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The paper describes the role of radionuclide technologies among the nuclear-physical methods used in medicine. The condition and prospects of the development of nuclear technology with use of radionuclides in medicine, and in particular, the method of brachytherapy are analyzed. The analysis of the current state of applying radionuclide facilities in medicine is provided.

Abstract Predicting wildfire spread behavior is an extremely important task for many countries. On a small scale, it is possible to ensure constant monitoring of the natural landscape through ground means. However, on the scale of large countries, this becomes practically impossible due to remote and vast forest territories. The most promising source of data in this case that can provide global monitoring is remote sensing data. Currently, the main challenge is the development of an effective pipeline that combines geospatial data collection and the application of advanced machine learning algorithms. Most approaches focus on short-term fire spreading prediction and utilize data from unmanned aerial vehicles (UAVs) for this purpose. In this study, we address the challenge of predicting fire spread on a large scale and consider a forecasting horizon ranging from 1 to 5 days. We train a neural network model based on the MA-Net architecture to predict wildfire spread based on environmental and climate data, taking into account spatial distribution features. Estimating the importance of features is another critical issue in fire behavior prediction, so we analyze their contribution to the model’s results. According to the experimental results, the most significant features are wind direction and land cover parameters. The F1-score for the predicted burned area varies from 0.64 to 0.68 depending on the day of prediction (from 1 to 5 days). The study was conducted in northern Russian regions and shows promise for further transfer and adaptation to other regions. This geospatial data-based artificial intelligence (AI) approach can be beneficial for supporting emergency systems and facilitating rapid decision-making.

Background: Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is associated with an increased risk of death, progression of heart failure, and the development of cardiogenic thromboemboli. Despite the significant success in the management of AF in the paroxysmal form, the results of the treatment for patients with persistent forms of AF remain unsatisfactory. Though the surgical approach provides higher rates of efficiency regarding the restoration of a sinus rhythm, transmural lesions are not always attainable, as a result, the rate of AF recurrence in the long-term period remains fairly high. It is also impossible to create ablative patterns to the mitral and tricuspid valves during thoracoscopic epicardial ablation, which can cause the development of recurrent AF, perimitral and typical atrial flutter. Therefore, the development of hybrid approaches combining the advantages of catheter and thoracoscopic techniques is an urgent task of contemporary surgical and interventional arrhythmology. Aims: to estimate the immediate results of a hybrid approach in the management of patients with persistent AF. Methods: We report the first experience of a hybrid treatment of patients with persistent AF. 6 patients aged 53-64 years (1 female, 5 males) were included in the study. At the first stage, thoracoscopic epicardial bipolar ablation was performed (modified GALAXY protocol); the second stage (in 3 to 6 months after the thoracoscopic stage) included an intracardiac electrophysiological study with three-dimensional endocardial mapping followed by endocardial ablation. Results: The thoracoscopic stage of the hybrid treatment included ablation according to the box lesion scheme using a bipolar irrigation equipment. No lethal outcomes and severe, life-threatening complications were registered. The duration of the inpatient period was 510 hospital-days. The 2nd stage of the hybrid treatment was limited to intracardiac electrophysiological examination only in 2 patients. In 4 patients, epicardial radiofrequency ablation was complemented by endocardial radiofrequency exposure. In 3 of the 4 patients who underwent endocardial radiofrequency ablation, catheter ablation of the mitral and cavotricuspid isthmus was required because of the induction of perimitral and typical flutter, respectively. After the 2nd stage of the hybrid treatment, at the time of discharge all the patients maintained a stable sinus rhythm. There were no severe complications or lethal outcomes. Conclusion: a hybrid approach in the AF management is a safe and effective method of treatment, which combines the advantages of minimally invasive surgery and endocardial intervention in patients with persistent AF. The technique is safe and has acceptable short-term results.

Background: The incidence of atypical trigeminal neuralgia (aNTN) varies from 1 to 7 per 100,000 population per year. The main cause of its development is compression of the trigeminal nerve (TN) root by a vein and/or artery in the cerebellar cistern. To date, the final tactics of treatment for patients with aNTN has not been specified. The effectiveness of conservative methods of therapy does not exceed 50%. The aim of this study was to evaluate the results of microvascular decompression using video endoscopy in the treatment of patients with atypical trigeminal neuralgia. Methods: In the period from 2014 to 2021, 34 patients with aNTN were operated on, of which 18 (53%) patients had neuropathic pain (more than 4 points on the DN4 scale), and 15 (44%) patients had transformation of classical trigeminal neuralgia into atypical neuralgia. The conservative therapy (carbamazepine, gabapentin, pregabalin), administered to all the patients in the preoperative period, was not accompanied by a significant relief of pain syndrome. The maximum intensity of pain upon admission to the hospital was, according to the visual analog scale (VAS), 10 points, according to the BNI (Barrow Neurological Institute) Pain Intensity Scale V (severe, persistent pain). All the patients underwent microvascular decompression of the trigeminal nerve root with the use of Teflon; in 12 (35%) patients, in addition to microscopy, video endoscopy was used. The average follow-up period after the surgery was 3.41.7 years (from 1 to 5 years). Results: In all (100%) patients, the pain was completely eliminated (BNI I) after the surgery. A total five-year excellent and good outcome of the disease on the J. Miller and BNI scale (I -II) was noted in 80% (n=27) of patients with aNTN. The risk of pain recurrence after microvascular decompression was 14% (n=3) in the first three years, and 34% (n=4) after 5 years. The use of video endoscopy made it possible to identify the blood vessels compressing the root of the trigeminal nerve with a minimal displacement of the cerebellum and cranial nerves when visualizing the neurovascular conflict. Conclusion: The microvascular decompression method with video endoscopy is effective in the treatment of patients with aNTN.

Aim. To assess the effect of iron-rich humic substances on hematological parameters in acute post-hemorrhagic and iron deficiency anemia.Materials and methods. Materials for the study were samples of iron-rich active pharmaceutical ingredients based on humic substances (Fe(III) hydroxide complexes with humic substances and polymaltose): HA-Fe3+, HA-PMFe3+, FA-Fe3+, and FA-PM-Fe3+. The anti-anemic activity of the substances was studied on 53 female Wistar rats of the conventional rat line in the model of acute posthemorrhagic and iron deficiency anemia. Anti-anemic activity was assessed by the hemoglobin level, erythrocyte count, hematocrit, and serum iron level.Results. The studied substances HA-Fe3+ and FA-Fe3+ are the most effective in correcting the consequences of both experimental acute posthemorrhagic anemia and iron deficiency anemia. Their effect is comparable to that of the positive control drug Ferrum Lek.Conclusion. Fe(III) hydroxide complexes stabilized by humic and fulvic acids exhibit anti-anemic activity.

