Medical Perspectives-Medicni Perspektivi最新文献

{"title":"Features of distribution of titanium and silver in the internal organs of laboratory rats and mice exposed to high doses of titanium dioxide nanoparticles and its composite with nanosilver","authors":"O. Yavorovsky, I. Andrusyshyna, V. M. Riabovol","doi":"10.26641/2307-0404.2023.1.276213","DOIUrl":"https://doi.org/10.26641/2307-0404.2023.1.276213","url":null,"abstract":"In Ukraine and worldwide more attention is paid to the study and application of titanium dioxide nanoparticles (TiO2 NPs). These nanoparticles find use in many industrics (medicine, cosmetology, materials science, environmental protection, etc.). The aim of the study was to study the features of the distribution of TiO2 nanoparticles, a composite of titanium nanodioxide with nanosilver (TiO2/Ag NPs) in the internal organs of laboratory animals (mice, rats) after acute intraperitoneal administration of TiO2 NPs and TiO2/Ag NPs. The objects of toxicological studies were TiO2 NPs (crystalline form - anatase, 21-28 nm in size) and TiO2/Ag NPs (17-22 nm in size, 4 wt% Ag) synthesized at the Frantsevich Institute for Problems of Materials Science NASU. Nanopowder suspensions were introduced in high doses (from 1,000 to 13,000 mg/kg) during a 14 days observation period. The content of che­mical elements Ti and Ag in organs (liver, kidneys, spleen, heart, lungs, adrenal glands, thymus, brain) was determined using the method of optical emission spectroscopy with inductively coupled plasma. It was found accumulation of metals in the internal organs on the 14th observation day after a single intraperitoneal injection. It was revealed that the kidneys and liver in rats are the most sensitive to the accumulation of TiO2 and TiO2/Ag NPs; accumulation in the thymus and adrenal glands is also shown. In an experiment on mice, it was found that the kidneys, liver and spleen accumulate titanium and silver after exposure at a dose of 4, 7 and 10 thousand mg/kg of NPs of TiO2 and TiO2/Ag.","PeriodicalId":41059,"journal":{"name":"Medical Perspectives-Medicni Perspektivi","volume":"18 1","pages":""},"PeriodicalIF":0.1,"publicationDate":"2023-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87401970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive analysis of pain syndrome in patients with rheumatoid arthritis","authors":"I. Grygus, A. Nogas","doi":"10.26641/2307-0404.2023.1.276049","DOIUrl":"https://doi.org/10.26641/2307-0404.2023.1.276049","url":null,"abstract":"Rheumatoid arthritis is a chronic systemic disease of connective tissue of immune genesis and unknown etiology. In the developed countries of the world, about 1 in 100 people suffer from rheumatoid arthritis, while in Ukraine the occurrence of the disease is 340 cases per 100,000 adult population. Chronic pain syndrome and limitation of joint functions significantly reduce the life quality of patients. At this stage, along with drug therapy, physical rehabilitation / therapy plays an important role in the restorative treatment of patients with rheumatoid arthritis. The purpose of the study is a comprehensive assessment of the main indicators of pain syndrome and morning stiffness of joints in patients with rheumatoid arthritis. 216 patients with rheumatoid arthritis were examined: 178 (82%) of them were women, 38 (18%) were men. The age of the patients is from 25 to 59 (average age is 46±0,24). The diagnosis was established on the basis of the ACR/EULAR 2010 criteria and in accordance with the Order of the Ministry of Health of Ukraine No. 263 dated November 04, 2014. A comprehensive analysis of the pain syndrome in patients with rheumatoid arthritis was carried out. Pain and severity of morning stiffness in the joints were determined using Huskisson’s visual analog scale (VAS, 100 mm). Statistical analysis was performed on the basis of the statistical analysis Statistica 10 (Serial Number: STA999K347150-W) and MEDCALC®. It was found that pain of low intensity was observed in 62 (28,7%), pain of medium intensity – in 120 (55,6%), and maximum intensity pain was experienced by 34 (15,7%) patients. It was found that in women with rheumatoid arthritis of radiological stage I, the average morning stiffness index according to VAS (100 mm) is 46,1±7,3, in men – 45,3±4,8; in women of radiological stage II, the average indicator is 52,6±7,9, in men – 50,3±6,1; in women of radiological stage III, the average indicator is 66,8±5,9, in men – 63,6±1,7. The