding, economical type of nutrition in favor of restricting protein foods and deviations in the process of angiogenesis. Conclusions. The importance of perinatal history as a factor that determines the increased risk of menstrual disorders, the frequency of infertility, the pathological course of gestation during pregnancy, the predisposition to placental insufficiency and the birth of a child with low weight. Women born with low birth weight and overweight are a contingent of increased perinatal risk, which is associated with a complicated own perinatal history on the background of obstetric pathology in their mothers. This fact complements the concept of intrauterine programming.
 
Article
The aim is to improve the results of surgical treatment of patients with gastric malignant tumors, complicated by gastrointestinal bleeding, by developing and implementing in clinical practice a new treatment tactic. Materials and methods. The study was conducted on the basis of the Kyiv City Center for Emergency Care of Patients with Gastrointestinal Bleedings and at the Kyiv City Clinical Ambulance Hospital (Ukraine) for the period from 2010 to 2020. A comprehensive examination and analysis of reatment’s results of 140 patients with malignant gastric tumors complicated by acute gastrointestinal bleeding, which amounted to 2.2 % of all reated patients with gastrointestinal bleeding during this period. Results. Radical operations were performed in 97 (69.3 %) patients, palliative and symptomatic – in 43 (30.7 %). Comparing the frequency of complications in the two periods of treatment of patients, a decrease in the second period, compared with the first period, the frequency of complications from 27.2 % to 11.4 % due to a decrease of 1.8 times (from 68.8 % to 37,5 %) complications after emergencies and related fatalities from 36.4 % to 0 and 2.2 times (from 20.8 % to 9.6 %) the incidence of complications after early delayed operations with a decrease in frequency fatalities from 20.9 % to 18.2 %. Conclusions. Operations at the height of acute bleeding in patients with gastric cancer are too dangerous due to the high postoperative mortality. The optimal standard is the use of a set of minimally invasive methods of endosurgical hemostasis to stop active bleeding and prevent its recurrence and operate on patients in the early delayed period. Adherence to such tactics is expedient from the point of view of reduction of risk for a life of the patient and possibility of carrying out radical operations.
 
Article
Parkinson's disease (PD) is one of the most common neurodegenerative diseases in the elderly. The aim of the study. To study apoptotic processes and their role in the formation of dopaminergic neurodegeneration and to develop new treatment regimens with a specific neuroprotective effect on the dopaminergic system. Materials and methods. The study was carried out on 90 Wistar rats at the age of 6 months weighing 220–290 grams. Parkinsonism was induced by the administration of the neurotoxin MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) to experimental rats with neuroprotective treatment: I – Intact (passive control); II – animals with experimental Parkinson's disease (PD, active control); III – PD + Amantadine (AM) IV – PD + AM + Cerebrocurin; V – PD + AM + Pramistar; VI – PD + AM + Gliatilin; VII – PD + AM + Noofen; VIII – PD + AM + Pronoran; IX – PD + AM + Melatonin. Results. The obtained data indicate that neuroprotective therapy of PD with drugs such as melatonin, cerebrocurin, pronoran and gliatilin in combination with amantadine leads to an increase in the expression of the HIF-1α, HIF-3α, HSP70 genes, bcl-2 proteins and decrease c-fos proteins with caspase-3 as markers of apoptosis and can also serve as a molecular marker for the activation of endogenous neuroprotection mechanisms under the conditions of an experimental PD. Conclusions. The study experimentally demonstrated a new target of neuroprotection in PD conditions – apoptosis of dopamine-producing neurons and substantiated modulators of this process – drugs for combined therapy with amantadine (melatonin, cerebrocurin, pronoran and gliatilin) as promising drugs for the treatment of PD.
 
Article
Streptococcus suis 2 is an important emerging zoonotic pathogen. It mainly causes meningitis in pigs. We use SS2 to infect bEnd.3 to get stable cDNA for next research on differences in gene expression and protein expression of cytokines. The paper presents an SS2 study for bEnd.3 infection to obtain stable cDNA for subsequent study of differences in gene expression and cytokine protein expression. Objective: The aim of this study was to extract the total RNA from mouse brain-derived Endothelial cells (bEnd.3) infected by Streptococcus suis serotype 2 (SS2) and transcript to complementary DNA (cDNA). Materials and methods: SS2 strain were obtained from Jilin University, China. BEnd.3 was from Henan institute of Science of Technology, China. Reverse transcription kit was from Takara company, Japan. Trizol was from Bioteke company,China. Nanodrop instrument was from Thermo company, USA. Polymerase chain reaction (PCR) instrument was from Biometra company, Germany. We used SS2 to infect bEnd.3 at a multiplicity of infection (MOI) of 100 for 12h. Cells were harvested and Trizol method was chose to extract the total RNA of bEnd.3 infected by SS2. Nanodrop instrument was used to measure the concentration of RNA and the values of OD260/280 and OD260/230. RNA were transcripted to cDNA with reverse transcription kit by PCR instrument. Results: trizol method used in this study was reliable and high-quality RNA were obtained. Stable cDNA were obtained by reverse transcription kit. Conclusion: in this experiment high-quality RNA was obtained and reverse transcribed to stable cDNA for subsequent detection of related cytokines. This study provides an approximate RNA extraction method and good experimental foundation for downstream research.
 
