Changes in the expression of HLA-DR on lymphocyte subpopulations of spouses having children with sporadic congenital heart defects without chromosomal diseases, under the influence of female’s autoserum

This study is aimed to investigate the effect of female autoserum on the HLA-DR expression in various subpopulations of lymphocytes obtained from spouses with children with sporadic congenital heart defects without chromosomal diseases. 78 married couples with children with congenital heart disease were included in the study group. The control group was formed from 35 married couples with healthy children. The immune response in a mixed culture of lymphocytes of spouses was evaluated by an increased HLA-DR expression in a mixed culture in relation to spontaneous cultures of lymphocytes. Primary staining of female and male lymphocytes by monoclonal antibodies to CD45 conjugated with various fluorescent dyes (PC-5 and PC-7) was performed to assess the immune response of female lymphocytes to male ones and vice versa. The activating effect of female autoserum on all subpopulations of female lymphocytes simultaneously occurred significantly less frequently in the study group compared to the control. The control group was characterized by the domination of the positive effect of female autoserum on HLA-DR expression for all subpopulations of female lymphocyte. For all female lymphocytes having HLA-DR molecule on its membrane, the blocking effect of female autoserum in the study group was significantly more expressed in relation to the control group. Thus, the effect of female autoserum is manifested in relation to the HLA-DR expression on its own lymphocytes, but not on the lymphocytes of the spouse

Диагностика и коррекция нарушений гемостаза в периоперационном периоде в хирургии печени

Hepatic surgical interventions are highly traumatic and time-consuming and during these operations the hemostatic system is exposed to compound actions that lead to impaired organ and tissue microcirculation, thromboses, and coagulopathic hemorrhages.Objective: to enhance the efficiency of instrumental diagnosis and correction of perioperative hemostatic disorders during major hepatic surgical interventions.Subjects and methods: 80 patients divided into 3 groups were examined. A control group comprised apparently healthy individuals (donors) the values of whose hemostatic parameters were taken as normal ones. A study group consisted of patients who received conventional preoperative intensive care. Thirty patients were given complex perioperative hemostatic correction.Results. During major hepatic surgical interventions, impairments of the basic links of the hemostatic system are characterized by the development of prethrombosis: the enhanced vascular thrombocytic and hypercoagulant state of enzymatic hemostatic links, and pronounced fibrinolytic suppression. Rapid hemoviscosimetric parameters correlate with classical biochemical parameters and have rather high sensitivity and specificity. The pathogenetically grounded use of a combination of low molecular-weight heparin and the antioxidant mexidole enhances the efficiency of correction of perioperative impairments of the basic hemostatic links during major hepatic operations. Оперативные вмешательства в хирургии печени характеризуются высокой травматичностью и большой продолжительностью, а система гемостаза во время подобных операций подвержена сложным воздействиям, которые приводят к нарушениям микроциркуляции в органах и тканях, тромбозам и коагулопатическим кровотечениям.Цель исследования . Повысить эффективность инструментальной диагностики и коррекции периоперационных нарушений истемы гемостаза при обширных оперативных вмешательствах в хирургии печени.Материалы и методы. Обследовано 80 человек, которые были разделены на 3 группы. Контрольную группу составили практически здоровые лица (доноры), значения показателей системы гемостаза которых были приняты за норму. Основную группу составили больные, которым проводилась стандартная периоперационная интенсивная терапия. 30 больным применили комплекс периоперационной коррекции системы гемостаза.Результаты. Нарушения основных звеньев системы гемостаза при обширных оперативных вмешательствах в хирургии печени характеризуются развитием предтромботического состояния: усилением сосудисто-тромбоцитарного и гиперкоагуляционным состоянием ферментативного звеньев гемостаза, выраженным угнетением фибринолиза. Показатели экспресс-гемовискозиметрии коррелируют с классическими биохимическими показателями, обладают достаточно высокой чувствительностью и специфичностью. Патогенетически обоснованное применение комплекса низкомолекулярного гепарина и антиоксиданта мексидола позволяет повысить эффективность коррекции периоперационных нарушений основных звеньев системы гемостаза при обширных операциях в хирургии печени.

ВЛИЯНИЕ ЖЕНСКОЙ АУТОСЫВОРОТКИ КРОВИ НА АЛЛОГЕННЫЕ ВЗАИМОДЕЙСТВИЯ В КРАТКОСРОЧНОЙ КУЛЬТУРЕ ЛИМФОЦИТОВ СУПРУГОВ, ИМЕЮЩИХ ДЕТЕЙ С КОНОТРУНКАЛЬНЫМИ ПОРОКАМИ

