Medicni perspektivi, 2022;27(2)
2022 Vol. XXVII N 2
Key words: 6-substituted pteridine-2,4,7(1H,3H,8H)-triones, diuretics, molecular docking, SAR analysis, mechanism of action
Abstract. Directed search for diuretics among 6-substituted pteridine-2,4,7(1H,3H,8H)-triones. Sokolova K.V., Stavytskyi V.V., Kovalenko S.I., Podpletnya O.A. Directed search for biologically active compounds among heterocycles still remains a relevant area of medical chemistry. Among the significant number of heterocyclic compounds, pteridines deserve special attention. Among the above-mentioned ones the drugs with antitumor, antimicrobial, antiviral, diuretic and other types of biological action are known. Nevertheless, 6-substituted pteridine-2,4,7(1H,3H,8H)-triones, which are structurally similar to triamterene (6-phenylpteridine-2,4,7-triamine) – a diuretic with potassium-sparing action are interesting objects for search for diuretics. All the more, they are characterized by prototropic tautomerism, able to form hydrogen and donor-acceptor bonds with various ligands, and it is likely that these structural features will provide their diuretic effect. The aim of the study is the directed search for diuretics among 6-substituted pteridine-2,4,7(1H,3H,8H)-triones using in silico and in vivo methodology and elucidation of the probable mechanism of action. 1-methyl-3-R-6- (2-oxo-2-aryl- (hetaryl-) ethyl) pteridine-2,4,7(1H,3H,8H)-triones were selected to study the effect on renal excretory function. and 1-methyl-3-R-6- (2-hydroxy-2-aryl- (hetaryl-) ethyl) pteridine-2,4,7(1H,3H,8H)-triones. Directed search for compounds that affect the excretory function of the kidneys of rats was conducted by the conventional method of E.B. Berkhin with water load. The content of creatinine, sodium, potassium and chlorides in blood and urine plasma was determined by biochemical methods using standard test kits of NPV "Philisit-Diagnostics" (Ukraine) and calculations were performed according to generally accepted methods. Research of the probable mechanism was conducted by flexible molecular docking, as an approach of finding molecules with affinity to a specific biological target. Macromolecular data were downloaded from the Protein Data Bank (PDB) namely, the crystal structures of Human carbonic anhydrase II (PDB ID – 3HS4) and epithelial sodium channel (ENaC) (PDB ID – 4NTX). Studies of the effect of the synthesized compounds on the excretory function of the kidneys of rats showed that 1-methyl-3-R-6- (2-oxo-2-aryl- (hetaryl-) ethyl) pteridine-2,4,7(1H,3H,8H)-triones containing 4-fluorophenyl, 2,4-difluorophenyl, 4-chlorophenyl fragments in the molecule increase diuresis by the second hour by 27.3-70.1% compared with the control group. According to the results of the impact on daily diuresis, it was found that the most active was 1-methyl-6- (2-oxo-2-phenyl) ethyl) pteridine-2,4,7(1H,3H,8H)-triones, which increased daily diuresis by 168.1%, exceeding the effect of Hydrochlorothiazide (41.8%) and Triamterene (49.1%). However, substituted 1-methyl-3-R-6- (2-hydroxy-2-aryl- (hetaryl-) ethyl) pteridine-2,4,7(1H,3H,8H)-triones are inactive compounds. In-depth studies using biological tests and molecular docking have suggested that 1-methyl-6- (2-oxo-2-aryl) ethyl) pteridine-2,4,7(1H,3H,8H)-triones 2.1, 2.5 and 2.6) probable mechanisms of diuretic action are disruption of sodium transport in the distal convoluted tubules, causing sodium excretion and water loss and possibly inhibition of epithelial sodium channels that promote sodium uptake and potassium secretion in the distal convolutions and tubules, which implements potassium-sparing action. A well-founded and developed strategy for the search for diuretics among 6-substituted pteridine-2,4,7(1H,3H,8H)-triones has identified a number of effective compounds that by diuretic effect are superior to the reference drugs "Hydrochlorothiazide" and "Triamterene". Importantly, the results of molecular docking suggested a mechanism of action of the compounds under study, similar to thiazide diuretics. This action may be related to the tautomerism of these compounds and, as a consequence, their ability to form coordination bonds with the zinc cation and the additional interaction of halogens in the active site of CA II. It was possible to detect the presence of potassium-sparing action, probably due to the ability to inhibit epithelial sodium channels (ENaC). The obtained results substantiate the further purposeful search for potential diuretics among this class of compounds.
Key words: generalized periodontitis, experiment, computed tomography, atomic emission spectrometry, strontium ranelate
Abstract. Mineral density and chemical composition of the rats’ mandibles in experimental models of generalized periodontitis. Matvieienko L.M. The most severe and difficult to treat symptoms of generalized periodontitis associated with diabetes mellitus are changes in bone tissue. The aim of the research was to conduct a comparative study of the mineral density and chemical composition of the mandibular bone tissue in rats in the modeling of generalized periodontitis, which develops against the background of metabolic disorders in type 2 diabetes mellitus, and after additional use of strontium ranelate. The study was carried out on 24 white male Wistar rats weighing 230-250 g, divided into three groups, 8 animals in each (in I group streptozocin and nicotinamide were administered, in II group - additionally penicylamine, in III group – additionally strontium ranelate) and 6 intact rats were used as a control. According to data of computer tomography, it was found that in the control group the average values of the mineral density are 1450.0±125.0 HU, in I group – 1320.0±120.0 HU (p>0.05), in II group –1100.0±110.0 HU (p˂0.05), in III group –1400.0±137.0 HU (p>0.05). Thus, the most pronounced decrease in mineral density is observed in the case of the combined use of nicotinamide, streptozotocin and penicylamine, while strontium ranelate helps to normalize this indicator. According to atomic emission spectrometry, the mineralization index – the ratio of calcium / phosphorus – was 1.14 in the control group, 1.05 – in I, 1.0 – in II and 1.26 – in III. The strontium content in the samples of the III group exceeded the control values by almost two times (p˂0.001) in comparison with its significant decrease in the samples of the I and II groups (p˂0.05). An increase in the strontium content led to a decrease in the content of other elements, which is explained by the competitive substitution in apatite crystals. So, strontium ranelate activates remineralization of the bone component of the periodontium.
