Экспериментальное исследование антибактериальной активности литического стафилококкового бактериофага ph20 и литического бактериофага синегнойной палочки ph57 при моделировании их импрегнации в ортопедические полимерные конструкции из полиметилметакрилата (костного цемента)

Background: The problem of bacterial colonization of implants used in medical practice continues to be relevant regardless of the material of the implant. Particular attention deserves polymeric implants, which are prepared ex tempore from polymethyl methacrylate, for example - duting orthopedic surgical interventions (so-called "bone cement"). The protection of such implants by antibiotic impregnation is subjected to multiple criticisms, therefore, as an alternative to antibiotics, lytic bacteriophages with a number of unique advantages can be used - however, no experimental studies have been published on the possibility of impregnating bacteriophages into polymethyl methacrylate and their antibacterial activity assessment under such conditions.Aims: to evaluate the possibility of physical placement of bacteriophages in polymethylmethacrylate and to characterize the lytic antibacterial effect of two different strains of bacteriophages when impregnated into polymer carrier ex tempore during the polymerization process in in vitro model.Materials and methods:  First stage - Atomic force microscopy (AFM) of polymethyl methacrylate samples for medical purposes was used to determine the presence and size of caverns in polymethyl methacrylate after completion of its polymerization at various reaction  temperatures (+6…+25°C and +18…+50°C).The second stage was performed in vitro and included an impregnation of two different bacteriophage strains (phage ph20 active against S. aureus and ph57 active against Ps. aeruginosa) into polymethyl methacrylate during the polymerization process, followed by determination of their antibacterial activity.Results: ACM showed the possibility of bacteriophages placement in the cavities of polymethyl methacrylate - the median of the section and the depth of cavities on the outer surface of the polymer sample polymerized at +18…+50°C were 100.0 and 40.0 nm, respectively, and on the surface of the transverse cleavage of the sample - 120.0 and 100.0 nm, respectively, which statistically did not differ from the geometric dimensions of the caverns of the sample polymerized at a temperature of +6…+25°C.The study of antibacterial activity showed that the ph20 bacteriophage impregnated in polymethyl methacrylate at +6…+25°C lost its effective titer within the first six days after the start of the experiment, while the phage ph57 retained an effective titer for at least 13 days.Conclusion: the study confirmed the possibility of bacteriophages impregnation into medical grade polymethyl methacrylate, maintaining the effective titer of the bacteriophage during phage emission into the external environment, which opens the way for the possible application of this method of bacteriophage delivery in clinical practice. It is also assumed that certain bacteriophages are susceptible to aggressive influences from the chemical components of "bone cement" and / or polymerization reaction products, which requires strict selection of bacteriophage strains that could be suitable for this method of delivery.Обоснование. Проблема бактериальной колонизации используемых в медицинской практике имплантатов из различных материалов продолжает оставаться актуальной, независимо от использованного для их изготовления материала. Отдельного внимания заслуживают имплантируемые в организм человека полимерные имплантаты, которые изготовляют ex tempore (по мере надобности) из полиметилметакрилата, например при ортопедических хирургических вмешательствах (так называемый костный цемент). Защита таких имплантатов путем импрегнации в них антибиотиков подвергается множественной критике, поэтому в качестве альтернативы антибиотикам могут быть использованы литические бактериофаги, обладающие рядом уникальных преимуществ, однако экспериментальных работ по изучению возможности импрегнации бактериофагов в полиметилметакрилат и антибактериальной активности в таких условиях в литературе не опубликовано. Цель исследования ― изучить возможность физического размещения бактериофагов в полиметилметакрилате и в модели in vitro охарактеризовать литический антибактериальный эффект двух различных штаммов бактериофагов при их импрегнации в изготавливаемый ex tempore полимерный носитель на этапе полимеризации. Методы. Первым этапом была проведена атомно-силовая микроскопия (АСМ) образцов полиметилметакрилата медицинского назначения для выяснения наличия и размеров каверн, образовавшихся после завершения полимеризации при различном диапазоне температур реакционной смеси (+6…+25 °C и +18…+50 °C). Вторым этапом in vitro было проведена импрегнация двух различных штаммов бактериофагов (ph20, активного в отношении Staphylococcus aureus, и ph57, активного в отношении Pseudomonas aeruginosa) в полиметилметакрилат на этапе полимеризации с последующим определением их антибактериальной активности. Результаты. В ходе выполнения АСМ установлена возможность размещения бактериофагов в кавернах полиметилметакрилата: медиана сечения и глубины каверн на внешней поверхности образца, полимеризованного при температуре +18…+50 °C, составила 100,0 и 40,0 нм соответственно, а на поверхности поперечного скола образца ― 120,0 и 100,0 нм соответственно, что статистически не отличалось от геометрических размеров каверн образца, полимеризованного при температуре +6…+25 °C. Изучение антибактериальной активности показало, что импрегнированный при +6…+25 °C в полиметилметакрилат стафилококковый бактериофаг ph20 утратил эффективный титр уже в течение первых шести суток с момента начала эксперимента, тогда как синегнойный бактериофаг ph57 сохранял эффективный титр как минимум в течение 13 сут. Заключение. В исследовании была подтверждена возможность импрегнации бактериофагов в полиметилметакрилат медицинского назначения с поддержанием эффективного титра бактериофага при его эмиссии во внешнюю среду, что открывает пути возможного применения такого способа доставки бактериофагов в клинической практике. Также сделаны предположения о вероятной подверженности некоторых бактериофагов агрессивным воздействиям со стороны химических компонентов «костного цемента» и/или продуктов реакции полимеризации, что требует строгого отбора пригодных для подобного способа доставки штаммов бактериофагов