analysis of the indicators showed that the severity of morning stiffness is more pronounced in women of all radiological stages than in men. All the above determines an urgent need to develop and implement in practice the concept of physical therapy for patients with rheumatoid arthritis in order to reduce the pain syndrome, severity of rheumatoid arthritis, eliminate morning stiffness, improve the functional condition and restore the motor functions of the joints, improve the health and quality of life of patients.","PeriodicalId":41059,"journal":{"name":"Medical Perspectives-Medicni Perspektivi","volume":"18 1","pages":""},"PeriodicalIF":0.1,"publicationDate":"2023-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81169596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The significance of assessment the relationship between the level of 25-(OH) vitamin D and excessive body weight in women on preconceptional period and during pregnancy","authors":"L. Maksymenko, O. Perkhulyn, N. Drohomyretska, N. Henyk","doi":"10.26641/2307-0404.2023.1.276031","DOIUrl":"https://doi.org/10.26641/2307-0404.2023.1.276031","url":null,"abstract":"The goal of this study was to determine the association between the level of 25-(OH) vitamin D and excessive body weight in women on preconceptional period and during gestation. There were studied 117 women. The first group included 68 overweight women (body mass index (BMI) 25.0-29.9 kg/m2), the second – 49 with normal body weight (BMI 18.5-24.9 kg/m2) before prepregnancy. Anthropometry was performed, BMI (kg/m2) by Quetelet formula. The 25-(OH) vitamin D blood serum level was studied by immunoenzymatic method. Fasting blood serum levels of glucose, insulin were determined by the immunoenzymatic method, insulin resistance index was calculated, serum concentrations of triglycerides, total cholesterol, high, low and very low density lipoproteins were determined. The results were statistically analyzed using Statistica 10 (Serial Number: STA999K347150-W) and MEDCALC®. It was found an inverse correlation between the level of vitamin D and BMI (r= – 0.71, p<0.001). Excessive body weight on precon­ceptional period reduces the chances of an adequate level of vitamin D (0.02; 0.00-0.10; p<0.001) and increases the chances of its deficiency (13.11; 4.89-35.30; p<0.001) during early gestational period. It was diagnosed that during pregnancy, the chances of vitamin D deficiency increase in women with normal body weight (3.16; 1.11-9.02; p=0.04), but remain significantly higher in the overweight (6.30; 2.80-14.18; p<0.001). It was shown that insufficiency/deficiency of vitamin D during pregnancy was accompanied by insulin resistance, hyper/dyslipidemia, which are the metabolic basis of gestational complications. The assessment of an inverse relationship between the level of 25-(OH) vitamin D and excessive body weight in women on preconceptional period and the increase of deficiency during pregnancy should be taken into account for the purpose of laboratory determination of the vitamin at the stage of pregnancy planning for the appointment of therapeutic correction.","PeriodicalId":41059,"journal":{"name":"Medical Perspectives-Medicni Perspektivi","volume":"49 1","pages":""},"PeriodicalIF":0.1,"publicationDate":"2023-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77947782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Features of lung impairment due to COVID-19 in patients of the first wave of the pandemic (literature review)","authors":"Y. Feshchenko, L. Iashyna, S. Opimakh, G. Gumeniuk, V. Ignatieva, M. Polianska, I. Zvol, S. Moskalenko","doi":"10.26641/2307-0404.2022.4.271118","DOIUrl":"https://doi.org/10.26641/2307-0404.2022.4.271118","url":null,"abstract":"During the COVID-19 pandemic number of patients suffering from symptoms, decreased work ability and the deterioration in quality of life for several weeks and even months after the onset of the disease is increasing. The aim of the literature review is to search and study the existing literature data regarding the lung impairment features in COVID-19, as well as the morphological and pathophysiological prerequisites for the long-term respiratory disorders in patients who have had this disease. The most common complaints of patients after acute COVID-19 are fatigue, dyspnea, cough and chest discomfort. In these cases restrictive pattern in the pulmonary function test, a reduced gas transfer and persistent changes in computed tomography