Zaporizhzhia State Medical University Research Articles

Changes of the pro-hormone levels of vitamin D 25(OH)D in patients with newly diagnosed pulmonary tuberculosis treatment failure

In Ukraine the number of patients with newly diagnosed tuberculosis (NDTB) who successfully complete the course of treatment reaches 60–65 % today. This is while the World Health Organization (WHO) criteria for successful treatment of this category of patients is 85 %. Scientists around the world are studying the possible pathogenetic factors of treatment failure of antimycobacterial therapy in patients with tuberculosis. Nowadays, the impact of vitamin D has been widely studied in this area. Studying of the dynamics of this indicator in patients with NDTB with widespread destructive tuberculosis in the lungs and bacterial excretion with the purpose of finding new markers of progression of a specific process and failure of treatment, as well as finding possible ways of additional pathogenetic therapy to accompany patients is actual. This approach will prevent treatment failure and, as a consequence, improve treatment efficiency.Purpose. To determine changes in the pro-hormone levels of vitamin D 25(OH)D in patients with NDTB treatment failure during the intensive phase of antimycobacterial therapy.Materials and methods. A prospective study involving 58 patients with NDTB lungs was performed. The patients were divided into 2 groups: 28 patients with pulmonary NDTB treatment failure were included in the 1st group (the main group), 30 patients, who subsequently successfully completed the course of treatment were included in the 2nd group (comparison group). The control group consisted of 29 healthy volunteer-donors. All the patients had been in inpatient treatment in Communal Institution “Zaporizhzhia Regional TB Clinical dispensary” during 2017–2019 years. Scientific medical-laboratory center of Zaporizhzhia State Medical University researched changes of the level of 25(OH)D in the blood serum by method of enzyme linked immunosorbent assay using immunoassay analyser Sirio S with “DIAsource ImmunoAssays S.A.” kit (Belgium) (ng/ml). Blood sampling was made after an overnight fast. Blood was collected uniformly throughout the year in all patients and volunteers to avoid the effect of seasonal variability in vitamin D in the blood.Results. While healthy volunteers have a reduction in the level of pro-hormone 25(OH)D only in 51.7 % of cases (deficiency in 13.8 % and insufficiency in 37.9 %), patients with NDTB with generalized specific process in the lungs, the presence of destruction of over 3 cm in diameter and bacterial excretion at the beginning of intensive phase of antimycobacterial therapy (0 doses), have its decrease in 96.5 % (81 % deficiency and 15.5 % insufficiency). 1/3 of patients (35.7 % at the 0th dose and 32.1 % at the 90th dose) with tuberculosis treatment failure have pro-hormone levels 25(OH)D less than 7 ng/ml, whereas in patients who successfully completed the course of treatment, this concentration of pro-hormone 25(OH)D was not even diagnosed. In the dynamics, after 3 months of intensive phase of antimycobacterial therapy (90 doses) in patients with NDTB treatment failure the levels of pro-hormone 25(OH)D continue to decrease significantly by 1.3 times relative to the initial values, which is 1.4 times lower than in patients who successfully completed the course of treatment.Conclusions. In the vast majority of patients with NDTB of lungs with a risk of ineffective treatment, a pronounced deficiency of vitamin D (1/3 patients with pro-hormone levels 25(OH)D less than 7 ng/ml) is determined at the beginning of treatment, and after 3 months of the intensive phase of antimycobacterial chemotherapy exacerbates vitamin D deficiency. Therefore, this indicator can be used as a prognostic for the tuberculosis treatment failure and reducing the level of pro-hormone 25(OH)D in the dynamics require consideration of the problem of methods of its correction by the addition of vitamin D.

Changes in the levels of adipokines in newly diagnosed pulmonary tuberculosis patients in case of treatment failure

Improving the treatment efficacy for patients with newly diagnosed tuberculosis by reducing the number of treatment failure cases is very urgent issue nowadays. Purpose. To define the characteristics of adipokines levels changes in newly diagnosed pulmonary tuberculosis patients in case of treatment failure by examining the levels of leptin, adiponectin and leptin/adiponectin ratio. Materials and methods . A total of 58 patients with newly diagnosed pulmonary tuberculosis were the subject of this prospective study. The patients were divided into 2 groups: the first group was made up of 28 patients with the ineffectively treated newly diagnosed pulmonary tuberculosis; the second group (experimental group) consisted of 30 patients with successful treatment completion. The control group included 29 healthy voluntary donors. Changes in the levels of adipokines by measuring the blood serum leptin and adiponectin via enzyme linked immunosorbent assay using immunoassay analyzer Sirio S with “Mediagnost” kit (Germany) (ng/ml) were studied at the Scientific Medical Laboratory Center of Zaporizhzhia State Medical University. Leptin/adiponectin ratio was calculated mathematically (relative units). Blood samples were collected after an overnight fasting. Statistica for Windows 13.0 (Copyright 1984–2018 TIBCO Software Inc., all rights reserved, Licence No. JPZ8041382130ARCN10-J) software was used for the statistical analysis. Results. The following significant changes in the adipokines levels have been found in patients with newly diagnosed pulmonary tuberculosis with massive pulmonary lesions and destructions of over 3 сm in diameter and positive sputum smear. These patients will be diagnosed with ineffective treatment. At the beginning of the antimycobacterial therapy, there was a significant 12.7 times decrease in leptin and 1.4 times increase in adiponectin indicators and 21 times decrease in the leptin/adiponectin ratio. The levels of leptin, adiponectin and leptin/adiponectin ratio were significantly worse than similar levels in patients, who completed the treatment efficiently. The level of the leptin was slightly increased during the antimycobacterial therapy, albeit being significantly reduced, and the level of the adiponectin continued to increase significantly. The leptin/adiponectin ratio was significantly lower than that in patients who completed the treatment efficiently. Conclusions. Patients with newly diagnosed pulmonary tuberculosis with the risk of treatment failure are diagnosed with severe disorders of adipocyte functional activity, that antimycobacterial chemotherapy could not even restore the balance to the adipokine system and smooth down resulting concomitant variations in immune response. The findings showed the prognostic value of the changes in leptin, adiponectin and leptin/adiponectin ratio indicators at the beginning of the treatment in relation to treatment failure among patients with newly diagnosed pulmonary tuberculosis.