Background. Antigen-presenting cells (APCs), especially macrophages, play an important role in the body defense against various pathogens. Their dysfunction and polarization are associated with most inflammatory and autoimmune diseases. The inflammatory process is regulated by activation and / or inhibition of genes differentially expressed by macrophages. Successful correction of inflammation leads firstly to elimination of inflammatory stimuli and then to remodeling and restoration of tissues and organs. It was experimentally confirmed that silvercontaining bionanocomposites based on natural humic substances (HS) obtained from coal of different origin, as well as initial matrices of these HS, are capable of activating pro- and anti-inflammatory properties of macrophages.Aim. To study cytotoxic, pyrogenic, and immunomodulatory properties (arginine balance) of initial HS samples and samples of silver nanoparticles ultradispersed in these HS matrices (HS-AgNPs) in the cell culture of peritoneal macrophages, as well as their effect on pro- and anti-inflammatory properties of APCs.Materials and methods. Cultural and biochemical methods were used in the study.Results. The study showed that the samples CHE-K, CHE-AgNPs, CHS-K, and CHP-K increased M1 macrophage polarization due to stimulation of the NO-synthase activity and inhibition of arginase. The samples CHI-K, CHIAgNPs, CHP-AgNPs, and CHS-AgNPs modulated an alternative M2 or M2-like state of macrophage activation. At the same time, HS are not cytotoxic at effective concentrations, and three out of four studied samples did not contain pyrogenic impurities.Conclusion. The use of HS and their silver-containing bionanocomposites, which have the ability to greatly affect the polarization of antigen-presenting cells, is a promising research area in correction of the inflammatory response for solving an important social and medical problem of treating chronic wounds.

Abstract Nowadays droplet microfluidics is widely used to perform high throughput assays and for the synthesis of micro- and nanoparticles. These applications usually require packaging several reagents into droplets and their mixing to start a biochemical reaction. For rapid mixing microfluidic devices usually require additional functional elements that make their designs more complex. Here we perform a series of 2D numerical simulations, followed by experimental studies, and introduce a novel asymmetric flow-focusing droplet generator, which enhances mixing during droplet formation due to a 2D or 3D asymmetric vortex, located in the droplet formation area of the microfluidic device. Our results suggest that 2D numerical simulations can be used for qualitative analysis of two-phase flows and droplet generation process in quasi-two-dimensional devices, while the relative simplicity of such simulations allows them to be easily applied to fairly complicated microfluidic geometries. Mixing inside droplets formed in the asymmetric generator occurs up to six times faster than in a conventional symmetric one. The best mixing efficiency is achieved in a specific range of droplet volumes, which can be changed by scaling the geometry of the device. Thus, the droplet generator suggested here can significantly simplify designs of microfluidic devices because it enables both the droplet formation and fast mixing of the reagents within droplets. Moreover, it can be used to precisely estimate reaction kinetics.

Cardiovascular complications including arrhythmias and cardiac conduction disorders are one of the main reasons of high mortality rate in acromegaly, while they have not been well explored. Aim.To estimate arrhythmias frequency in acromegaly, identify risk factors leading to the development of arrhythmia and cardiac conduction disorder, to determine the role of cardiac MRI in detecting structural and functional changes. Materials and methods.A single-center prospective cohort study, which included 461 patients (151 men and 310 women) with acromegaly, was conducted. All the patients underwent a standard medical examination, including hormonal blood test, electrocardiogram, echocardiography, electrocardiogram daily monitoring. 18 patients with arrhythmias (11 men and 7 women) had cardiac MRI with gadolinium-based contrast. Results.The results of our research show high frequency of arrhythmias and cardiac conduction disorders in patients with acromegaly 42%. Most frequent kinds of arrhythmias and cardiac conduction disorders were sinus bradycardia 19.1% of the cases and conduction disorders of bundle branch blocks 14.5%. Men were more likely to suffer from arrhythmias and cardiac conduction disorders than women (54.2% and 37.4%, respectively,p=0.0005). Not acromegaly activity but duration of the disease was a main risk factor of arrhythmias and cardiac conduction disorders. Patients with arrhythmias had a long anamnesis of acromegaly (10 and 7 years, respectively, p=0.04). Meanwhile, cardiac conduction disorders were commonly observed in the patients who were treated with somatostatin analogs comparing to the patients who didnt undergo this therapy (50% and 38.6% respectively,p=0.004). We showed that 61% of patients with acromegaly and cardiac conduction disorders who underwent magnetic resonance imaging (MRI) had the signs of myocardial fibrosis. The value of the ejection fraction of the left ventricle according to MRI was higher than with echocardiography (p=0.04). Conclusion.Arrhythmias and cardiac conduction disorders are often observed in patients with acromegaly even with remission of the disease. High risk group need careful diagnostic and monitoring approaches. Cardiac MRI is the gold standard for visualization of structural and morphological changes in the heart. Use of cardiac MRI in acromegalic patients expands our understanding of arrhythmias and cardiac conduction disorders in this disease. There are no specific laboratory markers of diffuse myocardial fibrosis, and the role of myocardial fibrosis in the occurrence of cardiac arrhythmias and conduction disorders needs further studying.