often in the form of fibrosis are observed, less often in the form of bullous-emphysematous changes, bronchiectasis and pleural effusion. The main pathophysiological mechanisms of acute lung impairment in COVID-19 are direct viral toxicity, impaired function of the immune system, hyperinflammatory response, endotheliopathy, microcirculatory disorders and increased blood clotting with small and large vessels thrombosis, which can lead to pneumonia or acute respiratory distress syndrome. After the acute phase of COVID-19 the pathology of the lung can be caused by an immunogenic and hyperinflammatory response, hypercoagulability and lead to pulmonary fibrosis. The possible mechanisms of the pulmonary fibrosis are thrombotic processes, hemosiderosis, necrotic capillaritis, angiogenesis, hypoxia, cytokine storm. Thus abnormal immune response, hyperinflammation, endothelial dysfunction and excessive coagulation not only cause pneumonia or acute respiratory distress syndrome in acute COVID-19, but also may persist for a long time and contribute to pulmonary fibrosis in some patients. The causes of a longer duration and increased severity of the lung impairment in some people compared to others are the subject of current investigations.","PeriodicalId":41059,"journal":{"name":"Medical Perspectives-Medicni Perspektivi","volume":"22 1","pages":""},"PeriodicalIF":0.1,"publicationDate":"2022-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73588391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heritability of body mass index and physical activity in Ukrainian adolescents","authors":"E. Omelchenko, O. Yelizarova, Nadia Polka, O. Polka, S. Hozak","doi":"10.26641/2307-0404.2022.4.271223","DOIUrl":"https://doi.org/10.26641/2307-0404.2022.4.271223","url":null,"abstract":"The article analyzed the lifestyle and physical development of Ukrainian adolescents and their parents and estimated the familial aggregation and heritability of body mass index and physical activity. 408 nuclear families were examined (1216 people with complete information).  Anthropometric measures such as weight, height were measured following standardized procedures of WHO. Questionnaires were used to estimate the levels of physical activity. The method of genetic epidemiology research was used to explore heritability (h2) and family aggregation (ρ). Analysis was performed using the software product S.A.G.E. The study showed that 12.0±1.6% of children were overweight or obese, 6.4±1.2% were underweight and 81.6±1.9% with normal weight. It was found that among adolescents aged 12-15 years, 17.5±3.1% of boys and 32.7±2.9% of girls were physically inactive. Body mass index values higher than 25.0 kg/m2 were found in 34.3±2.4 mothers and in 70.6±2.3% of fathers. The proportion of physically inactive persons was 45.7±2.5% among mothers and 51.1±2.7% among fathers. Heritability values were significant for both body mass index (h2 =0.41±0.09; p<0.001) and physical activity (h2 =0.23±0.07; p<0.001). Significant familial correlations were obtained between parents-offspring for physical activity (ρ=0.20±0.04; p<0.001) and body mass index (ρ=0.25±0.03; p<0.001). The study estimated that the familial correlations for physical activity between mother-son and mother-daughter pairs were higher than in father-son and father-daughter pairs. The highest is the mother-daughter aggregation (ρ = 0.29 ± 0.06; p <0.001), the lowest is the father-son (ρ=0.19±0.08; p<0.05) by body mass index. As physical inactivity and overweight increase the risk of non-communicable diseases development, the data obtained should be taken into account while planning preventive measures.","PeriodicalId":41059,"journal":{"name":"Medical Perspectives-Medicni Perspektivi","volume":"39 1","pages":""},"PeriodicalIF":0.1,"publicationDate":"2022-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73598940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implementation of the principles of the scientific concept “Medicine of borderline states” regarding donosological diagnosis and overcoming the risks of health deterioration in student youth","authors":"V. O. Korobchanskyi, V. Sarkis-Ivanova, O. Bohachova, Y. Oliinyk, S.V. Biеleсka","doi":"10.26641/2307-0404.2022.4.271227","DOIUrl":"https://doi.org/10.26641/2307-0404.2022.4.271227","url":null,"abstract":"Today, the methodological basis of disease pre­vention among various categories of the population, including students, is an innovative area