Efficiency and safety of peripheral regional anesthesia application in urgent traumatology

In Ukraine, more than 4.5 million people sustain injuries of varying severity annually, and damage to extremities constitutes 60–65 % in the structure of traumatism. Patients with traumatic limb injuries require effective anesthesia / analgesia at an early stage. An urgent anesthesia should provide a sufficient relaxation of the extremity, adequate operative and postoperative pain management and should be safe for patients of different age groups. Peripheral regional anesthesia meets the requirements indicated, but there are a number of outstanding issues: difficulties in identifying plexuses and nerves, high rate of complications. Neither a larger injection volume of local anesthetic nor plexuses and nerves identification using a neurostimulator solves the problem completely. At the same time, ultrasound-guided nerve block does not have the weaknesses mentioned and its use is increasingly covered in literature. The purpose of this work is to analyze the effectiveness and safety of the ultrasound-guided nerve block of the extremities in urgent traumatology. Material and methods. Cases of isolated mechanical traumatic injuries of the limbs in patients who were at the clinical base of the Department of Disaster Medicine, Military Medicine, Anesthesiology and Intensive Care of Zaporizhzhia State Medical University from 2016 to 2018 were analyzed. The average age of the trauma patients was 62.5 (47.0; 82.5) years with a body weight of 78.7 (64.3; 94.6) kg. All the patients underwent ultrasound-guided nerve block using an ultrasound device Logiq E with a standard 12 MHz linear array transducer or the “classical” method (anatomical landmark and paraesthesia technique of plexus location). Anesthesia was performed with 0.5 % bupivacaine at a dose of 1–2 mg/kg. Analgesia was performed with a solution of propofol at 1.5–2.0 mg/kg /h with the addition of ketamine at 1–2 mg/kg/h in case of need. The level of analgesia was evaluated on the Ramsay sedation scale. The study analyzed the duration of plexus and nerves location, block onset time, the duration of motor and sensory block; hemodynamics monitoring with the help of UM-300 monitor at the study stages; complications were recorded. Statistical analysis of the data included descriptive statistics methods. When the values did not follow a normal distribution, these data were expressed as a median (lower quartile; higher quartile). Mann-Whitney U test was used to compare variables; the categorical data were analyzed by Chi-square test with Yates correction and Fischer's exact test. In all statistical calculations, P < 0.05 was the level of significance. Data processing was performed using Statistica 10.0 software. Results . The ultrasound-guided method of plexus and nerves location was faster than the “classical” method by paresthesia (3.8 (2.8; 4.3) min and 7.2 (4.2; 9.4) min, respectively; P = 0.001). But the method of plexus and nerves location did not influence the block onset time and the motor and sensory block duration. However, the level of analgesia in patients with ultrasound-guided nerve block (according to the Ramsay sedation scale) at the III and IV study stages was lower than in those with the “classical” method by paresthesia (3.2 (2.4; 3.7 ) and 5.4 (3.8; 5.7) points, respectively; P = 0.027), indicating a greater efficiency of ultrasound-guided plexus and nerve sensory block. The absence of statistically significant changes in hemodynamic parameters at the study stages indicated an effective intraoperative analgesia in patients with ultrasound-guided nerve block which was complicated in 6 cases (6.0 %). But the “classical” method of plexus and nerve block by paresthesia was complicated in 16 cases (32.0 %). Therefore, the ultrasound-guided method of plexus and nerve block was safer. Thus, it can be concluded that ultrasound-guided location of plexuses and nerves was faster than paresthesia method (3.8 (2.8; 4.3) min and 7.2 (4.2; 9.4) min, respectively; P = 0.001) in urgent traumatology. The sensory block in patients according to the analgesia level on the Ramsay sedation scale at the III and IV study stages was lower as compared to the “classical” method by paresthesia (3.2 (2.4; 3.7) and 5,4 (3.8; 5,7) points, respectively, indicating a more effective ultrasound-guided block of plexuses and nerves. Ultrasound-guided block was effective for intraoperative analgesia based on hemodynamic parameters in urgent traumatology. The method of ultrasound-guided block of plexuses and nerves was safer (6.0 % of complications versus 32.0 % when using the “classical” method by paresthesia).

ВПЛИВ ЗАМІСНИКІВ РІЗНОЇ ПРИРОДИ У 3- ТА 5-МУ ПОЛОЖЕННЯХ 4Н-1,2,4-ТРИАЗОЛУ НА ПОВЕДІНКУ ПОХІДНИХ В УМОВАХ ГХ-МС-АНАЛІЗУ

Pharmaceutical products require appropriate quality control, which comprises a set of tests aimed at the determination of assays of the substances. Chromatographic methods are one of the most abundant analytical methods applied in routine analyses of pharmaceuticals. Information on the behavior of the compounds under certain analytical conditions is valuable in the process of analytical method development. This work was aimed at revealing the impact of substituents of various natures at two positions of triazole ring on the behavior of new 3-thio-1,2,4-triazoles under GC-MS conditions and evaluating the applicability of GC-MS method for the analysis of these compounds. Gas chromatography was used in combination with mass spectrometry. New 1,2,4-triazole derivatives were obtained at the Department of Natural Sciences for International Students and Toxicological Chemistry of Zaporizhzhia State Medical University. For the experiment, two groups of compounds were formed, each having different substituents at C-3 and C-5 of triazole molecule, respectively. The analysis was held using Agilent 7890B GC system coupled with Agilent 5977B mass selective detector. Compounds were separated on a non-polar column. The following parameters were assessed and compared for identification and study of chromatographic behavior of the compounds: mass spectra, retention times, symmetry factors, and relative responses (against reference compound). It was shown that there is no direct relation between melting point and retention time; instead, the nature of substituents significantly affects the chromatographic behavior. The strongest response belongs to compounds that have phenyl moiety at C-5 and alkyl substituent attached through thiol group at C-3 of the triazole ring. Thiophen-2-yl and methyl at C-5, as well as acetate and ester groups attached through thiol group at C-3 of the cycle, decrease chromatographic response. GC-MS can be applied for the analysis of biologically active 1,2,4-triazoles, though with several limitations. The higher the polarity of the compound, the worse the response and peak shape; these circumstances complicate GC-MS analysis of 1,2,4-triazole derivatives. Apart from providing information on physicochemical properties of the compounds, the obtained experimental data provide some valuable insights into permeability of the new triazole derivatives through biological membranes, which could be useful in drug design.

