Objective of research – studies of content and IVF programs outcome impact of certain regulatory and transport proteins: alfa2-macroglobulin (α2-MG), alfa1-antitrypsin (α1-АТ), pregnancy associated alfa2-glycoprotein (PAG), lactoferrin (LF), albumin (ALB), total protein (TP) and cytokines: tumor necrosis factor-alfa (TNF-α), interleukins 6 and 8 (IL-6 and IL-8), interferon gamma (INF-γ), vascular endothelial growth factor VEGF in blood serum of women with male factor infertility. Materials and methods. Examination was performed of 37 infertile patients with male genesis infertility (out of whom 20 – with primary infertility and 17 – secondary). Parameters under research prior to IVF program entry were compared against the data of 33 healthy fertile non-pregnant women. Infertile patients underwent IVF/ICSI program, resulting in pregnancy occurrence in 14 of them (38 %) and non-occurrence in 23 (62 %). Contents of α2-MG, α1-АТ, PAG and LF were determined by quantitative rocket immunoelectrophoresis with application of research test systems. ALB, TP concentration – by biochemical methods (with bromcresol green and biuret blue). Level of cytokines (IL-8, IL-6, TNF-α, IFN-γ, VEGF) was determined by EIA method using appropriate commercial test systems. Results. Serum levels of studied regulatory and transport proteins and cytokines did not have statistically significant difference between groups of healthy fertile women and patients with primary and secondary infertility of male genesis. As a result of multifollicular ovarian stimulation and introduction of final oocytes maturation trigger in IVF programs among patients with male factor infertility significant reduction was identified of ALB, IL-8 concentration and advancement in VEGF on the date of transvaginal follicular puncture as compared to levels of the given parameters prior to program entry. Such changes were characteristic for both the subgroup of women with pregnancy occurrence in IVF program and the subgroup with failed treatment outcome. Conclusion. Absence of significant differences of studied parameters levels in blood serum between healthy fertile non-pregnant women and infertile patients with primary and secondary infertility of male genesis allowed developing a range of reference values of certain regulatory and transport proteins (α2-MG, α1-АТ, PAG, LF, ALB, TP) and cytokines (TNF-α, IL-6 and IL-8, IFN-γ, VEGF) for women under the age of 35 years with retained ovarian reserve. Dynamic reduction of ALB and IL-8 concentration, as well аs increase in VEGF level in IVF program among patients with male factor infertility without impact on outcome of the given programs can be assessed as normal organism reaction in response to multifollicular ovarian stimulation by follicle stimulation hormone agents and introduction of human chorionic gonadotropin as trigger of final oocytes maturation.

Currently, phacoemulsification is the «gold» standard of cataract surgery. In a number of cases, post-surgical complications can develop in the form of an inflammatory reaction of varying degrees of severity. The purpose of the study was to develop a method for predicting the inflammatory reaction after phacoemulsification of cataract (PEC) by analyzing the clinical and immunological status of the patients. Material and methods of investigation. The study included 318 patients (318 eyes) with age-related cataracts who underwent PEC. In a number of the patients (49 patients, 49 eyes) with age-related cataract 3 days before the surgery day and after the operation we performed a tear fluid intake. In the obtained samples of tears, the content of alpha2-macroglobulin (alpha2-MG), immunoglobulin G (IgG), albumin and lactoferrin was determined. Results. All PEC operations were conducted according to the plan. In most operated patients, the post-surgical period proceeded smoothly, without an inflammatory response. Only in 19 patients (5.9 %) during the early post-surgical period we diagnosed an exudative reaction in the cavity of the eye. On the 1st day after the operation, the concentration of albumin in the tear fluid of the patients was sharply increased almost 2-fold, as well as the content of alpha2-macroglobulin. Conclusion. A method for predicting the development of post-surgical intraocular inflammation has been elaborated: 1) We determine the concentration of alpha2-MG in the tear fluid of the eyes of the patients with cataract before surgery. If it is below 1.03 mg/l, then the probability of inflammation is low (because the sum of the remaining risk factors namely sex, age of the patients, the degree of cataract maturity, etc. does not exceed 20 scores), we perform the PEC operation in a planned manner. 2) If the sum of scores is higher than 20, the probability of inflammation is high. With a high risk of developing inflammation before surgery we perform intensive local and systemic anti-inflammatory therapy.

