Immunoregulatory Index Research Articles

Case of acute enteroviral meningoencephalitis occurring concurrent with cytomegalovirus infection

Background: Outbreak of EV-71 was recorded in Rostov-on-Don, Russia in 2013. 165 children and 4 adults were suffered. Mild or moderate forms were observed in almost all cases. Very severe course of disease occurred in one adult. Methods & Materials: A retrospective analysis of medical record of severe enteroviral meningoencephalitis in 25-year-old woman was performed Results: The patient had morbid obesity (Grade III). She fell ill at the same time with 3-year old son. Mild form of EV-71 was diagnosed in child. In his mother a conclusion about enterovirus EV-71 as the causative agent of meningoencephalitis was made based on clinical and epidemiological data. The patient was hospitalized with tonic-clonic convulsions, headaches, repeated vomiting, fever (38 °C). Elements maculopapular rash were observed on palms and feet. In CSF cytosis was 640/3 (36% lymphocytes), glucose of 2.3 mmol/l. Enterovirus RNA in CSF was negative. Anti-EV IgM and IgG in blood were negative, but anti-CMV IgM and IgG were detected. MRI revealed signs of cerebral edema, with displacement of midline structures (2-7 mm). The patient's condition was very severe and for 4 weeks she was on ventilator. The fever persisted for 2 days. Immune status was: CD3+ - 74%, CD3 + CD4+ 44%, CD3+ CD8+ - 30%, CD16+ 11%, CD19+ - 13%, IgA - less than 0,66 g/l, IgM - 6.8 g/l, IgG - 7.8 g/l, CIC -206 UE, CD25+ a- 5.5%, HLA-DR+ 15%, CD95+ - 5.3%, anti -DNA 0.65 IU/ml. Repeated MRI after a week revealed negative dynamics with the appearance of inflammatory foci in CNS. Additionally, cardiomyopathy and left-side lower lobe pneumonia were diagnosed. The patient received intensive supportive therapy. Only after one month positive dynamics was detected. Full recovery was observed after one year. Conclusion: The peculiarity of this case was the combination of enteroviral meningoencephalitis with reactivation of CMV. This can be attributed to the severe immunosuppression metabolic syndrome characterized by violation of the immunoregulatory index and the processes of intercellular cooperation and the lack of switching synthesis IgM to IgG. These changes in the immune status were the most likely a cause of severe illness.

Immunological monitoring for prediction of clinical response to antitumor vaccine therapy.

Immunotherapy has shown promising results in a variety of cancers, including melanoma. However, the responses to therapy are usually heterogeneous, and understanding the factors affecting clinical outcome is still not achieved. Here, we show that immunological monitoring of the vaccine therapy for melanoma patients may help to predict the clinical course of the disease.We studied cytokine profile of cellular Th1 (IL-2, IL-12, IFN-γ) and humoral Th2 (IL-4, IL-10) immune response, vascular endothelial growth factor (VEGFA), transforming growth factor-β 2 (TGF-β 2), S100 protein (S100A1B and S100BB), adhesion molecule CD44 and serum cytokines β2-microglobulin to analyze different peripheral blood mononuclear cell subpopuations of patients treated with dendritic vaccines and/or cyclophosphamide in melanoma patients in the course of adjuvant treatment.The obtained data indicate predominance of cellular immunity in the first adjuvant group of patients with durable time to progression and shift to humoral with low cellular immunity in patients with short-term period to progression (increased levels of IL-4 and IL- 10). Beta-2 microglobulin was differentially expressed in adjuvant subgroups: its higher levels correlated with shorter progression-free survival and the total follow-up time. Immunoregulatory index was overall higher in patients with disease progression compared to the group of patients with no signs of disease progression.

Interconnection of the immune system and the intensity of the oxidative processes under conditions of prolonged exposure to small doses of radiation

This research studied the interrelationship between the immune and oxidative-antioxidant systems in a group of individuals who had lived for a long time in areas contaminated with radionuclides after the Chernobyl catastrophe and as a result experienced prolonged exposure to small doses of ionizing radiation. We have examined a group of 100 students aged 18–24, where 50 of them formed the control group and the remaining 50 belonged to the experimental group as they arrived from the territories of enhanced radioecological control (IV radiation zone, density of soil contamination by isotope 137Cs 3.7 x 104 – 18.5 x 104 Bq/m2). Here we determined the level of cortisol, leukocytes and their populations, the levels of lymphocyte subpopulations with phenotypes CD3+, CD5+, CD4+, CD8+, CD16+, CD72+, immunoregulatory index CD4+/CD8+, indicators of phagocytic activity of neutrophils and monocytes, IgG (H), IgM (H), IgA (H), malondialdehyde (MDA), ceruloplasmin (CP), transferrin (Tr), sulfhydryl (SH); and also calculated the oxidative stress index (OSI). We performed the analysis twice: in the absence/presence of additional emotional stress such as an examination session. The studies showed an increase in the oxidative stress index in the group examined from the experimental cluster, especially in terms of emotional stress. At the same time, the neutrophil level increased, but phagocytic activity of neutrophils and monocytes, the relative and absolute number of lymphocytes with phenotypes CD3+, CD5+, CD4+, CD4+/CD8+, and IgG levels decreased. Consequently we revealed the negative correlation between the indexes of oxidative stress in the group of examined (the oxidative stress index (ISO)/the level of malonic dialdehyde (MDA)) and the parameters of phagocytic activity of monocytes, the immunoregulatory index CD4+/CD8+, and the number of lymphocytes with the CD16+ phenotype. In this study we demonstrated the decrease in the participation of ceruloplasmin (CP) as an important antioxidant factor in maintaining the immune homeostasis of the group examined from radiation-contaminated areas compared with control group. The evidence of this is the lack of reliable correlation between ceruloplasmin level and immune system parameters. Moreover we found that radiation-induced intensification of oxidative processes in the experimental group grew in conditions of additional stresses of an emotional nature. Besides, it was accompanied by a significant correlation in the level of oxidative stress and phagocytic activity parameters. Reducing phagocytic activity and the CD4+/CD8+ index on the background of oxidative stress increase can be considered as a sign of immune system ageing, while a decrease in the number of lymphocytes with the CD16+ phenotype is a sign of antitumor defense inhibition. Thus, we draw the conclusion that the inhabitants of the territories of strengthened radioecological control, undergoing exposure to small doses of ionizing radiation from birth, show a significant imbalance of redox homeostasis, which creates the preconditions for immunoreactivity pathology development at the level of both innate and acquired immunity.