ДО ПИТАННЯ ВПРОВАДЖЕННЯ ЛІЦЕНЗІЙНОГО ІНТЕГРОВАНОГО ІСПИТУ З МЕДИЦИНИ У ЗАКЛАДАХ ВИЩОЇ ОСВІТИ УКРАЇНИ

Introduction. The entry of the Ukrainian state into the European educational space, bringing in line domestic educational standards of future medical profe-?sionals’ training to European ones led to the reform of higher medical education, expanding the content of educational programs, introducing new methods and technologies of teaching students and improving forms of cooperation of teachers and students in medical establishments of higher education. In this regard, the Ministry of Health of Ukraine decided to introduce a licensed integrated exam for students of medicalestablishments of higher education, which aimed to identify not only the level of training of graduates of domestic medical establishments, but also to compare their training with European and world levels.The purpose of the article is to reveal the history of the introduction of a licensed integrated medical exam in Ukraine, the content of the system of students’ training for it, the positive aspects and shortcomings of the first experience of this form of state certification in various medical establishments of higher education. Methods. During the work on the article the following main research methods were used: analysis, synthesis, comparison, generalization, descriptive. Results. The history of the introduction of the licensed integrated exam in medicine in Ukraine during the end of the 20th – the first quarter of the 21st century in Ukraine is revealed in the article. The sites of the Ministry of Health of Ukraine and the Testing Center at the Ministry of Health of Ukraine, which contain state documents on the feasibility of the system of implementation of a licensed integrated medical exam; information about the experiment in some medical etablishments of higher education of Ukraine and the first experience of implementing licensed state certification in medical universities, schools, colleges and academies in the Ukrainian state are presented and analyzed. It was established that the experiment was initially conducted in some establishments of higher education since 1996 with further discussion of its results, and in 1998 the licensed integrated exam has become mandatory for all medical establishments of higher education of Ukraine that train specialists in “Medicine” and “Pharmacy”. Since 2000 it has become mandatory for specialists in “Dentistry”, and since 2004 exams have become mandatory for interns and in 2007 they have become mandatory for interns-dentists. Particular attention is paid to the content, structure and stages of implementation of this exam, analysis of the first results of its implementation and assessment of training for the exam by teachers and students of Ukrainian medical establishments of higher education. A comparative description of the methods of training, organization of the exam, information material for it, forms of independent training for the exam of students in medical establishments of higher education of different levels of accreditation is given. The experience of teachers’ work at such medical establishments of higher education as Bukovynian State Medical University, Vinnytsia National Medical University named after M.I. Pyrohov, Zaporizhzhia State Medical University, Ternopil State Medical University named after Ivan Horbachevsky, Kharkiv National University of Pharmacy, Zhytomyr Institute of Nursing, Dnipropetrovsk Medical Academy and others. Originality. The experience of introduction of the licensed integrated examination in medical estab-?ishments of higher education of Ukraine of different levels of accreditation is systematized for the first time.

АЛГОРИТМ ФОРМУВАННЯ ГРУПОВОГО ТА ПЕРСОНАЛЬНОГО НАВЧАЛЬНОГО СЕРЕДОВИЩА ЗАСОБАМИ СТРУКТУРУВАННЯ ОСВІТНЬОГО ПРОСТОРУ УНІВЕРСИТЕТУ НА БАЗІ СЕРВІСІВ MS OFFICE365ТА MS TEAMS

The algorithm of formation of a personal learning environment (PLE) and learning group environment for the organization of electronic distance learning in medical higher education institutions is offered. It was noted that the introduction of the COVID-19 quarantine raised the issue of reorganization of the learning space and accelerated the process of introducing the distance learning model. The experience gained by the authors during quarantine made it possible to form the stages of deploying the learning environment in the medical higher education institution and to define the educational space of the group as the main element of this environment. The main technological steps of creating subsystems of the educational space of the university for using cloud services MSO365 were considered using the example of Zaporizhzhia State Medical University. The conditions that allow creating a hierarchy of the learning environment were defined, namely: a project of the structure of the learning environment with the coordination of departments; registration of all participants of the learning process and creation of their accounts in Active Directory of the university; automated procedure of transferring group members to AD MSO365. The paper provides an example of a hierarchy of names, which is a reflection of the structure of university departments in terms of staffing and determines the rights of access to the usage of services that ensure the implementation of the corresponding functions. The authors found that the user account is the first integrating service that allows the user to form a personal learning environment using OneDrive, web-site MS SharePoint, MS Forms and other office applications. It was noted that the user account is the lowest level of the hierarchy of the learning environment, the usage of which provides a learning space for groups. According to the authors, it is reasonable to use MS Groups to form academic groups. Using MS Teams, a teacher gets a flexible tool to form a learning environment for various organizational forms, namely: lectures, seminars, practical classes, independent work, etc. The authors proposed rules for forming group names in MS Groups and MS Teams. They presented an algorithm for deploying the department's learning environment and proposed a suggestion of structuring the subject's learning environment using MS Teams channels for a small number of groups in the department.

