СУЧАСНІ ПІДХОДИ ДО ТЕРАПІЇ УРОГЕНІТАЛЬНИХ РОЗЛАДІВ У ЖІНОК У ПЕРИМЕНОПАУЗІ

The aim of the study – to increase the effectiveness of treatment of perimenopausal women with urogenital disorders by studying the effect of local application of liquid vaginal suppositories "Vaginal-panten" (Angie). Materials and Methods. We examined 176 women with urogenital disorders in perimenopausal period, whose average age was (52.2±4.8) years. In group I – 86 (48.8 %) patients received traditional treatment. Group II included 90 (51.1 %) patients who, in order to eliminate the symptoms of bacterial vaginosis due to individual intolerance to local HRT, were prescribed “Vaginal-Panten” liquid suppositories intravaginally to restore the vaginal microbiota. Results and Discussion. As a result of the treatment, there was a decrease in vaginal dryness and itching in 87.7 % of cases, no vaginal burning sensation in 74.4 % of cases, normalization of the clinical analysis of urine samples, a significant decrease in nocturia by 3 times, a positive cough test by 2 times and pollakiuria by 2.5 times (p˂0.05). Conclusion. Vaginal suppositories “Vaginal-Panten” can be successfully used in the treatment of urogenital disorders in perimenopause, which is especially important for women with contraindications to the use of synthetic estrogen-containing drugs.Цель исследования – повышение эффективности лечения женщин в перименопаузе с урогенитальными нарушениями путем изучения влияния локального применения жидких вагинальных свечей «Вагинал-пантен» (Энжи). Материалы и методы. Нами обследовано 176 женщин с урогенитальными расстройствами в перименопаузальном периоде, средний возраст которых составил (52,2±4,8) года. В 1 группе 86 (48,8 %) пациенток получали традиционное лечение. Во 2 группу вошли 90 (51,1 %) пациенток, которым с целью устранения симптомов бактериального вагиноза в связи с индивидуальной непереносимостью местных ЗГТ интравагинально для восстановления микрофлоры назначали жидкие свечи «Вагинал-пантен». Результаты исследования и их обсуждение. В результате лечения происходили уменьшение сухости влагалища и зуда в 87,7 % случаев, отсутствие жжения в 74,4 % наблюдений, нормализация клинического анализа мочи, достоверное уменьшение никтурии в 3 раза, положительного кашлевого теста – в 2 раза и поллакиурии – в 2,5 раза (р˂0,05). Выводы. Вагинальные свечи «Вагинал-пантен» могут успешно применяться в лечении урогенитальных нарушений в перименопаузе, особенно у женщин, имеющих противопоказания к применению синтетических эстрогенсодержащих препаратов.Мета дослідження – підвищення ефективності лікування жінок у перименопаузі з урогенітальними порушеннями шляхом вивчення впливу локального застосування рідких вагінальних свічок «Вагінал-пантен» (Енжі). Матеріали та методи. Нами обстежено 176 жінок з урогенітальними розладами в перименопаузальному періоді, середній вік яких склав (52,2±4,8) року. У 1 групі 86 (48,8 %) пацієнток отримували традиційне лікування. У 2 групу увійшли 90 (51,1 %) пацієнток, яким із метою усунення симптомів бактеріального вагінозу у зв᾽язку з індивідуальною непереносимістю місцевих ЗГТ інтравагінально для відновлення мікрофлори призначали рідкі свічки «Вагінал-пантен». Результати дослідження та їх обговорення. У результаті лікування отримано: в 87,7 % випадків – зменшення сухості піхви і свербежу, в 74,4 % спостережень – відсутність печії, нормалізація клінічного аналізу сечі, достовірне зменшення ніктурії в 3 рази, позитивного кашльового тесту – в 2 рази і полакіурії – в 2,5 раза (p˂0,05). Висновки. Вагінальні свічки «Вагінал-пантен» можуть успішно застосовуватися в лікуванні урогенітальних порушень у перименопаузі, особливо у жінок, які мають протипоказання до застосування естрогеновмісних препаратів