ACUPUNCTURE IN ADULT PATIENTS WITH OTITIS MEDIA WITH EFFUSION

The basis of conservative treatment of patients with otitis media with effusion is pharmacotherapy which can increased by acupuncture. Under observation were 64 patients aged 20 to 60 years with unilateral otitis media with effusion in the secretory stage, a duration of disease of more than 1 month and the presence of conductive hearing loss. Patients were divided by simple randomization into two comparable groups: group 1 received basic pharmacotherapy within 14 days, group 2 in addition to pharmacotherapy received 7 sessions of acupuncture according to the developed method using of general and local points. The combination of acupuncture with pharmacotherapy increased the effectiveness of pharmacotherapy: by 5.5% in clinical indices, 10.0% - improvement in the otoscopic pattern, 18.1% - in the opening of the ear canal, 8.8% - in the hearing threshold, 17,3% with acoustic muscular reflex, restoration of the barofunction of the auditory tube to the 1 degree by 7.5%, an increase in the immunoregulatory index by 6.1%. In smears-reprints from the mucosa of the mouth of the auditory tube there was an increase in the number of fibroblasts by 14.1%, macrophages by 31.4%; the index of incomplete phagocytosis decreased by 7.1%. In the long term, the frequency of recurrence decreased by 8.6%.

CLINICAL, AMNESTIC AND IMMUNOLOGICAL PARAMETERS IN HIV-INFECTED PATIENTS WITH GASTROENTEROLOGICAL DISEASES

Nowadays the relevance of questions of comorbidity of different pathologies, including HIV infection diseases of the digestive system. Structural and functional changes in HIV infection can occur in various organs of the digestive system: mouth, esophagus, stomach, liver and in the intestine. The aim of the study was to examine features of the social, epidemiologic, somatic and immune status in HIV infected patients with gastroenterological diseases. Materials and methods. The study involved 500 HIV infected patients consisting on the dispensary account in the Center for the prevention and control of AIDS of the Tyumen region. Results. Sex-age structure and epidemiological history among HIV infected patients with gastrointestinal pathology did not differ (p>0,05) of the total cohort of HIV infected Tyumen region — predominance of males, middle-aged with intravenous by HIV infection in the non-medical use of psychoactive substances. The most common gastrointestinal abnormalities in HIV infection are diseases of the gastroduodenal zone (68,2%) and diseases of the bile ducts (31,8 per cent). Indicators CD4, CD8, and LN of HIV infected to determine the diversity and severity of clinical symptoms resulting from lesions of the digestive tract. The prevalence of gastrointestinal disease in HIV infected patients had inverse correlation of medium strength with immunoregulatory index CD4/CD8 (r=-0,537; p<0,05). Conclusion. Pathogenetic defeat of the digestive system in HIV infection may be caused by direct impact of the virus on the gastrointestinal tract and opportunistic infections, and the indirect influence during chronic systemic inflammatory response and immunodeficiency condition, and also result from prolonged administration of drugs.

CHANGES IN THE CELLULAR IMMUNE PROTECTION OF ORGANISM IN THE PROCESS OF CHRONIZATION OF EXPERIMENTAL BACTERIAL-IMMUNE PERIODONTITIS