The relevance of household contacts tracing among child contacts of patients with multidrug-resistant tuberculosis

BACKGROUND. The World Health Organization (WHO) reports an unknown contact history of pediatric tuberculosis (TB), especially in children younger than 5 years old. Tracing pediatric household contacts of patients with multidrug-resistant TB (MDR-TB) is considered to be a highly effective intervention for detection of new cases of chemoresistant TB in children and timely prevention of its transmission. OBJECTIVE. To study the nature of TB process manifestations and concordance of mycobacterium tuberculosis (MBT) drug resistance profiles in household child contacts of patients with MDR-TB. MATERIALS AND METHODS. The nature of TB process manifestations and concordance of MBT drug resistance profiles in 12 household child contacts of patients with MDR-TB in 6 households (6 adult MDR-TB index patients, IP) were studied. Adults and children were examined and treated in the Pulmonary Tuberculosis Department No 3 and in the Pediatric Department of the Clinical Base of the Department of Phthisiology and Pulmonology of Zaporizhzhia State Medical University at the Municipal Institution “Zaporizhzhia Regional Tuberculosis Clinical Dispensary”. RESULTS AND DISCUSSION. The tracing of children who were household contacts of the MDR-TB IP revealed the following features. The incidence of child TB was 2 times higher than that of contact adults (44 % vs. 20 %). Moreover, the incidence among children younger than 2 years of age was almost 3 times higher than in children across other age groups (54.5 % vs. 18.2 % in children younger than 5 years of age and 18.2 % in children aged 5 years and older). The children were non-BCG vaccinated in 63.6 % of cases. There was an alarmingly high rate of non-BCG vaccinated children, namely 83.3 % among individuals younger than 2 years of age and all of those younger than 5 years of age (100 %). The children mostly presented small clinical forms of non-destructive TB: intrathoracic lymph node TB (36.4 %), MBT complex (36.4 %) and focal TB (18.2 %). Most of the children (63.6 %) who developed TB were detected within the first year of IP with MDR-TB follow-up, and it is worthy of note that in the majority of cases (4 households; 66.6 %). With respect to the concordance of MBT drug resistance profiles between the children and MDR-TB IP in the households, diagnosis in children was microbiologically confirmed in only 3 cases (3 households) demonstrating the complete concordance of profiles in each one. At the same time, the complete concordance of MBT drug resistance profiles between adult household contacts and the MDR-TB IP was also recorded in 3 cases. As is evident, across the household contacts group aged between 0 and 18 years who were exposed to the MDR-TB IP, the most susceptible to develop TB were non-BCG vaccinated children younger than 2 years. More worryingly is that among 3 microbiologically conformed individuals of this age group, 2 children younger than 2 years were found to have their own drug resistant MTB isolates. CONCLUSIONS. Tracing household child contacts of MDR-TB IP is particularly effective for timely detection of active TB within the first year of MDR-TB IP follow-up. Non-BCG vaccinated children younger than 2 years of age are at the highest risk for MDR-TB followed by non-BCG vaccinated children younger than 5 years of age. The early detection and timely antimycobacterial therapy initiation based on drug susceptibility test results of a MDR-TB IP is a guarantee not only for an effective treatment but also for a reduction in the MDR-TB transmission to other persons.

Experimental evaluation of the specific activity of the new Angiolin dosage form in the research corneal burn's condition

Visual organ injuries are still one of the main causes of blindness and occupational disability. Despite the good protection of the eyeball by the bone walls of the orbit and adnexa oculi, its injuries are 5–10 % of the total number of all damages in peacetime and about 20 % in wartime. Employees of the Department of Pharmaceutical Chemistry of Zaporizhzhia State Medical University (ZSMU) together with the specialists of the SPA “Farmatron” under the supervision of professor I. A. Mazur synthesized a new compound, called Angiolin. The aim of the research is to study the anti-inflammatory, wound-healing, reparative activity of the Angiolin eye drops action during a chemical burn of the cornea rabbits modeling. Materials and methods: The pharmacological efficacy of the prepared Angiolin eye drops in concentrations: 0.5 %, 1.0 %, 1.5 %, 2.0 % and 2.5 % has been studied. All studies were carried out on 40 eyes of 20 Chinchilla breed rabbits of both sexes weighing 2.1–3.5 kg. The chemical burn model was reproduced according to the Obenberger method using 10 % sodium hydroxide solution (application of8 mm blotting paper), exposure time 20 seconds, after preliminary installation anesthesia with 0.5 % Alcaine solution. Results. Based on experimental data, it can be noted that Angiolin eye drops in concentrations: 1.0 %, 1.5 %, 2.0 %, 2.5 % show almost the same pharmacological activity, and 1 % Angiolin eye drops were the most effective, that gives us the opportunity for further study. Conclusions. Angiolin eye drops exhibit high anti-inflammatory, wound healing, reparative activity in the treatment of eye burn. As a result of the study, it was found that 1 % of Angiolin eye drops turned out to be the most effective. The obtained results are an experimental rationale for further study of 1 % Angiolin eye drops.