Article
Reproduction is a crucial issue at the present stage in the pig husbandry development. Infertility of breeding sows leads to excessive use of feed, increased costs associated with failed inseminations, insufficient breed and early culling of sows. Aim of the research. Study of infertility types and prevention of postpartum diseases in sows in order to develop methods to control them. Methods. A two-stage experiment was carried out in 2019–2020 at the LLC "Ryasnyanske" farm in Sumy region, Ukraine. The first stage involved development of a method for prevention and control of infertility in sows. The second stage focused on the method of postpartum pathology prevention. Results. The conducted research established that surfagon and vitamins manifested the highest efficiency in case of alimentary infertility as they increased fertilization by 20.8 %. In terms of symptomatic infertility, the best results were achieved through a combined use of surfagon and gonadotropic hormone for both primary and multiple fertilization of sows, especially considering extremely low values in the control group - 15 % and 6.5 % of piglets, respectively. Aminazine proved to be the most effective remedy for immune infertility, the obtained results were 17.2 % higher than in the control group. Surfagon at a dose of 5 ml together with estrofan twice a day fully prevented inflammatory postpartum pathologies in sows. Conclusions. Pathologies of the reproductive organs in sows are widespread at pork-producing farms. Individual use of surfagon was justified for treatment of alimentary, symptomatic and immune infertility of sows and prevention of postpartum pathologies. A combined use of tissue therapy and biologically active drugs proved to be the most effective. The treatment regimens described above reduce infertility and prevent postpartum pathologies in sows.
 
Article
Aim of research is the establishment of structural features of the course of the adaptive-compensatory and regenerative processes in the cortical substance of the rat kidney in late terms after experimental burn skin injury and the use of HAES-LX-5 % is relevant for theoretical and practical medicine.Materials and methods.The article presents and analyzes the results of an experimental study on the structural changes of the cortical substance of the kidneys in rats in late terms after burn injury of the kidney with the condition of administration of intravenous infusion of 0.9 % NaCl solution and complex colloid-hyperosmolar solutions of lactoprotein with sorbitol and HAES-LX-5 %. Comparative analysis showed that functionally different cells of the nephrons under the infusion of detoxification solutions in the conditions of development of burn disease die by necrosis, apoptosis and anoikis. Also in epithelial cells of nephron tubules there weremitophagy and mitoptosis.Result. Mitoptosis in epithelial cells of rat nephron tubules with experimental burn skin injury was carried out in two ways, which are related to I – destruction of the outer mitochondrial membrane; II – preservation of the outer mitochondrial membrane and attachment of autophagic (mitophagic) mechanisms to release the cell from degraded mitochondrial material. In the first case, the mitochondria first condensed, after which its matrix swelled and the fragmentation of the cross occured due to the destruction of the cross compounds. Finally, the outer mitochondrial membrane broke and the remnants of the crystals (in the form of vesicles) went into the cytoplasm. In the second case, the mitochondria condensed, vesicular fragmentation of the sac occured, but the outer mitochondrial membrane retained its integrity and the mitochondria were absorbed by the autophagosome. Next, autophagosomes merged with lysosomes and formed autophagolysosomes, which, subject to effective content processing, were transformed into vacuoles. The latter were emptied by exocytosis and ensured the cell was free from degraded material.Conclusions. Only a lactoprotein with sorbitol has a membrane-plastic effect aimed at strengthening the mitochondrial membrane, in part of the mitochondria of epithelial cells of nephron tubules is ultrastructurally increased by the electron density and thickness of all components of the mitochondrial membrane. The maximal membrane effect of the action of lactoprotein with sorbitol on the mitochondria manifests itself fourteen days after the experimental burn skin injury and gradually (twenty-one and thirty days later) disappears, which coincides with the improvement of the overall clinical condition. There is every reason to believe that increased structuralization of mitochondria is a safeguard for the spread of mitoptosis and mitophagy, the excessive nature of which can lead to cell death.
 