One of the important factors that leads to damage of structures of the periodontal complex and leads to the formation of inflammatory process of varying degrees is the disruption of immunological processes.&#x0D; The aim of the study was to clarify the pathogenetic role of cellular adaptive immunity in the process of formation of chronic inflammatory reaction in the late period of the experimental bacterial-immune periodontitis. The study was conducted on white, non-breeding, clinically healthy male rats. Experimental bacterial-immune periodontitis in experimental animals was caused by insertion into the tissues of the periodontal complex a mixture of microorganisms diluted with egg protein. The obtained digital data was statistically processed using parametric and nonparametric statistical methods.&#x0D; The article represents the results of research on the parameters of cellular immune defense, determined by the relative number of CD3+ (common T-lymphocytes), CD4+ (T-helpers), CD8+ (cytotoxic cells, T-killers), CD19+ (B-lymphocytes), CD16+ (natural killers, NK-cell) and immunoregulatory index (CD4+ / CD8+) in intact animals and on the 30th day of experimental bacterial-immune periodontitis development. It was established that the nature of the course of experimental inflammation in the tissues of the periodontal complex depended on changes in the cellular immune status, accompanied by a decrease of the content of common mature T-lymphocytes (CD3+) in the blood of animals with experimental bacterial-immune periodontitis on the 30th day of the study. In the process of the development of the experimental bacterial-immune periodontitis there was a decrease of the content of T-lymphocytes-helper (CD4+) in the blood of animals and on the 30th day of the study an increase in T-suppressors (CD8+), an increase in the content of natural killers (CD16+) and a decrease in the relative content of B-lymphocytes (CD19+). The immunoregulatory index (CD4+ / СD8+) decreased in comparison with this indicator of a group of intact animals. In rats with bacterial-immune periodontitis, an immunosuppressive state developed in the late period of the inflammatory reaction due to both T-helper cells and cytotoxic T-suppressors / killers. These changes can be considered as signs of formation of the chronic course of the inflammatory process in the tissues of periodontal complex.

Features of regulation of the immune system and sexual development in girls suffering from acne

Comparative analysis of immune status and pubertal development in healthy girls and those suffering from acne disease. It is revealed that the immune status of girls suffering from acne disease, characterized by a decrease in cytotoxic lymphocytes, increase T-lymphocytes helper cells and immunoregulatory index. In the peripheral blood of these girls there was an increase in interleukin-4 and serum tumor necrosis factor, level of circulating immune complexes, mainly due to the low was significantly lower than in g concentration of serum interferon healthy girls. In girls suffering from acne in puberty the concentration of luteinizing and follicle-stimulating hormone in peripheral blood was significantly lower than girls in the control group. While menarche in girls 14-13 years old, with acne, there were significantly less than in the control group. The formation of breast and pubic hair at puberty, they lagged behind in comparison with girls in the control group. The indicators of basal metabolism indicate that girls with acne disease higher rates of creatinine and glucose, and also lower essential fatty acids and enzyme activities of alanine and aspartic transferases than girls in the control group. Thus, ladies suffering from acne, was characterized by delayed and at the same time disharmonious puberty. They are characterized by a later menarche, delayed the establishment of the rhythm of the menstrual cycle, some changes of rhythm humoral regulation and biochemical homeostasis.

Особливості імунного профілю у крові щурів з гострим поширеним перитонітом на тлі гіпотиреозу

Introduction. Peritonitis remains one of the most common complications of surgical diseases of the abdominal cavity [5, 11]. According to individual authors, in severe forms of disseminated purulent peritonitis, the mortality reaches 50–80 % [3, 13, 15]. All this points to the need for further improvement of the methods of diagnosis and treatment of this pathological process.The aim of the study – establishment of features of the immune system cellular and humoral units functioning in rats with acute widespread peritonitis on the background of experimental hypothyroidism.Materials and Methods. White Wistar rats were used in the work. Hypothyroidism was modeled by the administration of Mercazolil at a dose of 25 mg / kg for 21 days. Acute common peritonitis was modeled by injecting 0.5 ml of 10 % filtered fecal suspension into the abdominal cavity of the animals under study. Cellular (CD4+, CD8+, CD22+-lymphocyte) and humoral (IgA, IgM, IgG) immunity were measured. The animals were decapitated under thiopental anesthesia after 24 hours, on the 4th, 7th and 10th days from the beginning of peritonitis modeling.Results and Discussion. It was found that in animals with acute widespread peritonitis against hypothyroidism, there is a significant decrease in CD4+ lymphocytes, a violation of the ratio of the main subpopulations of lymphocytes (CD4+ and CD8+), which is accompanied by a significant decrease in the immunoregulatory index. The dynamics of changes in B-lymphocytes CD22+, which are producers of immunoglobulins, was indicative. These changes correlated with the state of specific humoral immunity – the concentration of immunoglobulins in the serum of the corresponding groups of animals.When simulating common peritonitis, euthyroid animals showed a decrease in IgG concentration and an increase in IgM and IgA. Against the background of hypothyroidism, we noted a decrease in the level of immunoglobulins of all classes after 24 hours of the duration of the pathological process with a further decrease to the tenth day. The indices of all classes of immunoglobulins were also significantly lower than those of euthyroid animals with acute widespread peritonitis.Conclusions. In animals with acute common peritonitis, hypothyroidism is significantly reduced CD4+ lymphocytes, a violation of the ratio of the main subpopulations of lymphocytes (CD4+ and CD8+), which is accompanied by a significant decrease in the immunoregulatory index. The insufficiency of the cellular part of the immune response was found to reflect an increase in the mutual negative effect of the inflammatory process in the peritoneum and systemic disorders of immune defense in conditions of concomitant hypothyroidism. There is a direct relationship between the reduced level of CD22+ lymphocytes and the indices of immunoglobulins of classes A and G.In acute widespread peritonitis against the background of mercazolil-induced hypothyroidism, there is a violation of the functionality of the immune system, manifested by an imbalance of immunoglobulins in the bloodstream and a decrease in the resistance of the humoral link of the immune system.

