Репозиторий Университета

© 2018 by the Serbian Biological Society. The aim of present study was to investigate the difference between α-linolenic acid (ALA, omega-3) and linoleic acid (LA, n-6) on the redox status and cardiac function of the isolated rat heart. ALA or LA were administered for 6 weeks by gavage to all animals, which were randomly divided into 4 groups: male rats treated with a linoleic acid (M-LA), dose of 7.3 mg/kg/day; female rats treated with a linoleic acid (F-LA), dose of 7.3 mg/kg/day; male rats treated with an α-linolenic acid (M-ALA), dose of 165 mg/kg/day; female rats treated with α-linolenic acid (F-ALA), dose of 165 mg/kg/day. Using the Langendorff technique, markers of heart function were evaluated: the maximum and minimum rates of pressure development in the left ventricle (LV; dp/dt max, dp/dt min), systolic and diastolic left ventricle pressure (SLVP, DLVP, respectively), heart rate (HR) and coronary flow (CF). We measured the concentrations of prooxidative markers: nitrites (NO2-), superoxide anion radicals (O2-) and hydrogen peroxide (H2O2), as well as the index of lipid peroxidation (TBARS) in the plasma and effluent. In the lysate, we measured the concentrations of reduced glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD). ALA more negatively influenced the isolated rat heart, especially in females. In contrast, the administration of LA was linked to more prominent oxidative stress, while the application of ALA was associated with improved activity of the antioxidative defense system (with better values in males).

© 2018, Peter the Great St. Petersburg Polytechnic University. Nanocomposite layers consisting of an acrylic paint and single-walled carbon nanotubes (∼1.5 wt.%) have been investigated. The investigated samples had a disk shape with a diameter of 20-30 mm and a thickness of 2-50 μm. After exposure in water for 350 h, the layer mass remained almost invariable (a mass loss of ≤ 1.5%) and the layer samples exhibited high adhesion to glass substrates and a conductivity of ∼ 40 S/m. The layers consisting of the nanotubes and acrylic paint exfoliated from the substrates for ∼1 h. After heat treatment at a temperature of 140 °C, all the layers exhibited a semiconductor-type temperature dependence of the resistance. The prospects of using these layers in various medical products, e.g. implants for wireless energy transmission, have been discussed.

© 2018 Nutritec. All rights reserved. Specialized sports nutrition is one of the most important factors in the extension of the functional potential of athletes, providing adaptive resistance to physical stress, which determines the high physical performance and prolongs athletic longevity of the athletes. The study involved 30 skiers-racers (the average age of 19.5±1.8 years). 12 skiers of the main group within 21 days consumed a specialized food product, obtained on the basis of fermented milk whey containing amino acids, several vitamins, minerals and trace elements, live culture of lactic acid bacteria: L. lactis, L. thermophilus, L. bulgaricus (1.2 × 10s CFU/cm3). The control group consisted of 18 skiers, those taking the placebo (food starch of the same consistency). After a course of product intake, blood level of hemoglobin increased by 6%, of leukocytes - by 10% due to an increase in the number of granulocytes by 32%, and segmented neutrophils by 16% (p<0.05), there was a tendency to increase the number of red blood cells by 7% with a significant decrease in lymphocyte count by 19%. Erythrocyte sedimentation rate in blood of the skiers from the comparison group increased by 41% (p<0.05), while in the athletes of the main group it decreased by 16% (p>0.05). After product intake it has been established by the method of laser Dopplerflowmetry that there was a tendency to increase blood perfusion by 15%, a statistically reliable increase in the flux by 53%, which is based on the improvement of the internal mechanisms of microcirculation regulation. According to the mathematical analysis of cardiac rhythm, centralization of regulation decreased while the activity of an autonomous mechanism for controlling the work of the heart increased. The revealed functional changes ensured an increase of absolute (by 31%, p<0.05) and relative (by 33%, p<0.05) physical performance and aerobic endurance of skiers, contributed to the improvement of short-Term memory. The conclusion is made about the expediency of the intake of the specialized food product to enhance the adaptive capacity of athletes under the influence of systematic physical loads.