Models of toxicological parameters of different classes of fungicides prediction (linear regression equations) 
Article
Abstract. It has been established that there is a significant correlation (p<0.05) between fungicides of studied class toxicological parameters (LD50 per os, LD50 per cut, NO(A)EL, LC50 inhal.) and their physical and chemical properties (molecular weight, vapor pressure, water solubility, surface tension). It was proved that the proposed calculation models for forecasting the hazard of pyrazolecarboxamides, carboxamides, triazoles, carbamates fungicides classes are adequate and significant according to the Fisher test (р<0.05). The developed algorithm makes it possible to substantially simplify the conduction of toxicological experiments provided that there are data on the physical and chemical properties of the studied compounds and to accelerate the procedure for registration of new fungicides of the studied classes. Key words. Fungicides, toxicology, calculation models, regression equations.
 
Article
Colorectal cancer (CRC) ranks 2nd in the structure of mortality from malignant neoplasms (MN). One of the criteria for the prognosis of CRC may be a tumor stroma, which has not been widely used in clinical practice. The aim was to determine the main morphological features of the stroma CRC T3N0-2M0 and search for prognostic criteria for their recurrence and lethal outcome according to the operating material and autopsy. Materials and methods. Group I included primary CRC without recurrence. The average recurrence-free period was 5 years (62.5±16.5 months). Group II – primary CRC with recurrence; IIA – with recurrences within 5 years from the date of tumor removal that did not lead to death; IIB – with the appearance of recurrence and lethal consequence of the generalization of the tumor process within 5 years from the moment of removal of the primary tumor. CRC micropreparations made according to the standard method with G + E staining were studied; immunohistochemical study was performed using monoclonal antibodies to smooth muscle actin alpha. Results. Stromal-parenchymal ratio >50 % is a prognostic criterion for recurrence (p
 
Article
The aim of the work was to justify the feasibility of developing a new drug with a dry extract of hop cones in the form of hard gelatin capsules for the treatment of gastrointestinal diseases.Methods. In order to study the range of medicines based on hop cones on the pharmaceutical market of Ukraine, a marketing analysis of registered drugs has been conducted. The marketing analysis was carried out using the information of retrieval system "Drugs" by "Morion" LLC and the State Register of Medicines of Ukraine, which allows quickly tracking changes in the structure of offers. To systematize the main characteristics of the studied drug of hop cones, to assess its strengths and weaknesses, opportunities and threats, a modern marketing method – SWOT-analysis has been used. In the process of research, methods of system analysis, monitoring, logical generalization, grouping of marketing research, etc. were used.Results. The methodology of research has been developed and justified. The main types of pharmacological activity of extracts from hop raw materials have been reviewed. A comprehensive study of the drug from hop cones using the SWOT-analysis method has allowed analyzing its strengths and weaknesses, which can contribute to or hamper the progress and consolidation of this drug in a certain market segment. It was revealed that the strengths of the drug are much greater than the weaknesses, and this speaks in favor of its competitiveness in the pharmaceutical market of Ukraine.The discussion of the results. The medical and marketing expediency of developing a new medicinal preparation with a dry extract of hop cones in the form of capsules for use in gastroenterology have been proved
 
Article
The development and introduction into practice of emergency neurology of new drugs capable of influencing secondary neuronal damage in patients with traumatic brain injury (TBI) has made a significant impact on the recovery of such patients.Aim of the work was to evaluate the magnitude of cerebroprotective action of amantadine sulfate in terms of impaired carbohydrate metabolism of the brain against the background of experimental TBI.Materials and methods. The experimental model of severe TBI was caused by the action of a carbon dioxide flow under pressure, which was created using a gas balloon of pneumatic gun. The therapeutic effect of amantadine sulfate on TBI model was evaluated with a 5 mg/kg dose. The pseudo-operated animals and control group received 0.9 % NaCl solution at a dose of 2 ml/kg with IV administration.Results. The obtained results confirm the formation of a hypo-energetic state in the brain cells of rats on the background of TBI, which is probably a consequence of the suppression of the processes of oxidative phosphorylation and its conjugation with tissue respiration. TBI is accompanied by activation of anaerobic glycolysis and inhibition of aerobic glucose oxidation, proving that there is an imbalance between the levels of lactate and pyruvate intermediates. 8-day infusion of rats with traumatic brain injury of amantadine sulfate, inhibited anaerobic glycolysis hyperactivation, stimulated tissue respiration processes, reduced signs of lactic acidosis and development of secondary alteration of brain cells by non-oxidized products.Conclusions. In the course of the experiment, it was found that the treatment of rats, with TBI model, with 0.9 % NaCl solution did not significantly contribute to the restoration of impaired energy metabolism (p<0.05) and did not reduce the manifestation of metabolic acidosis in the damaged brain (p<0.05). The use of amantadine sulphate in TBI rats significantly corrects carbohydrate metabolism disorders than 0.9 % NaCl solution and contributes to the reduction of metabolic acidosis in the damaged brain (p<0.05).
 