The evaluation of the effectiveness of the application of bischofite-modified yellow clay (an experimental studi)

The topical problems in balneotherapeutics and health resort activities in general are the development of the yellow clay-based preparations enriched in the natural mineral bischofite and the investigation of their therapeutic effects with the purpose of improvement of their curative potential. The objective of the present study was to evaluate the effectiveness of the course of the experimental therapeutic applications of the yellow clay obtained by the open pit mining of its deposits located in the vicinity of Pyatigorsk and modified by the addition of bischofite. The experiments were carried out with the use of 57 eugamic Wistar male rats with adjuvant arthritis. The yellow clay supplemented with bischofite in various concentrations was applied in 12 procedures each 15 minutes in duration every other or every two days beginning from the 38th day of experimentally-induced arthritis. The animals were allocated to five groups as follows: group 1 included the healthy animals that served as controls (n=5), groups 2-5 were comprised of the animals with adjuvant arthritis. The animals included in group 2 served as the experimental model of adjuvant arthritis (n=8), those comprising group 3 were treated by the applications of yellow clay without additives (n=14), group 4 was composed of the animals with adjuvant arthritis treated by the applications of yellow clay containing 10% of bischofite (n=15), the animals in group 5 having adjuvant arthritis were treated by the applications of yellow clay containing 20% of bischofite (n=15). The study has demonstrated the reduction of the reactively enhanced relative abundance of, activated T-cells, and B-lymphocytes down to the respective control values in the animals with adjuvant arthritis after the course of applications of the yellow clay preparations. Simultaneously, normalization of the immunoregulatory index, IRI, (the T-helpers to cytotoxic T-lymphocytes ratio) was documented. The treatment was associated with the strong dependence of the interleukin (IL-1β) contents on the cortisol level and the well apparent relationship between the levels of interleukins and IRI. Specifically, the relation between IL-1β and IRI following the application of non-modified yellow clay was characterized as (r=+0.8, p=0.03) in comparison with the relation between IL 6 and IRI (r=+0.8, p=0.03) after the treatment with yellow clay containing 10% of bischofite or between IL 6 and IRI (r=+0.8, p=0.004) after the application of yellow clay containing 20% of bischofite. The results of the study give evidence of the immunomodulatory action of yellow clay modified by the addition of bischofite. They suggest the promising opportunities for the application of these preparations for the management and rehabilitation of the patients presenting with the diseases of the musculoskeletal system in the future.

ЗМІНИ КЛІТИННОГО ІМУНІТЕТУ У ВІЛ-ІНФІКОВАНИХ З ХРОНІЧНОЮ ХВОРОБОЮ НИРОК

Мета роботи – встановити значення імунограми в оцінці ураження нирок ВІЛ-інфікованих осіб.Пацієнти і методи. Обстежено 292 хворих на ВІЛ-інфекцію, які перебували на амбулаторному спостереженні в Чернівецькому обласному центрі з профілактики та боротьби зі СНІДом. Результати. У ВІЛ-інфікованих осіб з хронічною хворобою нирок виявлено відхилення з боку абсолютного вмісту Т-хелперів, цитотоксичних Т-клітин, а також імунорегуляторного індексу.На рівні субпопуляцій Т-лімфоцитів проявляються і статеві відмінності: у чоловіків порівняно з жінками підтверджено достовірно нижчий відсоток Т-хелперних лімфоцитів (CD3+CD4+), суттєво вищу частку цитотоксичних Т-клітин (CD3+CD8+) і, відповідно, зниження імунорегуляторного індексу (в усіх випадках р&lt;0,05). У ВІЛ-інфікованих з ураженням нирок достовірно знижені абсолютне й відносне числа CD3+CD4+-клітин, імунорегуляторний індекс, а також абсолютне й відносне значення цитолітичних Т-лімфоцитів (CD3+CD56+) порівняно з ВІЛ-інфікованими без патології нирок (р&lt;0,05). При наростанні рівня протеїнурії у крові знижується абсолютне число лімфоцитів і Т-лімфоцитів (CD3+), а також зростає відсоток та абсолютне число цитотоксичних Т-клітин (CD3+CD8+). Однак кореляційний аналіз рівня протеїнурії та показників типової імунограми жодного значущого зв’язку не виявив.Висновки. Можна стверджувати, що ураження нирок в осіб з ВІЛ-інфекцією розвивається на тлі суттєвішого падіння числа переважно Т-хелперної субпопуляції лімфоцитів.

Physiological characteristics of puberty for adolescent girls suffering from acne

The physiological characteristics of sexual development and immune status in girls suffering from acne disease have been analyzed. It is revealed that at puberty, in girls suffering from acne, the concentration of luteinizing and follicle-stimulating hormone in peripheral blood was significantly lower than girls in the control group. While menarche was in girls 14-13 years old with acne there indexes were significantly less than in the control group. The formation of breast and pubic hair at puberty, they lagged behind in comparison with girls in the control group. The immune status of acne was characterized by a decrease in cytotoxic lymphocytes and increased T-lymphocytes helper cells and immunoregulatory index. In the peripheral blood of these girls there was an increase in interleukin-4 and serum tumor necrosis factor, level of circulating immune complexes, mainly due to the low concentration of serum interferon γ was significantly lower than in healthy girls. The indicators of basal metabolism indicate that girls with acne disease higher rates of creatinine and glucose, and also lower neeterificirovannah fatty acids and enzyme activities of alanine (Alat) and aspartic (AST) transferases than girls in the control group. Thus, ladies suffering from acne, was characterized by delayed and at the same time disharmonious puberty. They are characterized by a later menarche, delayed the establishment of the rhythm of the menstrual cycle, some changes of rhythm humoral regulation and biochemical homeostasis. (For citation: Pilnik EN, Pyatibrat AO, Pyatibrat ED. Physiological characteristics of puberty for adolescent girls suffering from acne. Reviews on Clinical Pharmacology and Drug Therapy. 2017;15(4):69-74. doi: 10.17816/RCF15469-74).