Rationale: Most people infected with SARS-CoV-2 have asymptomatic or minor clinical manifestations and recover without any aggressive therapy. However, there are patient categories in need of specific treatment and those at high risk of severe disease. Control of viremia with antiviral therapy may not be the best therapeutic strategy, since, in addition to substantial toxicity, antiviral agents can suppress the production of antiviral antibodies and disintegrate adoptive immunity against SARS-CoV-2. Due to a high correlation between the symptoms severity in patients with COVID-19 and inflammation, anti-inflammatory corticosteroids have been proposed to treat the disease. However, clinical data do not support the systemic administration of corticosteroids for the treatment of patients with severe COVID-19. Such treatment may have a negative effect due to suppression of the adoptive immune system. In this regard, the development or use of already available of agents that modulate inflammation without compromising the adoptive immune response could be the most effective therapeutic strategy.Aim: To evaluate clinical efficacy and safety of the cell biotherapy technique, the extracorporeal photopheresis (ECP), in the treatment of patients with moderately severe new coronavirus disease COVID-19.Materials and methods: The study included four patients (three women and one man, age 42 to 60 years), with SARS-CoV-2 infection confirmed by gene amplification. All patients had CT-confirmed bilateral multisegmental viral pneumonia (grades > 2, i.e. with 25 to 60% involvement of the lungs). Prior to admission, all patients received antibiotics (azithromycin 500 mg daily and levo-floxacin / amoxicillin clavulanate 500 mg BID) and antipyretics for torpid fever of up to 38.5-39 °C. The outpatient treatment lasted for 8 to 14 days, with signs of progressive respiratory failure. In addition to the moderately severe and torpid course of viral pneumonia, three patients showed hematology test abnormalities, such as hypochromic anemia, leukopenia, leukopenia/lymphopenia, and moderate thrombocytopenia. Three patients had high C-reactive protein (CRP) levels. Inpatient treatment consisted of azithromycin 500 mg daily, levofloxacin 500 mg BID, hydroxychloroquine 200 mg BID, and low molecular weight heparin (enoxaparin 0.4 ml, 4000 anti-Xa IU, s.c. BID). Despite the treatment, the patients showed signs of progressive respiratory failure, with increasing dyspnea and gradual decrease in saturation from 96% to 92%. Isolation of peripheral blood mononuclear cells was done in an intermittent blood separator "Haemonetics MCS+” (USA), with subsequent cell irradiation with an extracorporeal blood irradiator (OKUFKE 320/400-600/650-01 "Yulia”, ZAO NPKF "METOM”, Russia). Ammifurin (ZAO "Pharmcenter VILAR”, Russia) was used as a photosensitizer. Three patients had two ECP sessions with an interval of 24 hours, and one patient had one ECP session.Results: In three patients who had received two ECP sessions, there was a regression of radiographic signs of viral pneumonia from CT2 to CT1 (less than 25% of lung tissue involvement) during the next four days (96 hours). In one patient, the follow-up CT showed resolving pneumonia with less than 5% involvement of the lungs. The patients (n = 3) with baseline high CRP levels showed their normalization at 4 days after two ECP sessions. At 24 hours after a single ECP session, leukocyte count and differential, as well as platelets were restored. In three patients, viral RNA tests within 2 to 4 days after ECP were negative. These results were associated with normalization of body temperature, no further progression of respiratory failure, and a reduction in hospital stay.Conclusion: The use of ECP in 4 patients with moderately severe SARS-CoV-2 infection has contributed to the rapid relief of clinical symptoms, resolution of the inflammation and restoration of respiratory abnormalities in all of them. These observations allow us to consider ECP as an effective and safe method of treatment for moderately severe COVID-19 and a promising adjuvant method in the high-risk patients in order to prevent an unfavorable disease outcome.

Currently the development of technologies for labeling somatostatin with technetium-99m for diagnosing radionuclide neuroendocrine tumors is under way. Somatostatin analogues are binded with technetium99m only by the preliminary addition of a chelating agent. Therefore, it is important to develop a method for preparation of an octreotide derivative by modifying octreotide with precursors: ligands with high chelating ability for its tight binding with technetium-99m. ω-Bis(pyridin-2-ylmethyl)amino)aliphatic acids can be used successfully as such precursors.The purpose of the study was to develop a method for obtaining a new octreotide derivative for diagnosing neuroendocrine tumors.Materials and methods. The somatostatin octreotide analogue was used as the object of the study; succinimid-1-yl 6-(bis(pyridin-2-ylmethyl)amino)hexanoate was used as a chelating agent. Methods of high performance liquid chromatography and mass spectrometry were used to separate and analyze the synthesized compounds.Results. A method to produce an original octreotide derivative using a succinimid-1-yl 6-(bis(pyridin2-ylmethyl)amino)hexanoate as a chelating agent was proposed. The conditions of analytical and semipreparative HPLC for the analysis and purification of the active octreotide derivative (a monosubstituted derivative of the amino acid residue of D-phenylalanine) were suggested.Conclusion. The synthesized derivative of octreotide has a chelating center for strong binding to technetium-99m in its structure, which can be useful for diagnosing neuroendocrine tumors.

The aim of the work was to study the effect of fractions from Saussurea controversa and Мeadowsweet extracts on hemopoiesis and regeneration of bone tissue, which are the main target indicators in experimental osteomyelitis.Materials and methods. In the experiment we used butanol, water and element-organic fractions from the Saussurea controversa extract as well as ethyl acetate, butanol and water fractions from the Мeadowsweet extract, obtained by liquid extraction of the extracts from corresponding plants with the help of organic solvents. After modeling osteomyelitis of the right femur in rats and course treatment for 28 days, the state of bone marrow hemopoiesis was evaluated and morphological examination of the affected limb was performed.Results. The butanol fraction (at a dose of 10 mg/kg) containing flavonol glycosides, the water fraction (at a dose of 80 mg/kg) containing polysaccharides in its composition and the element-organic fraction (at a dose of 10 mg/kg) represented by organic calcium showed the highest osteogenic activity in the Saussurea controversa extract. The water fraction from the Meadowsweet extract (at a dose of 50 mg/kg) demonstrated pronounced hemopoietic activity due to stimulating erythro-, granulo- and lymphopoiesis in the bone marrow of rats with experimental osteomyelitis.

Currently, chemotherapy combined with surgery and radiation therapy is the most effective treatment for cancer. At the same time, the use of this method is accompanied by serious side effects caused by the lack of specificity of most chemotherapeutic agents. In this regard, the development of drug delivery systems (DDS) capable of addressing a chemotherapeutic agent to cancer cells, as well as its controlled release, is a promising approach for the effective treatment of cancer. The aim of the study is to synthesize a new DDS based on surface-modified microparticles of zero-valent iron, to study its properties as a carrier of a chemotherapeutic agent (encapsulation efficiency, loading capacity, possibility of controlled release of a chemotherapeutic agent) and safety. Materials and methods. The microparticles were synthesised by reduction of iron (III) chloride with sodium borohydride followed by in situ surface modification by 4-carboxybenzyldiazonium tosylate. To confirm the occurrence of the reaction, FTIR spectroscopy (Nicolet iS5 Infrared Spectrometer (Thermo Scientific, USA)) was used. Hydrodynamic diameter and surface charge of the microparticles in solution were investigated by dynamic light scattering (DLS) and z-potential. DOX release studies were performed in simulated physiological conditions (pH 3.3; 5.5; 7.4) to evaluate the effect of the external pH on the release rate. Release studies under ultrasound irradiation were performed simultaneously in the same conditions. The effect of surface modification on encapsulation efficiency was evaluated at various pH values (3.3; 5.5; 7.4) and doxorubicin concentrations (0.2; 0.35; 0.5; 0.75; 1.0 mg/ml). To demonstrate the safety of the developed system, cytotoxicity studies were performed on HeLa cell lines (ATCC® CCL-2™). Results. An original method of preparation of the drug carrier, based on iron zero-valent microparticleswith covalently attached chitosan (Fe-CS) on their surface was proposed. Prepared microparticles demonstrated high encapsulation efficiency, drug loading capacity of DOX (0.9 mg per 1 mg of FeCS microparticles), low cytotoxicity and also a possibility to modulate the release rate by ultrasound irradiation and by changing pH of the external environment. Conclusion. A carrier based on microparticles of zero-valent iron with covalently attached to the surface chitosan (Fe-CS) was obtained. The efficiency of encapsulation, the loading capacity of doxorubicin was determined and the possibility of its controlled release under the influence of an ultrasonic field at different pH values was confirmed. In an in vitro experiment on the HeLa cell line (ATCC® CCL-2™), no toxicity was established for all samples (Fe0, Fe-COOH и Fe-CS), regardless of their concentration.