of medical science and health care practice, namely medicine of borderline conditions. The development of a system of prenosological diagnosis of pathological conditions in young students and their hygienic correction for disease prevention are important both from a scientific and practical point of view. The study was conducted in the conditions of a natural experiment on the basis of three types of educational institutions, at the place of study of representatives of both sexes aged 14 to 23 years, adolescents and yound adults. In order to achieve the relevant objectives, the study used the following methods: analytic addressed at the study of educational programs, curricula, schedules, profile and regulatory documents; sanitary-hygienic; psychophysiological; psychological, statistic. Set of risk factors related to the educational process among young people studying in three types of educational institutions – secondary educational institutions, higher educational institution, Professional Agrarian Lyceum was analyzed. It is established that unfavorable living conditions affect donosological mental states of asthenic, hypochondriac and depressive nature.","PeriodicalId":41059,"journal":{"name":"Medical Perspectives-Medicni Perspektivi","volume":"138 1","pages":""},"PeriodicalIF":0.1,"publicationDate":"2022-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86614996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improvement of liver fibrosis verification using new minimally invasive markers in patients with chronic diffuse liver diseases","authors":"Y. Stepanov, V. I. Didenko, I. Klenina, O. Tatarchuk, O. Petishko","doi":"10.26641/2307-0404.2022.4.271181","DOIUrl":"https://doi.org/10.26641/2307-0404.2022.4.271181","url":null,"abstract":"The aim of our research was to obtain new minimally invasive serum markers of fibrotic changes of liver in patients with chronic diffuse liver diseases of different etiology and compare them with traditional markers. 364 patients aged 30 to 66 years were examined: 221 women (60.7%) and 143 men (39.3%). Depending on the etiological factors, all patients were divided into 4 groups: group I consisted of 108 patients with non-alcoholic fatty liver disease (NAFLD), group II – 143 patients with chronic hepatitis associated with virus C (CHC), group III – 56 patients with alcoholic liver disease (ALD), group IV – 57 patients with toxic drug-induced hepatitis (TH). The control group consisted of 30 practically healthy people. Using correlation and ROC-analyzes, we obtained minimally invasive diagnostics markers that show the risk of developing liver fibrosis. For patients with NAFLD these were the levels of HOMA-IR, TNFα/IL-10 and α1-acid glycopeptide content, which are better in quality of the diagnostic model than the traditional Forns index, APRI, FIB-4, AAR. For patients with CHC, these were the protein-bound hydroxyproline (HPp/b) /HPf ratio, phospholipids content, and IL-6, CD4+ levels, which are better diagnostic models than the traditional Forns index, APRI, FIB-4, AAR. The following markers were obtained for patients with ALD – TNFα levels, HPp/b and glycosaminoglycans content, which are better diagnostic models than the traditional Forns index, APRI, FIB-4, AAR. For patients with TH, these were medium molecular weight peptides content, IL-6/IL-10 ratio and CD4+/CD8+, which are better diagnostic models than the traditional Forns index, APRI, FIB-4, AAR. Thus, new minimally invasive markers of fibrosis in patients with chronic diffuse liver diseases have been obtained.","PeriodicalId":41059,"journal":{"name":"Medical Perspectives-Medicni Perspektivi","volume":"24 1","pages":""},"PeriodicalIF":0.1,"publicationDate":"2022-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73788411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ischemic heart disease in the evacuated adult population as a cause of health loss in the long term after the Chernobyl accident. Results of epidemiological studies 1988-2016","authors":"O. Kapustynska","doi":"10.26641/2307-0404.2022.4.271241","DOIUrl":"https://doi.org/10.26641/2307-0404.2022.4.271241","url":null,"abstract":"Ischemic heart disease (CHD) is one of the most common diseases of the circulatory system, which is the main cause of death in Ukraine. The purpose of this study was to analyze the incidence, disability, mortality from ischemic heart disease, its individual nosological forms in the adult population evacuated from the 30 km zone