THE USE OF INFORMATION-EDUCATIONAL ENVIRONMENT OF REMOTE TRAINING OF STUDENTS OF HIGHER EDUCATION INSTITUTIONS

Abstract. Lately, the growing popularity of distance education: in 2014 on Google the most common search question was complete higher education. The development of education based on the principles of continuity, equal access, personal orientation forms a conceptually new model of education is "Open education". Therefore, the problem arises to use the appropriate modern educational technologies. The use of the information educational environment for student learning is one of the main implementations in institutions of higher education. The article presents the use of information and educational environment while training in the Ivano-Frankivsk national medical University and in the Zaporizhzhia state medical University, briefly discloses the use of Microsoft Office 365 and SharePoint. According to the developed questionnaire questioning of students of various forms of training and courses, interest in e-learning using Office 365 and summed up in the use of information and educational environment of the students of Ivano-Frankivsk national medical University and Zaporozhzhia state medical University.&#x0D; Research methods: analysis was conducted on the basis of materials of scientific works of contemporary researchers in the field of cloud services, questionnaires, processing of online sources and modern literature to clarify how to use Office 365. During the research were used such methods as analysis of theoretical sources on the use of Internet resources in educational process, study and generalization of experience of organization of independent work of students using information-educational environment.&#x0D; According to the Order of the MESU of April 25. 2013 №. 466 «On approving decree of distance education». Virtual education expands and updates the assignment of the teacher, make him a coach-consultant who shall coordinate the educational process, continually improve the courses that he teaches, increase creativity and skills in accordance with the innovations and innovation.&#x0D; The questionnaire has been made for surveying students of full-time and part-time forms of education. The results of usage the virtual learning environment by students of the full-time and part-time form of education are presented due to the prepared strict questions.&#x0D; After analyzing the forms of education and knowledge of students in the use of the material presented to them in Microsoft Office 365 and SharePoint, of course, it can be argued that the students of day form of education are more likely to use the site to prepare for couples and testing even at home.

Efficiency of medical and physical rehabilitation in patients who suffered from cerebral ischemic stroke

Objective. The purpose is to increase the efficiency of medical and physical rehabilitation in patients who suffered from cerebral ischemic stroke (CIS) with the help of differentiated use of rehabilitation measures depending on the severity of neurological disorders and comorbid states.Materials and methods. In the clinic of nerve diseases of Zaporizhzhia State Medical University we observed 305 patients (213 men and 92 women, average age is 57.93 ± 0.43 years old) in the recovery period of CIS. All patients were clinically and neurologically examined according to a specially designed protocol using modern scales – NIHSS, mRS on the 10th, 30th, 90th and 180th day of the disease and differentiated treatment in accordance with standards and protocols for the assistance to patients who suffer from stroke. Patients with CIS were divided into four groups. The first group included 111 patients (36.4 %) with CIS, among whom the severity of post-stroke disorders was mild (state on NIHSS ≤ 7 points), without comorbid conditions. The second group consisted of 120 patients (39.3 %) also with a mild degree of post-stroke disorders (state on NIHSS ≤7 points) and the comorbidity (heart pathology, diabetes mellitus, chronic obstructive pulmonary disease of the IInd stage). The third group included 36 patients (11.8 %) with CIS, among whom the severity of post-stroke disorders was moderate and obvious (state on NIHSS &gt; 7 points), without comorbidity. The fourth group consisted of 38 patients (12,5 %) with moderate and severe post-stroke disorders (state on NIHSS &gt; 7 points) and comorbid pathology. Statistical analysis was carried out using descriptive statistics methods. The interrelation between qualitative features was evaluated according to the criterion of the Pearson’s chi-square test.Results. As a result of the treatment among the patients in group I, 97 patients (87.4 %) (index mRS 0–2) had a favorable outcome, relatively favourable one (index mRS ≥3 points) – only 14 (12.6 %); In group II, 104 patients (86.7 %) achieved favorable treatment, relatively favorable one – 16 (13.3 %); in group III – a favorable outcome was recorded in 13 patients (36.1 %), relatively favorable – in 23 (63.9 %), and in group IV – a favorable outcome was revealed in 13 patients (34.2 %), relatively favorable one – in 25 (65.8 %).Conclusions. The differentiated application of medical and physical rehabilitation in patients with CIS in different groups, taking into account the individual prognosis of the recovery period and selection of methods and ways of treatment, has improved significantly the effectiveness of rehabilitation measures.

Physical-chemical properties of 2-((5-(3-,4-fluorophenyl)-4-R2-1,2,4-triazol-3-il)tio)-1-arylethanons and their reduced systems

The aim of work is the investigation of properties of 2-((5-(3-,4-fluorophenyl)-4-R2-1,2,4-triazol-3-yl)thio)-1-arylethanones and 2((5-(3-,4-fluorophenyl)-4-R2-1,2,4-triazol-3-yl)thio)-1-arylethanols using modern physical-chemical methods.Materials and methods. Modern physical-chemical studies of 2-((5-(3-,4-fluorophenyl)-4-R2-1,2,4-triazol-3-yl)thio)-1-arylethanones and 2-((5-(3-,4-fluorophenyl)-4-R2-1,2,4-triazol-3-yl)thio)-1-arylethanols was conducted on certified and licensed equipment of the physical-chemical laboratories of the Zaporizhzhia State Medical University in accordance with approved research plans. As starting compounds for the synthesis of the corresponding 2-((5-(3-,4-fluorophenyl)-4-R2-1,2,4-triazol-3-yl)thio)-1-arylethanones, we used 5-(3-fluorophenyl)-4-methyl-1,2,4-triazol-3-thiol, 5(4-fluorophenyl)-4-methyl-1,2,4-triazol-3-thiol, 5(3-fluorophenyl)-4-amino-1,2,4-triazole-3-thiol and 5-(4-fluorophenyl)-4-amino-1,2,4-triazole-3-thiol.Results. The research objects of our choice are promising not only as end compounds for the search of biologically active molecules, they can later be used as starting materials for subsequent chemical transformations. It is also known that the presence of keto-group causes the appearance of different types of pharmacological activity, and the transition to alcohols reduces toxicity.According to the results of the experiment a number of new compounds, which were not previously described in the literature, have been obtained, as well as physical-chemical constants have been given.Conclusions. The reactions of 5-(3-fluorophenyl)-4-methyl-1,2,4-triazole-3-thiol, 5-(4-fluorophenyl)-4-methyl-1,2,4-triazole-3-thiol, 5-(3-fluorophenyl)-4-amino-1,2,4-triazole-3-thiol and 5-(4-fluorophenyl)-4-amino-1,2,4-triazole-3-thiol with some (2-bromo-1-phenylethanone, 2-bromo-1-(2-bromophenyl)ethanone, 2-bromo-1- (2-, 3-, 4-fluorophenyl)ethanone and 2-bromo-1- ( 4-methoxyphenyl)ethanone), a series of novel 2 - ((5-(3-,4-fluorophenyl)-4-R2-1,2,4-triazol-3-yl) thio)-1-arylethanones were synthesized. A new series of 2-((5-(3-,4-fluorophenyl)-4-R2-1,2,4-triazol-3-yl)thio)-1-aryl-ethanols were synthesized in the experiment.