Phase transition in waters with different content of deuterium

According to kinetics of temperature changes and laser light scattering on density heterogeneities we investigated waters with different content of deuterium in the area of their phase transition. It has been found out that protium/deuterium ratio substantially affects the process of phase transition water-ice-water in non-equilibrium conditions (the rate of temperature changes—2°C/min): temperature of light water ice melting (D/H = 4.2 ppm) constitutes 1.1 ± 0.3°C against 0.0 ± 0.3°C for high ohmic deionized water (D/H = 140 ppm) and 3.8 ± 0.3°C—for heavy one. Determined are special features of changes in phase state of water on the basis of concepts about water as a colloid system containing deuterium and stabilized gigantic heterophase clusters. © 2015, Allerton Press, Inc

Phase transition in waters with different content of deuterium

According to kinetics of temperature changes and laser light scattering on density heterogeneities we investigated waters with different content of deuterium in the area of their phase transition. It has been found out that protium/deuterium ratio substantially affects the process of phase transition water-ice-water in non-equilibrium conditions (the rate of temperature changes—2°C/min): temperature of light water ice melting (D/H = 4.2 ppm) constitutes 1.1 ± 0.3°C against 0.0 ± 0.3°C for high ohmic deionized water (D/H = 140 ppm) and 3.8 ± 0.3°C—for heavy one. Determined are special features of changes in phase state of water on the basis of concepts about water as a colloid system containing deuterium and stabilized gigantic heterophase clusters. © 2015, Allerton Press, Inc

Experience in the correction of genital prolapse with laparoscopic lateral suspension in patients underwent total or subtotal hysterectomy

Experience in the correction of genital prolapse with laparoscopic lateral suspension in patients underwent total or subtotal hysterectomy M.V. Gavrilov1,2, I.A. Lapina1,2, V.V. Taranov1, T.G. Koltinova1 1Pirogov Russian National Research Medical University, Moscow, Russian Federation 2Group of companies «Medsi», Moscow, Russian Federation Genital prolapse (GP) is still an important issue of modern gynecology. Advances in treatment approaches to this disorder based on its severity and many other factors are reported every year. Patients and Methods: 36 women with verified apical genital prolapse (i.e., 24 women with posthysterectomy vaginal vault prolapse and 12 women with genital prolapse after supracervical hysterectomy) were enrolled in the study. At admission, the most common complaints were foreign body sensation in the perineum (31 women, 86%), dyspareunia (10 women, 28%), and obstructed defecation (6 women, 17%). 34 women (94%) had vaginal delivery. POP-Q system was used to stage pelvic organ prolapse. POP-Q stage 2 was diagnosed in 16.7%, stage 3 in 38.9%, and stage 4 in 44.4%. All women underwent laparoscopic lateral suspension with mesh. Results: 6 and 12 months after the surgery, no recurrent genital prolapse was diagnosed by gynecological (vaginal) examination and pelvic ultrasound. The quality of life assessed by the PFIQ-7 questionnaire has improved (19.8±3.7). Sexual activity assessed by the PISQ-12 questionnaire has significantly improved (20.1±2.4). Conclusion: laparoscopic lateral suspension with synthetic mesh is an effective, simple, and safe technique for genital prolapse surgery. This procedure provides minimal early and late postoperative complications and significantly improves the qulity of life. Key words: sacrocolpopexy, laparoscopic lateral suspension, genital prolapse, apical prolapse, mesh implant, mesh erosion. For citation: Gavrilov M.V., Lapina I.A., Taranov V.V., Koltinova T.G. Experience in the correction of genital prolapse with laparoscopic lateral suspension in patients underwent total or subtotal hysterectomy. Russian Journal of Woman and Child Health. 2019;2(1):28–32.<br

New prospects of the integrative therapy for polycystic ovary syndrome in women with the disorders of carbohydrate and lipid metabolism: a comparative study.