Key words: erythrocytes, hemoglobin, hematocrit, alimentary protein deprivation, toxic injury, acetaminophen
Abstract. Blood erythrocyte indices in rats under conditions of acetaminophen-induced toxic injury against the background of alimentary protein deficiency. Kopylchuk H.P., Nykolaichuk I.M. Despite the available information on variations in the erythrocyte chain of homeostasis under the conditions of drug-induced toxic damage, the question of the biochemical characteristics of erythrocytes in the expose of toxic doses of paracetamol on the background of dietary imbalance in protein remains open. 96 white nonlinear rats were used for the study. During the experiment, the animals consumed a semi-synthetic diet AIN-93 in accordance with the recommendations of the American Institute of Nutrition on the principle of paired nutrition, taking into account the amount of dietary protein per kilogram of diet. Modelling of acute toxic lesions was performed by administration to experimental animals of acetaminophen per os at a rate of 1250 mg/kg body weight. We found that toxic damage by acetaminophen is a key factor in reducing the level of total hemoglobin in the blood of animals (40% compared to control) with a simultaneous decrease in its average concentration (18%) and content in a single erythrocyte (35%), indicating the development of hypochromia, which is an indicator of iron deficiency in the body (iron deficiency anaemia). The synergistic effect of nutritional protein deficiency and the exposition of toxic doses of acetaminophen is accompanied by a decrease in total erythrocytes (50% compared to control) due to their increased hemolysis (up to 32% in 0.9% NaCl) with a simultaneous decrease in hematocrit up to 16% and the average volume of erythrocytes (1.4 times compared with the control). At the same time, the established changes in oxyhemoglobin decrease against the background of increased fetal hemoglobin content under the conditions of toxic damage and alimentary protein deficiency may serve as an additional criterion for comprehensive assessment in the diagnosis of anaemic syndrome in inflammatory diseases of different genesis against nutrient-associated conditions. Thus, the study of changes in erythrocyte indices in the development of acetaminophen-induced lesions on the background of nutrients’ alimentary deprivation can increase the effectiveness of monitoring the course of these pathologies and approaches to their correction.
Key words: periodontitis, coronary artery disease, statins, treatment
Abstract. Pleiotropic effects of statins in treatment of generalized periodontitis in patients with coronary artery disease: clinical and experimental study (literature review). Martovlos (Hodovana) O.I., Skybchyk O.V., Solomenchuk T.M. The high prevalence of generalized periodontitis in patients with coronary artery disease (CAD) requires improving the existing ways of periodontal treatment of this category of cardiac patients and finding new ones. Statins are a group of lipid-lowering medications that are widely used for primary and secondary prevention of cardiovascular diseases due to atherosclerotic vascular lesions. In addition to the cholesterol-lowering effect, statins have several pleiotropic effects, including anti-inflammatory, immune-stimulating, antibacterial, antioxidant, osteotropic etc. The analysis of scientific studies of native and foreign authors devoted to studying the influence of pleiotropic effects of statins on the condition of periodontal tissues revealed improvement of periodontal indicators, in particular, gum structure, reduction of the periodontal pockets depth, gum bleeding, and tooth mobility in patients on statin therapy. Experimental in vitro and in vivo studies show a decrease in proinflammatory cytokines (IL-6, IL-8, IL-1β, TNF-a, etc.), which play a key role in the development of generalized periodontitis, as well as the acceleration of reparative processes in alveolar bone tissue when administering topical statins. Despite the prospects of using statins as the main or additional agent in the treatment of periodontal diseases, the question of dosage and method of local delivery of the medication for avoiding the undesirable side effects remains controversial and requires further research.
Key words: forensic assessment, lifespan of injury, duration of death, death
Abstract. Assessing survival and prescription of injury establishment in forensic medical practice (literature review). Erhard N.M., Biliakov A.M., Volobuiev O.E. Determining the prescription of organ and tissue damage in forensic practice is of pivotal role in establishing an objective picture of the facts and circumstances. Nowadays, when the latest research methods and modern laboratory and instrumental equipment appear, there is a need to improve forensic diagnostics to establish the prescription of injuries. Although experts and scientists are trying to invent new methods and techniques for diagnosing the age of injury, this area of research will not lose relevance, given the complexity of solving problems. The purpose of this work is to analyze literature data on the use of various diagnostic methods in forensic practice to establish the prescription of injuries and assessing survival. In our study we analyzed scientific papers and data of international scientific literature on the problem of various diagnostic methods in forensic practice to establish the prescription of injuries and assessing survival. Methods used: scientific research, analytical and generalizing. The authors cite publications that set out the methods and criteria to address this issue. In particular, promising areas of application of histological, immunohistochemical methods, postmortem computed tomography are shown. The issues of establishing the prescription of cranio-cerebral injuries are considered. The role of manifestations of the body's systemic response to trauma, in particular, the neuroendocrine system, is also shown. Examples of the use of non-ischemic heart disease to diagnose the duration of dying are given. The role of tropopnin I, creatine kinase, brain natriuretic peptide (NT-pro BNP) in the diagnosis of the duration of the traumatic process is shown. Based on a review of the literature, the authors conclude that new methods and criteria for assessing survival and prescription of injuries in forensic practice in order to unify the results of the study and avoid diagnostic errors are promising.