© 2018 Ima-Press Publishing House. All rights reserved. The paper analyzes the concepts of personality profiles and demonstrates the possibility of applying this approach to comparatively assessing the psychological characteristics of patients with essential arterial hypertension (EAH). It sets forth the fundamentals of the concepts by F. Alexander, H.F. Dunbar, M. Friedman, and R. Rosenman, which emphasize the importance of emotional, personal, and behavioral factors for the etiology and pathogenesis of EAH and analyzes in detail the psychological study of the characteristics of the so-called type D (distressed) personality that is characterized by a combination of the predominance of negative emotions, social isolation, and inability to regulate these factors. The authors present the results of their own empirical study of personal characteristics (through the Cattel's 16 personality factors questionnaire) in patients with office hypertension (OH) versus those with classical EAH and healthy individuals. OH patients are shown to be significantly less sociable, less emotionally stable, more overwrought and shy, and more prone to self-control and feelings of guilt. The experimental psychological study (by simulating of emotional stress and by using the modified variant of the procedure developed by S. Rosenzweig to examine frustration reactions) has revealed that the patients with OH tend to experience the most intense negative sthenic emotions and they significantly more frequently resort to repression of these emotions. The findings prove that the EAH group is e heterogeneous and confirm the assumption that OH patients show negative affectivity and lower social activity.

© 2018 Ima-Press Publishing House. All rights reserved. Anxiety disorders are an important biomedical problem due to the high prevalence and significant negative impact on the quality of life and the course of concomitant somatic and neurological diseases. Cognitive impairment (CI) is one of the most intensively studied aspects of pathological anxiety. Impairments in attention, executive functions, memory, cognitive deficit, as well as abnormal cognitions and metacognitions are identified in anxiety disorders. Moreover, the treatment of the latter with the most frequently used drugs (antidepressants, atypical antipsychotics, anticonvulsants, tranquilizers) does not lead to a significant improvement in cognitive functions, and often contributes to their worsening. In this connection, in addition to psychotherapy, cognitive function-improving agents play a large role in treating anxiety diseases associated with cognitive dysfunction. Ginkgo Biloba extract (EGb 761, Tanakan®) that positively affects cognitive functions, especially in the domains of memory, concentration and attention deserves special attention.

© 2018, Bionika Media Ltd. All rights reserved. Objective. To investigate the signs of neoplastic transformation of the epithelium in the foci of ovarian endometriosis (OE). Material and methods. Histological and immunohistochemical examinations were used to study 78 and 35 OE cases, respectively, and 8 adenocarcinomas. Anti-Ki-67, anti-Bcl-2, anti-p53, and anti-hepatocyte nuclear factor-1β (HNF-1s) antibodies were employed. Results. The epithelium of endometrioid cyst walls showed papillary syncytial changes (39.7%), metaplasia with clear cytoplasm сells (15.4%), and epithelial atypia with a low-to-relatively low Ki-67 and Bcl-2 expression and with a low p53 expression (41.0%). The expression of HNF-1β in the foci with and without atypia was revealed in 94.7 and 56.3% of cases, respectively; it was detected only in clear cell adenocarcinomas. Conclusion. HNF-1s hyperexpression suggests the adaptive nature and histogenetic relationship of OE to clear cell tumors of the ovary.

© 2018 Media Sphera Publishing Group. All rights reserved. The objective of the present study was to determine the biological age of the unidentified dead subjects based on the morphometric characteristics of the sella turcica in comparison with other methods available for the purpose in order to narrow the range of the alleged ages of the human remains being examined. The parameters of the sella turcica were measured in the corpses immediately after cephalotomy provided no pathological changes could be identified in the sellar region. A total of 86 skulls of the Caucasoid subjects representing the Eastern-Slavic group at the age varying from 22 to 87 years were available for the examination. The study has demonstrated the undulating dynamics of dimensional characteristics of the sellae turcica during the course of a lifetime. The regression analysis was employed to predict the age of the subjects above 22 years of age based on the measurements of the length and depth of the sella turcica and to classify the sample of interest within a given age period. It is concluded that the morphometric characteristics of the sells turcica can be used as the additional clues for the purpose of age determination in forensic medical investigations.