Article
Ovarian cancer remains one of the most fatal pathologies among women around the world due to late diagnosis on the advanced stages of the tumor process. Serous ovarian carcinomas (SOC) often recur, which worsens the prognosis for patients’ recovery and survival. The identification of prognostic clinical and morphological factors that predict the appearance of recurrence remains an urgent problem. The aim of the research was studying relationships between the phenomenon of epithelial-mesenchymal transformation (EMT) and the expression of surface cancer stem cells (CSCS) markers to identify recurrence predictors among women with low grade serous ovarian carcinomas (LGSC). The material were paraffin blocks and slides of 43 patients with LGSC I-IV FIGO stage. The study included 30 cancers without recurrence and 13 tumors with it within 24 months. The expression of E-cadherin, Vimentin, CD44 and CD117 was studied using immunohistochemical (IHC) method. Results. Development of recurrence is typical for women with stage III-IV (p=0,01), the expression of Vimentin at level 51–100 % (p=0,001) and E-cadherin at 10–50 % (p=0.04). CD44 was expressed in 51.16 % of tumors and level didn`t depend on age, recurrence, but depended on disease stage (p=0.001). Recurrent LGSCs are characterized by the expression of CD117> 10 % (p=0.0001), its direct correlation with the stage (p=0.0001) and the recurrence (p=0.0001). A direct relationship was found between the CD117 and Vimentin expression. Conclusions. Prognostic markers of recurrence should be considered stage III-IV, levels of Vimentin 51–100 %, E-cadherin 10-50 % and CD117> 10 %. A correlation between CD117 and Vimentin expression indicates the commonality of EMT and CSCS in progression and recur. CD44 has no independent prognostic role.
 
Article
The analysis of the structure and results of surgical treatment of 72 patients who were hospitalized in the department of vascular surgery Lviv regional hospital for the period 1995 to 2017. Among the 42 cases was diagnosed carotid body tumors (1-st study group) and at 30 patients was (2-nd control group) other tumors of the neck. In first group structure of surgery operation was: tumor removal and suturing the vascular wall defects - 76%, resection and shortening of the common carotid artery - 21%, expansion of the internal carotid artery - 3%, ligation of the external carotid artery - 10%, lymphadenectomy - 28%, prosthetic vascular wall - 3%, the tumor resection - 3%, internal jugular vein ligation - 7%, excision of fragment muscle - 3%, nerve resection - 14%. In the second group, the following surgical operations were performed: removal of the tumor and suturing of the defects of the vascular wall - 96%, lymphadenectomy - 48% tumor resection - 30%, ligation of the internal jugular vein - 14%, removal of the muscle fragment - 4% , resection of nerves - 13%. In group 1, intraoperative complications were observed in 1 (3.4%) cases, which were manifested by massive bleeding from the tumor, requiring a repeated surgical intervention to stop the bleeding. Postoperative complications were observed in 1 (3.4%) cases when acute cerebral ischemia developed. In 1 (3.4%) cases, tumor recurrence was observed after 9 years.Clinic experience shows that surgery is an effective treatment for carotid body tumor and tumors with invasion into vessels of the neck, providing a low rate of complications, a full recovery or long-term remission
 