Key words: respiratory support, traumatic brain injury, mechanical ventilation, ventilator weaning, arterial blood gas
Abstract. Respiratory support in severe traumatic brain injury (literature review). Krishtafor D.A., Klygunenko O.M., Kravets O.V., Yekhalov V.V., Krishtafor A.A. Patients with traumatic brain injury (TBI) are the largest group of victims at the emergency departments. Up to 20% of patients with severe TBI require endotracheal intubation and prolonged mechanical ventilation. The ventilation parameters choice should be focused on the normal arterial blood gas composition. Hypoxia causes secondary damage to the brain tissue, and hyperoxia carries risks of oxygen toxicity. Hypercapnia leads to cerebral vasodilatation, increased intracranial pressure (ICP) and the risk of cerebral edema. Hypocapnia promotes cerebral vasoconstriction, which reduces cerebral blood flow and ICP, but also leads to cerebral tissue ischemia, so prolonged hyperventilation in TBI is not currently recommended. Patients with TBI often require sedation to synchronize with the respirator. The drugs of choice are propofol and midazolam. Routine use of muscle relaxants is not recommended. The initial ventilation mode should provide a certain respiration rate to achieve normocapnia, while allowing the patient to make breathing attempts. Support ventilation modes are used while weaning from mechanical ventilation. Promising in predicting extubation success is the assessment of the VISAGE score, which includes visual pursuit, swallowing, age, and the Glasgow coma score. Modern principles of respiratory support in severe TBI include: tracheal intubation by Glasgow coma score ≤8 ; early mechanical ventilation; PaO2 80-120 mm Hg (SaO2 ≥95%); PaCO2 35-45 mm Hg; tidal volume ≤8 ml/kg; respiratory rate ≈20/min; PEEP ≥5 cm H2O; head elevation by 30°; sedation in poor synchronization with the respirator; weaning through support ventilation modes; extubation when reaching 3 points on the VISAGE scale; early (up to 4 days) tracheotomy in predicted extubation failure.
Key words: Sage (Salvia officinalis), herbal medicine, market analysis, phytobalm, COVID-19
Abstract. Relevance of research of the pharmacological properties of salvia (Salvia officinalis) (literature review). Zalyhina Ye.V. Salvia officinalis (sage) attracts attention as it is widely cultivated on the territory of Ukraine. It is known that it has long been used in traditional medicine, as it contains large amounts of borneol, camphor, caryophyllene, cineole, ale, humulene, chilling, pinene and thujone. The purpose of this review is to collect and analyze information on the relevance of using the medicinal properties of raw Salvia officinalis (sage), since it reveals oncoprotective, antimutagenic, antioxidant, hepatoprotective, anti-inflammatory, antimicrobial, antifungal action, normalizes metabolic processes, and has successfully proven itself in the composition of cosmeceuticals. Taking into account the current COVID-19 pandemic situation in the world, as well as the anti-inflammatory, antimicrobial, antiviral properties of Salvia officinalis (sage), its positive effect on the normalization of the level of lipid peroxidation, antioxidant enzymes (superoxide dismutase and catalase), as well as a significant effect on reducing pulmonary fibrosis, dosage forms based on Salvia officinalis, can be used for prevention, comprehensive treatment and rehabilitation after a COVID-19 infection. The analysis of the pharmaceutical market showed that in Ukraine, medicines based on Salvia officinalis are used in the treatment of diseases of the upper respiratory tract, as well as in climacteric syndrome and psychoemotional stress, in the complex therapy of chronic diseases of the gastrointestinal tract and genitourinary system. The collected and systematized information indicates that medicinal plant Salvia officinalis (sage) can be used in a more diverse way. Therefore, we consider it expedient to further study the pharmacological properties of Salvia officinalis and develop a technology for the manufacture of new dosage forms for internal use based on it.
Key words: intermittent fasting, ultrasound assessment of carotid arteries, transcranial Doppler, arterial hypertension, headache, cephalalgia
Abstract. Doppler and clinical characteristic of cephalgia in patients with arterial hypertension during intermittent fasting. Chun Liu, Pohorielov O.V., Baranenko O.M. There were examined 142 patients with recurrent headache (cephalgia) and arterial hypertension, a mean – 49.26±1.33 years, of whom 69 men, 73 women who used intermittent fasting (patients spent 24 hours without food, 1 time per week, four repetitions). The control group consisted of 32 people of comparable age without hypertension (n=32; mean age 51.0±1.99 years). The purpose of the study was to increase the effectiveness of diagnostic and therapeutic methods in patients with hypertension and headache by establishing the meaning and peculiarities of the influence of intermittent fasting on headaches, neck carotid and intracranial circulation. There were 51 (35.9%±4.03) patients aged 25-44 years’; 45-59 years – 42 (29.58%±3.83) patients; 60-75 years – 49 (34.51%±3.99) patients. It was found that the structural pathology of the main arteries of the head consisted mainly in the thickening of the intima-media from 0,8 to 1,4 mm in 62.7% at the age of 25-44 years; in 71,4% at the age of 45-59; in 51% at the age of 60-75 years. Local thickenings in the bifurcation zone from 1.5 mm without hemodynamically significant stenosis were found in 9.8% at the age of 24-44 years, in 28.6% at the age of 45-59 years and in 49% at the age of 60-75 years. Statistical differences in linear circulatory velocity between the control group and the group of patients were significant already at the age of 25-44 years, for peak systolic velocity in the internal carotid artery (78.03±4.67 vs. 61.0±2.54 in control, p<0.05). At the age of 45-59 years, linear circulatory velocity affected all carotid and vertebral arteries, as in the group aged 60-75. The effect of intermittent fasting on aged hemodynamics consists mainly in changes of velocity of flow in arteries with better results in younger patients. Changes in the elastic-tonic characteristics of the main arteries of the head according to the index of resistance (index was 0.72±0.01 for common carotid artery and 0.63±0.01 after intermittent fasting in patients at the age of 25-44 years; 0.78±0.01 before and 0.67±0.01 after at the age of 60-75 years were revealed). The use of the intermittent fasting method caused mainly an increase in diastolic flow rates in the main arteries (with age dependences) and a decrease in systolic velocity in the age group 25-44 years. The pathophysiological interpretation of such changes is in the reducing the resistance, values of the main arteries of the head.