© 2018 Publishing House of the Union of Pediatricians. All rights reserved. Background. Cystic fibrosis is a hereditary disease that occurs as a result of mutations in the regulator gene of chloride ion transmembrane transport (CFTR). Finding mutations in the CFTR gene is necessary for identification of the clinical features of cystic fibrosis. Objective. Our aim was to identify genotype-phenotype correlations between mutations of the first class of pathogenicity and clinical manifestations of cystic fibrosis based on studying the prevalence and structure of CFTR gene mutations. Methods. The study included children under 18 years with cystic fibrosis admitted to hospital between 2013 and 2017. Biallelic mutations in the CFTR gene were the non-inclusion criterion. The CFTR gene variants were analyzed by next-generation sequencing method. Results. In 125 patients with cystic fibrosis, 59 different variants of the CFTR gene were detected, 11 of them not previously described. The most common was the deletion c.1521-1523del found in 98 (39.2%) of the 250 analyzed CFTR gene alleles and the deletion c.1545-1546del found in 22/250 (8.8%) alleles. It has been shown that the mutation c.1545-1546del, p.Y515∗ was more often found in children of the Chechen nation-odds ratio (OR) 139 (95% confidence interval 15-1,257). It has been established that meconium ileus, pancreatic deficiency and cirrhosis are more common in patients with mutations of the first category of pathogenicity: OR 3.9 (95% CI 1.0-15.0), 4.4 (95% CI 1.8-11.1), and 351 (95% CI 17.5-7,046), respectively. The association of CFTR gene mutations with the development of bronchiectases and polypous pancinusitis has not been found. Conclusion. Correlations between the genotype and clinical manifestations of cystic fibrosis in Russian children with CFTR gene mutations of the first class of pathogenicity have been established.

© 2018 Tomsk National Research Medical Center of the Russian Academy of Sciences. All rights reserved. We studied capabilities of the Bruker Microflex MALDI-TOF device for species identification of anaerobic gramnegative cocci isolated from clinical specimens of cancer patients. Seventy clinical isolates of Veillonella spp. and one Acidaminococcus spp were analyzed. All isolates were identified to the species level with a scores greater than 1.9. The most common species were V. parvula (37 strains), followed by V. dispar (16), V. atypica (16) and V. denticariosi (1). Susceptibilities of the isolates were determined by the E-test methodology. All Veillonella isolates were susceptible to imipenem, whereas high resistance rates were observed for penicillin G, amoxicillin/clavulanate and metronidazole. The proportion of resistant isolates of V. parvula, V. dispar and V. atypica to penicillin was 86 %, 85 % and 100 %, respectively. The resistance to amoxicillin/clavulanate was observed in 28.6 % of V. parvula isolates, 23.1 % of V. dispar isolates and in 6.7 % of V. atypica isolates. Resistance to metronidazole (MIC = 8 μg/ml) of V. parvula, V. dispar and V. atypica was 88.6 %, 53.8 % and 40 %, respectively.

Glycosaminoglycan-peptide complex (GPC) (Rumalon®) is an injectable slow-release anti-inflammatory agent (SRIA) that has complex anti-inflammatory and metabolic effects. GPC has been successfully used in the treatment of osteoarthritis (OA) for several decades. The agent now returns again to Russian clinical practice. Objective: to evaluate the efficacy and tolerability of GPC in patients with knee OA, in whom other SRIAs have been previously ineffective. Subjects and methods. A study group consisted of 104 patients (92.3% women) (mean age, 63.2±8.5 years; body mass index (BMI), 28.5±5.4 kg/m2) with severe joint pain (?40 mm on a 100-mm visual analogue scale (VAS)) and/or the need to regularly use nonsteroidal anti-inflammatory drugs (NSAIDs). All the patients received oral SRIAs in the last 6 months and had no improvement. At baseline, VAS pain intensity was 59.4±13.1 mm; the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain was 227.3±90.8; WOMAC stiffness, 97.9±42.1; WOMAC function, 769.2±326.1; total WOMAC scores, 1095.1±426.6. GPC was used by the standard scheme: 25 intramuscular injections every other day per treatment cycle; the results of treatment were assessed at 8 and 12 weeks by VAS and WOMAC pain scores, needs for NSAIDs, satisfaction with treatment (measured on a 1- to 5-pont scale where 1 = no improvement or deterioration and 5 = the best result). Results and discussion. At 8 and 12 weeks, VAS pain scores decreased by 30.1±18.3% and 36.9±16.9%, respectively; the reductions in WOMAC pain scores were 29.8±16.3 and 38.2±23.4%; WOMAC stiffness scores, 29.2±15.4 and 31.6±17.4%; WOMAC function scores, 27.7±14.7 and 30.6±18.4%; and total WOMAC scores, 27.2±13.5 and 33.6±18.0%. The changes in pain intensity and WOMAC scores were statistically significant in both followup periods (p<0.001). The majority of patients rated their treatment result as good or excellent: 70.2% at 8 weeks and 75.9% at 12 weeks. 31.7% of the patients completely stopped taking NSAIDs at 12 weeks. Two patients were noted to have adverse reactions (pain at the injection site and allergic skin reaction) that did not require treatment discontinuation and completely resolved without consequences after completion of a GPC treatment cycle. Conclusion. GPC is an effective and safe agent for the treatment for OA, as well as in patients with severe OA and inefficiency of oral SRIAs.