of the Chernobyl nuclear power plant in the post-accident period, taking into account the age at the date of the accident, sex and time after the accident for further improving the system of dispensary observation evacuees and reducing the risk of cardiovascular complications. The study used epidemiological surveillance data (1988-2016) for the category of the adult evacuated population (18-60 years old as of the date of the accident) with a population of 42 982 people, of which 58.7% are women according to the data of the State Register of Ukraine of persons injured in as a result of the Chernobyl disaster (GRU). The research results were assessed both in general for ischemic heart disease and the main nosological forms according to ICD-9 and ICD-10. In the study, epidemiological, analytical, mathematical and statistical methods were used, as well as the method of internal comparison (with indicators of 1988-1992). As the results of the study have shown, in the structure of the causes of morbidity, disability and mortality of the adult evacuated population from diseases of the circulatory system, IHD takes a leading place. The statistically significant influence of age, calendar observation period, gender was established. Among nosological forms, chronic CHD is in the lead. Evacuees at the age of 18–39 years show an increase in the incidence of coronary artery disease with a maximum rate after 17 years, and at the age of 40-60 years – at the beginning of the observation with a subsequent noticeable decrease since 2003. In recent years (2013-2016), there has been a significant decrease in the incidence of coronary artery disease at the age of 40-60 years by 9.3 times, and at the age of 18-39 years, on the contrary, an increase by 3.8 times. During the post-accident period, the level of disability and mortality of the studied contingents from ischemic heart disease has significantly increased. High rates of growth of disability in recent years in persons aged 18-39 at the date of the accident. The mortality rate of the evacuees in recent years has increased in comparison with the early observation period by 5.8 times, higher mortality rates in men compared to women. Further more in-depth studies are required to assess the contribution of non-cancer diseases to the total radiation damage to human health.","PeriodicalId":41059,"journal":{"name":"Medical Perspectives-Medicni Perspektivi","volume":"44 1","pages":""},"PeriodicalIF":0.1,"publicationDate":"2022-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79941589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compensation pathways for venous drainage of the brain in superior sagittal sinus occlusion by parasagittal meningioma","authors":"A. Sirko, L. A. Dziak, V. Perepelytsia, Y. Cherednychenko","doi":"10.26641/2307-0404.2022.4.271177","DOIUrl":"https://doi.org/10.26641/2307-0404.2022.4.271177","url":null,"abstract":"This study aims to determine the existing pathways of collateral cerebral circulation in parasagittal meningiomas that cause superior sagittal sinus occlusion based on literature review and analysis of own clinical observations. Results of clinical and instrumental examination of 221 patients treated in Dnipropetrovsk Regional Clinical Hospital named after I.I. Mechnikov from 2000 to 2021 were subjected to retrospective and prospective analysis. Inclusion criteria were: patient age of 18+, parasagittal extracerebral tumor according to computed tomography/magnetic resonance imaging, histologically verified meningioma, superior sagittal sinus occlusion (type V-VI according to M.P. Sindou and J.E. Alvernia) according to selective cerebral angiography. This study is based on the analysis of examination of 43 patients who met the inclusion criteria. The selected patients were analyzed for demography (sex, age), brain computed tomography/magnetic resonance imaging before and after intravenous contrast enhancement, and computed tomography angiography and selective cerebral angiography data. Transformed venous drainage pathways were analyzed depending on the location of superior sagittal sinus occlusion by parasagittal meningioma: anterior, middle, or posterior third of the superior sagittal sinus. It was determined that preoperative diagnosis of parasagittal meningiomas that, based on brain computed tomography/magnetic resonance imaging, has signs of type V or VI superior sagittal sinus invasion according M.P. Sindou and J.E. Alvernia, must include