Study of Consistent Characteristics of the Ointment with Octopirox

Effective therapy of seborrheic dermatitis remains an actual task for the dermatological practice. Octopirox has a significant antimycotic activity and a wide spectrum of antibacterial effect both against gram-negative and gram-positive pathogenic microorganisms. On a base of the complex physical-chemical, pharmaco-technological and biopharmaceutical investigations the compositions of applicative dosage forms with octopirox and for external use with octopirox and deresined naphthalene for therapy and prophylaxis of seborrheic dermatitis were developed by the department of technology of medications at Zaporizhzhia State Medical University. The aim of this work is assessment of the consistent properties of the developed ointment compositions with octopirox and refined naphthalene to determine the optimal composition of the combined soft dosage form based on the results of rheological study. Materials and methods. As the objects of the study the ointments on the base of sodium carboxymethylcellulose and methylcellulose glycerogels, which provide optimal octopyrox releasing from these hydrophilic delivery vehicles were used. Results . Establishment of dependence of the effective viscosity value from the shear speed for the experimental ointments with octopirox and refined naphthalene revealed that the deformation speed decreases with rising of tangential shear stress, and viscosity of compositions decreases. This is an evidence of structure in studying systems. Obtained results allow to predict the ointment composition with octopirox and refined naphthalene on the base of sodium carboxymethylcellulose glycerogel as more perspective for the further study. Conclusions. It was revealed that consistent characteristics of the ointment composition on the base of sodium carboxymethylcellulose delivery vehicle are practically completely situated within the limits of rheologic optimum of consistency for ointments, and “mechanical stability” value (2.37) characterizes the system as exceptionally thixotropic providing system recoverability after loading and allows to predict the stability of rheologic characteristics during long term of storage. Location of the rheogram of ointment with octopirox and refined naphthalene on the base of methylcellulose glycerogel practically out the limits of rheologic optimum of consistency for ointments indicates an inexpediency of further study of this applicative system for the topical administration. Calculated factors of dynamic flow of composition on the sodium carboxymethylcellulose delivery vehicle show positive spreading extent during application on the skin or during technologic operations of manufacturing.

Dynamics of indicators of oxidative stress and bone metabolism during treatment with thiotriazolin in patients with combined type 2 diabetes mellitus and osteoporosis course who reside in anthropogenic pressure conditions

The aim of the study. To investigate the effect of thiotriazolin on oxidative stress and bone metabolism in patients with a combined course of type 2 diabetes and osteoporosis, who permanently reside in industrial region.Materials and methods. On the basis of the educational and scientific medical center University Hospital of Zaporizhzhia State Medical University, 44 patients with combined course of type 2 diabetes and osteoporosis, who permanently resided in Zaporizhzhia, were examined for the period from 2016–2017. 22 patients received standard basic therapy for type 2 diabetes and osteoporosis, and 22 patients additionally received thiotriazolin. Patient groups were comparable in age, sex, and duration of type 2 diabetes mellitus. All patients studied the concentration of markers of oxidative stress (nitrotyrosine, 8-hydroxyguanine) and bone metabolism (osteocalcin and deoxypyridinoline).Results. Patients with a combined course of type 2 diabetes mellitus and osteoporosis who received basic therapy with thiotriazolin supplementation registered a significant decrease in the concentration of oxidative stress. Thus, in patients of the second group, there was a significant decrease in the serum level of nitrotyrosine by 5.5 times (pl0.05) and 8-hydroxyguanine by 2.1 times (pl0.05). When evaluating markers of bone metabolism in patients of the second group, the level of osteocalcin increased by 24 % (pl0.05), and the concentration of deoxypyridinoline significantly decreased in individuals of both groups, but in the group with the addition of thiotriazolin, its rate decreased by 30%, and in the first group only 16 % (pl0.05).Conclusions. In patients with a combined course of type 2 diabetes and osteoporosis, which, in addition to basic therapy, thiotriazolin was included, a significant decrease in markers of oxidative stress was registered in a daily dose of 600 mg for 3 months. Under the influence of basic therapy with the addition of thiotrazoline, a significant increase in bone formation and a decrease in bone resorption were observed in patients with a combined course of type 2 diabetes and osteoporosis

PECULIARITIES OF APOPTOTIC MARKER EXPRESSION IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND ARTERIAL HYPERTENSION

It is known that both chronic obstructive pulmonary disease and arterial hypertension are multifactorial diseases, and develop as a result of a complex interaction of genetic and environmental factors. The purpose of this work was to study the metabolism of caspase-7 and caspase-9 in patients with chronic obstructive pulmonary disease (COPD) in combination with arterial hypertension (AH). Materials and methods. We examined 23 patients with a diagnosis of essential hypertension stage II and COPD stage II without a clinically significant concomitant pathology. The plasma level of caspase-7 and caspase-9 was determined using the appropriate ELISA test systems (manufacturer – Bender Medsystems, Austria) at the Medical and Laboratory Training Centre of Zaporizhzhia State Medical University in accordance with the instructions attached to the kit. The analysis of the dynamics of the studied cysteine ​​proteases indicates a statistically significant elevation of these apoptosis markers in the conditions of hypertension and COPD. The value of caspase-7 in the cohort of patients with COPD + AH significantly exceeded similar figures for the groups of patients with a single pathology presented by AH or COPD, and averaged 0.41 ± 0.09 ng / ml. A statistically significant elevation of the caspase-9 level in patients with COPD + AH up to 2.16 ± 0.29 ng / ml compared with other groups also indicates a more significant induction of apoptotic processes in comorbid pathology than in isolated AH or COPD. Conclusion. The obtained results require further clarification of the nature of the relationship between changes in the metabolism of cysteine ​​proteases and the primacy of pathogenetic processes in the mechanisms of risk formation for complications and progression of ventilation disorders in patients with COPD and comorbid essential hypertension.