© 2018, The Author(s). Studies on the methods of nanoparticle (NP) synthesis, analysis of their characteristics, and exploration of new fields of their applications are at the forefront of modern nanotechnology. The possibility of engineering water-soluble NPs has paved the way to their use in various basic and applied biomedical researches. At present, NPs are used in diagnosis for imaging of numerous molecular markers of genetic and autoimmune diseases, malignant tumors, and many other disorders. NPs are also used for targeted delivery of drugs to tissues and organs, with controllable parameters of drug release and accumulation. In addition, there are examples of the use of NPs as active components, e.g., photosensitizers in photodynamic therapy and in hyperthermic tumor destruction through NP incorporation and heating. However, a high toxicity of NPs for living organisms is a strong limiting factor that hinders their use in vivo. Current studies on toxic effects of NPs aimed at identifying the targets and mechanisms of their harmful effects are carried out in cell culture models; studies on the patterns of NP transport, accumulation, degradation, and elimination, in animal models. This review systematizes and summarizes available data on how the mechanisms of NP toxicity for living systems are related to their physical and chemical properties.

© 2018, Springer International Publishing AG. Multifactorial nature of human health and need in personifying the approach to each person leads to the fact that full implementation of healthy life style (HLS) technologies is possible only on the basis of artificial intelligence technologies, widely implemented in the preventive medicine via modern Internet technologies. Modern computer systems allow considering simultaneously big data of separate factors in health assessing and selecting of individualized recommendations for personal HLS. This article presents a concept and a structure of intelligent Internet technology for personalized health-saving support, which allow assessing health and preparing individual optimal recommendations for HLS.

© The Author 2018. SLURP-1 is a member of three-finger toxin-like proteins. Their characteristic feature is a set of three beta strands extruding from hydrophobic core stabilized by disulfide bonds. Each betastrand carries a flexible loop, which is responsible for recognition. SLURP-1 was recently shown to act as an endogenous growth regulator of keratinocytes and tumor suppressor by reducing cell migration and invasion by antagonizing the pro-malignant effects of nicotine. This effect is achieved through allosteric interaction with α7 nicotinic acetylcholine receptors (alpha-7 nAChRs) in an antagonist-like manner. Moreover, this interaction is unaffected by several well-known agents specifically alpha-bungarotoxin. In this work, we carry out the conformational analysis of the SLURP-1 by a microsecond-long full-atom explicit solvent molecular dynamics simulations followed by clustering, to identify representative states. To achieve this timescale we employed a GPU-accelerated version of GROMACS modeling package. To avoid human bias in clustering we used a non-parametric clustering algorithm Affinity Propagation adapted for biomolecules and HPC environments. Then, we applied protein-protein molecular docking of the ten most massive clusters to α7-nAChRs in order to test if structural variability can affect binding. Docking simulations revealed the unusual binding mode of one of the minor SLURP-1 conformations.