Research objective: Study of the content as well as the effect on the outcomes of in vitro fertilization (IVF) programs of some regulatory and transport proteins: (alfa-2-macroglobulin (α2-МG), alfa-1-antitrypsin (α1-АТ), pregnancy associated alfa-2-glycoprotein (PAG), lactoferrin (LF), and albumin (ALB) in blood serum and follicular fluid in women with adenomyosis and tubal factor of infertility. Materials and methods. The study included 89 patients, among them in 31 women the cause of infertility was adenomyosis (as a result of IVF, 12 patients got pregnant and 19 did not), and 58 patients with tubal infertility (24 patients got pregnant and 34 did not). The content of alfa-2-macroglobulin (α2-MG), alfa-1-antitrypsin (α1-АТ) and pregnancy associated alfa-2-glycoprotein (PAG), lactoferrin (LF) was determined by the quantitative rocket ummunoelectrophoresis method with the application of research test systems developed on the basis of research laboratory (RL) of immunology at Novokuznetsk State Institute for Further Training of Physicians. The concentration of albumin was determined by biochemistry methods (with bromcresol green). Results. The research revealed that serum levels of alfa-2-macroglobulin, alfa-1-antitrypsin, pregnancy associated globulin, lactoferrin and albumin in women with adenomyosis generally over the group did not reliably differ from such indexes in women with tubal infertility. In the group of women with adenomyosis the low level of alfa-2-macroglobulin (less than 1.75 g/L) and alfa-1-antitrypsin (less than 1.9 g/L) in blood serum was associated with negative IVF program outcome. In tubal infertility negative outcome of IVF program was registered at the reduction in the blood serum albumin level below 41.5 g/L. Conclusion: The revealed changes, namely the α2-MG level below 1.75 g/L and α1-AT below 1.9 g/L in the infertile patients with adenomyosis, as well as the serum albumin level below 41.5 g/L in women with tubal infertility can be considered as predictors of the negative outcome of IVF programs. When these results are obtained, it is expedient to solve the problem of delayed transfer of embryos for the purpose of additional immunomodulatory therapy in the framework of preimplantation preparation in IVF programs.

Research objective. Study of the content as well as the effect on IVF program outcomes of certain cytokines (tumor necrosis factor-alfa (TNF-α), interleukins 6 and 8 (IL-6 and IL-8), as well as interferon gamma (IFN-γ) in blood serum and follicular fluid in infertile female with polycystic ovarian syndrome (PCOS) and tubal factor of infertility. Materials and methods: The study included 68 female patients undergoing treatment for fertility regeneration with the IVF method, among them 31 patients with PCOS, out of whom 16 women (51.6 %) with positive IVF outcome and 15 women (48.4 %) with no pregnancy occurred. The comparison group included 37 women with tubal factor of infertility, among those in 18 (48.6 %) pregnancy occurred and in 19 cases (51.4 %) it did not. The content of IL-8, IL-6, TNF-α, IFN-γ was determined by EIA method with application of corresponding commercial test systems («Vector-Best» JSC, Novosibirsk, Russia). Results. The levels of TNF-α, interleukin-6 and interleukin-8 in blood serum of the women with PCOS was statistically significantly lower than in the women with tubal factor of infertility, and IFN-γ on the contrary was higher. IL-8 level was below 100 pg/ml in follicular fluid in the patients with PCOS suggests negative IVF program outcome with the probability of 95 %. In tubal factor of infertility the increase in serum level of IL-6 with threshold value over 2.5 pg/ml can serve as a predictor of negative IVF program outcome. Conclusions. The level of IL-8 below 100 pg/ml in the follicular fluid of the infertile patients with PCOS, as well as the increase in serum IL-6 of more than 2.5 pg/ml in the women with tubal infertility can be recommended as predictors of the negative outcome of the IVF programs . When obtaining such results during the IVF program, it is advisable to resolve the issue of delayed transfer of embryos for the purpose of conducting an additional course of immunomodulatory therapy in the framework of preimplantation preparation.

Prenatal diagnosis of intrauterine infection is difficult in pregnant women who are the asymptomatic carriers of pathogens. Objective – to create a mathematical model for prognosis of individual risk of infectious diseases in the newborn based on clinical and laboratory parameters of the mother. Methods. We studied the pregnancy outcomes of 201 women in the southern Kuzbass region with asymptomatic carriage of perinatally significant infections (Staphylococcus aureus, Candida albicans), IgG to Herpes simplex 1, 2, Chlamydia trachomatis or mixed-carriage, during the neonatal period and newborns by analysis of quantitative and dichotomous variables by logistic regression. Results. We have revealed 32 significant variables, including the clinical findings (albumin, lactoferrin and alpha-2-macroglobulin levels in the blood of pregnant women and in the amniotic fluid of women in labor), mother’s complicated history associated with immunity defects (obesity, myoma, asthma, urolithiasis disease) and labor peculiarities facilitating the infection penetration to the fetus (low placentation, labor discoordination, umbilical cord entanglement). The resulting formula allows us to calculate prenatally the risk of infectious diseases in the early neonatal period. A computer program based on this formula is recommended to be used for considering the plan of pregnant women referral to the in-patient setting, for managing the labor with the risk of fetal infection in the Intensive Care Unit, reducing the morbidity rate in children and mortality rate in infants. Conclusion. Taking into account the clinical and immunological predictors the integrated approach allows us to estimate the risk of intrauterine infection and the risk of complications during the neonatal period with a probability of 90 %.