Highlights The findings of this original study ensure the detection of violations in the humoral regulation of the maternal immune interactions with semiallogeneic fetus, considered as a risk factor for developing sporadic conotruncal heart malformations in the next generation.Aim To study the role of female autoserum blood in limiting allogeneic interactions in short-term lymphocyte cultures of parents having children with conotruncal heart malformations.Methods 21 married couples (the study group) with children suffering from conotrucnal heart malformations (Tetralogy of Fallot) without chromosomal diseases were examined. The control group consisted of 21 families with three or more healthy children. The immune response in a mixed lymphocyte culture of parents was assessed by the increase in HLA-DR expression in the mixed culture with respect to spontaneous lymphocyte cultures. Primary staining of female and male lymphocytes with monoclonal antibodies to CD45, conjugated with various fluorescent dyes (PC-5 and PC-7), allowed assessing the immune response of female lymphocytes to male and vice versa.Results The effects of female autoserum on the mixed lymphocyte culture of parents were assessed. The obtained results reported that the birth of children with conotruncal heart malformations is associated with the interfering effect of female autoserum on HLA-DR expression on subpopulations of female lymphocytes (CD3+, HLA-DR+) and the activating effect on subpopulations of female lymphocytes (CD3-, HLA-DR+). The observed role of female autoserum in the study group may be associated with the absence of HLA-DR-blocking autoantibodies and high synthesis of cytokines by T2 and T3 helper lymphocytes.Conclusion The effects of female autoserum on allogeneic lymphocyte interactions of parents may be observed in short-term mixed lymphocyte cultures. The evaluation of the activating and interfering effects ensures timely identification of any violations in the humoral regulation of the maternal immune interactions with the HLA semiallogenic fetus, considered as a risk factor for developing sporadic conotruncal heart malformations in the next generation.Основные положения Полученные данные оригинального исследования позволят выявлять нарушения в гуморальной регуляции иммунных взаимодействий матери и полуаллогенного по HLA эмбриона/плода, как фактора риска формирования спорадических пороков конотрункуса в последующем поколении.Цель Изучение роли женской аутосыворотки крови в ограничении аллогенных взаимодействий в краткосрочной культуре лимфоцитов супругов, имеющих детей с пороками конотрункуса.Материалы и методы Для выполнения поставленной цели обследована 21 семейная пара (основная группа), имеющая детей с пороками конотрункуса (тетрада Фалло) без хромосомных заболеваний. Контрольную группу составила 21 семья, имеющая трех и более здоровых детей. Иммунный ответ в смешанной культуре лимфоцитов (СКЛ) супругов оценивали по увеличению экспрессии HLA-DR в смешанной культуре по отношению к спонтанным культурам лимфоцитов. Первичная окраска женских и мужских лимфоцитов моноклональными антителами к CD45, конъюгированными с различными флуоресцентными красителями (PC-5 и PC-7), позволила оценить иммунный ответ женских лимфоцитов на мужские и наоборот.Результаты Проведена оценка эффекта женской аутосыворотки на СКЛ супругов. Результаты исследования показали, что рождение детей с пороками конотрункуса ассоциировано с блокирующим эффектом женской аутосыворотки в отношении экспрессии HLA-DR на субпопуляции женских лимфоцитов (CD3+, HLA-DR+) и активирующим эффектом на эти реакции в отношении субпопуляции женских лимфоцитов (CD3-, HLA-DR+). Эти эффекты женской аутосыворотки в опытной группе могут быть связаны с отсутствием блокирующих HLA-DR аутоантител и высоким синтезом цитокинов Т2- и Т3-хелперными лимфоцитами.Заключение В краткосрочной СКЛ отражаются эффекты женской аутосыворотки крови на аллогенные взаимодействия лимфоцитов супругов. Исследование коэффициента прироста и блокирующего коэффициента позволит выявлять нарушения в гуморальной регуляции иммунных взаимодействий матери и полуаллогенного по HLA эмбриона/плода, как фактора риска формирования спорадических пороков конотрункуса в последующем поколении.

Population features of prevalence and clinical-diagnostic role of NOD2 gene polymorphisms associated with Crohn’s disease

Aim of review. To discuss features of prevalence and the clinicodiagnostic role of R702W, G908R and 3020insC NOD2 gene polymorphisms associated to Crohn's disease (CD) in various populations and regions of the world. Key points. It is established that there are significant differences in prevalence and clinical manifestations of R702W, G908R and 3020insC polymorphisms of NOD2 gene associated to CD in different countries, as well as in different regions of the same country and in representatives of different ethnic groups enhabiting different regions. Some populations are characterized by high prevalence of the above-mentioned polymorphisms in the absence of CD association, the others are characterized by low prevalence while the association to CD is present, in the third the absence of associations to the Crohn's disease risk is combined to integration of polymorphisms to specific features of the course of disease, treatment efficacy and surgery rate. Conclusion. According to literature data analysis it is possible to conclude that there are clear populationrelated features of the prevalence, clinical and diagnostic role of NOD2 genetic polymorphism associated to Crohn's disease that requires development of the international data bank of all genetic nucleotide polymorphisms associated to various stages of CD pathogenesis in different countries and populations. It will allow not only to increase efficacy of early diagnosis and the CD risk prognosis, but to define environmental factors affecting clinical utilization of genetic factors that is a premise for development of pathogenic justified management algorithm encompassing both populationbased and regional factors