© Pushkareva M.V., Shevyreva M.P., Goncharuk N.N., May I.V., Andrishunas A.M., 2018. The article contains information on hazardous chemical wastes, reasons that cause their occurrence and accumulation in the environment as well as issues related to accumulation of persistent organic pollutants (POPs) in the environmental objects. The authors outline specific features of POPs and their possible influence on the environment and a human body; they also dwell on priority activities accomplished in the RF in relation to POPs after Stockholm Convention on Persistent Organic Pollution was ratified. Provisions of international law in the sphere of providing chemical safety are being consolidated now and operating bodies of Basel, Rotterdam, and Stockholm Conventions interact with each other in order to fix concentrations for chemicals which are persistent organic pollutants and to determine their low contents in wastes. The European Union countries and Canada have submitted their proposals on concentrations of 21 various chemicals in wastes for consideration by all the concerned parties. Scientific validity of the proposed concentrations has been analyzed; the analysis results are given in the article. Given the hazards caused by chemicals wastes that contain POPs for people and the environment, the authors suppose that additional research should be performed on substantiation of POPs safe concentrations in wastes. Taking into account national security and common provisions of international laws related to solving global, national, and regional tasks, the authors note that it is necessary to update legislation on state regulation in the sphere of providing chemical safety; they also give grounds and outline conceptual approaches to creation of the Federal Law "On chemical safety". The article gives a basic idea of this law; its purpose; an object of its regulation; people or economic entities whose activities are subject to its force; a place this law, when passed, is going to have in the RF federal legislation and a system of international agreements that are ratified by the RF. It should be noted that when the Federal Law "On chemical safety" is adopted, it will allow to reduce negative effects produced by hazardous chemical wastes on population and the environment and will have both medical and social-economic outcomes.

This paper presents a literature review considering the role and mechanism of apoptosis in the pathogenesis of ischemic stroke (IS). The authors introduce a new concept: the functional request of the patient as a set of external (the nature and intensity of rehabilitation measures, characteristics of everyday life, diet, etc.) and internal (genetic factors, internal picture of the disease, availability of rental and other psychological facilities and etc.) attributes. This concept allows a new angle in understanding the pathogenesis of IS and creates fundamental and clinical potential for more successful approaches to therapy and rehabilitation after IS.

© 2018, SPb RAACI.  Modern studies have shown a high plasticity and phenotypic diversity of neutrophilic granulocytes (NG) provided by different receptors, which are diagnostic markers for the functional capacity of the cell in the course of their activities. We investigated NG from peripheral blood, obtained from healthy people of both sexes aged from 26 to 66 years. Evaluation of the neutrophil membrane receptor expression was carried out by flow cytometry. The relative amount of neutrophilic granulocytes expressing membrane CD62L, CD63, CD66d receptors and the intensity of their expression were determined according to their fluorescence intensities. The surface NG membrane receptors, i.e., CD62L, CD63, CD66d were studied upon the in vitro experimental influence of the following bacterial peptides: N-formyl-methionyl-leucyl-phenylalanine (FMLP, model 1); glucosaminylmuramyldipeptide (GMDP, model 2), and simultaneous incubation of NG blood with fMLP and GMDP (model 3). The in vitro treatment with fMLP in the in vitro model was used to transform the NG phenotype of conventionally healthy subjects, expressing CD62, CD63, CD66d molecules. The treatment caused a significantly decrease in both CD62L and the CD62L expression in relative amounts of neutrophilic granulocytes with a parallel increase of CD63 expression density. The effect of GMDP on the NG phenotype of conditionally healthy subjects did not change the amount of CD62L + NG and CD63 + NG, and did not affect CD62L and CD63 expression density on the surface of NG. However, the amount of CD66d + NG was significantly increased with the unchanged expression of CD66d molecules. GMDP introduced together with the bacterial fMLP peptide was shown to neutralize some features of the NG phenotype transformation caused by fMLP, i.e., the amount of CD62L + NG was restored by 22 % and the CD62L expression density increased significantly. At the same time, GMDP did not correct the negative effect of fMLP upon the number of CD63 + NG and CD66d + NG, and on the CD63 and CD66d expression. Simultaneous addition of fMLP and GMDP did significantly increase the amount of CD66d + NG and expression density of CD63 molecules on the CD63 + NG membrane as compared to intact NG of conditionally healthy subjects. The obtained data are important in order to justify some new immunotherapeutic strategies aimed at correction of the negatively transformed NG phenotype, which accompanies some infectious and inflammatory diseases of bacterial etiology with atypical clinical course.