ОСОБЛИВОСТІ ЦИТОКІНОВОЇ РЕГУЛЯЦІЇ І ГЕМОДИНАМІЧНИХ ПОКАЗНИКІВ ШИЙКИ МАТКИ ПРИ ФІЗІОЛОГІЧНИХ ПОЛОГАХ

The aim of the study – to learn the features of immunological regulation and hemodynamic characteristics of the cervix in preparation for physiological labour. Materials and Methods. We examined 75 pregnant women at 38–40 weeks of gestation. General clinical studies, immunological studies – determination of serum concentration of cytokines IL-6, IL-1β and TNF-α, ultrasound and Doppler studies – determination of hemodynamic parameters in the common uterine artery in the descending and ascending sections, in the arteries and veins of the cervical stroma and in the isthmus, the resistance index (IR) and the systolic-diastolic ratio (SDR) were measured, for venous vessels – the average venous velocity (V mean). Results and Discussion. Evaluation of the nature of production of the main cytokines involved in preparing for the labour (IL-1β, IL-6 and TNF-α) showed high concentrations of the studied proinflammatory cytokines in the blood serum of pregnant women with a mature cervix before the labour compared with women with insufficiently mature cervix. The results of the study of the main indicators of cervical hemodynamic in pregnant women of the studied groups showed significant differences in the indices of vascular resistance in the cervix vessels. A direct correlation (r=0.78) was revealed between the content of the studied cytokines and the levels of peripheral vascular resistance indices of the descending and ascending parts of the common uterine artery, as well as indicators of hemodynamic in the vessels of the cervical stroma. Such a relationship may demonstrate the important immunoregulatory effect of cytokines during pregnancy on the processes of vascularization and blood supply in the uterine vessels at the end of pregnancy. Conclusions. The process of preparing for the labour is associated with immunological restructuring, which is characterized by a change in the systemic content of cytokines and is associated with an increase in the hemodynamics of the cervix. An integrated approach to the study of the features of various pathogenetic options for ensuring the readiness of a pregnant woman᾽s body for labour will make it possible to form objective approaches to the issues of predicting the effectiveness of induction and pre-induction of labour, as well as the occurrence of abnormalities of labour.Цель исследования – изучить особенности иммунологической регуляции и гемодинамические характеристики шейки матки при подготовке к срочным родам. Материалы и методы. Обследовано 75 беременных в сроке беременности 38–40 недель. Проводили общеклинические исследования, иммунологические исследования – определение сывороточной концентрации цитокинов ИЛ-6, ИЛ-1β и ФНО-α; эхографическое и допплерометрическое исследования – определение показателей кровотока в общей маточной артерии в нисходящем и восходящем отделах, в артериях и венах стромы шейки матки и в области перешейка; измеряли индекс резистентности (ИР) и систоло-диастолическое отношение (СДО), для венозных сосудов – среднюю венозную скорость (V mean). Результаты исследования и их обсуждение. Оценка характера продукции основных цитокинов, участвующих в подготовке организма к родам (ИЛ-1β, ИЛ-6 и ФНО-α), показала высокие концентрации изученных провоспалительных цитокинов в сыворотке крови беременных со зрелой шейкой матки накануне родов по сравнению с женщинами с недостаточно зрелой шейкой матки. Результаты исследования основных показателей цервикального кровотока у беременных исследованных групп показали достоверные различия индексов сосудистого сопротивления в сосудах, питающих шейку матки. Выявлена ​​тесная прямая корреляционная связь (r=0,78) между содержанием изученных цитокинов и уровнями индексов периферического сосудистого сопротивления нисходящего и восходящего отделов общей маточной артерии, а также показателями кровотока в сосудах стромы шейки матки. Такая связь может демонстрировать важное иммунорегуляторное влияние цитокинов во время беременности на процессы васкуляризации и кровоснабжения в маточных сосудах в конце беременности. Выводы. Процесс подготовки организма к родам связан с иммунологической перестройкой, которая характеризуется изменением системного содержания цитокинов и связана с усилением гемодинамики шейки матки. Комплексный подход к исследованию особенностей различных патогенетических вариантов обеспечения готовности организма беременной к родам позволит сформировать объективные подходы к вопросам прогнозирования эффективности индукции и преиндукции родов, а также возникновения аномалий родовой деятельности.Мета дослідження – вивчити особливості імунологічної регуляції і гемодинамічні характеристики шийки матки при підготовці до термінових пологів. Матеріали та методи. Відповідно до мети дослідження обстежено 75 вагітних при терміні вагітності 38–40 тижнів. Проводили загальноклінічні дослідження, імунологічні дослідження – визначення сироваткової концентрації цитокінів IЛ-6, IЛ-1β та ФНП-α; ехографічне та доплерометричне дослідження – визначення показників кровотоку в загальній матковій артерії в низхідному та висхідному відділах, в артеріях та венах строми шийки матки та в ділянці перешийка; вимірювали індекс резистентності (ІР) та систоло-діастолічне відношення (СДВ), для венозних судин – середню венозну швидкість (Vmean). Результати дослідження та їх обговорення. Оцінка характеру продукції основних цитокінів, що беруть участь у підготовці організму до пологів (ІЛ-1β, IЛ-6 та ФНП-α) показала високі концентрації вивчених прозапальних цитокінів у сироватці крові вагітних із зрілою шийкою матки напередодні пологів порівняно з жінками з недостатньо зрілою шийкою матки. Результати дослідження основних показників цервікального кровотоку у вагітних досліджених груп показали достовірні відмінності індексів судинного опору в судинах, які живлять шийку матки. Виявлено тісний прямий кореляційний зв᾽язок (r=0,78) між вмістом вивчених цитокінів та рівнями індексів периферичного судинного опору в артеріях низхідного та висхідного відділів загальної маткової артерії шийки матки, а також показниками кровотоку в судинах строми шийки матки. Такий зв᾽язок може демонструвати важливий імунорегуляторний вплив цитокінів під час вагітності на процеси васкуляризації та кровопостачання в маткових судинах наприкінці вагітності. Висновки. Процес підготовки організму до пологів пов᾽язаний із імунологічною перебудовою, яка характеризується зміною системного вмісту цитокінів і пов᾽язана з посиленням гемодинаміки шийки матки. Комплексний підхід до дослідження особливостей різних патогенетичних варіантів забезпечення готовності організму вагітної до пологів дозволить сформувати об᾽єктивні підходи до питань прогнозування ефективності індукції та преіндукції пологів, а також виникнення аномалій пологової діяльності