Aim. To compare fecal calprotectin (FC) concentration with laboratory and diagnostic methods in patients with inflammatory bowel diseases (IBD). Materials and methods. The level of FC was measured in 110 patients with established IBD. Crohn diseases (CD) was diagnosed in 50 patients, ileocolitis - in 38 and terminal ileitis in 12 individuals. Ulcerative colitis (UC) was diagnosed in 60 patients, total colitis in 35, left-side colitis in 21 and 4 patients have proctitis. Laboratory data include measurement of FC, leukocytes, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), fecal occult blood. All patients underwent colonoileoscopy (CIS) at the start of disease flare and after 12 weeks of treatment. Results and discussion. We found linear correlation between level of FCP and endoscopic activity of CD, analyzing FCP level and endoscopic activity of CD before (during disease flare) and after 12 weeks treatment (r=0.66, p

Background: We have previously shown that the FAS, TNFR2, TRAIL, DR3, DR4/5 gene expression in patients with newly diagnosed chronic lymphoblastic leukemia (CLL) correlates with clinical manifestations of the disease: they are minimal in patients with high activity of the proapoptotic genes and low activity of the apoptosis-inhibiting genes, and advanced in patients with high expression of the anti-apoptotic and low expression of the pro-apoptotic genes.Aim: To compare the levels of expression of the external apoptosis pathway genes in patients with newly diagnosed CLL before and after chemotherapy with fludarabine, cyclophosphamide and rituximab (FCR), taking into account baseline clinical data and the response to treatment.Materials and methods: This prospective one-center cohort study included 23 patients with newly diagnosed CLL, who underwent clinical and diagnostic assessments and treatment from November 2014 to December 2017. Immunophenotyping of peripheral blood lymphocytes for CLL diagnosis was done by fourcolor flow cytometry. Expression of the external apoptosis pathway genes was assessed by realtime reverse transcriptase polymerase chain reaction. All patients were treated with a standard FCR regimen with subsequent maintenance treatment with rituximab.Results: There were more men (n = 16) than women among our 23 CLL patients. Median age was 64 years (range, from 47 to 77 years). Sixteen (16) patients had CLL Rai Grade I and II, and 7 patients had CLL Grades III and IV. For convenience of analysis, all patients were divided into two groups depending on the FAS gene expression. At baseline, the patients with high FAS expression had higher TNFR2 (p < 0.0015) and TRAIL (p < 0.0053) expression levels. Before FCR therapy, the patients with low FAS expression had higher lymphocyte counts (р = 0.0016) and lower erythrocyte counts (р = 0.0159). At baseline, there were more Grade I and II patients in the group with higher FAS expression (р = 0.0205). At day 3 after the end of a four day FCR cycle, there was an increase only of the FAS (p = 0.0025) and TRAIL (p = 0.0045) expression. After the completion of the first FCR cycle, lymphocyte counts in the patients with low FAS expression decreased earlier than those in the patients with high FAS expression (p = 0.0019). After six FCR cycles, complete or partial remission was obtained in 82% (19/23) of the patients. The patients with high FAS expression had higher complete remission rate (р = 0.026). No adverse events related to FCR were registered.Conclusion: The external apoptosis pathway genes are one of the key factors of the tumor progression in CLL. Our data on the effect of FCR therapy on the FAS and TRAIL gene expression make it possible to consider them as a target for this combination regimen and may become the rationale to develop new pharmaceutical molecules.

The purpose of the study is to study the urinative and antidepressant activities of liquid extracts based on flowers, shoots, leaves and fruits of Crataegus sanguinea Pall. to substantiate their use in the development and manufacture of drugs for the complex treatment of cardiovascular diseases.Materials and methods. The comparative study of the diuretic and antidepressant activity of liquid extracts based on leaves, flowers, shoots and fruits Crataegus sanguinea was conducted. The liquid extracts were obtained on the basis of dried leaves, flowers, shoots and fruits of Crataegus sanguinea. All liquid extracts were obtained in the ratio “raw – extractant” 1 : 1, in all cases the extracting agent was ethyl alcohol 70%. The studies were conducted using outbred white rats of both sexes. All preparations were examined in a dose of 100 μl/kg. The diuretic activity of Crataegus sanguineaof liquid extracts in chronic experiments was determined, 4 h and 24 h portions of urine were collected. The antidepressant activity was tested using the “Desperation” testResults. During the experiment, the diuretic activity of the liquid extract Crataegus sanguinea, as well as the antidepressant activity of liquid extracts of Crataegus sanguinea, shoots and fruits were revealed. Conclusion. Crataegus sanguinea preparations have complex nephrotropic and neurotropic action and can be recommended for use in the cardiovascular pathology treatment.

The purpose of the study is an analysis of the consumption of antibacterial drugs in the therapy of salpingoophoritis in hospital settings and evaluation of changes in the real clinical practice of antibiotic therapy after the introduction of the “Order of medical care for the profile “obstetrics and gynecology...”.Materials and methods. In a retrospective study, an assessment was made of the prescriptions of antibacterial drugs in the therapy of salpingoophritis in specialized treatment and prophylactic institutions of the city of Tomsk in the period 2010–2014. The analysis included 160 case histories. The structure of prescriptions was evaluated on the basis of the application of anatomical-therapeutic-chemical classification and international non-proprietary names (INN), the structural improvement factor K. Gatev was calculated. To quantify the consumption of medications, the calculated daily dose (PDD) was used.Results. Comparative analysis of antibacterial therapy of salpingoophoritis in hospital before and after the introduction of the “Order of medical care for the profile of «obstetrics and gynecology...”. Leading groups of antibacterial drugs were identified. А comparative analysis of the frequency of assignment of various INN was made. The К. Gate’s coefficient was 0.281. The calculation of the average prescribed daily doses of antibacterial drugs was performed.Conclusion. The review of the consumption of antibacterial drugs for salpingoophoritis therapy in hospital settings before and after the introduction of the “Order of medical care for the profile “obstetrics and gynecology...”, showed that the range of antibacterial drugs used increased from 18 to 24 INN, mainly due to the inclusion of modern medicines. In the structure of appointments in 2013–2014, the proportion of drugs not recommended for use by the «Order of medical care for the profile of «obstetrics and gynecology» was 37.5%. It was found that PDD clarithromycin, clindamycin and cefotaxime did not meet the recommended dosing regimens specified in the clinical recommendations for antibiotic therapy. The gap between actual clinical practice and existing clinical recommendations determines the need for in-depth pharmacoepidemiological evaluation to identify the causes and develop measures of an organizational and educational nature to optimize the use of medications.