Article
Expert diagnostics of forensic causal determinations should be based on a dialectical-materialistic approach, provided with a modern level of specially applied theoretical knowledge of pathology, etiology and pathogenesis of traumatic processes, as well as stimulated by urgent requests of the theory and practice of forensic medical expertise (FME). The aim of this work is to determine causal estimates of the components of forensic objects: natural and causal – through retrospective causal modelling.Materials and methods. The research material was archival documents of the Vinnytsia Regional Bureau of Forensics (Ukraine) for 2009–2012 with cases of violent death from injuries. 27 deterministic models were constructed by modelling the regular relationships in traumatic processes.Result. The qualitative unity of the forensic object is simulated: empirical (natural) and causal (determinant). The existence of an object determinant in concordance of the determinant object with the deterministic object is stated. The method of investigation of the determinants of expertise was proposed – logical retrospective modelling of object determinants dependencies. An assumed model of the dependency model is a multi-link time-chain of forensic medical determination. The adequacy of the proposed method of logical modelling of determinants in forensic examination is confirmed with the help of known scientific knowledge about dual, causal determination, causal diagnostics of determinants and forensic cause and effect relationships. It is proved that forensic expertise is a multidisciplinary branch of science and reflects the realized integration of different scientific knowledge. However, diagnosis of "causes of violent and non-violent death" requires the development of an applied methodology for FME from the standpoint of modern philosophical concepts of causality and general theory of systems, the achievements of which must be used in the construction of the methodology of FME.Conclusions. From the results of this study, it follows that causation is only a moment of determination, and purely causal modelling as an exploration of a particular type of determination cannot give a complete explanation for the deterministic relationship. The property of necessity of a specific reason determines the tendency, the orientation of development in the form of possibility, which is actualized only by the complete set of determinants - causal and noncausal, conditional.
 
Characteristics of the main and control groups of the study
Article
Aim: to investigate a fecal microbiota composition and to identify candidate biomarkers of celiac disease (CD) by serum metabolomics analysis.Methods: the quantitative real-time polymerase chain reaction was used for fecal microbiota assessment. Serum metabolomic assays were conducted using the GC–MS.Results: serum of CD patients showed significant increases in stearic acid, 2-HIVA, succinate, fumarate and benzoate compared to HC. A decrease in the level of eicosadiene and an increase in AA in blood were determined. The ratio of AA to EDA was statistically significant (4.84 vs. 3.28, p=0.033). The elongase activity index in patients with celiac disease tended to increase (p=0.067). The colon microbiome in CD was characterized by decreasing in the level of butyrate-producing Faecalibacterium prausnitzii (F.p.) and Bifidobacterium spp.. Significant negative correlations were observed; between the levels of Bifidobacterium spp. and F.p. and the concentration of succinic acid (rs=–0.343 [p=0.026] and rs=–0.430 [p=0.005], respectively); the F.p. and the fumaric acid (r=–0.429, p=0.005); the benzoic acid and the amount of Bifidobacterium spp. (r=–0.341, p=0.025).Conclusion: significant changes in serum levels of microbial and endogenous metabolites, reflecting some metabolic pathways disturbances were observed in CD. Metabolites and metabolomic index reflecting the balance between pro-inflammatory and anti-inflammatory components, may be considered as candidate biomarkers of chronic inflammation and metabolic dysbiosis in CD. An increased B. fragilis/F.p. ratio can serve as available biomarker for intestinal pro-inflammatory dysbiosis in CD.
 
Article
Children frequently are admitted to pediatric intensive care units due to acute respiratory failure and up to 64 % of them need to be mechanically ventilated and later weaned. The aim was to develop strategy of weaning from mechanical ventilation in children with different types of respiratory failure. Materials and methods. The work was based on results of treatment of 237 patients aged from 1 month to 18 years old, who were divided into control and study group. Patients of study group were randomized into group I (83 patients) and received traditional ICU monitoring and treatment and group II (79 patients), where was used proposed by us methods of monitoring and treatment. Results. There was supplemented data on the etiology of respiratory failure in children with taking into account function of diaphragm, changes in hemodynamics, nutritional status, electrolyte balance and central nervous system function. It was established new mechanisms of inadequacy of spontaneous breathing during mechanical ventilation and found causes of unsuccessful weaning from mechanical ventilation. In addition, it was developed a weaning strategy with goal-directed therapy for disorders treatment according the type of respiratory failure and children`s age. As a result, important scientific problem was solved and the results of treatment of children with respiratory failure was improved. Conclusions. It was found that proposed strategy of weaning from mechanical ventilation allowed to reduce the duration of mechanical ventilation and the frequency of complications (reintubations). There were no significant differences in the frequency of tracheostomy among patients of I and II groups.
 
Top-cited authors
Anna Ihorivna Kriukova
  • National University of Pharmacy
Viacheslav Lebedynets
  • National University of Pharmacy
Antonenko Anns
  • Bogomolets National Medical University
Olena Tkachenko
  • National University of Pharmacy
O. P. Vavrinevych
  • Bogomolets National Medical University