Quantum Zakharov Model in a Bounded Domain

We consider an initial boundary value problem for a quantum version of the Zakharov system arising in plasma physics. We prove the global well-posedness of this problem in some Sobolev type classes and study properties of solutions. This result confirms the conclusion recently made in physical literature concerning the absence of collapse in the quantum Langmuir waves. In the dissipative case the existence of a finite dimensional global attractor is established and regularity properties of this attractor are studied. For this we use the recently developed method of quasi-stability estimates. In the case when external loads are $C^\infty$ functions we show that every trajectory from the attractor is $C^\infty$ both in time and spatial variables. This can be interpret as the absence of sharp coherent structures in the limiting dynamics.Comment: 27 page

CLINICAL AND RADIOLOGICAL CHARACTERISTICS OF ANCA-ASSOCIATED VASCULITIS: 7 YEARS OF EXPERIENCE IN DIAGNOSIS AND TREATMENT

The aim of the research is to study nosological structure, features of kidney, lung damage, deaths in patients with ANCA – associated vasculitis underwent medical treatment in a multidisciplinary hospital. Material and methods. Selection and subsequent retrospective analysis of the medical histories of 38 inpatient patients observed in nephrological, rheumatological, pulmonological and surgical thoracic departments for the period from January 2012 to december 2018 were carried out. The disease main clinical symptoms, variants of the X-ray picture, and causes of death were assessed in the patients according to the clinical and laboratory examination. Results and discussion. The most common diagnosis was eosinophilic granulomatosis with polyangiitis (EGPA) – 16 cases; microscopic polyangiitis was diagnosed in 11 patients, granulomatosis with polyangiitis – in 9 persons. in 2 cases, ANCA-associated vasculitis was diagnosed without specifying the nosological form. The most common symptoms in patients with ANCA-vasculitis were fever, progressive shortness of breath, weakness, artalgia, eosinophilia, which occurred mainly in patients with EGPA. Among analyzed 38 cases, there were 6 men and 32 women. The average age of patients was 50.72 ± 12.6 years. There were 5 deaths and, in 2 cases, the outcome could not be clarified. All deaths occurred during the first year from the disease onset caused by infectious complications or severe manifestations of the main disease

The European internet-based patient and research database for primary immunodeficiencies: results 2006-2008