Search and synthesis of glucose derivatives for nuclear medicine is of great current interest. Being a promising analogue of glucose, D-glucosamine iodine labeled glucose derivatives can be applied in rheumatoid arthritis radionuclide diagnostics and therapy as a radiopharmaceutical.The purpose of the study. Synthesis of a new iodine labeled D-glucosamine derivative; development of the iodine-123 labeling method and the obtained glucose derivative biostudy.Materials and methods. Synthesis of 2-N-(6-iodohexanoyl)-D-glucosamine was carried out through established techniques in organic chemistry. Infrared spectroscopy and nuclear magnetic resonance spectroscopy were used to establish the test compound structure. Isotope change between iodine-127 and iodine-123 of glucosamine derivative was conducted using the heating of mix of the compound and Na123I in acetone. The radio-TLC method was applied to estimate the radiochemical purity of 2-N- (6-iod-123-hexanoyl) -D-glucosamine. The safe application and test of drug pharmacokinetic parameters study was performed on intact Wistar male rats.Results. An original 2-N-(6-iodohexanoyl)-D-glucosamine synthesis method was proposed. According to the method, an intermediate synthesis succimide-1-yl 6-iodohexanoate was obtained by the cyclohexanone oxidative cleavage reaction. The radiochemical purity of 2-N-(6-iodo-123-hexanoyl)-D-glucosamine was more than 97%.Conclusion. 2-N-(6-iodohexanoyl)-D-glucosamine was synthesized and iodine-123 labeled. When investigating the proposed radiopharmaceutical safety and pharmacokinetics, it was shown the drug lacks acute toxicity through intravenous injection and is excreted renally by glomerular filtration.

Background: Recoverin is a 23 kDa protein, belonging to the superfamily of EF-hand Ca2+-binding proteins. One of the functions of recoverin is to regulate the activity of the rhodopsin kinase GRK1, which regulates the activity of rhodopsin. In dim ambient light, the level of calcium in the rod cells of the retina is high, so recoverin binds to and inhibits rhodopsin kinase, leaving rhodopsin very sensitive to photons to enable the eye to detect visual signals even under low-light conditions. Many biophysical methods have previously been used to study the conformational dynamics of recoverin, including NMR, SPR and fluorescence spectroscopy. Here we describe fluorescent solvatochromic dyes suitable for spectroscopic observation of conformational changes in recoverin. Methods: We tested four fluorescent dyes, which were covalently attached to Cys39 of recoverin via the thiol-maleimide interaction. Results: Two out of four labeled recoverin samples showed EGTA-induced changes in the fluorescence lifetime and excitation and emission spectra. Conclusion: Our experiments show solvatochromic fluorescent dyes that can be successfully used for spectroscopic observation of conformational dynamics in proteins.

Calcium chelidonate [Ca(ChA)(H2O)3]n was obtained by semi-synthesis using natural chelidonic acid. The structure of the molecular complex was determined by X-ray diffraction analysis. The asymmetric unit of [Ca(ChA)(H2O)3]n includes chelidonic acid coordinated through three oxygen atoms, and three water ligands. The oxygen atoms of acid and oxygen atoms of water from each asymmetric unit are also coordinated to the calcium of another one, forming an infinite linear complex. Calcium geometry is close to the trigonal dodecahedron (D2d). The intra-complex hydrogen bonds additionally stabilize the linear species, which are parallel to the axis. In turn the linear species are packed into the 3D structure through mutual intercomplex hydrogen bonds. The osteogenic activity of the semi-synthetic CaChA was studied in vitro on 21-day hAMMSC culture and in vivo in mice using ectopic (subcutaneous) implantation of CaP-coated Ti plates saturated in vitro with syngeneic bone marrow. The enhanced extracellular matrix ECM mineralization in vitro and ectopic bone tissue formation in situ occurred while a water solution of calcium chelidonate at a dose of 10 mg/kg was used. The test substance promotes human adipose-derived multipotent mesenchymal stromal/stem cells (hAMMSCs), as well as mouse MSCs to differentiate into osteoblasts in vitro and in vivo, respectively. Calcium chelidonate is non-toxic and can stimulate osteoinductive processes.

Currently, there is a urgent need to search for new diagnostic methods that allow us to reveal malignant tumors with the overexpression of Her-2/neu with high accuracy. In recent years radioisotope methods have been actively developing to identify specific tumor targets, with antibodies being the “targeting” module.The purpose of the study. Creation of a chemically stable radiochemical compound for the imaging of cells with the overexpression of Her-2/neu.Materials and methods. The study was conducted using two human adenocarcinoma cell lines with expression (BT-474) and without expression (MCF-7) Her-2/neu. The specificity of the binding of the test complex with Her-2/neu receptor was determined by direct radiometric and planar scintigraphy. To evaluate the differences in quantitative characteristics between the groups a non-parametric Mann – Whitney test was used.Results. The yield of the labeled complex was more than 91% and the radiochemical frequency was more than 94%. When performing a visual scintigraphic evaluation, a much higher accumulation rate of the studied radiopharmaceutical preparation (RFP) was observed in the culture of cells with overexpression of the surface Her-2/neu receptor. Direct radiometric results also demonstrated a higher accumulation of RFPs in the human BT-474 mammary adenocarcinoma cell line with Her-2/neu overexpression in comparison with the control group.Conclusion. Preclinical studies demonstrated high stability of the test compound, as well as its accumulation in the group of cells with Her-2/neu overexpression

