Aim: To assess the influence of the treatment with 5-azacytidine (5-aza) on the profile of metal-containing proteins and factors of their regulation in Guerin carcinoma cells in vivo. Materials and Methods: The study was conducted on Wistar rats transplanted with wild-type Guerin carcinoma (Guerin/WT) and its strains resistant to cisplatin (Guerin/CP) or doxorubicin (Guerin/Dox). Animals were distributed in 6 groups treated with 5-aza and control animals without treatment. 5-Aza was injected by i.v. route (1 injection in 4 days at a dose of 2 mg/kg starting from the 4th day after tumor transplantation, 4 injections in total). Ferritin levels in blood serum and tumor tissue were measured by ELISA, transferrin and free iron complexes — by low-temperature EPR, miRNA-200b, -133a and -320a levels and promoter methylation — by real-time quantitative reverse transcription polymerase chain reaction. Results: The study has shown that 5-aza treatment caused demethylation of promoter regions of fth1 and tfr1 genes in all studied Guerin carcinoma strains. 5-Aza treatment resulted in a significant decrease of ferritin levels in tumor tissue (by 32.1% in Guerin/WT strain, by 29.8% in Guerin/Dox and by 69.1% in Guerin/CP). These events were accompanied by 3.5-fold and 2-fold increase of free iron complexes levels in tumor tissue of doxorubicin and cisplatin resistant strains, respectively. Also, 5-aza treatment resulted in significantly elevated levels of miR-200b, -133a, 320a expression in tumor tissue. After 5-aza treatment, ferritin levels in blood serum of animals with Guerin/Dox were increased by 23.9%, while in Guerin/Wt and Guerin/CP they were decreased by 17 and 16%, respectively. Conclusion: Alterations of epigenetic regulation upon in vivo treatment with 5-aza change the levels of metal-containing proteins due to DNA demethylation and altered miRNA expression profiles in Guerin carcinoma cells.

Contemporary methods diagnose congenital heart diseases (CHD) with high accuracy but postnatal diagnostics of vascular rings (VR) remains difficult. From 2004 to 2017 in our Center were performed 7740 primary fetal echocardiograms and more than 65,000 echocardiograms for children. From 2004 to 2017 18589 operations of congenital heart disease were performed, of them 95 (0,51%) were VR surgery. Of all patients treated with VR 21 (22,1%) had prenatal diagnosis, 74 (77,9%) – had postnatal. Since 2011 during postnatal and prenatal echocardiography, we introduced a new protocol with necessary views for VR visualization. Thanks to the use it increased the number of operations on the VR. Surgical treatment of VR has excellent results with low surgical risk. For the successful VR surgical treatment is necessary CT to perform for required to clarify the anatomy of the VR and the trachea. Prenatal and postnatal Echo can help of VR detection in a group of asymptomatic patients.

Vascular ring (VR) is hard to diagnose prenatally and requires knowledge of anatomy of the large vessels, anatomical variants of VR and special echocardiographic views. In this study we aimed to find echocardiographic parameters which may predict diagnosis of VR. From 2011 to 2017 diagnosis of the isolated VR was established prenatally and confirmed by computer tomography after birth in 39 cases (the main group). A control group comprised 47 fetuses with normal heart anatomy. The sizes of all heart structures in both groups were evaluated according to normograms corresponding to the pregnancy term and Z-scores were calculated. Our study has shown, that in both study groups Z-score for majority of heart structures were in the normal range. Despite differences in Z-scores of mitral valve annular dimensions (MV), tricuspid valve and ductus arteriosus diameter were statistically significant, this difference was not clinically relevant and did not have predictive value for VR diagnostics. This finding was confirmed using non-parametric ROC-analyses. We may conclude that only routine use of special views is an effective method of prenatal ultrasound diagnostics of VR.

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