Аналіз показників клітинної та гуморальної ланок імунної системи у вагітних з парвовірусною інфекцією у різні періоди гестації

The article covers the topic Parvovirus infection in pregnant women caused the development of immunopathological reactions. 129 in fected pregnant women and 16 women with physiological pregnancy in the 1st, 2nd and 3rd trimesters were examined. In infected pregnant women, activation of the cellular level of immunity was observed, a significant increase in the number of natural killers in the peripheral blood and an increase in the immunoregulatory index were detected, with greater deviations from the control indicators found in the 1st trimester. In pregnant women, in which clinical complications were noted, the population composition of lymphocytes was characterized by an increased number of NK cells, low infection with the number of cytotoxic CD8+-lymphocytes and a shift in the ratio of CD4+/CD8+totheside, which indicates an increase in helper mechanisms. Increasing the number of T-lymphocytes, T-helpercells, NK/Т cellsandactivated CD25+-lymphocytes in pregnant women with out clinical complications at different periods of pregnancy can contribute to effective elimination of the virus and to prevent severe fetal lesions. Violation of the humoral link of the immune system in the infection of pregnant parvovirus infection was shown in an increase in the serum IgM content in different periods of pregnancy (by 79.1%, 54.2% and 38.5%), and a decrease in IgA levels in the 1st and 2nd trimesters (p&gt;0.05), to a greater extent such changes were found in women with clinical complications of pregnancy and especially in the first trimester. Key words: pregnancy, parvovirusinfection, cellular and humoral immunity.

Імунний статус телят, хворих на гастроентерит

It has been established that there is a violation of the immunocompetence of the macroorganism at diseases of the gastrointestinal tract which are accompanied by diarrhea. Since the immune system is one of the most important homeostatic systems in the body, these disorders play an important role in the pathogenesis of the disease. Thus, the purpose of the work was to study the indicators of natural resistance and immunological reactivity in calves with gastroenteritis. The research was carried out at the state enterprise «Milk Rinks»Pravda LTD in Brody district of Lviv region on 1.5–2-month-old-calves. 15 calves were selected for the study: 5 healthy ones and 10 patients with gastroenteritis. Blood for research was taken from the jugular vein before the early feeding.In the study of indicators of natural resistance, it was found that in calves with gastroenteritis, the content of circulating immune complexes in serum is authentically (P &lt; 0.001) greater than 45.1%, bactericidal and lysozyme activity of serum is authentically (P &lt; 0.01 ) lower at 15.1 and 26.3% and phagocytic activity of neutrophils – by 8.6% compared with healthy animals. In the study of lymphocytes and their subpopulations, it was found that the relative amount of T-total and T-active lymphocytes is authentically (P &lt; 0.01) less by 8.6 and 11.7%, respectively, compared with healthy animals, the relative number of T-helper cells – less than 16.4% (P &lt; 0.01). There is no probable difference in the relative number of T-suppressors between patients and healthy animals, but the immunoregulatory index in calves, patients with gastroenteritis, is 19.4% smaller, compared with healthy ones. The relative number of B-lymphocytes was authentically (P &lt; 0.01) less in sick animals by 14.5% compared with clinically healthy ones, and the content of immunoglobulins in serum was lower by 16.3% (P &lt; 0.01). Conclusion: in calves, patients with gastroenteritis, there are a number of violations of the immune system, characterized by a decrease in the parameters of cellular and humoral immunity, which require correction in the process of treatment.

Pneumonias in immunocompromised patients: improvement of treatment using the immunomodulator