The purpose of the study is to determine the composition of the phenolic compounds of ethanol extracts isolated from three species of duckweed: Lemna minor L., Lemna trisulca L. and Lemna polyrrhiza L. (the synonym is Spirodella polyrrhiza Schleid.) and to study its effect on immune system activation.Materials and methods. The objects of the study are: air-dried grass samples of Lemna minor L., Lemna trisuica L. and Lemna polyrrhiza L. collected during their growing season in 2010–2011 in low-flow and stagnant ponds of Kozhevnikovsky and Tomsk districts of Tomsk region. Isolation of polyphenolic complexes (PFC) was carried out by extraction of air-dried raw material with ethyl alcohol. In qualitative and quantitative analysis of the samples studied the method of reversed-phase high-performance liquid chromatography on an Agilent 1100 Series instrument (USA) was used in isocratic mode. In the experiments, 200 male C57BL / 6 and BALB / C mice aged 8–12 weeks were used to determine immunomodulatory activity. Cell proliferation was assessed by a colorimetric method. The absorption of the obtained solutions was measured with a multi-channel spectrophotometer at the wavelength of 540 nm. The determination of antibody-forming cells in the spleen was performed by local hemolysis. The titer of antibodies in serum was evaluated in the hemagglutination reaction. The local hypersensitivity reaction of immediate type was assessed by the author’s modification.Results. For the first time the study of the qualitative composition and quantitative content of PFC of Lemna minor L. (LM) , Lemna trisulca L. (LT) trisulkas, and Lemna polyrrhiza L. (LP) : (4,7 ± 0,4)%, (3,3 ± 0,3)%, (12,8 ± 0,7)% was carried out. The highest content of phenolic acids (10,76%) and the sum of flavonoids, isoflavonoids and coumarins (14,7%) were found in the LP sample. The content of chlorogenic and 3,5-dihydroxybenzoic acids was 2–9 times higher in LP than in other species of duckweed. In LM and LT with concentrations of 5 μg/ml and LP in the range of 0,5–160 μg/ml did not have a toxic effect on antigen presenting cells. When incubated with LT (20 μg/ml), the proliferation of macrophages was reduced by 1,2 times, and when incubated with LM and LT (80 μg/ml), by 1,2 and 1,8 times, respectively. PFC duckweed (LP) did not have a similar effect. LM and LP had a stimulating effect on the production of nitrites in the concentrations of 5 and 20 μg/ml, increasing it by 1,3–1,6 times. Course introduction of LT and LP led to a significant decrease in the number of antibody-forming cells by 1,5 and 2,3 times and a decrease in the local hypersensitivity reaction by 1,9 and 1,5 times, respectively.

Abstract Although cisplatin plays a central role in cancer chemotherapy, the mechanisms of cell response to this drug have been unexplored. The present study demonstrates the relationships between the intracellular pH (pHi), cell bioenergetics and the response of cervical cancer to cisplatin. pHi was measured using genetically encoded sensor SypHer2 and metabolic state was accessed by fluorescence intensities and lifetimes of endogenous cofactors NAD(P)H and FAD. Our data support the notion that cisplatin induces acidification of the cytoplasm early after the treatment. We revealed in vitro that a capacity of cells to recover and maintain alkaline pHi after the initial acidification is the crucial factor in mediating the cellular decision to survive and proliferate at a vastly reduced rate or to undergo cell death. Additionally, we showed for the first time that pHi acidification occurs after prolonged therapy in vitro and in vivo, and this, likely, favors metabolic reorganization of cells. A metabolic shift from glycolysis towards oxidative metabolism accompanied the cisplatin-induced inhibition of cancer cell growth in vitro and in vivo. Overall, these findings contribute to an understanding of the mechanisms underlying the responsiveness of an individual cell and tumor to therapy and are valuable for developing new therapeutic strategies.

The study objective is to conduct a pharmacoeconomic analysis of naftidrofuryl effectiveness in patients with ischemic stroke.Materials and methods. The work is based on the results of clinical studies of effectiveness, tolerability, and safety of naftidrofuryl in patients who suffered an ischemic stroke. The study design included data on 1000 patients of 45 and older with first-time acute cerebrovascular disease of ischemic type.Results. Direct medical costs for the chosen patient cohort per the Standard of stroke treatment current at the time of the study were 730 575 189 rubles, in case of naftidrofuryl inclusion they were 476 467 620 rubles. Cost minimization is 254 107 569 rubles. Indirect nonmedical costs associated with temporary incapacity for work for treatment per the Standard of stroke treatment were 124 156 950 rubles, and 64 559 180 rubles for naftidrofuryl use which demonstrates the drug’s economic benefit. Budget impact analysis has shown that the possible savings constitute 7.59 %.Conclusion. Inclusion of naftidrofuryl into treatment of patients with ischemic stroke is justified as it decreases duration of rehabilitation. This leads to a positive economic effect expressed as decreased direct and non-direct medical costs.

Materials and methods. 18 native humic acids (HAs) were received from nine representative types of peat of the Tomsk region. Two extraction methods were used: sodium hydroxide and sodium pyrophosphate. Molecular structure parameters were investigated by IR-spectroscopy. The assessement of qualitative and quantitative features of the IR-spectra of 18 different humic acids was made. When HAs with mouse macrophages were cultured their ability to influence the NO-stimulation was determined. Thus, the biological activity of HAs and its dependence on the parameters of the molecular structure were studied.Results. The results of infrared spectroscopy showed that the HAs of upland types of peat contain more carbonyl, carboxyl, and ester groups, and HAs of lowland types of peat contain more aromatic carbon, phenolic and alcoholic hydroxyl, ether and carbohydrate fragments. The results of biological activity showed that HAs from upland types of peat induce the formation of nitrogen oxide, wherein the cell activation decreases with HAs obtained by alkali. All types of HAs from lowland types of peat contain an admixture of endotoxin. Some HAs obtained by sodium pyrophosphate have higher immunotropic activity; the HAs can cause antigen-specific stimulation of cells. The activity of HAs does not depend on endotoxin admixture. The results of molecular spectroscopy showed that the most biologically active HAs have higher aromaticity and higher concentration of oxygen-containing functional groups. This result can be used as a marker factor in the standardization of HAs.

The purpose of the paper is to study qualitative composition and quantitative content of primary exchange compounds in duckweed (Lemna minor L.), trisulki duckweed (Lemna trisulca L.) and spirodela (Spirodella polyrrhiza (L.) Schleid).Materials and methods. The subject of the study was air-dried samples of grass collected during their 2010- 2011 growing season in low-flow and stagnant water bodies of Kozhevnikovsky and Tomsk districts of the Tomsk region. The concentration of free monosaccharides was determined by direct-phase high-performance liquid chromatography. The concentration of the bound sugars was determined by capillary electrophoresis using Applied Biosystem 273T (Thermophischer Ltd., USA). To obtain data on the qualitative composition and quantitative content of amino acids, the amino acid analyzer Hitachi 835 (Japan) was used.Results. It was found out that the least amount of amino acids contained in the water extract from duckweed trifoliate – 96,14 mg, which is 2 times less than in extracts of Lemna minor and Lemna multirooted (205,65 and 208,38 mg, respectively). In duckweed the minimum content of free and bound monosaccharides was determined to be 10,54%, while in the Lemna trifoliate and Lemna multirooted their content was 14,30% and 15,35%, respectively. This study showed the qualitative and quantitative differences of free and bound monosaccharide and amino acid composition between previously mentioned species.