Key words: coronary artery calcification score, glomerular filtration rate, coronary artery disease
Abstract. Calcification of heart structures in patients with suspected coronary heart disease depending on renal function. Kuryata O.V., Karavanska I.L., Semenov V.V., Nikutova A.M. Cardiovascular disease is the leading cause of death in the world. The use of the coronary artery calcification score (CACS) allows to determine the risk of coronary artery disease (CAD). Chronic kidney disease (CKD) is a one of the major risk factors for coronary artery disease. With a decrease in renal function, impaired calcium-phosphorus metabolism leads to excessive tissue calcification. It is likely that patients with different kidney function experience different types of calcium deposition. The use of CACS is an opportunity to assess the condition of the coronary arteries without using a contrast agent, which is very important for patients with CKD. One of the most accessible and significant research methods for clinical screening use is computed tomography with non-invasive assessment of coronary calcium (quantitative analysis of the calcium index). To evaluate it, the method of A. Agatston is used, which allows to measure calcium in units. Our aim was to investigate the pattern of calcification of heart structures depending on renal function in patients with suspected coronary heart disease. The patients in the presented study had a high incidence of diabetes mellitus (49.4%) and arterial hypertension (83.1%). In patients with suspected coronary artery disease, borderline values of systolic and diastolic blood pressure and total cholesterol were found. In the majority of the patients CACS was 1-100 Agatston units (AU). After the distribution of patients into groups depending on glomerular filtration rate (GFR), it was found that the groups of patients with lower GFR, were of older age. The proportion of patients with total CACS >100 AU was the highest in the group of patients with GFR 30-59 ml/min. There were no significant differences in the structure of general and vascular CACS between patients with GFR 90-120 ml/min and GFR 60-89 ml/min. Valvular CACS was significantly lower in patients with GFR <60 ml/min. In all cases of visual comparison of CACS depending on GFR, significantly higher CACS indices differed in patients with GFR <60 ml/min compared to patients with GFR ≥60 ml/min.
Key words: physical therapy, sternal precautions, cardiac rehabilitation, supportive devices
Abstract. Specifics of using thoracic bandage after cardiac surgery via sternotomy and its impact on reducing pain during therapeutic exercises. Vitomsky V.V., Vitomska M.V., Lazarieva O.B. Purpose: to investigate specifics of using thoracic bandage after cardiac surgery via sternotomy and its impact on reducing pain during therapeutic exercises. In order to study specifics of using a postoperative thoracic bandage on the seventh postoperative day patients (n=252) were asked two questions about the force of thorax compression exerted by the bandage. As soon as the questions were answered, the degree of thoracic bandage tension was also assessed by a physical therapist. Thereafter, some patients (n=44; who did not take painkillers within 12 hours before the examination) assessed pain on a numeric rating scale (10 points – maximum pain, 0 points – no pain) as follows: at rest, when coughing and moving their upper extremities (arms forward, sideward, upward), when wearing a bandage with and without a load (dumbbells 1 and 2 kg for each arm); then all points of the scale were assessed without wearing a thoracic bandage. Most of the patients noted that the bandage exerted light compression (184 patients) and did not restrict deep breathing (220 patients). The evaluation performed by a physical therapist found that a thoracic bandage had only a slight degree of tension in most of the patients (194 patients or 76.98%), since it was easy to slip the hand between the patient’s back and the bandage, stretching the latter with minimal effort. The use of a thoracic bandage had no impact on the pain when patients moved their upper extremities. The obtained pain rates were very low. The highest pain rates were obtained during coughing. When moving arms the level of pain did not change statistically as compared with the state of rest. Arm position and load increase within specific limits had no impact on pain level. The use of a postoperative thoracic bandage is characterized by its mild tension, which does not limit deep breathing and, consequently, cannot limit the increase of chest circumference during dehiscence. The assessment of tension performed by physical therapists was consistent with the patients’ responses. The use of a bandage did not reduce the level of pain when patients moved their upper extremities and coughed.
Key words: heart failure, dyslipidemia, yoga, full yogic breathing
Abstract. The effect of yoga practice on lipid profiles in patients with chronic heart failure. Babkina T.M., Smyrnova G.S., Mykhailenko L.A., Kozarenko T.M., Globa M.V., Kundina V.V. The aim of the present study was to assess the efficiency of yoga practice in addition to the standard medical therapy in patients with chronic heart failure (HF) and dyslipidemia. One hundred and two patients with chronic HF and dyslipidemia were divided into the control group (CG) – 54 patients and the yoga group (YG) – 48 patients. The CG was prescribed standard therapy for chronic HF (angiotensin converting enzyme inhibitors, β-blockers, aldosterone antagonists, digoxin, loop diuretics, statins, antiplatelet agents) and dyslipidemia. The YG additionally followed lifestyle modification in the form of 1 h daily practice of yoga for a period of 3 months. All patients completed the questionnaire reporting on their age, gender, medical history and treatment. The fasting blood samples were analyzed for total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, C-reactive protein, interleukin-8 and tumor necrosis factor -α on admission to the department and after 3 months of treatment. The pre-specified duration of the enrollment period was two years and during that time we interviewed 168 patients. Forty-two did not meet the inclusion criteria for the study, 24 patients refused to participate. A total of 102 patients were enrolled, of them, 54 were included into the control group and 48 into the yoga group. At baseline, there were no significant (p>0.05) differences between the groups in clinical characteristics of the patients. On admission to hospital the patients of both groups received standard therapy in comparable doses. By the end of the study, a significant (p<0.05) reduction in TC, TG and LDL-C levels was observed in both groups with a tendency to more considerable changes in YG. Correlation analysis revealed the positive correlation relationship between TC, LDL-C levels and cytokines. The present study has shown that the practice of yoga in addition to the standard therapy in patients with HF and dyslipidemia could be associated with lipid profile improvements.