Primary immunodeficiencies (PID) are rare diseases; therefore transnational studies are essential to maximize the scientific outcome and to improve diagnosis and therapy. In order to estimate the prevalence of PID in Europe as well as to establish and evaluate harmonized guidelines for the diagnosis and treatment of PID, the European Society for Immunodeficiencies (ESID) has developed an internet-based database for clinical and research data on patients with PID. This database is a platform for epidemiological analyses as well as the development of new diagnostic and therapeutic strategies and the identification of novel disease-associated genes. Within 4 years, 7430 patients from 39 countries have been documented in the ESID database. Common variable immunodeficiency (CVID) represents the most common entity, with 1540 patients or 20.7% of all entries, followed by isolated immunoglobulin (Ig)G subclass deficiency (546 patients, 7.4%). Evaluations show that the average life expectancy for PID patients varies from 1 to 49 years (median), depending on the type of PID. The prevalence and incidence of PID remains a key question to be answered. As the registration progress is far from finished we can only calculate minimum values for PID, with e.g. France currently showing a minimum prevalence of 3.72 patients per 100,000 inhabitants. The most frequently documented permanent treatment is immunoglobulin replacement; 2819 patients (42% of all patients alive) currently receive this form of treatment

Ezrin Is Highly Expressed in Early Thymocytes, but Dispensable for T Cell Development in Mice

Ezrin/radixin/moesin (ERM) proteins are highly homologous proteins that function to link cargo molecules to the actin cytoskeleton. Ezrin and moesin are both expressed in mature lymphocytes, where they play overlapping roles in cell signaling and polarity, but their role in lymphoid development has not been explored.We characterized ERM protein expression in lymphoid tissues and analyzed the requirement for ezrin expression in lymphoid development. In wildtype mice, we found that most cells in the spleen and thymus express both ezrin and moesin, but little radixin. ERM protein expression in the thymus was differentially regulated, such that ezrin expression was highest in immature thymocytes and diminished during T cell development. In contrast, moesin expression was low in early thymocytes and upregulated during T cell development. Mice bearing a germline deletion of ezrin exhibited profound defects in the size and cellularity of the spleen and thymus, abnormal thymic architecture, diminished hematopoiesis, and increased proportions of granulocytic precursors. Further analysis using fetal liver chimeras and thymic transplants showed that ezrin expression is dispensable in hematopoietic and stromal lineages, and that most of the defects in lymphoid development in ezrin(-/-) mice likely arise as a consequence of nutritional stress.We conclude that despite high expression in lymphoid precursor cells, ezrin is dispensable for lymphoid development, most likely due to redundancy with moesin

Gene Targeting Implicates Cdc42 GTPase in GPVI and Non-GPVI Mediated Platelet Filopodia Formation, Secretion and Aggregation

Background: Cdc42 and Rac1, members of the Rho family of small GTPases, play critical roles in actin cytoskeleton regulation. We have shown previously that Rac1 is involved in regulation of platelet secretion and aggregation. However, the role of Cdc42 in platelet activation remains controversial. This study was undertaken to better understand the role of Cdc42 in platelet activation. Methodology/Principal Findings: We utilized the Mx-cre;Cdc42 lox/lox inducible mice with transient Cdc42 deletion to investigate the involvement of Cdc42 in platelet function. The Cdc42-deficient mice exhibited a significantly reduced platelet count than the matching Cdc42 +/+ mice. Platelets isolated from Cdc42 2/2, as compared to Cdc42 +/+, mice exhibited (a) diminished phosphorylation of PAK1/2, an effector molecule of Cdc42, (b) inhibition of filopodia formation on immobilized CRP or fibrinogen, (c) inhibition of CRP- or thrombin-induced secretion of ATP and release of P-selectin, (d) inhibition of CRP, collagen or thrombin induced platelet aggregation, and (e) minimal phosphorylation of Akt upon stimulation with CRP or thrombin. The bleeding times were significantly prolonged in Cdc42 2/2 mice compared with Cdc42 +/+ mice. Conclusion/Significance: Our data demonstrate that Cdc42 is required for platelet filopodia formation, secretion an

Evolution of Highly Polymorphic T Cell Populations in Siblings with the Wiskott-Aldrich Syndrome