Aim. Clinical and economic examinations were made to study whether it is appropriate to use antiplatelet therapy (APT) with ticagrelor in combination with acetylsalicylic acid (ASA) versus a combination of clopidogrel and ASA in patients with acute coronary syndrome (ACS) following coronary artery bypass surgery (CABS). Materials and methods. A budget impact analysis was used. Data on the efficiency and safety of APT were taken from a relevant analysis in the subgroups of the randomized controlled trial PLATO. Direct medical cost due to APT and expenses on therapy for acute myocardial infarction, stroke, and massive bleeding, and those on medical care for patients dying from cardiovascular events and other causes, as well as indirect cost - gross domestic product (GDP) losses due to untimely death, were taken into account. The findings were assessed from the perspectives of society. Results. The analysis indicated that direct medical costs per patient following CABS, both in case of calculation based on the recorded price for ticagrelor and on the median registered prices for clopidogrel generics, and based on the auction prices for comparison agents proved to be lower when clopidogrel was administered because of the higher cost of ticagrelor-based APT. At the same time GDP losses due to untimely death, as calculated per patient with ACS during post-CABS therapy with clopidogrel + ASA, were more than twice above average losses per patient taking ticagrelor in combination with ACA (107,122 and 221,645 rubles, respectively). From the registered price for ticagrelor and the median registered prices for clopidogrel generics, the total costs per patient with ACS following CABS were lower if Brilinta was used in combination with ASA versus therapy with clopidogrel in combination with ASA (210,092 and 273,257 rubles per year, respectively; the cost savings were 63,165 rubles per patient per year when ticagrelor was administered). On the basis of the auction prices for comparison drugs, the total costs per patient with ACS after CABS proved to be lower if Brilinta was used in combination with ASA versus therapy with brand name clopidogrel in combination with ASA (201,018 and 293,982 rubles per patients year, respectively; the cost savings were 92,963 rubles per patient per year when ticagrelor was used). Conclusion. The use of ticagrelor in combination with ASA ensures resource savings to treat ACS patients undergoing CABS as compared with a regiment including a combination of clopidogrel and ASA.

Background: Providing quality insurance for radiation therapy implies high level of precision for determining absorbed dose, and therefore high level of precision for fitting radial dose function. 3-5 degree polynomials provide required precision, however, uncertainty of their coefficients may cause substantial errors. Aim: To investigate dependence of errors of calculating radial dose function with consideration of uncertainty of coefficients from different degrees of fitting polynomial. Materials and methods: Calculations were performed with software package GEANT4.9.6. Geometry and materials of the source correspond to the model BEBIGCo0.A86. Spectral structure of the source corresponds to the NuDat 2.6 database. Statistical processing was done using nonlinear least-square method. Results: Values of the radial dose function of Cobalt source for brachytherapy were calculated for given geometry. Conducted comparison of precisions of 3 to 5 degree polynomial approximations and possible uncertainties of results of radial dose function calculations. Conclusion: Withrequired precision of 25% and higher at the radius of 10 cm the optimal choice for radial dose approximation is the 3rd degree polynomial.

Background: Therapeutic efficiency in treatment of acute myeloid leukemia (AML) ranges from 20 to 45%. One of the causes of the latter is a drug resistance acquired by leukemic cells under the influence of treatment with antitumor medicines. More important cause is a development of the primary resistance of myeloid leukemic cells to induction of cellular death associated with elemental microenvironment within the bone marrow. Studying primary resistance is very important, and first of all, to prevent development of drug resistance of leukemic cells and, correspondingly, to increase the efficiency of medicamental therapy. Aim: To study the mechanisms of primary resistance of AML cells to induction of cellular death. Materials and methods: Human AML cells of THP-1 line and mononuclear cells of the bone marrow were used in the study of patients with diagnosed AML. Multicellular aggregates were formed during cell cultivating on the 1.5% agarose. To cut off intercellular adhesion, the cells were cultivated in the medium with methylcellulose (0.9%). The viability of the cells was assessed by reduction of Alamar Blue indicator. Results: Within multicellular aggregates, about 75±5% of THP-1 cells were resistant to the activity of recombinant protein izTRAIL, 70±5% – to etoposide, and 40±7% – to sorafenib. Cutting off intercellular contacts decreased the resistance to them. Within multicellular aggregates of primary mononuclear cells, 45±5% of cells were resistant to sorafenib, 57±4% – to etoposide, and all cells were resistant to izTRAIL. Cutting off intracellular adhesion reduced the resistance to sorafenib and etoposide but not to izTRAIL. Conclusion: In multicellular aggregates, AML cells of THP-1 line and mononuclear cells of the bone marrow showed increased resistance to activity of recombinant protein izTRAIL, etoposide, and sorafenib. Diminishing intracellular adhesion in the medium including methylcellulose decreases cellular resistance to cytotoxic agents.

Aim: To assess efficacy of the “7 + 3” regimen in non-selective groups of patients with acute myeloid leukemia (AML).Materials and methods: We retrospectively assessed medical documentations (inand out-patient case histories) of 105 AML patients who were on treatment in MONIKI from January 2002 to December 2011, with evaluation of clinical and hematological characteristics of patients, remission rates depending on age, serum lactate dehydrogenase (LDH) levels and time from diagnosis to the start of treatment, as well as overall survival.Results: In total, the standard regimen “7 + 3” was effective in 58% of AML patients. Remission was achieved in 70.5% of 17 patients with normal LDH levels and in 50.9% of 53 patients with high LDH levels (р < 0,05). In the patients aged from 18 to 30 years, the remission rate was 81%, in those from 31 to 60 years, in 61%. In the elderly patients (from 60 years and older), remission was achieved in 29% of cases (р < 0.05 compared to each of two other age groups). Remission was associated with the time from diagnosis to the start of treatment, being 16.7% in those where this time period exceeded 10 days and 60.8% in those where this time was less than 10 days (р < 0.05). The median overall survival was 11 months in the total group, 15 months in the patients who achieved remission after 2 treatment cycles and 6 months in those who did not respond to treatment. Comparison of the 2 groups with different AML types did not reveal any difference in the treatment results: overall survival in М0–М2 was 11 months and in М4–М5 10 months. Conclusion: Treatment of AML patients with “7 + 3” regimen provides a good anti-tumor effect. Achievement of remission depends on patient age, time to the start of treatment and LDH levels. The results obtained in non-selective group of patients are comparable to those published on selected group of patients.