Abstract. Human alpha–2–macroglobulin (α2–MG) acts as a broad–spectrum cytokine and proteasebinding protein, and it represents an evolutionarily conserved arm of innate immune system. Meanwhile, previous studies have shown that rheumatoid arthritis (RA) development may cause alterations in α2–MG conformation and lessen its ability to bind and utilise regulatory substances. We investigated serum contents of α2–MG–IgG and α2–MG–plasmin complexes, as well as total concentrations ofα2–MG, plasmin (Pl), IgG, IL–6, IL–1β, TNFα and Rf–IgM, in order to evaluate the levels of anti–α2–MG antibody production in sera of patients with different degrees of RA activity and some interrelations of preformed immune complex with some other substances implicated in RA development. Serum samples were obtained in acute phase of RA, before the treatment was started. We have revealed significantly increased levels of α2–MG–IgG complex in the groups with severe RA, accompanied by increase in total IgG levels, without significant changes in total α2–MG concentrations. We have also demonstrated that increased levels of Pl–α2–MG complex did correspond to the severity of disease, and showed statistically high correlation with α2–MG–IgG levels. We have found a significant increase of IL–1β, IL–6, TNFα and Rf–IgM in RA, in absence of significant correlations with α2–MG–IgG contents. The results obtained allow us to suggest that abundant accumulation of serum antibodies to α2–MG or Pl–α2–MG complex during inflammation in the people with innate α2–MG deficiency, followed by increased levels of proinflammatory cytokines, may provoke a cascade–like development of RA. Serum levels of α2–MG may serve as prognostic marker in RA. (Med. Immunol., 2005, vol.7, № 5–6, pp. 557–562)

We have studied levels of a 2-macroglobulin (a 2-MG), its circulating complex with IgG (a 2-MG-IgG), of lactoferrin (LF), IgG, IL-6, IL-8, IL-1fi, TNF-а and IFN-y in blood serum of patients with vulgar psoriasis depending on the disease gravity, according to the index of PASI, before and after the treatment. In was found out, that the levels of LF, as well as the content of IL-8, IL-6, IFN-y have significantly increased before and after the treatment regardless the severity of skin manifestations, and a 2-MG is reduced only in the severe form, followed by significant increase of a 2-MG-IgG complex concentrations. The number of significant correlations between content of a 2-MG or LF and the levels of the studied cytokines was found. The obtained data confirms the participation of a 2-MG and LF in psoriasis pathogenesis and based on this fact they can be recommended as an additional prognostic tool for this disease.

We had investigated the concentrations of alpha-2-macroglobulin (a2-MG), lactoferrin (Lf), albumin (Alb), IL-6, IL-8, TNF-α in maternal sera, sera from umbilical cord and in amniotic liquid from women in labor with IgG antibodies against Chlamydia trachomatis, for evaluation of their possible role in intrauterine infection development. It was shown, that intrauterine infection development at the presence of antibodies to Chlamydia trachomatis in blood of women in labor leads to significant increase of a2-MG, Alb, IL-8, TNF-α levels and decrease of Lf levels in amniotic liquid, following by increase of Lf, IL-6, TNF-α concentrations in maternal sera and increase of Lf, IL-6 levels in sera from umbilical cord. Moreover, the correlations between proteins concentrations in above mentioned biological fluids were different in control group and in group of women with antibodies to Chlamydia trachomatis. These results can be accepted as the evidence of penetration of hemato-amniotic barrier during intrauterine infection development, and as the evidence of abnormal synthesis and breaching of functions of polyfunctional Lf and a2-MG what leads to damages of their regulation of cytokine synthesis and to direct damage of tissues.

The analysis was applied to serum and supernatants of day cultures of blood cells of patients with autoimmune thyroiditis and healthy women to determine the content of cytokins (IFN-γ, TNF-α, IL-1β, IL-6, IL-10, IL-17) and lactoferrin. The test-system CytokinStimul-Best was applied. It is established that in patients with autoimmune thyroiditis the proliferative response of cells to mitogen stimulation is lowered in vitro: the levels of α-tumor necrosis factor, interleikin-6, lactoferrin. The stimulation index of α-tumor necrosis factor, interleikin-6, 1β, 10 and interferon was statistically reliably lower in supernatants of mitogen stimulated cultures of cells of patients with autoimmune thyroiditis as compared with indicators of healthy women.