Key words: dexamethasone, bupivacaine, anesthesia, cesarean section
Abstract. Adding dexamethasone to intrathecal bupivacaine 0.5%; comparing the anesthetic ability with bupivacaine 0.5% alone among cesarean section patients. Seyed Mohammad Nasirodin Tabatabaei, Alireza Rahat-Dahmarde, Jamshid Ordoni Avval, Hossein Ali Khazaie. A perfect anesthesia technique is one in which anesthesia can be done in the shortest possible time with minimal hemodynamic changes and side effects This study is aimed to investigate the effects of concomitant administration of dexamethasone with bupivacaine on the duration of anesthesia and the quality of anesthesia-induced in patients undergoing cesarean section. This is a quasi-experimental study done on patients undergoing cesarean section by spinal anesthesia. All patients underwent standard monitoring after admission, then Ringer serum (5 cc/kg) was administered to the patients. The patients was then seated and subjected to intrathecal anesthesia with a midline approach in L3-L4 space. Patients were matched for baseline conditions. After recording background information, type and dosage of drugs used, blood pressure, heart rate, number and frequency of nausea and vomiting were listed in the checklist, and the data were analyzed using SPSS software. In this study, 70 pregnant women who were candidates for cesarean section were included. All our studied parameters, including the mean time to the start of analgesia, mean time of analgesia duration, analgesia duration, mean time to first request for analgesics were significantly improved among the intervention group. The use of dexamethasone and bupivacaine to induce spinal anesthesia during cesarean section can significantly shorten the onset time of analgesia and reduce postoperative nausea and vomiting. Dexamethasone can be used as an effective drug in cesarean section.
Key words: pancreaticoduodenectomy, pancreaticogastrostomy, pancreatojejunostomy
Abstract. Experience of pancreaticodigestive anastomosis performing in pancreaticoduodenectomy. Kutovyi O.B., Denysova K.O. The aim of the study was to analyze the short-term and long-term results of pancreaticoduodenectomy (PD) on condition of performing different types of pancreaticodigestive anastomoses. The results of 108 PD of the period from 2008 to 2021 performed in the Department of Surgery N 2 on the basis of the Dnipro Regional Hospital named after І. Mechnikov were analyzed. Pancreatojejunostomy (PJ) was formed in 88 (81.5%) cases, pancreaticogastrostomy (PG) ‒ in 20 (18.5%). Depending on the transverse size of pancreatic isthmus and body, diameter of the pancreatic duct the method of PJ was chosen: telescope-type PJ «end-to-end» (n=26), Wirsung-jejunostomy (n=28), original method (n=34). In the PJ group the dense parenchyma of the pancreas was in 51 (58.0%) cases, soft parenchyma ‒ in 37 (42.0%), and in the PG group the dense gland was observed in 12 (60%) cases, soft ‒ in 8 (40%) patients (p>0,05). The number of the early postoperative complications was 43 (39,8±4,7%), among them there were (15,7±3,5%) patients with severe complications who required additional interventions. Mortality was 6.5±2.4%. The best results for the early postoperative complications were obtained in the groups of PG and original PJ. There were statistically significant differences in the total number of cases of the early postoperative complications between the groups of PG (20.0±8.9%) and telescope-type PJ (50.0±9.8%, p=0.037) and Wirsung-jejunostomy (50.0±9.4%, p=0.034), as well as while comparing the total number of patients with complications in the groups of PG and PJ (44.3±5.3%, p=0.045). There were not any statistically significant differences among the late postoperative complications (p>0.05).
Key words: postthrombotic syndrome, paratibial fasciotomy, chronic venous diseases
Abstract. Long-term results of pathogenetically-grounded methods of treatment of patients with postthrombotic syndrome of the lower extremities according to three-year follow-up. Orynchak V.A., Gudz O.I. The aim of this study was to evaluate the effectiveness of surgical treatment using a modified method of correction of venous hemodynamic disorders of the lower extremities by the state of function of the leg muscle pump during long-term follow-up in the postoperative period of patients with postthrombotic syndrome of the lower extremities. 148 patients with lower limb postthrombotic syndrome (С5, 6, S, Es, As, d, p, Pr, LI by CEAP classification) were divided in two groups. The first group included 71 patients, which were treated by traditional methods of surgical intervention (crossectomy and venecseresis). The second group consisted of 77 patients who underwent closed separation of the perforating veins and paratibial fasciotomy in the complex of surgical treatment. The function of the leg muscle pump was studied using three methods: a 6-minute marching test measuring the circumference of the limbs, the amplitude indices of movements in the ankle joint with a protractor, and electromyography using a multichannel electromyography with skin electrode application. The quality of life was studied using the CIVIQ questionnaire, the severity of venous pathology by the VCSS scale and disability rates by the VDS disability scale. The examination was performed before the surgery, after 1 year and after 3 years of observation. In both groups of patients, there was a decrease in the basal levels of a 6-minute marching test, the movement amplitude in the ankle joint, the electromyography indicators, the presence of a strong correlation between these parameters, indicating venous dysfunction in the lower extremities. In the postsurgical period (in 1 and 3 years), there was a reduced circumference of the legs during the marching test, an increased amplitude of movements in the ankle joint and electromyography indicators – the mean and maximum amplitude of oscillations. In patients of group II, the results were better than in patients of group I. In the pre-surgical period, a significant deterioration of the life quality was observed in terms of the CIVIQ questionnaire, the severity of venous pathology – by the VCSS scale and a decrease in working capacity – by the VDS disability scale in both groups. In the long-term postsurgical period, there was an improvement of these indicators, more pronounced in patients of group II. Clinical study of long-term results of the closed separation of perforating veins and paratibial fasciotomy operation confirmed the high efficiency of this method and allowed us to consider it as a pathogenetically-grounded method of surgical treatment of patients with postthrombotic syndrome of the lower extremities.