Copyright © 2018 Loppini, Gizzi, Ruiz-Baier, Cherubini, Fenton and Filippi. We numerically investigate the role of mechanical stress in modifying the conductivity properties of cardiac tissue, and also assess the impact of these effects in the solutions generated by computational models for cardiac electromechanics. We follow the recent theoretical framework from Cherubini et al. (2017), proposed in the context of general reaction-diffusion-mechanics systems emerging from multiphysics continuum mechanics and finite elasticity. In the present study, the adapted models are compared against preliminary experimental data of pig right ventricle fluorescence optical mapping. These data contribute to the characterization of the observed inhomogeneity and anisotropy properties that result from mechanical deformation. Our novel approach simultaneously incorporates two mechanisms for mechano-electric feedback (MEF): stretch-activated currents (SAC) and stress-assisted diffusion (SAD); and we also identify their influence into the nonlinear spatiotemporal dynamics. It is found that (i) only specific combinations of the two MEF effects allow proper conduction velocity measurement; (ii) expected heterogeneities and anisotropies are obtained via the novel stress-assisted diffusion mechanisms; (iii) spiral wave meandering and drifting is highly mediated by the applied mechanical loading. We provide an analysis of the intrinsic structure of the nonlinear coupling mechanisms using computational tests conducted with finite element methods. In particular, we compare static and dynamic deformation regimes in the onset of cardiac arrhythmias and address other potential biomedical applications.

© 2018 by the authors; licensee Modestum Ltd., UK. Objective: The relationship of situational (reactive) and personal anxiety in the sample of respondents with post-trauma stress disorder (PTSD) has been considered in the article. The study found that a significant level of situational anxiety and an average level of personal anxiety is observed in respondents with post-trauma stress disorder. Method: The survey and testing of respondents was conducted on the basis of their voluntary and anonymous participation among the staff of public authorities and law enforcement bodies. Clinical, psychopathological and statistical research methods were used in this work. While conducting a psychopathological survey, the Mississippi scale (MS), military and civilian variants, the severity questionnaire for psychopathological symptoms (AFPS), and the scale for assessing the level of reactive and personal anxiety (Charles D. Spilberger, Yu. L. Khanin) were used to determine the qualitative and quantitative parameters. The levels of reactive and personal anxiety were determined on a scale: up to 30 points-low anxiety; from 31 to 45 points-moderate anxiety; 46 points or more-high anxiety. The statistical processing of research results included the calculation of the arithmetic mean value for the quantitative (M) and qualitative (P) indices and their errors (m and p). When comparing the data obtained in groups and subgroups, the Student’s t-test was used, while the correlation analysis of interrelationships-the Spearman correlation coefficient was used. The sample comprised respondents with signs that meet the diagnostic criteria for PTSD (ICD-10 \ DSM-R). Results: The manifestation of the influence of the experienced psychological trauma on the level of anxiety is: an increased heart rate; Blanchet syndrome; a nervous condition; tension of all groups of muscles; feeling a sense of guilt; a feeling of fever followed by shivers; long confusion; insomnia; migraine; uncontrollable anger. The symptoms of anxiety persist and accumulate, at the time of a stressful situation, and after its resolution, contributing to a decrease in performance, fatigue and exhaustion. In addition, the results of the study indicate that anxiety and its level plays an important role, both in clinical findings and in the pathogenesis of PTSD. At the same time, differences were found among men and women. Men with PTSD are characterized by an increase in the level of situational anxiety as the severity of the disorder increases. Women are characterized by a moderate level of situational anxiety, regardless of the severity of the disorder. For both male and female subjects, high indices of personal anxiety are more significant than situational in the development of PTSD of different severity levels. Conclusion: Anxiety and its level, plays an important role both in clinical findings and in the pathogenesis of PTSD. At the same time, differences were found among men and women. Men with PTSD are characterized by an increase in the level of situational anxiety as the severity of the disorder increases. Women are characterized by a moderate level of situational anxiety, regardless of the severity of the disorder. High indices of personal anxiety are more significant for both male and female subjects than situational one in the development of PTSD of different severity levels. The level of personal anxiety in men increased as the severity of PTSD increased. In women, the high level of anxiety increased with increasing severity of the disorder and stabilized with severe PTSD. Most women and men with PTSD are characterized by a high level of personal anxiety. Moreover, the prevalence of women with a high level of personal anxiety in comparison with men is essential with a mild severity of the disorder. With a moderate degree of the disorder, the differences in the proportion of men and women with a high level of personal anxiety are practically insignificant, and in case of a severe degree of the disorder, their proportion levels off, reaching 100%, both among men and women.