Molecular and genetic diagnostics of inflammatory bowel diseases

Background: In the last two decades, more attention  has  been   paid  to  the   development and implementation of molecular and genetic technologies  for  the   diagnosis   and   prediction of the  development and  course  of inflammatory bowel diseases (IBD). However, the published evidence   on   their   diagnostic   significance   are rather   controversial   and   equivocal   that   may be explained by some characteristics of their frequencies, differences  in pathogenetic, clinical and diagnostic vales of the genetic polymorphisms in various countries and regions.Aim: To evaluate the frequency, clinical, diagnostic, and prognostic significance  of  the  3020insC  and  G2722С nucleotide  polymorphisms  of the CARD15 (NOD2) gene  in Crohn's disease (CD) and ulcerative colitis (UC) in  the   Kemerovo  Region  of  the   Russian Federation.Materials and methods:  The study included 144 patients with IBD (58 with CD, 86 with UC), and 44 patients  without  any gastrointestinal tract disorders in the control group. The 3020insC and 2722С allelic frequencies  of the CARD15 gene were determined. All patients  were of the Russian ethnicity  and  were  living in the  territory  of the Kemerovo Region at the time of the study.Results: The frequency of the 3020insC allele of the CARD15 gene  in CD patients  was significantly higher than in those with UC (16% vs 3%, p < 0.001) and in the control  group   (5%,  р = 0.04).  The  homozygous genotype of 3020insC/insC was found only in the CD patients. The carriage  of the  3020insC allele was associated  with an average  3.5-fold increase of the probability of CD development (odds ratio [OR] 3.6;  95% confidential  interval  [CI]:  1.3–10.3) and was not significantly linked to an increased risk of UC (OR 0.6; 95% CI: 0.1–2.5). The 3020insC allelic frequency in the pooled group of the patients with complicated  CD variants (with stricture formation and  penetrative)  was  significantly  higher, compared to those with the luminal forms (79% vs 21%, р = 0.03) and with the penetrative CD forms compared to  the  luminal (50% vs 21%, р = 0.05). The 3020insC allele carriage in the CD patients was associated with a 3.3-fold increase in the risk of the penetrative forms of the disease  (OR 3.3; 95% CI: 1.8–6.1) and with a 14-fold increase of the overall risk of the complicated  CD variants (OR 14.1; 95% CI: 7.1–27.9). The 2722С allelic frequency in CD and UC patients  and  in the  control  group  were  not significantly different.Conclusion: The detection of the  3020insC allele of the  CARD15 gene  in the Kemerovo Region of the Russian Federation is appropriate for the early CD diagnosis, assessment of the prognosis for the risk of development of CD phenotypic variants, as well as for the differential diagnosis between CD and UC

5-Aminolevulinic acid photodynamic diagnosis of laryngeal papillomatosis

Photodynamic diagnosis is a promising method in the treatment of laryngeal papillomatosis, which includes an assessment of the increased visual and spectrometric contrast of papillomatosis masses against the background of the introduction of the photosensitizer. We have developed a method of treatment of laryngeal papillomatosis in two stages: intraoperative diagnosis using the domestic preparation of 5-aminolevulinic acid hydrochloride and subsequent surgical treatment using a carbon dioxide laser. Using the new method, we treated 21 patients, of which 13 (61.9%) had the inter-recurrent period longer than 12 months

Diagnosis and Correction of Perioperative Hemostatic Disorders at Hepatic Surgery

Hepatic surgical interventions are highly traumatic and time-consuming and during these operations the hemostatic system is exposed to compound actions that lead to impaired organ and tissue microcirculation, thromboses, and coagulopathic hemorrhages.Objective: to enhance the efficiency of instrumental diagnosis and correction of perioperative hemostatic disorders during major hepatic surgical interventions.Subjects and methods: 80 patients divided into 3 groups were examined. A control group comprised apparently healthy individuals (donors) the values of whose hemostatic parameters were taken as normal ones. A study group consisted of patients who received conventional preoperative intensive care. Thirty patients were given complex perioperative hemostatic correction.Results. During major hepatic surgical interventions, impairments of the basic links of the hemostatic system are characterized by the development of prethrombosis: the enhanced vascular thrombocytic and hypercoagulant state of enzymatic hemostatic links, and pronounced fibrinolytic suppression. Rapid hemoviscosimetric parameters correlate with classical biochemical parameters and have rather high sensitivity and specificity. The pathogenetically grounded use of a combination of low molecular-weight heparin and the antioxidant mexidole enhances the efficiency of correction of perioperative impairments of the basic hemostatic links during major hepatic operations