Key words: opportunistic pathogenic microflora, urogenital tract, enterobacteria, β-lactamases, antibiotics, resistance
Abstract. Monitoring of Enterobacteria strains with producing β-lactamases in males with infectious-inflammatory diseases of urogenital tract. Sklyar T.V., Lavrentievа K.V., Kurahina N.V., Lykholat T.Yu., Papiashvili M.G., Lykholat O.A., Stepanskyi D.O. This article presents the findings of investigation of the microflora of 257 males with infectious-inflammatory diseases of the urogenital tract using the test system “Androflor”. The role of representatives of conditionally pathogenic microflora as the main etiological agent in occurrence of infectious-inflammatory diseases of the urogenital tract in males was shown. Its composition in 39.3±3.0% of cases was represented by bacteria of family Enterobacteriaceae, in 10.9±1.9% – by Enterococcus spp., in 3.1±1.1% – by Haemophilus spp. and in 0.4±0.1% of cases – by P. aeruginosa. Out of 101 strains of enterobacteria, 27 representatives had the ability to synthesize β-lactamases 26.7±4.4% of cultures), in particular: 16 isolates of E. coli, 5 isolates of P. mirabilis and 6 isolates of K. pneumoniae. The selected strains of enterobacteria producing β-lactamases appeared to be resistant at least to 6 tested antibiotics, which allowed referring them to categories of multi-resistant. All cultures producing β-lactamases showed resistance to penicillinеs – ampicillin and amoxiclav. In this case, resistance to at least one of the antibiotics of cephalosporin group of the third generation was noted. In addition, 83.3±2.1% of the examined isolates were characterized by resistance to macrolides – erythromycin and azithromycin, as well as to co-trimoxazole and fosfomicin. The obtained data are of practical importance to develop efficient schemes of antibiotic therapy for infectious-inflammatory diseases of the urogenital tract, caused by strains of enterobacteria producing β-lactamases.
Key words: endometrium, mammary gland, cervix, immunodeficiency, estrogen, progesterone, epidermal growth factor hormone, precancerous state
Abstract. Triple-negative transformation of the endometrium, cervix and mammary gland on the background of immunodeficiency. Lytvynenko M.V., Gargin V.V. Precancerous processes of the female reproductive system continue to be an issue that is being actively studied, despite the successes of recent years. One of the key prognostic factors is the characterization of the receptor set, primarily the mammary gland and endometrium, namely estrogen (ER), progesterone (PR), epidermal growth factor-2 (HER2) receptors. Purpose – to identify the features of the distribution of estrogen, progesterone and epidermal growth factor receptors in the tissues of the endometrium, cervix and mammary gland with a combination of HIV infection and alcohol abuse. Fifty women of reproductive age from 20 to 40 years were studied. After routine conduction and immunohistochemical staining, ER and PR expression were determined by a modified D.Allred scale. HER2 expression was determined by a semi-quantitative method. The obtained digital data were statistically processed. A morphometric study indicates that the combination of HIV infection and alcohol abuse significantly affects the distribution of receptors in the female reproductive system. To a greater extent, the overall score is reduced by reducing the number of cellular elements with the expression of ER and PR. HER2 receptor expression is significantly reduced in the endometrium and mammary gland. These changes may be facilitated by atrophic changes in these organs, which occurs in immunodeficiency. According to the D.Allred scale, the mean score decreases from 5.45±0.63 to 3.10±0.88 in the endometrium, from 4.68±0.65 to 2.47±0.58 in the cervix, from 6.57±0.67 to 3.57±0.77 in the mammary gland (p<0.05). HER2 expression decreased from 3.24±0.47 to 2.21±0.23 in the endometrium, from 3.43±0.66 to 2.36±0.32 in the mammary gland (p<0.05). The development of immunodeficiency is characterized by the restructuring of female reproductive organs with a change in the receptor set of the endometrium, cervix and mammary gland and a decrease in both the qualitative and quantitative composition of the receptors, which may serve as a prerequisite for the development of a triple-negative phenomenon in tumors of these organs.
Key words: human immunodeficiency virus, herpes virus skin diseases, clinical course, melatonin
Abstract. Clinical course of herpes virus skin diseases on the background of HIV. Liadova T.I., Dorosh D.M., Volobuieva O.V., Popov М.М., Martynenko O.V., Kadyhrob I.V., Sorokina O.G. Dermatological diseases are widespread among the HIV-infected population. Due to the continuing increase in the incidence of HIV, skin manifestations are becoming more common, especially herpes virus infections. Many of them are not unique in this group but the disease may not be typical, severe and systemic, which always complicates the diagnosis. Many studies demonstrate the specifics of the clinical course of HIV, in particular opportunistic infections, but a separate systematization of herpetic manifestations of HIV has not been conducted to date. On the other hand, the introduction of highly active antiretroviral therapy has been accompanied by some reduction in skin manifestations associated with HIV, and for clinicians the low efficacy of acyclovir in this category of patients, remains the main problem and therefore requires new approaches. The aim of this article was to study and compare the clinical course of herpes virus skin diseases on the background of HIV, taking into account the severity and stage of the underlying disease, based on the international classification of HIV adopted by the Centers for Disease Control (CDC). From September, 2018 to October, 2020, herpes was studied in 59 HIV patients and it was found that the nature of dermatological manifestations of herpes virus infections depends on the level of CD4+ cells. To expand drug provision, treat comorbid conditions and improve the quality of life of each patient, the dissertation, research «Clinical and immunological significance of IL-31 and melatonin in herpes virus skin diseases on the background of HIV infection and methods of their correction» is planned.