Population level evolutionary processes can occur within a single organism when the germ line contains a mutation that confers a cost at the level of the cell. Here we describe how multiple compensatory mutations arose through a within-individual evolutionary process in two brothers with the immune deficiency Wiskott-Aldrich Syndrome (WAS). As a result, both brothers have T lymphocyte populations that are highly polymorphic at the locus of the germ line defect, and no single allele achieves fixation. WASP, the gene product affected in this disease, is specific to white blood cells where it is responsible for regulating actin cytoskeleton dynamics in a wide range of cellular responses. The brothers inherited a rare allele predicted to result in truncated WASP lacking the carboxy-terminal VCA domains, the region that directly catalyzes actin filament generation. Although the brothers' T cell populations are highly polymorphic, all share a corrective effect relative to the inherited allele in that they restore the VCA domain. This indicates massive selection against the truncated germ line allele. No single somatic allele becomes fixed in the circulating T cell population of either brother, indicating that a regulated step in maturation of the affected cell lineage is severely compromised by the germ line allele. Based on the finding of multiple somatic mutations, the known maturation pathway for T-lineage cells and the known defects of T cells and precursor thymocytes in mice with truncated WASP, we hypothesize that the presence of truncated WASP (WASPΔVCA) confers an extreme disadvantage in early developing thymocytes, above and beyond the known cost of absence of full-length WASP, and that the disadvantage likely occurs through dominant negative competition of WASPΔVCA with N-WASP, a protein that otherwise partially compensates for WASP absence in developing thymocytes

Management of Work and Procedure for the Laboratory Diagnostics of Infectious Diseases during the Winter XXII Olympics and XI Paralympics, 2014

Analyzed is the management system for laboratory diagnostics of infectious diseases during the XXII Olympics and XI Paralympics, 2014 in Sochi. Reviewed is piece of work, executed in the pre-Olympic period as regards provision of laboratory facilities deployed for clinical material investigation, development of normative and regulatory documentation which considers peculiarities of the situation, identification of diagnostic capacities of the laboratories, and forecasting of the probable volume of laboratory studies by reference to various groups of infections. Put forward is the procedure for arrangement of work at the different stages of laboratory diagnostics, cooperation and response in case of emergency situation in the sphere of sanitary-epidemiological welfare of the population. Discussed is the role of geo-information system and current means of monitoring over epidemiological situation in the participating states and in the region of the Olympics in laboratory support organization

Patients with primary immunodeficiencies are a reservoir of poliovirus and a risk to polio eradication

ABSTARCT: Immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) have been isolated from primary immunodeficiency (PID) patients exposed to oral poliovirus vaccine (OPV). Patients may excrete poliovirus strains for months or years; the excreted viruses are frequently highly divergent from the parental OPV and have been shown to be as neurovirulent as wild virus. Thus, these patients represent a potential reservoir for transmission of neurovirulent polioviruses in the post-eradication era. In support of WHO recommendations to better estimate the prevalence of poliovirus excreters among PIDs and characterize genetic evolution of these strains, 635 patients including 570 with primary antibody deficiencies and 65 combined immunodeficiencies were studied from 13 OPV-using countries. Two stool samples were collected over 4 days, tested for enterovirus, and the poliovirus positive samples were sequenced. Thirteen patients (2%) excreted polioviruses, most for less than 2 months following identification of infection. Five (0.8%) were classified as iVDPVs (only in combined immunodeficiencies and mostly poliovirus serotype 2). Non-polio enteroviruses were detected in 30 patients (4.7%). Patients with combined immunodeficiencies had increased risk of delayed poliovirus clearance compared to primary antibody deficiencies. Usually, iVDPV was detected in subjects with combined immunodeficiencies in a short period of time after OPV exposure, most for less than 6 months. Surveillance for poliovirus excretion among PID patients should be reinforced until polio eradication is certified and the use of OPV is stopped. Survival rates among PID patients are improving in lower and middle income countries, and iVDPV excreters are identified more frequently. Antivirals or enhanced immunotherapies presently in development represent the only potential means to manage the treatment of prolonged excreters and the risk they present to the polio endgame. Keywords: Poliovirus eradication, Immunodeficiency-associated vaccine-derived polioviruses, Oral poliovirus vaccine, Humoral immunodeficiency, Combined immunodeficiency, Primary immunodeficienc