Aim of research: to optimize the approach to the treatment of pneumonias in patients on the background of acute leucosis from positions of immunoresistance based on using disodium glutamyl-cysteinile-glycine by the method of extracorporal pharmacotherapy.Materials and methods. Research group – 39 patients with pneumonia on the background of acute leucosis, who underwent the treatment according to the form and stage of the disease on the base of the hematological center “MI city multi-profile clinical hospital No. 4» Dnipro city, 2015–2016. Mean age of patients 31,5±6,5 years, 11 women and 38 men. Patients of the main group were additionally administered with disodium glutamyl-cysteinile-glycine in 2 ml of 3 % solution (60 mg) i/v No. 5 each second day. The parameters of the immune response were studied: Т and В-lymphocytes and their subpopulational composition (CD3+, CD4+, CD8+, CD19+, CD16+, CD56+) by the method of flow laser cytoflourometry (BeckmanCoulter–USA). There were additionally determined; immunoregulatory index, leuco T-cellular index, leuco B-cellular index and index of leucocytes activation; phagocytosis state was assessed by the parameters: phagocytic number, phagocytic indicator, NBT-tests. The state of humoral immunity was assessed by levels of immunoglobulins of classes A, M and G by the method of immunoturbidimetry (BeckmanCoulter–USA).Results. The analysis of parameters of cellular and humoral immunity of patients with pneumonias on the background of AL by the improved method of treatment of pneumonia using the immunomodeling preparation disodium glutamyl-cysteinile-glycine proved the positive influence on the immune reactivity of patients’ organism, manifested by the reliable increase of the relative quantity of the pool of T-helpers (CD4+), NК-cells, increase of immunoregulatory index, PI, PN and increase of humoral immunity indices.Conclusions. The improved method of pneumonia treatment on the background of AL using the immunomodeling preparation disodium glutamyl-cysteinile-glycine by ECPT method proved the positive influence of the immune reactivity of patients’ organism, manifested by the reliable activation of phagocytosis and anti-infectious protection, manifested by the more expressed effect of pneumonia treatment: improvement of the clinical course of disease; decrease of the prognosticated number of ABT days and earlier return to the program treatment of AL. The obtained effects of the improved method of pneumonia treatment in patients with acute leucosis at using the immunomodeling preparation disodium glutamyl-cysteinile-glycine by ECPT method proves the pathogenetic validity of the possibility of optimization of pneumonia treatment from positions of immunoresistance

OPPORTUNISTIC INFECTIONS AND IMMUNE DEFICIENCY IN WOMEN WITH POOR IVF RESPONSE

The aim of the study is the improvement of the efficiency of IVF on the basis of the determination of immunological and infectious risk factors for miscarriage. The materials and methods. The object of research were 21 female infertility patients included in the program of ancillary reproductive technologies (ART) for the period of 2014-2016, who had in a history from one to four ineffective IVF response. The average age of studied women was 33.5±0.9 years, the number of years with infertility amounted to 7,3±1,0. In the preparation for IVF women received a complete course of general clinical examination to identify the causes of infertility. The study of the immune status was carried out with the use of one - and two-parameter phenotyping, the results included data obtained with the flow-through cytofluorometer BECKMAN COULTER EPICS XL-II (USA), treated according to standard protocols. The control group consisted of 30 fertile women. The results of the study. Infertility women planning IVF, were found to be characterized by presenting a combination of persistent opportunistic infections of herpes group: HSV and CMV. In the 90,5% of women there were identified various immunodeficiency states from both cellular and humoral immunity: the characteristic increase in the content of HLA-DR, a reduction in CD19+ cells. In primary infertility states changes in cellular immunity were more pronounced, additionally there was the decline in immunoregulatory index (IRI), the increase in the content of CD8+, CD25+, IgM. An imbalance of the immune system in women with persistence of several opportunistic infections was both more pronounced, than in cases with monoinfection and manifested by such abnormalities of cellular immunity as the gain in the content of CD8+, NK cells CD16+, CD56+, CD25+, a decline in IRI. The conclusion. In the course of the preparation for IVF in an examination mode of women with the primary infertility and the presence of markers of several opportunistic infections, it is advisable to include an evaluation of the immune status. The identification of secondary immune deficiency is an indication for inclusion of immunocorrective therapy in the comprehensive treatment.

Looking at the problem of cytomegalovirus and Epstein-Barr viral infection in gynecology and possible solutions

In recent years, there has been an increase in the number of patients suffering from chronic recurrent herpes-viral infections, which in many cases are accompanied by a pronounced disturbance in overall well-being and a number of therapeutic complaints. In particular, on transplantology and gynecology often have diseases and syndromes caused by cytomegalovirus (type V herpes viruses) and Epstein-Barr virus (type IV herpes viruses). The article presents the results of the effectiveness and experience of using an antiviral drug with the immunomodulatory action of Groprinosin® (inosine pranobex) in the treatment of chronic persistent conditions caused by cytomegalovirus infection and infection of the Epstein-Barr virus.Patients with verified cytomegalovirus infection and Epstein-Barr virus infection were examined. Group I included 56 women with active cytomegalovirus infection; group II – 49 women with active Epstein-Barr virus infection. The control group consisted of 30 healthy women.All patients received in complex therapy Groprinosin® 50 mg per kg of body weight per day for 2 weeks, then 2 tablets (1000 mg) once a day, regardless of body weight for 2 weeks (3 such courses during the 3 months). The daily dose of Groprinosin® was divided into 3–4 doses.After 3 months, the cytomegalovirus DNA was detected in spittle of 3 (5.3%) patients of group I, Epstein-Barr virus DNA – in 2 (4.0%) patients of group II. After treatment in patients receiving complex therapy Grosprinosin®, the quantitative indices of T-lymphocyte subpopulations were restored and their imbalance was eliminated (the immunoregulatory index was normalized), the same dynamics was also observed with regard to the number of natural killers.Based on the conducted studies, it was found that the inclusion of Grosprinosin® in the complex therapy of cytomegalovirus infection and infection with the Epstein-Barr virus promotes an increase in the immunological reactivity of the organism, allowing to significantly improve the clinical course of the disease. Grosrinosin® is well tolerated by patients and can be recommended for the treatment of both of these infections.