Pharmacoepidemiological and pharmacoeconomical analysis of endometrit drug therapy at special treatment-and-prophylactic institutions of the city of Tomsk. Estimate the intensity of the appointment of antibacterial drugs endometrit therapy using the methodology of the WHO ATC/DDD, calculated indicators of the intensity of the consumption of drugs in the course of treatment per patient. It was shown that 70% of the established daily dose had to beta-lactam antibiotics and macrolide. For the most common options for antibiotic therapy established nosology of the indicators of clinical efficacy. The calculation of the cost of the schemes of antibiotic therapy, which showed that the cost of treatment is maximal during therapy with ceftriaxone + clarithromycin (4902 RUR); further descending follow: amoxicillin / clavulanic acid + roxithromycin (4658 RUR); benzylpenicillin and gentamicin (4231 RUR). Economic efficiency of antibacterial treatments endometritis a “cost – effectiveness”. The cost of the patient, achieved remission, made during therapy with amoxicillin/clavulanic acid and roxithromycin (5416 RUR), During therapy with ceftriaxone and clarithromycin (6052 RUR), the treatment of benzylpenicillin and gentamicin (14420 RUR). Pharmacoeconomic evaluation results showed that the least acceptable scheme of antibacterial therapy of endometrit in the hospital is the combination of benzyl penicillin and gentamicin. Тhe antibiotic therapy for endometrit may be recommended by a combination of amoxicillin / clavulanic acid and roxithromycin and clarithromycin and ceftriaxone, for which there was no statistically significant differences in clinical efficacy and cost of antibiotic therapy.

This article is a clinical case description of a young female (37 yrs) with ischemic stroke of unknown origin. Neurologic and cardiovascular investigations failed to find out any potential reason for stroke in this case. Genetic test on prothrombotic mutations helped to identify several genetic abnormalities associated with high thrombotic risk that could lead this patient to ischemic event on the background of dysplasia of one of the brain arteries. The authours suggest an algorithmic approach to diagnose young patients (< 50 yrs) with stroke of unknown origin.

Amyloids are protein fibrils with a characteristic spatial structure. Amyloids were long perceived as the pathogens involved in a set of lethal diseases in humans and animals. In recent decades, it has become clear that amyloids represent a quaternary protein structure that is not only pathological but also functionally important and is widely used by different organisms, ranging from archaea to animals, to implement diverse biological functions. The greatest biological variety of amyloids is found in prokaryotes, where they control the formation of biofilms and cell wall sheaths, facilitate the overcoming of surface tension, and regulate the metabolism of toxins. Several amyloid proteins were identified in the important model, biotechnological and pathogenic bacterium Escherichia coli. In previous studies, using a method for the proteomic screening and identification of amyloids, we identified 61 potentially amyloidogenic proteins in the proteome of E. coli. Among these proteins, YghJ was the most enriched with bioinformatically predicted amyloidogenic regions. YghJ is a lipoprotein with a zinc metalloprotease M60-like domain that is involved in mucin degradation in the intestine as well as in proinflammatory responses. In this study, we analyzed the amyloid properties of the YghJ M60-like domain and demonstrated that it forms amyloid-like fibrils in vitro and in vivo.

Antagonists of α1-adrenergic receptors (α-blockers) are among the most effective drugs for the treatment of patients with lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH; LUTS/BPH). Based on the results of treatment outcome analysis, the American Urological Association acknowledged these drugs as drugs of choice for the treatment of BPH [1].

Today it is difficult to think of a clinician who does not utilize a multitude of pharmacotherapeutic options. The modern clinical pharmacology has significantly expanded the opportunities for conservative, medicinal treatment of diseases for which surgery was the only method of cure in the past. The growth in the arsenal of drugs, however, often results in prescription of a multitude of drugs at the same time. It becomes increasingly important therefore to assess drug interactions to enhance efficacy of treatment and prevention of adverse reactions.

Aim. The aim of the study is to assess the efficiency of early invasive treatment versus conservative treatment for patients with non-ST acute coronary syndrome (ACS), and to study immediate results of percutaneous coronary intervention (PCI) in terms of the risk of adverse events. Material and methods. The investigation includes 112 patients with non-ST ACS having risk of adverse outcome determined by the GRACE system. More than half of the patients (77/68.8%) underwent diagnostic coronary angiography within 72 hours of admission, and the decision was made on a subsequent treatment strategy (early invasive or conservative approach). In-hospital outcomes (cardiac deaths, nonfatal MI, reMI), cumulative frequency of these events have been studied according to the risk assessment scale GRACE and treatment strategy. Results. Low risk was determined in 33.9% of patients, intermediate - in 32.1%, and high - in 33.9%. On the whole, frequency of myocardial revascularization was assessed as 56.3%. Fifty-one (45.5%) patients received early invasive treatment, 12 (10.7%) - coronary artery bypass grafting (CABG). A conservative approach was used in 49 cases (43.8%). An early invasive treatment was given to 20 patients (52.6%) from each of the low- and high-risk groups, 11 (30.6%) - from the intermediate risk group. In-hospital cardiac deaths were observed only in the high-risk group, and this number was higher in case of conservative treatment versus early invasive treatment: 3 (30%) versus 1 (50%). Non-fatal MIs in the form of re(MI) were also diagnosed only in the high-risk group following conservative treatment: 2 (20.0%). Nevertheless, no reliable difference in the frequency of each complication was found (p = 0.095; p = 0.1). Significant differences in the high-risk group were proven while comparing the impact of early invasive and conservative approaches on the cumulative frequency of in-hospital death and (re)MI cases (50.0% versus 5.0%; p = 0.009). No benefits of an early invasive approach were identified for low-risk and intermediate risk groups. Conclusion. Early invasive approach compared with a conservative approach in high risk patients with non-ST acute coronary syndrome can improve clinical outcomes with a decrease in the total frequency of in-hospital death, reMI.

The earlier pathomorphological studies of toxic properties of peat humic acids (PHAs) at intraperitoneal injection revealed that one of the causes of lethality is the direct cardiotoxic action of PHAs. For the further study of the mechanism of cardiotoxic action, electrocardiogram was recorded and ventricular fibrillation threshold was determined in male rats after intraperitoneal injection of humic acids in knowingly lethal dose – 480 mg/kg bwt. A single intraperitoneal injection of PHA to rats in knowingly lethal dose caused a significant decrease of the ventricular fibrillation threshold in comparison with intact animals. It was found that the PHA injection exerted no significant effect on the heart rate in rats and change of the PQ, QT, and QTc intervals. At the same time, the significant shortening of the QRS complex in comparison with intact animals was observed. Judging from the results obtained, the single injection of humic acids in the lethal dose induced a decrease in the electrical stability of heart, as evidenced by the drop of the ventricular fibrillation threshold. This decrease of the electrical stability of heart can be a cause of sudden cardiac death of trial rats. Disorder of the heart electrical stability is likely connected with the ionophoric action of humic acids and change of electrophysiological properties of cell membranes.