Key words: dental caries of temporary teeth, deft index, severity of dental caries,pathology of musculoskeletal system, markers of connective tissue
Abstract. Аssociation between incidence of caries of temporary teeth and pathology of the musculoskeletal system in preschool children, considering biochemical markers of connective tissue metabolism. Bodnaruk N.I., Smolyar N.I., Chukhray N.L., Mashkarinets O.O., Gan I.V. The aim is study biochemical markers of connective tissue metabolism in children with musculoskeletal disorders and their association with dental caries of temporary teeth. There were examined 232 children at the age of 5 (202 children with musculoskeletal disorders and 30 conditionally healthy children without somatic pathology). Among children with musculoskeletal disorders 68 (33.66%) had flat feet, 59 (29.21%) – postural impairment and 75 (37.13%) – combined pathology of the musculoskeletal sestem. For further research, the children were divided into three groups, 30 people in each. Group І included children with pathology of the musculoskeletal system, dental caries, without oxyproline in urine; group ІІ – with pathology of the musculoskeletal system, dental caries and oxyproline in urine; group ІІІ – with dental caries and without oxyproline in urine. Urinary excretion of glycosaminoglycans using a nephelometric test with cetylpyridinium chloride was determined. The concentration of creatinine in urine was measured in units of weight in the formation of a chromogenic complex of a solution of picric acid with creatinine in an alkaline medium. Dental status was assessed in terms of caries prevalence, deft index and severity of dental caries. The prevalence of caries of temporary teeth in 5-years old children with musculoskeletal disorders was on average 90.6±2.05%, deft index ─ 6.62±0.20, being significantly higher than in children without somatic pathology (respectively 70.83±4.45% and 5.15±0.34, р<0.001). Oxyprolin was detected only in the urine of children with combined pathology of musculoskeletal system (on average 3.53±0.11 units). The excretion rates of glycosaminoglycans in children with pathology of the musculoskeletal system, dental caries and oxyproline in urine (gr.ІІ) were two times higher than the reference range (415.37±15,09 CPCh units / 1 g creatinine, р<0.001). In the absence of oxyproline in urine, both in somatically healthy children (gr. ІІІ) and in children with pathology of the musculoskeletal system (gr. І), the levels of excretion of glycosoaminoglycans were within the reference range (respectively 198.83±10.71 and 203.87±12.52 CPCh units / 1 g creatinine. The levels of daily excretion of creatinine were within the normal range in children of gr. ІІІ (1.17±0.13 g/day; in children of gr. І they were 2.85 times lower (0.41±0.05 g/day, p<0.001); in children of gr. ІІ – 6.5 times lower (0.18±0.02 g/day р<0.001). In children of gr. ІІ, a negative correlation was found between the levels of creatinine and oxyproline (τ= -0.68, p<0.05). The absence of oxyproline in the urine of children of gr. І and ІІІ indicates the absence of collagen decay in their bodies. In children with pathology of the musculoskeletal system against the background of undifferentiated connective tissue dysplasia (gr. ІІ), a strong, positive correlation was found between the deft index and levels of urinary excretion of oxyproline (τ= +0.77, p<0.05) and glycosaminoglycans (τ= +0.90, p<0.05), which indicates that the development of dental caries depends on the severity of the pathology of the musculoskeletal system.
Key words: mandibular fractures, children, osteosynthesis
Abstract. Optimization of surgical treatment of mandibular fracture in children with a variable bite. Kovach I.V., Zub H.E., Kriachkova L.V., Kucherenko O.M., Khotimska Yu.V., Lavreniuk Ya.V., Vlad M.I. Children aged 6 to 12 are characterized by increased activity, begin to engage in active sports and this increases the risk of traumatic injuries of the facial skeleton. Among such lesions, fractures of the mandible rank first. Using acrylic mandibular splints and mandibulomaxillary fixation are considered to be a traditional method of treating mandibular fractures in children. In the period of variable occlusion due to physiological changes of teeth, caries and its complications, loss of teeth due to traumatic injuries and unexpressed equatorial teeth, mandibulomaxillary fixation is difficult or impossible and using acrylic mandibular splints is ineffective when line of fracture goes out of dental arc. Due to these and other circumstances, there is a need for open reposition and internal fixation of fragments with miniplates. Children have a risk of damage to the rudiments and roots of permanent teeth or mandibular canal when miniplates are fixed with screws. In order to prevent complications in the surgical treatment of mandibular fractures during variable occlusion in children, we analyzed cone-beam computerized tomograms and identified areas for safe fixation of screws, established a safe depth of immersion of screws in bone tissue.
Key words: pregnant women, prevention, dental caries, periodontal diseases, gingival bleeding index, oral hygiene index
Abstract. Optimization of prevention of dental diseases in pregnant women. Gadzhula N.G., Cherepakha O.L. Effective prevention of dental diseases during pregnancy, as well as the correct tactics of a dentist and obstetrician-gynecologist is important factors in improving the level of dental health in pregnant women. The aim of research was to increase the effectiveness of the prevention of dental caries and periodontal diseases by introducing a complex of prophylactic and therapeutic measures in pregnant women. The implementation of the prophylaxis scheme is performed in 136 women aged 18-35 years. In the main group (70 women) prophylaxis was carried out using the complex of prophylactic and therapeutic measures developed by us, which includes: professional oral hygiene, oral health treatment, nutrition correction, prescribing the medicines of systemic and local action, training in proper teeth brushing, active sanitary and educational work. In the control group (66 women), the generally accepted prophylaxis scheme was used. Evaluation of the effectiveness of prophylactic and therapeutic measures was determined by indicators of caries incidence during pregnancy, reduction of caries, the dynamics of Papillary-Marginal-Attached Index and Papillary Bleeding Index. The effectiveness of the proposed algorithm of dental diseases prevention for pregnant women was confirmed by 3.45 times lower incidence of dental caries in women of the main group compared to the control group (0.44±0.06 versus 1.52±0.13 tooth, respectively); significant decrease (p<0.001) of Papillary-Marginal-Attached Index values (14.01±1.17 versus 49.25±1.86%), as well as bleeding indices (0.32±0.08 versus 1.82±0.13) and Green-Vermilion (0.89±0.08 versus 1.71±0.12 scores). Regular prophylactic and therapeutic examinations of pregnant women by a dentist, hygienic education and training of expectant mothers, active motivation of women to carry out individual oral hygiene with a constant monitoring of its implementation, correction of nutrition and mineral metabolism, influence on cariogenic and periodontal microbiota of the oral cavity, improvement of physiological enamel mineralization and increasing of hard tooth tissues resistance contributed to the reduction of caries incidence by 71.05±5.42% and the effectiveness of periodontal diseases treatment by 88.46±3.81% in the main group versus 36.84±5.94% in the control group (p<0.001).