Yu.E.&nbsp;Dobrokhotova, I.A.&nbsp;Lapina, T.G.&nbsp;Chirvon, V.V.&nbsp;Taranov Pirogov Russian National Research Medical University, Moscow, Russian Federation Background: long-term combined estrogen-progestin oral contraceptive pills (COCPs) are the first-line treatment for polycystic ovary syndrome (PCOS). However, this therapeutic option does not affect metabolic disorders that are more severe in women with the second PCOS phenotype thus increasing the risk of cardiometabolic complications. Aim: to assess the effect of myo-inositol and D-chiro-inositol at a 5:1 ratio on metabolic parameters in women of reproductive age with the second PCOS pathogenetic type and the disorders of carbohydrate and lipid metabolism. Patients and Methods: 60 overweight and obese women with PCOS were enrolled in this randomized prospective study. Group 1 women (n=30) received COCP and a drug containing two isoforms of inositol at a 5:1 ratio (myo-inositol 1,000 mg plus D-chiro inositol 200 mg). Group 2 women (n = 30) received COCP only. Hemostasis, lipid panel, fasting glucose level, body mass index (BMI), and waist circumference were measur ed before and 90 days after treatment begins. Results: in group 1, the significant (p&lt;0.05) improvement of lipid parameters was reported as demonstrated by the reduction of the levels of total cholesterol (TC) by 16.9%, triglycerides by 15.7%, low-density lipoprotein cholesterol (LDL–C) by 17.8%, fibrinogen by 15.8%, and fasting glucose by 16.9% as well as the increase of high-density lipoprotein cholesterol (HDL–C) by 28.5%. Meanwhile, no significant changes were seen in group 2. Additionally, the reduction of waist circumference by 4.5% and BMI by 9.1% was reported in group 1. Conclusions: a medication containing myo-inositol and D-chiro-inositol at a 5:1 ratio is promising for the prevention of cardiometabolic complications in women with PCOS. Further large studies of the investigated drug are needed to demonstrate its efficacy and to assess its properties. Keywords: polycystic ovary syndrome (PCOS), treatment, prevention, obesity, metabolic syndrome, lipid panel, inositol, oral contraceptive pills. For citation: Dobrokhotova Yu.E., Lapina I.A., Chirvon T.G., Taranov V.V. New prospects of the integrative therapy for polycystic ovary syndrome in women with the disorders of carbohydrate and lipid metabolism: a comparative study. Russian Journal of Woman and Child Health. 2020;3(3):169–173. DOI: 10.32364/2618-8430-2020-3-3-169-173. </p

Pre-pregnancy preparation in women with polycystic ovary syndrome and obesity: state-of-the-art

I.A.&nbsp;Lapina, T.G.&nbsp;Chirvon, Yu.E. Dobrokhotova, V.V.&nbsp;Taranov Pirogov Russian National Research Medical University, Moscow, Russian Federation In recent decades, extensive growth in the number of overweight or obese individuals is reported thus making this issue important for the medical community. According to some authors, 8% of overweight women and 18% of obese women have troubles with realizing reproductive function. Glucose and lipid metabolism disorders and hypertension that are common in women with polycystic ovary syndrome (PCOS) allow for referring this condition to metabolic diseases. Metabolic syndrome is an umbrella term for a set of metabolic abnormalities arising from insulin resistance and hyperinsulinemia. PCOS may also be considered as one of its manifestations being regarded as the most common cause of infertility in overweight and obese women. The treatment should be complex to recover reproductive function and to address metabolic disorders. Adherence to lifestyle changes, diet, and regular physical activity is still poor. Therefore, the use and assessment of the efficacy of pharmaceutical s for pre-pregnancy preparation to lose weight and to improve reproductive outcomes in PCOS. Keywords: polycystic ovary syndrome, PCOS, obesity, metabolic syndrome, infertility, pre-pregnancy preparation, treatment, prevention, ovulation. For citation: Lapina I.A., Chirvon T.G., Dobrokhotova Yu.E., Taranov V.V. Pre-pregnancy preparation in women with polycystic ovary syndrome and obesity: state-of-the-art. Russian Journal of Woman and Child Health. 2021;4(2):137–143. DOI: 10.32364/2618-8430-2021-4-2-137-143. </p

