A little studied question is the development mechanism, timely diagnostics, treatment and prevention of the fibrocystic breast disease at patients with insulin resistance. One of the possible perspective directions of pathogenetic impact on tissues of a mammary gland at the mastopathy associated with a giperinsulinemiya and insulin resistance is use of metformin. Now clinical trials on use of metformin at cancer of mammary glands continue. Data on use of medicines of this group at patients with fibrocystic breast disease in domestic and foreign literature are absent.Objective:assessment of influence of metformin on clinical displays of fibrocystic breast disease and ultrasonic characteristics of a parenchyma of mammary glands at patients with insulin resistance.Materials and methods.As therapy of fibrocystic breast disease patients received metformin in a dose of 1500 mg a day. Dynamic control of a clinical picture of a disease and ultrasonic indicators of a parenchyma of a mammary gland carried out in 3 and 6 months from the beginning of therapy.Results and conclusion.In 6 months of therapy there was a reliable decrease in frequency of a mastalgiya, change of an ultorasound picture of mammary glands: echogenicity of a parenchyma of mammary glands – became sredeny in 95,9% of cases, there was a reliable reduction of thickness of a parenchyma of mammary glands (from 15.5 mm to 10. 5 mm) and diameter of lacteal channels (from 1.7 mm to 0.9 mm). The obtained data on positive influence of metformin on the clinical course of mastopathy and structural changes of a parenchyma of mammary glands at patients with fibrocystic breast disease and insulin resistance allow to consider similar approach as the perspective direction of pathogenetic influence at such pathological association.
Резюме. В исследовании определены клинические, гормональные и иммунологические факторы, позволяющие прогнозировать исход цикла ЭКО у больных репродуктивного возраста с сочетанны-ми формами бесплодия. Показатели гонадотропной стимуляции яичников в цикле ЭКО у больных репродуктивного возраста с сочетанными формами бесплодия зависят от их возраста и содержания в фолликулярной жидкости цитокинов. Эффективность стимуляции яичников гонадотропинами об-ратно зависит от возраста больных; его увеличение сочетается с возрастанием содержания в фоллику-лярной жидкости провоспалительных цитокинов, а в эндометрии -повышением экспрессии рецеп-торов хемокинов ССR1 и снижением ССR3; эффективность стимуляции яичников гонадотропинами зависит от концентрации цитокинов в фолликулярной жидкости, о чем свидетельствует наличие до-стоверной прямой корреляции между количеством растущих фолликулов, ооцитов и содержанием в ней IL-10, IL-15, эотаксина, MIP-1β, RANTES, ТNFα, IFNγ и GM-CSF; уровень свободного тесто-стерона коррелирует положительно -с количеством ооцитов, полученных при пункции яичников; экспрессией в эндометрии CXCR2 и CCR3; отрицательно -с содержанием в фолликулярной жидко-сти IL-4. У больных с отрицательным результатом цикла ЭКО уровень IL-13 в фолликулярной жид-кости яичников во время стимуляции в 2 раза выше такового у больных с наступившей после ЭКО беременностью. Прогноз наступления беременности в цикле лечения у больных репродуктивного возраста с сочетанными формами бесплодия определяется комплексом клинико-анамнестических, гормональных, эмбриологических факторов и позволяет повысить точность прогнозирования исхода ЭКО. С целью определения вероятности наступления беременности после цикла ЭКО рекомендуется рассчитывать прогностический индекс с чувствительностью теста -93% и cпецифичностью теста -89%.Ключевые слова: бесплодие, цитокины, экстракорпоральное оплодотворение.
At the present time, a broad spectrum of CD8+ T lymphocyte subsets is revealed, including naïve cells, memory cells and regulatory subpopulations. Along with cells with high cytolytic activity, some subsets with marked regulatory activity were found there. Each subpopulation is characterized by a set of produced mediators, surface and intracellular markers allowing to suggest their differential in vivo functional activity. The present review article proposes a classification of CD8+ Т cells which takes into account their morphological and functional features. According to conventional view, the CD8+ Т lymphocytes is a cell population exhibiting high cytotoxic ability which is of critical significance in pregnancy, under the conditions of semi-allogenic fetal cell invasion into the endometrium. The fraction of CD8+ T cells is rather high in decidual structures. The review discusses the known mechanisms of differentiation regulation, selective migration and activity of CD8+ T cells in decidual membrane and placenta in the course of pregnancy. Perforine and granzyme are the main cytotoxicity factors of CD8+ Т cells. IL-2, IL-5, IL-13, IFNγ, IL-17, TGF-β and IL-10 cytokines are considered regulatory mediators of CD8+ cells. To induce the effector properties of CD8+ T cells, an antigenic stimulation is required, which is provided by interactions between the CD8+ Т cells and activated CD4+ Т cells or dendritic cells, cytokine effects. Specific differentiation of the CD8+ T cells is determined by differences in microenvironvent. In the course of pregnancy, accumulation of CD8+ Т cells is observed in decidual membrane, but their phenotype and functional properties differ from CD8+ Т cells in peripheral blood. At present time, the mechanisms of selective CD8+ T cell migration to decidual membrane are studied. These events are suggested to be mediated by means of CXCR3 and CCR5 chemokine receptors, IL-6 and IL-15 cytokines. The features of CD8+ Т cell activities, and production of some cytokines, e.g., CSF2, IFNγ, IL-1β, IL-2, IL-6, IL-8,IL-10, IL-12 and TNFα in decidual membrane and is of critical significance for effective invasion of trophoblast cells. In turn, the trophoblast and placental cells promote development of regulatory CD8+ Т lymphocytes in decidual membrane, being able to induce CD8+ T cell apoptosis in decidual membrane. Hence, interaction between the maternal CD8+ T cells and trophoblast in the area of uterine-placental contact is an important link during development of immunological tolerance in the maternal/fetal system.
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