THE EFFECT OF NOS3 AND AGTR1 GENOTYPES ON THE COURSE OF THE ARTERIAL HYPERTENSION FOR THE OVERWEIGHT OR OBESE PATIENTS.

OBJECTIVE: The aim: Objective of the research is to determine the effect of NOS3 and AGTR1 genotypes of patients with arterial hypertension and high body mass index in the course of the disease. PATIENTS AND METHODS: Materials and methods: 58 patients (22 men and 36 women) with AH and high BMI were examined. The average age of the examined patients was 53.6±8.7 years. The analysis of rs1799983 polymorphisms of the NOS3 gene (localization 7q36.1; 7:150999023) and AGTR1 (type 1 receptor for angiotensin 2 1166 A>C) was performed using TaqMan assay (Thermo Fisher Scientific, USA) by real-time PCR (Applied Biosystems, USA) using TaqMan probe amplification products. Genomic DNA samples were isolated from stabilized blood using a Genomic DNA Mini Kit reagent (Invitrogen, USA). The Statistica 10 program (StatSoft Inc.) was used for statistical processing of the obtained data, USA). The independent samples were compared using the Mann-Whitney (U) criterion. In all cases of statistical evaluation, the reliability of differences was taken into account at a value of p<0.05. CONCLUSION: Results and conclusions: Polymorphism of the NOS3 and AGTR1 genes is associated with early development and complicated course of cardiovascular pathology. The combination of NOS3 and AGTR1 gene polymorphism in patients with the high body mass index increases the risk of complications in hypertension. Using a mathematical model to predict the probability (95%) of genetic mutations in two genes (NOS3 and AGTR1) increases the effectiveness of diagnosis for patients with the high risk of developing cardiovascular complications.

Effect of Propionic Acid on Diabetes-Induced Impairment of Unfolded Protein Response Signaling and Astrocyte/Microglia Crosstalk in Rat Ventromedial Nucleus of the Hypothalamus.

Background: The aim was to investigate the influence of propionic acid (PA) on the endoplasmic reticulum (ER), unfolded protein response (UPR) state, and astrocyte/microglia markers in rat ventromedial hypothalamus (VMH) after type 2 diabetes mellitus (T2DM). Methods: Male Wistar rats were divided: (1) control, (2) T2DM, and groups that received the following (14 days, orally): (3) metformin (60 mg/kg), (4) PA (60 mg/kg), and (5) PA+metformin. Western blotting, RT-PCR, transmission electron microscopy, and immunohistochemical staining were performed. Results: We found T2DM-associated enlargement of ER cisterns, while drug administration slightly improved VMH ultrastructural signs of damage. GRP78 level was 2.1-fold lower in T2DM vs. control. Metformin restored GRP78 to control, while PA increased it by 2.56-fold and metformin+PA-by 3.28-fold vs. T2DM. PERK was elevated by 3.61-fold in T2DM, after metformin-by 4.98-fold, PA-5.64-fold, and metformin+PA-3.01-fold vs. control. A 2.45-fold increase in ATF6 was observed in T2DM. Metformin decreased ATF6 content vs. T2DM. Interestingly, PA exerted a more pronounced lowering effect on ATF6, while combined treatment restored ATF6 to control. IRE1 increased in T2DM (2.4-fold), metformin (1.99-fold), and PA (1.45-fold) groups vs. control, while metformin+PA fully normalized its content. The Iba1 level was upregulated in T2DM (5.44-fold) and metformin groups (6.88-fold). Despite PA treatment leading to a further 8.9-fold Iba1 elevation, PA+metformin caused the Iba1 decline vs. metformin and PA treatment. GFAP level did not change in T2DM but rose in metformin and PA groups vs. control. PA+metformin administration diminished GFAP vs. PA. T2DM-induced changes were associated with dramatically decreased ZO-1 levels, while PA treatment increased it almost to control values. Conclusions: T2DM-induced UPR imbalance, activation of microglia, and impairments in cell integrity may trigger VMH dysfunction. Drug administration slightly improved ultrastructural changes in VMH, normalized UPR, and caused an astrocyte activation. PA and metformin exerted beneficial effects for counteracting diabetes-induced ER stress in VMH.

THE EFFECTIVENESS OF THERAPY BY CRYOPRESERVED HUMAN PLASMA IN PATIENTS WITH DEFICIENCY OF MANNOSE BINDING LECTIN SUFFERING FROM HERPES VIRUS INFECTION.

OBJECTIVE: The aim: To research the ef f ectiveness of cryopreserved blood plasma replacement therapy in patients with primary mannose binding lectin (MBL) def i ciency, suf f ering from chronic active herpes virus infections. PATIENTS AND METHODS: Materials and methods: Patients of the study group (SG) n= 36 additionally received cryopreserved blood plasma therapy Octaplas (Octapharma, Switzerland). Patients of the control group (CG) n=36 received only chemotherapy with Valganciclovir 450 mg 2/day per os for 1-3 months. The diagnosis of active herpes virus infection was established by PCR of blood leukocytes. Statistical analysis of the obtained information was processed by the calculation of the chi-square (χ2) Pearson criterion, the odds ratio and the associated 95% conf i dence interval (95% CI). RESULTS: Results: The adding cryopreserved blood plasma substitute to standard therapy with valganciclovir for the treatment of chronic active herpes virus infection in patients with total serum MBL def i ciency below 50 ng/ml, allowed to get more negative PCR results. The ef f ectiveness of combination therapy was 50% higher in carrier of HHV-6 (χ2=8,533 and р=0,004; Yeats correction 6,533 and signif i cance 0,011; OR=11,667 and 95% CI=1,939-70,180) and 43% in carrier of HHV-7 (χ2=8,846 and р=0,003; Yeats correction 7,165 and signif i cance 0,008; OR=6,375 and 95% CI=1,711-23,758), compared with monotherapy. The close association between def i cit MBL compensation and the results of antiviral treatment is also reported. The ef f ect of such treatment in patients with chronic EBV infection was less (27%). CONCLUSION: Conclusions: We assumed, that virostatic ef f ect of valganciclovir is increased by MBL-mediated clearance of blood serum from viral particles.