МЕТОД ДВУМЕРНОГО ДИНАМИЧЕСКОГО СВЕТОРАССЕЯНИЯ ДЛЯ ОПРЕДЕЛЕНИЯ ПОДЛИННОСТИ МАТЕРИАЛОВ И ЛЕКАРСТВЕННЫХ СРЕДСТВ

A method of two-dimensional dynamic backscattering (2D-DLS) with data processing according to a mathematical model of topological descriptors is proposed. The set of topological descriptors makes it possible to fingerprint of the surface, which is in one-to-one correspondence with the chemical composition and the method of its preparation. The 2D-DLS method was introduced at a pharmaceutical enterprise to control powdered medicinal substances obtained in fluidized bed chambers, as well as at two plants for the production of water with a modified isotopic composition for operational control of drugs in terms of the performance of distillation columns in terms of "authenticity".Предложен метод двумерного динамического обратного светорассеяния (2D-DLS) с обработкой данных по математической модели топологических дескрипторов. Метод основан на изменении топологии светорассеяния от поверхности при низкочастотном колебаниях супрамолекулярных комплексов. Набор дескрипторов позволяет формировать фингерпринт поверхности, находящийся во взаимно-однозначном соответствии с химическим составом и способом его приготовления. Метод 2D-DLS внедрен на фармацевтическом предприятии для контроля порошкообразных лекарственных веществ, получаемых в камерах псевдоожиженного слоя, а также на двух заводах по производству воды с измененным изотопным составом для оперативного контроля препаратов

Sleep latency in poor nappers under exposure to weak 2-Hz and 8-Hz electromagnetic fields

It was hypothesized that human sleep might respond to the fields emitted by such natural sources as magnetic activity of the sun and the earth’s magnetic fields. However, the experiments aimed on testing this hypothesis remain scarce. Previously, we found an increase in the amounts of stages N2 or N3 during napping of good sleepers under exposure to low-level (0.004 μT) electromagnetic fields of frequencies 1 Hz or 2 Hz. It remains unexplored whether these fields might additionally decrease latency to stage N1. In this study, we selected 13 people with falling asleep problems to examine the effects of low-level electromagnetic fields on sleep latency. Sleep of these study participants was polysomnographically recorded during three 50-min afternoon napping attempts, either with exposure to either 2 Hz/0.004 μT or 8 Hz/0.004 μT electromagnetic fields or without exposure. We did not find that the sham exposure differed from the 2 Hz and 8 Hz exposures in latency to N1, while latency to N2 after the sham exposure was even shorter than after either the 2 Hz or 8 Hz exposure. We concluded that, although the effects of tested fields might be beneficial for sleep intensity (e.g., due to prolongation of N3), they might not be additionally effective against the falling asleep problems. © 2021 Informa UK Limited, trading as Taylor & Francis Group

An hour in the morning is worth two in the evening: association of morning component of morningness–eveningness with single nucleotide polymorphisms in circadian clock genes

Sub-constructs of morning–evening preference might be differentially related to polymorphisms in circadian clock genes. We previously reported significant association between a single nucleotide polymorphism in PER3 (rs2640909) and Morning but not Evening Lateness scale of the Sleep–Wake Pattern Assessment Questionnaire. To further explore such a scale-specific relationship, seven single nucleotide polymorphisms in five circadian clock genes were studied using exploratory and confirmatory samples (in total, n = 698). The association of rs2640909 with Morning Lateness scale was not replicated in the confirmatory sample but remained significant in the merged sample. Moreover, we found and confirmed an association of this scale with rs1159814 in RORα. The results provided further evidence for differential relationship of polymorphisms in circadian clock genes with morning and evening components of morning–evening preference. We also suggested possibility to take into account the pattern of geographic variation in allele frequency for prioritization of circadian clock polymorphisms in candidate gene studies. © 2017 Informa UK Limited, trading as Taylor & Francis Group

Effects of exposures to weak 2-Hz vs. 8-Hz electromagnetic fields on spectral characteristics of the electroencephalogram in afternoon nap

The human brain seems to be able to respond to low-level extremely low-frequency electromagnetic fields. Controlled laboratory studies of human sleep under exposure to such fields are scarce, especially on the effects of 1 Hz–16 Hz fields overlapping with the frequencies of the electroencephalographic (EEG) signal (e.g., delta, theta, alpha, and sigma activities). In a double-blind placebo-controlled study, we examined the effects of exposure to low-level electromagnetic fields of frequencies 2 Hz and 8 Hz on the EEG power density spectra in the range from 1 Hz to 16 Hz and sleep structure. Sleep of 14 young healthy volunteers was polysomnographically recorded during three 50-min afternoon naps (either without exposure or with 2 Hz/0.004 μT or 8 Hz/0.004 μT electromagnetic field). During the first 30 min of a nap the sham, 2 Hz or 8 Hz/0.004 μT exposures had the same effect. For the remaining 20 min, amount of stage 3 sleep and powers in 1 Hz-8 Hz range continued to build up under the 8 Hz/0.004μT and, especially, under the 2 Hz/0.004 μT exposure, whereas they did not change in the sham condition. Therefore, the low-level 2 Hz electromagnetic fields might stimulate deep sleep in the afternoon nap. © 2020 Informa UK Limited, trading as Taylor & Francis Group