The Effect of Vitamin D3 on Neutrophil Extracellular Trap Formation in High-Glucose Conditions.

NETosis, i.e., the formation of neutrophil extracellular traps (NET), and neutrophil autophagy are important elements in the pathogenesis and the development of complications of type 2 diabetes mellitus (T2DM). Therefore, the search of drugs that can regulate the level of NETosis and autophagy in T2DM is relevant. Here we studied an ex vivo NET formation and neutrophil death in whole blood from healthy subjects upon the addition of glucose up to a high concentration of 15 mM or/and the phorbol ester PMA (phorbol-12-myristate-13-acetate). Their individual and combined action caused neutrophil death and an increase in NET content. It can be hypothesized that this resulted from activation of NETosis and autophagy. It was also shown that this activation of NETosis and autophagy is completely prevented by daily intake of 1000 IU vitamin D3 for 14 days. Therefore, vitamin D3 supplementation can be considered as a preventive measure against the development of T2DM complications.

[Features of proliferative response of T-cells on hepatitis c virus antigens in healthy individuals contacting with this virus].

AIM: Evaluation of CD3+ and CD3-/CD56+ proliferative response on hepatitis C virus antigens in healthy medical workers. MATERIALS AND METHODS: The study included 15 medical workers with length of service of 2 and more years without common risk factors (blood and blood products transfusion, abdominal operations, invasive procedures, use of intravenous drugs). Control group consisted of 9 healthy individuals without risk factors. Peripheral mononuclears were isolated from blood and then incubated 72 hours in the presence of mitogen/PHA, Core+NS4 1b genotype HCV, NS4 HCV2a+3a genotypes or medium. Proliferative activity was registered by the presence of cell division marker ki67 by using FACS. RESULTS: The initial immunogram of medical workers differed from the control group by a significantly lower quantity of CD3+ lymphocytes, in particular CD3+/CD8+ population. Incubation with PHAresulted in a decrease of quantity of CD3+/ ki67+, CD4+/ki67+ and CD3-/CD56+/ki67+ in the medical workers group. Cultivation with HCV antigens resulted in a significant decrease of Treg (CD3+/CD25high/FoxP3+) and activated T-lymphocytes population in the case of stimulation by Core and NS4 1b genotype antigens. Analysis of cell response on virus antigens based on proliferative activity index detected significant differences only for CD8+/ki67+. Stimulation by Core and NS4 1b genotype antigens resulted in an increase of quantity of these cells whereas in the case of NS4 2a+3a genotypes their decrease was observed. CONCLUSION: The described changes may reflect exhaustion of cell reactivity due to extra antigen load in the group of medical workers, while differentiated immunologic shifts on hepatitis C viruses of various genotypes are noted.

[Immunogenetic predictors of a rapid virologic response to antiviral therapy in patients with chronic hepatitis C].

AIM: To determine the correlation between interleukin 28B (IL28B) gene polymorphism in patients with chronic hepatitis C (CHC), the presence or absence a rapid virologic response to antiviral therapy, and a number of immunological characteristics as a basis for a personalized approach to treating the patients. SUBJECTS AND METHODS: Seventeen CHC patients infected with hepatitis C virus genotype 1b were examined and underwent genetic testing for IL28B gene polymorphism for rs12979860 (CC, CT or TT genotypes) and rs8099917 (TT, TG or GG genotypes) using the modified method of adjacent samples, which revealed single nucleotide substitutions in the genes. Their immunological parameters were identified by a flow cytometry technique by taking into account whether a rapid virologic response had been achieved. RESULTS: The key phenomena of a rapid virologic response in the representatives of different IL28B genotypes are the nonspecific proliferative activity of blood natural killer cells before treatment, as well as the count of regulatory T cells before and 4 weeks after therapy start. CONCLUSION: To predict the efficiency of antiviral therapy for CHC, it is desirable to supplement genetic studies with immunological data.

[Immunological aspects of HCV/HIV coinfection].

AIM: To evaluate effects of HCV/HIV coinfection on blood lymphocyte phenotype including cells CD56+. MATERIAL AND METHODS: We studied standard immunogram, subpopulational composition and functional activity of blood cells CD56+ in 67 patients with verified diagnosis of HIV infection and virus hepatitis C. RESULTS: We discovered some pathogenetically sound indices of immune status in patients with HCV/HIV coinfection. Some of the immune shifts detected changed in response to intake of narcotic drugs, antiretroviral treatment, hepatic cirrhosis, pneumonia. CONCLUSION: Parameters of subpopulational composition and functional activity of cells CD56+ in the blood of patients with HCV/HIV coinfection elucidate some unknown features of the above infectious process which should be considered in this coinfection treatment and prophylaxis.

[Association between expression of lectin type receptors by natural killers and intensity of liver fibrosis during chronic hepatitis C].

AIM: To study functional activity of natural killers on different stages of fibrosis during chronic hepatitis C. MATERIALS AND METHODS: Functional activity of CD3-/CD56+/CD16+ lymphocytes measured as expression of natural killers receptors (NKR) and natural cytotoxicity receptors (NCR) was assessed by flow cytometry. RESULTS: At stage I of fibrosis, decrease of number of CD3-/CD56+/NKG2D+ cells was observed, whereas at precirrhotic stage III--sharp decrease of CD3-/CD56+/CD94+ and CD3-/ CD56+/NKG2D+ populations, and at cirrhotic stage--decrease of number of CD3-/CD56+/ NKG2D+ cells and increase of cytolytic activity of natural killers carrying CD107a marker compared to precirrhotic stage. CONCLUSION: Obtained data demonstrate that natural killers during chronic hepatitis C receive regulatory signals mainly through lectin type receptors (CD94 and NKG2D).

[Transplacental passage of the antiviral agent, bonafton]. / Issledovanie transplatsentarnogo perekhoda protivovirusnogo preparata bonaftona.

The ability of 14C-bonafton to penetrate the placental bar was studied in female Wistar rats. The drug was shown to penetrate through the placenta in insignificant amounts. The maximal quantities of the drug which entered the fetuses proper during the last third of pregnancy do not exceed 0.55% of 14C-bonafton content in the mother's blood. It was revealed that bonafton transplacental penetration is barred by fetal envelopes.