Key words: water pollution, potassium stearate, sanitary and hygienic characteristics, hazard class
Abstract. Sanitary and hygienic characteristics of potassium stearate as a source of anthropogenic pollution of water reservoirs. Lototska O.V., Krytska H.A., Kucher S.V. Monitoring of surface water quality indicates deterioration of its quality due to anthropogenic pollution. Among them, potassium stearate (PS) occupies a prominent place. The purpose of the study is to substantiate regulations of potassium stearate in the water of reservoirs on the basis of sanitary and hygienic assessment of potassium stearate, study its stability and transformation, the impact on the organoleptic properties of water, the sanitary condition, self-cleaning processes and the sanitary condition of reservoirs. Research methods – bibliographic, analytical, statistical, sanitary and hygienic. It was found that the average effective concentration of PS by taste for the threshold of sensation (1 point) was at the level of 6.43 mg/dm3. The intensity of the taste of 1-2 points was maintained for 10 days. Potassium stearate is a hydrolyzing and non-chlorinating substance. As a result of assessing the impact of potassium stearate on the processes of self-purification of water from organic pollution by observing the dynamics of water oxidation, dissolved oxygen concentration and biochemical oxygen demand (BOD), the processes of ammonification, nitro- and nitrification, it was found that the limiting potassium stearate for reservoirs is BOD. On the basis of threshold and inactive concentrations by all limiting signs of harmfulness one allows recommending the maximum permissible concentration for potassium stearate at the level of 0.25 mg/dm3. The limiting indicator of harm is sanitary. Comprehensive assessment of the obtained experimental and calculated data by the hygienic rationing of PS in general the water of open reservoirs allows classifing it as the 4th class of danger (practically non-toxic substances).
Key words: public health system, development strategy, management model
Abstract. Strategy for the development of the public health system of Ukraine in line with modern changes in society. Khomenko I.M., Ivakhno O.P., Pershehuba Ya.V., Zakladna N.V. The purpose of this study: scientific substantiation of the strategy for the development of the public health system of Ukraine in modern conditions of its functioning. The work used analytical, epidemiological, sociological, expert, statistical research methods, which are aimed at determining methodological approaches to the development of the competencies of public health specialists in Ukraine in the preventive block of the system, a model for staffing and industry management. According to a specially developed author's program, 120 experts - specialists of the Center for Disease Control and Prevention of the Ministry of Health of Ukraine, gave their conclusions on the need to: consolidate at the legislative level the network of institutions and staffing of the industry; employment of public health specialists who have received specialized higher medical education in the relevant positions; use adequate mechanisms for the functioning of the public health system on the basis of contractual relations with the National Health Service of Ukraine in the preventive block; creation of a unified information fund on the state of health of the population and the environment, real working conditions in different sectors of the country's economy; development of an effective and efficient program of recreational activities available at all levels of administration in Ukraine; the formation of the economic interest of the whole society in the preservation and strengthening of the country's health; to strengthen the preventive activities of the public health system of Ukraine. The environmental situation in the country requires prompt resolution of issues of risk management for public health.
Key words: dry eye syndrome, substitution therapy medications, seasonal variations, retail
Abstract. Study of the seasonal dynamics tendencies of sales of substitution therapy medications for dry-eye syndrome treatment in Ukraine. Tomashevska Yu.O., Kryvoviaz O.V., Makarenko O.V., Koval V.M. The purpose of the article was to study the seasonality of retail sales of substitution therapy medications for dry eye syndrome treatment over the period of five years (2016-2020) in comparison with the annual monthly variations, taking into consideration the probable atypy of the 2020 indices due to the influence of the pandemic. To achieve the stated goal, retrospective, structural and graphic methods were used; a marketing analysis of the national pharmaceutical market from the point of presence of substitution therapy medications for dry eye syndrome was conducted. The next stage was the identification of seasonal variations in the time series of sales of the medications for treatment of conditions accompanied by the dry eye syndrome in Ukraine over the period of 2016-2020. The analysis of retail sales of substitution therapy medications for dry eye syndrome treatment over the period of 2016-2020 indicates a steady presence of seasonal peaks in March, August and December. The information received in the course of the study is necessary both for the patients and the employees of pharmaceutical companies engaged in wholesale and retail sales of medicines and medical devices. In terms of the patients, there a possibility to use preventative measures in order to limit the influence of a number of studied aggressive factors. And on the Based on the indexes of the seasonal demand for dry eye syndrome substitution therapy medications, pharmaceutical enterprises will be able to form the corresponding stock of the necessary medications thus ensuring the exists actual availability of substitution therapy medications for the population. This will indirectly but positively impact the treatment of patients with dry eye syndrome.
A CASE FROM PRACTICE
Key words: dyspnea, sequela, COVID-19, Godoy method®
Abstract. Lymphatic therapy by Godoy method in the treatment of dyspnea after COVID- 19: case report. Jose Maria Pereira de Godoy, Livia Maria Pereira de Godoy. Despite all efforts, this disease has been a major cause of mortality as well as sequelae after the infectious event. Issues regarding an effective form of treatment for the virus have led to efforts focused on the acute manifestations of the disease. The aim of the present study is to describe the first observational result of the treatment of a pulmonary sequela of COVID-19 with important symptomatic limitations. One month ago, the patient contracted COVID-19 and was treated clinically, but the case progressed with important respiratory and physical limitations. An increase occurred in the lymphedema and the patient sought treatment. She would waken at night with dyspnea and was unable to walk more than a few steps or climb stairs. Intensive treatment of the lymphedema was proposed using the Godoy Method®. The Godoy method for reversing fibrosis was useful in improving dyspnea in a short period of time in a patient with sequelae resulting from COVID-19.
Key words: atypical course, complications of peptic ulcer disease, perforated duodenal ulcer
Abstract. Peculiarities of diagnostics of atypical course of perforated duodenal ulcer (clinical case). Liesnyi V.V., Filonenko V.O., Liesna A.S. Aim – to describe a clinical case of atypical course of complications of peptic ulcer disease and the possibility of timely urgent diagnosis. Materials and methods – a clinical case of atypical course of a perforated duodenal ulcer. The clinical case described demonstrates the difficulties of diagnosis in case of lack of time, a dubious clinical picture, ambiguous X-ray data, which requires a more thorough clinical analysis of the available information by urgent brigade of surgeons. For the timely diagnosis of surgical complications of peptic ulcer disease, it is necessary to use modern imaging methods.