The study of structural-mechanical characteristics of suppositories with clopidogrel

During last years clopidogrel keeps leading positions among medicines with platelet antiaggregation mechanism. The rectal dosage form with clopidogrel, namely suppository containing 0.075 g of active substance on hydrophilic base with addition of 2 % twin-80 was proposed by the Department of Medicinal Preparations Technology (Zaporizhzhia State Medical University on the base of complex investigations. The aim of present work is the study of structural-mechanical characteristics of rectal dosage form with clopidogrel depending on the temperature of technological process of supposirory manufacturing. The study of structural-mechanical characteristics of suppository mass with clopidogrel was carried out using the rotational viscosimeter “Rheotest2”with cylinder device at the human body temperature (37 oС) and at temperature of manufacturing technological process. Results . Results testify presence of structure in suppository mass system, because limit shear stress increases and effective viscosity decreases with deformation speed rising. Conclusions . Study of consistent characteristics of suppository mass with clopidogrel on polyethylenoxyde base with addition of 2 % twin-80 at the human body temperature was carried out. It was established that it is structural system with expressed thixotropic properties and with the uniform distribution of active substance and excipients both at the moment of manufacturing and during administration or long storage. It was revealed that increasing of temperature of suppository mass to 50 oС doesn't lead to essential modification of its structural-mechanical characteristics and transformation into Newtonian system. Taking obtained results into account it was determined that temperature rate of manufacturing of rectal suppositories with clopidogrel on the hydrofiflic base (processes of mixing, homogenization, pouring into forms) within 50–55 oС creates sufficient fluidity of mass for unhampered technological process and thixotropy of suppository mass providing the uniform distribution of active substance and excipients in this dosage form.

ФОРМИ КОНТРОЛЮ В МЕДИЧНОМУ ВНЗ України: СТАРИЙ – НОВИЙ УСНИЙ ІСПИТ

Мета роботи – аналіз проведення іспиту як основної форми контролю в сучасній системі вищої освіти з точки зору його ефективності; дослідження позитивних сторін та недоліків даної форми рубіжного контролю; аналіз шляхів поновлення іспиту, його нових форм та можливість їх використання в практиці викладання в медичному ВНЗ.&#x0D; Основна частина. У статті представлені різноманітні форми контролю знань, що застосовуються у Запорізькому державному медичному університеті: вхідний (попередній, діагностичний), поточний (здійснюється безперервно, відстежує рівень знань, умінь і навичок студентів на практичних заняттях), рубіжний (контроль знань, умінь і навичок після закінчення модуля або курсу), відстрочений та підсумковий. Підсумковий контроль ­ державна атестація ­ проводиться у вигляді державних іспитів, у тому числі захисту випускної кваліфікаційної роботи.&#x0D; Висновки. Основною формою диференційованого рубіжного контролю в ВНЗ є іспит. Іспитом закінчується вивчення предмета або його основного розділу, причому викладач не може відмовитися від даної форми контролю хоча б тому, що вона вказана в навчальному плані, обов’язковому документі, якого необхідно дотримуватись.

Synthesis and physicochemical properties 4-((R))amino)-5-methyl-4H-1,2,4-triazole-3-thiols

Purposeful synthesis of derivatives of 1,2,4-triazole is one of the most important branches of modern pharmaceutical science&#x0D; Modern pharmaceutical market of domestic medicines requires constant updates of existing range. It makes possible the synthesis of new compounds with a predicted biological activity.&#x0D; The main advantage of derivatives of 1,2,4-triazole is high efficiency and low toxic. That is promising factor for creation of new chemical compounds.&#x0D; Analysis of literary data of past few years has showed that there is not enough information about synthesis, physical, chemical and biological properties of derivatives of 4-amino-5-methyl-4H-1,2,4-triazole-3-thiol in the literature.&#x0D; So synthesis and further research of derivatives of 4-amino-5-methyl-4H-1,2,4-triazole-3-thiol is topical.&#x0D; The research took place at the Department of toxicological and inorganic Chemistry of Zaporizhzhia State Medical University (the head of the department – professor O. I. Panasenko).&#x0D; During the work the research were the physicochemical properties of newly synthesized of compounds in accordance with the methods described in the State Pharmacopoeia of Ukraine.&#x0D; As starting substance was used 4-amino-5-methyl-4H-1,2,4-triazole-3-thiol obtained by cyclization of of potassium 2-atsetilgidrazinkarboditioata in the medium hydrazine hydrate.&#x0D; It is planned to research of the compounds obtained in the antimicrobial, act-protective, antioxidative and hypolipidemic activity.&#x0D; 9 new compounds of ylidene derivatives of 4-amino-5-methyl-4H-1,2,4-triazole-3-thiol were synthesized in a research. The structure of the new synthesized of substances was confirmed by with by means of modern of instrumental methods analysis (1H-PMR-spectroscopy, chromato-mass-spectrometry, elemental analysis). The obtained data is possible to use in purposeful synthesis for the further research of biologically active compounds.