ХАРАКТЕРИСТИКА IМУННОГО СТАТУСУ У ЖІНОК З ЛАТЕНТНОЮ ПАПІЛОМАВІРУСНОЮ ІНФЕКЦІЄЮ ШИЙКИ МАТКИ

Мета дослідження – аналіз змін показників, що характеризують стан імунітету, у жінок з генітальною латентною папіломавірусною інфекцією, часто поєднаною з урогенітальною інфекцією, на початку обстеження та через 6 місяців спостереження.Матеріали та методи. Обстежено жінок репродуктивного віку (від 18 до 45 років, 1200 осіб), що звернулись до гінекологічних відділень Перинатального центру та клінічної лікарні № 18 м. Києва за період з 2011 до 2016 рр. Контрольну групу склали 15 здорових жінок. Дослідження проведено за допомогою таких методів, як: цитологічний, кольпоскопічний, бактеріологічний, методу ПЛР, фенотипування лімфоцитів периферичної крові та статистичних методів.Результати дослідження та їх обговорення. При обстеженні 1200 жінок у 210 (16,0 %) виявлена ДНК вірусу папіломи людини (ВПЛ) за відсутності клінічних та морфологічних ознак інфекції, що свідчило про латентну папіломавірусну інфекцію (ПВІ). З них у 84 – діагностована моноінфекція, у 126 – поєднана папіломавірусна та урогенітальна інфекції (УГІ). Інфікування ВПЛ і вірогідність подальшого розвитку захворювання (елімінація або персистенція вірусу) значною мірою визначається клітинними та гуморальними факторами імунітету. Для з’ясування ролі імунної системи людини при латентній ПВІ проведено фенотипування лімфоцитів периферичної крові з використанням моноклональних антитіл та визначення рівня імуноглобулінів (Ig) А, М, G за методом радіальної імунодифузії на початку обстеження і через 6 місяців. У 140 жінок встановлена транзиторна ПВІ, у 70 – персистуюча.У жінок з латентною ПВІ шийки матки виявлені деякі ознаки вторинної імунної недостатності, що виражалось у зниженні відсотка Т-лімфоцитів та Т-хелперів з одночасним підвищенням кількості цитотоксичних лімфоцитів та природних кілерів (NK) на тлі активації гуморальної ланки імунітету. Супутня УГІ статевих органів підтримувала, а іноді і посилювала виявлені особливості імунореактивності при ПВІ. У жінок з транзиторною ПВІ спостерігалась нормалізація показників клітинного та гуморального імунітету, а подальша персистенція ВПЛ у шийці матки призводила до більш суттєвого пригнічення реакцій не тільки клітинної, а й гуморальної ланок імунітету (зниження кількості NK та імунорегуляторного індексу, рівня IgA).Висновок. Таким чином, у жінок з латентною ПВІ ШМ виявлялись деякі ознаки вторинної імунної недостатності, що виражалось у зниженні відсотку Т-лімфоцитів та Т-хелперів, з одночасним підвищенням кількості цитотоксичних лімфоцитів та природних кілерів на тлі активації гуморальної ланки імунітету.

The dynamics of cellular and humoral immunity during the treatment of pneumonia in patients on a background of acute leukemia

Pneumonia is often life threatening infectious complication on a back ground of software treatment in patients with acute lymphoblastic leukemia (ALL). The existing consensus documents on the treatment of pneumonia in patients with impaired immunity focuses on antibac terial therapy, at the same time, questions about the need for correc tion of the immune status of patients remain poorly understood. A promising direction is the use of glutamyl cysteinyl glycine sodium in the treatment of pneumonia in patients with OL to enhance the activ ity of the immune system and improve the anti infective protection. The aim of the study : was the analysis of indicators of cellular and humoral immunity in the process of applying immunocorrigirutee drug glutamyl cysteinyl glycine sodium (Glutoxim) in patients with pneu monia, which arise on the background of ALL optimization approach es in the treatment of pneumonia in patients with impaired immunity. Materials and methods . Study group of 87 patients with pneumonia on the background of ALL that took place a software based treatment of hematological centre «SE City Multidisciplinary Clinical Hospital No. 4» (str) for 2014 2015, the average age of patients was from 28 to 39 years old. ALL diagnoses of pneumonia was verified in accordance with generally accepted clinical and morphological criteria. Patients from the main study group (n=57) was additionally appointed glu tamyl cysteinyl glycine sodium to 2 ml of 3% (60 mg), N 10, in the morning, intravenous, total dose of 600 mg. All patients investigated indicators immunogram: T lymphocytes, b lymphocytes and indicators subpopulation composition (CD3+, CD4+, CD8+, CD19+, CD19 , CD16+, CD56+). The study was conducted using flow through laser cytofluometry (BeckmanCoulter, USA) and calculated the derived indices. Indicators of immunogram in patients of study groups were evaluated in the dynamics of treatment. Statistical processing was per formed using packages of applied programs «Excel» and «Statistic 10». Results . The analysis of indicators of cellular and humoral immunity of patients with pneumonia accompanied by АLL in the process of applying glutamyl cysteinyl glycin sodium showed significant activation of phagocytosis and anti infective protection of the results of increasing the relative amount of T helpers (CD4 +), PC cells, increased immunoregu latory index, FA and FC. The results of the dynamics of humoral immu nity also confirm the positive influence of the use of glutamyl cysteinyl glycine sodium on the immune reactivity of patients with reliable change indices of IgA and IgM, which are responsible for neutralizing infectious agents, bacterial toxins and indirectly activate phagocytosis. Conclusion . The use of immunomodulatory therapy with the drug glu tamyl cysteinyl glycine sodium (Glutoxim) in patients with pneumo nia on the background of ALL leads to improved clinical manifesta tions of the disease, reduces the duration of ABT improves the quality of life and leads to earlier return (average 3 4 days) to the program treatment АLL. The results of the research prove the possibility of optimizing the treatment of pneumonia by the using of immunomodu latory therapy glutamyl cysteinyl glycine sodium (Glutoxim) patients with pneumonia on a background of АLL.