selective cerebral angiography. Dynamic images of selective cerebral angiography in the venous phase allows to fully assess the established pathways of collateral blood flow and the blood flow direction. Information on collateral venous circulation in case of superior sagittal sinus occlusion by parasagittal meningioma is extremely important in a surgery planning. It helps avoiding iatrogenic damage to eloquent veins, which increases radical tumor removal with maintaining/improving a patient’s functional state in the early postoperative period and improving long-term treatment outcomes.","PeriodicalId":41059,"journal":{"name":"Medical Perspectives-Medicni Perspektivi","volume":"82 1","pages":""},"PeriodicalIF":0.1,"publicationDate":"2022-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88461884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and search for prospective diuretics (CA II Inhibitors) among aroylhydrazones of esters quinone oxime using in silico and in vivo methodology","authors":"K. Sokolova, V. Stavytskyi, S.O. Konovalova, O. Podpletnya, S. I. Kovalenko, A. Avdeenko","doi":"10.26641/2307-0404.2022.4.271120","DOIUrl":"https://doi.org/10.26641/2307-0404.2022.4.271120","url":null,"abstract":"The design and search for new selective inhibitors of CA II with a better pharmacological profile, which would cause minimal electrolyte disturbances in the body, remains an urgent problem of medical chemistry and pharmacology today. It is important that the discovered new classes of inhibitors do not always contain the main “pharmacophoric” function (sulfamide), which is characteristic of “classic” drugs (Acetazolamide, Methazolamide, Ethoxzolamide, Dorzolamide and others), but are derivatives of phenols, polyamines, coumarins/thiocoumarins, ureas, thioureas, hydroxamates, etc. These molecules also bind in the active site of the enzyme, but do not interact directly with the catalytic zinc ion or interact through zinc-coordinated water molecules/hydroxide ion. However, this leads to an increase in their selectivity and, as a result, pharmacological action. Continuing the search for compounds that affect urination, we were interested in aroylhydrazones of esters of quinone oxime. Firstly, they are characterized by certain structural features (dynamic and geometric isomerism); secondly, they exhibit redox properties; thirdly, the presence of aromatic fragments makes it possible to create a voluminous combinatorial library for analysis. These compounds are ligands in complexation reactions, and an additional increase in the number of hydrogen acceptors in the molecule due to structural modification will improve ligand-enzymatic interactions with carbonic anhydrase (CAII) and, as a result, reveal new promising diuretics. The aim – design and search for potential diuretics (CA II inhibitors) among aroylhydrazones of esters of quinone oxime using in silico, traditional synthesis and in vivo methodologies. Methods of organic synthesis, physico-chemical methods of analysis of organic compounds (NMR 1H-spectroscopy, elemental analysis). Prediction of affinity to the biological target, prediction of toxicity and lipophilicity of the combinatorial library of benzohydrazides O-aroyl esters of quinone oxime using computer services. The study of compounds affecting the excretory function of rat kidneys was carried out according to the generally accepted method of E.B.Berkhin with water load. The investigation of the probable mechanism was carried out using flexible molecular docking, as an approach to search for molecules that have affinity for human carbonic anhydrase type II (CA II). Macromolecular data of the crystal structure of CA II (PDB ID – 3HS4) were downloaded from the Protein Data Bank (PDB). The design was developed and the search for diuretic agents among benzohydrazides of O-aroyl esters of quinone oximes was developed using in silico methods (prediction of affinity, lipophilicity, toxicity and enzyme-ligand interactions), traditional organic synthesis, and in vivo methods (effect on excretory function of rat kidneys). The synthesis of benzohydrazides of O-aroyl esters of quinone oxime was carried out by the interaction of aroylhydrazines with 4-","PeriodicalId":41059,"journal":{"name":"Medical Perspectives-Medicni Perspektivi","volume":"21 1","pages":""},"PeriodicalIF":0.1,"publicationDate":"2022-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81053500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}