© ISUCT Publishing. Macrolide antibiotics represent a valuable class of broad-spectrum, high active natural compounds with polyketide structure. A well-known FOF1 ATP-synthase inhibitor,[1] namely oligomycin A (1), is a 26-membered α,β-unsaturatedpolyketide lactone with conjugated diene, fused to spiroketal moiety. Oligomycin A possesses strong antifungal, antiactinomycotic and cytotoxic activity, but lacks antibacterial activity. According to recent investigations, the development of anti-cancer drugs based on oligomycin A is quite perspective due to its high cytotoxic activity toward tumor cells, ability to inhibit a multidrug resistance protein p-gp and to prevent an activation of oncogenic K-Ras by inhibition of its localization at the plasma membrane.[2-4] However, high toxicity for mammalian cells and low water solubility are significant limitations of oligomycin A, making it unacceptable for clinical application. Chemical modification is a promising way to improve pharmacological properties of natural compounds. Recently we have found that site-selective modifications of oligomycin A afforded semi-synthetic derivatives with high antiproliferative activity against tumor cell lines[5-7] or selective antifungal activity against Candida spp.[8] and, at the same time, with lower toxicity toward mammalian cells. Also, semi-synthetic oligomycin A derivatives are useful tools for molecular genetic studies of additional targets for this family of antibiotics.[9,10] Previously Ramirez F. et al. have described the reaction of oligomycins with sodium borohydride resulting in mixture of diastereomeric 7-dihydro-and 7,11-tetrahydro derivatives without further separation and characterization of individual products.[11] Also, there is no data on biological activity of these reduced oligomycins against fungal/actinomycetes strains and tumor cell lines in article mentioned above. Thus, in this paper we report regio-and stereoselective methods for borohydride reduction of oligomycin A, structure determination of obtained derivatives and investigation of theirs antiproliferative, antifungal and antiactinomycotic properties. The feasibility of regio-and stereoselective reduction of C7-carbonyl group in a core structure of oligomycin A was proposed due to the presence of haptophilic hydroxyl groups[12] at C5 and C9 positions and sterical hindrance of C-11 carbonyl group. Actually, treatment of oligomycin A with bulky sodium triacetoxyborohydride in acetic acid according to the method[13] led to (7S)-dihydrooligomycin A (2) in a good yield. The second carbonyl group (C-11) reduced in more harsh conditions: only the extended treatment of (7S)-dihydrooligomycin A with sodium borohydride in ethanol give (7S,11R)-7,11-tetrahydrooligomycin A (3) as major product. Reaction proceeds with acceptable stere-oselectivity and gives tetrahydro derivative 3, but in low yield (35 %), which associated with low stability of oligomycins in basic conditions.[14] Structure of compounds 2 and 3 was confirmed by high resolution mass spectrometry (HRMS ESI) and NMR spectroscopy. Absolute configurations at C7 and C11 positions of obtained derivatives were unambiguously confirmed by observed interactions between neighboring protons in corresponding1H-1H ROESY spectra. Testing of antimicrobial properties of oligomycins 2 and 3 against Candida spp., filamentous fungi and S. fradiae (strain, extremely sensitive to oligomycins) that of the parent antibiotic in comparison with starting oligomycin A revealed that reduction of carbonyl groups led to decreasing of activity (except strain M. canis). Also, reduced derivatives 2, 3 were less potent against human colon carcinoma cell line HCT116 and its doxorubicin-resistant subline HCT116(-/-), while activity against leukemia cell line K562 and doxorubicin-resistant subline K562/4 retained at the same level as for 1. It might be pointed that biological properties of (7S)-dihydrooligomycin A and (7S,11R)-7,11-tetrahydrooligomycin A are quite similar, consequently C7-carbonyl group has a greater influence on biological activity of oligomycin A than C-11 carbonyl group.

© Bionika Media Ltd. The article highlights the clinical and pathogenetic relationships between endometriosis/adenomyosis and chronic endometritis (CE) within reproductive failures. It describes a cause-and-effect relationship between endometriosis/ adenomyosis and CE by the example of its clinical symptomatology and the pathogenic mechanisms involving an autoimmune process, aseptic inflammation, and altered endometrial receptivity. Endometriosis/adenomyosis and CE have a number of common pathogenetic mechanisms of development and clinical manifestations (infertility, miscarriages, and assisted reproductive program failures). This implies the necessity to qualitatively assess the endometrium in women with endometriosis and adenomyosis during pregravid preparation, as well as the search for new therapeutic ways to correct autoimmune disorders. The use of sodium desoxyribonucleate (derinat) showing the pharmacological properties of an activator of the cellular and humoral immune system and a stimulator of reparative and regenerative processes is a promising approach to drug therapy.