PERSPECTIVES IN ACTIVE SPECIFIC IMMUNOTHERAPY WITH AUTOLOGOUS IMMATURE DENDRITIC CELLS COMBINED WITH PHOTODYNAMIC THERAPY AND CYCLOPHOSPHAMIDE IN PATIENTS WITH DISSEMINATED MELANOMA RESISTANT TO STANDARD THERAPY

There are described the results of clinical and immunological efficacy assessment of active specific immunotherapy with autologous immature dendritic cells (DC) combined with photodynamic therapy (PDT) and cyclophosphamide (C) in disseminated melanoma patients, resistant to standard therapy. 27 patients treated in the N.N. Petrov Research Institute of Oncology were included in the study from 2007 till 2016. Immunotherapy was conducted in a 21-day cycles. Therapy included following steps: 1) preparation of individual vaccine preparation from bone-marrow derived DC with immune phenotype CD34-/CD14VCD1a+/CD83VCD80-/+/CD86-/+/HLA-DR+; 2) Intramuscular 300 mg C injection in day 1 of treatment cycle for elimination T-lymphocytes with immunosuppressing activity; 3) PDT with chlorin salts at day 4 six hours before start of vaccinotherapy; 4) Daily intralesional injections of DC vatccine in irradiated lesions in the dose 1х106 DC cells/ kg. Clinical and immunological efficacy was assessed in 27 patients. Fourteen (52%) patients received 1-2 cycles of therapy, 13(48%) received 3 or more cycles. No complete response was seen. Partial response (RECIST 1.1) was found in 2 (7,4%) patients, stable disease in 8 (29,6%) patients. Seventeen (63%) patients progressed. Median time to progression (TTP) was 2.5 month, median overall survival (OS) 8.4 month. One-year survival was 5% and 37% for TTP and OS, respectively. No adverse events (AE) of grade 4-5 (CTC AE v4) were seen. Grade 3 fever was registered in 4% of patients. Grade 1-2 AE were found in 54% of patients. Immunologic assessment revealed significant decline of immunoregulatory index (CD/ CD8) caused by prevalence of cytotoxic T-lymphocytes in peripheral blood of responding patients (patients with clinical benefit). Tendency for elevation of absolute number of activates T-helpers and cytotoxic T-lymphocytes together with low T-regulatory cells concentration was also found. Combination therapy using immunomodulatory effects of C, PDT and DC vaccine in 21-day treatment cycles produce promising activity and favorable toxicity profile in heavily pretreated disseminated melanoma patients.

Вплив пробіотика та фітобіотика на показники Т- і В-клітинного імунітету відлучених поросят за гастроентериту незаразної етіології

In the use of colostral protective factors and insufficient activity of piglets immune system, against the background of immunodeficiency after weaning from sows developing diseases, often caused by conditionally-pathogenic or pathogenic microorganisms, including non-contagious gastroenteritis. The article presents analyzes of T- and B-cell immunity parameters in weaned piglets with non-contagious gastroenteritis and after their treatment with probiotic TOYOCERIN 10⁹ and phytobiotic EXTRACT™ 6930 as part of the basic diet in combination with antibiotic (10 % solution of enrofloxacin hydrochloride) in the modern pig farm. It was established that in piglets after weaning with non-contagious gastroenteritis decreased of T- and B-cell immunity parameters. In particular, in blood decreased number of total and active T-lymphocytes, T-helpers and T-suppressors also decreased number of B-lymphocytes, which may indicate the development in these immunodeficient condition. It was established positive effect of probiotic and phytobiotic in combination with antibiotic on T-cell immunity of pigs, as indicated by the increased number of total T-lymphocytes in blood to the clinical healthy animals level. A similar tendency was observed in the number of T-helper cells, their number was higher in groups of weaned piglets which added probiotic TOYOCERIN 10⁹ and phytobiotic EXTRACT™ 6930. As to the immunoregulatory index, which is a quantitative ratio of T-helper to T-suppressor, there was no significant alteration of values in control and experimental groups of pigs. It was established positive effect of probiotic and phytobiotic in humoral immunity of piglets by increasing number of B-lymphocytes to the level of clinical healthy animals which indicate increased body ability to the active synthesis of protective antibodies. The use of probiotic TOYOCERIN 10⁹ and phytobiotic EXTRACT™ 6930 for weaned piglets with non-contagious gastroenteritis normalized number of T- and B-lymphocytes, which are the leading immunocompetent blood cells that characterize the level of animal body defense and condition of specific immunity. Perspectives for further research will be directed at determining the therapeutic effectiveness of probiotic TOYOCERIN 10⁹ and phytobiotic EXTRACT™ 6930 for weaned piglets with non-contagious gastroenteritis.