Study of influence of the surface-active substances concentration on releasing of praziquantel from the rectal suppository

Acne dermatosis (rosacea, perioral dermatitis, seborrheic dermatitis etc.) are one of the most actual problem in dermatology. Praziquantel is an antiparasitic medication effective towards trematodes, cestodes. Investigations developed by domestic scientists revealed antidemodicosis activity of praziquantel. Use of semisolid dosage forms for rectal administration will allow to increase its efficacy and minimize the risks of adverse reactions.&#x0D; On the department of technology of medications Zaporizhzhia State Medical University research of development of praziquantel rectal dosage form for therapy of acne dermatosis, complicated with demodicosis, and its technology is carried out. As a result of biopharmaceutical investigations it was determined that combination of excipients – the base (confectionary fat 60%, 10% paraffin, 30% cocoa butter) and surfactant (distilled monoglycerides) provides with the optimal praziquantel releasing.&#x0D; The aim of this work is study of excipient using in manufacturing of suppository (bases and surfactants) influence on the biopharmaceutical characteristics of praziquantel rectal dosage form.&#x0D; Investigation was carried out by the one-factors dispersive analysis with repeated observations By way of a parameter of optimization praziquantel releasing was chosen as the first step of bioavailability investigation. Praziquantel releasing from suppository was studied by the equilibrium dialysis by Kruvchinsky’s method at temperature 37 ± 0,5 °С through a cellophane semipermeable membrane «Kuprofan» film using Franz diffusion cell apparatus. Ethyl alcohol was chosen as a dialysis medium considering the solubility of praziquantel. Concentration of released praziquantel after 30 minutes of the dialysis was determined by spectrophotometric analysis.&#x0D; As a result of biopharmaceutical investigation of praziquantel suppositories it was determined that surface-active substances (distilled monoglycerides) concentration has a statistically significant influence on its releasing from rectal dosage form. It was ascertained that 0,5% concentration of distilled monoglycerides provides with the optimal releasing of praziquantel from rectal suppositories.

Establishment of diuretic activity indicators for (3-thio-4-R-4-H-1,2,4-triazole-5-yl)(phenyl)methanols and their derivatives

Diuretic drugs are drugs that, by blocking the transport systems of the renal tubules, promote the removal of excess electrolytes and water from the body, normalization of the internal environment. They eliminate edema, reduce the fluid content in the body cavity. Diuretic drugs differ in their chemical structure, the mechanism of on the urinary tract function of the kidneys and on the mechanisms of regulation of this function. It should be noted that the use of the above mentioned agents can lead to undesirable side effects, such as nausea, vomiting, unpleasant sensations in the stomach, headache, facial hyperemia. To date, there is evidence that 5-R-1,2,4-triazole derivatives have diuretic activity. The advantage of synthetic triazole derivatives is that, along with the expressed pharmacological of the compound, there are relatively low rates of acute and chronic toxicity, but almost no side effects. Therefore, it is important to create new low-toxic substances of derivatives (3-thio-4-R-4- H -1,2,4-triazole-3-yl)(phenyl)methanols and study their diuretic properties. The purpose of the work is the purposeful search for new low-toxic and highly effective diuretic compounds among the derivatives of (3-thio-4-R-4- H -1,2,4-triazole-5-yl)(phenyl)methanols. Materials and methods. To establish the influence of compounds, which have been synthesized at the Physical and Chemical Chemistry Department of ZSMU, the method of E. B. Berchin was used on the excretory function of kidneys. Experiments on diuretic were conducted at the Department of Clinical Pharmacy, Pharmacotherapy and MFE of FPE, Zaporizhzhia State Medical University. Results. The diuretic of derivatives (3-thio-4-R-4 H -1,2,4-triazole-5-yl)(phenyl)methanols was investigated. The study and analysis of the obtained experimental data were compared with the reference diuretic hypothiazide. Regularities structure – activity were established. The studies indicate that (3-thio-4-R-4H-1,2,4-triazoles-3-yl)(phenyl)methanol are not able to exceed hypothiazide diuretic effect, but 4-(5-hydroxy(phenyl)methyl-4-phenyl-4 H -1,2,4-triazolе-3-ylthiomethyl)benzonitrile showed the results closer to the reference drug. Conclusion. By the method of E.B. Berchin the diuretic of derivatives (3-thio-4-R-4 H -1,2,4-triazol-5-yl)(phenyl)methanols was investigated. Derivatives (3-thio-4-R-4H-1,2,4-triazole-3-yl)(phenyl)methanols do not excee the diuretic of hypothiazide. Patterns structure – action were established. The most active compound was 4-(5-hydroxy(phenyl)methyl-4-phenyl-4 H -1,2,4-triazolе-3-ylthiomethyl)benzonitrile.

Gastric duplication in infants

Clinicians pay close attention to the questions related to the diagnosis and treatment tactics of stomach defects with its obstruction in view of their stable frequency and lack of consensus on these diseases development mechanisms. The insufficient individual experience of every clinician leads to the difficulties in early diagnostic and the most adequate surgical intervention choice, and so, high rates of mortality. Purpose of the work. Improvement of the diagnostic and treatment tactic in infants with gastric duplication. Materials and methods. Clinical experience of two cases of the newborn children treatment with rare variants of digestive tract developmental defects is presented. In one child it was a case of stomach cystic duplication; and the other had a cystic duplication of stomach and duodenum. Results. There have been 5 cases of the stomach duplication treatment in the last 5 years in the Pediatric Surgery Clinic of Zaporizhzhia State Medical University. Two children were diagnosed with this pathology in neonatal period. Clinical analysis of these cases is described in the article. Both infants have undergone the early operative intervention. Type and extent of the operation depended on the peculiarities of localization, sizes, clinical signs of the defects and the general state of patients. The main stages and methods of medical-diagnostic process of such patients’ management are presented. Conclusions. The analysis shows that the efficacy of stomach obstruction rare forms diagnosis is achieved by usage of algorithms based on the staged modern diagnostic methods, taking into account their resolution and congenital anomaly type. In congenital stomach and duodenum duplication maximal informativness can be achieved using ultrasound and CT (or MRI) of the abdominal cavity. The most effective and non-invasive is ultrasound method by high-resolution devices. The discussed clinical cases are examples of early diagnosis of the stomach duplication and the right choice of active tactics for such children management that has made it possible to obtain a successful treatment outcome.