Insulin resistance and need for a lifestyle change to eliminate it.

The AIM of our work is to point out the relationship between insulin resistance and metabolic compensation of diabetes mellitus, as well as to explore the possibilities of improving these parameters by non-drug measures. The rising incidence of insulin resistance associated with many comorbidities, especially due to the increase in obesity and unhealthy lifestyles, is a serious medical problem today. It is therefore necessary to be able to recognize and evaluate the presence of insulin resistance, prevent its occurrence, and ensure its elimination in high-risk individuals. In our study, we evaluated 106 patients with diabetes mellitus based on glycated hemoglobin parameters, ratio of triacylglycerols to high-density lipoproteins, and body mass index before and after adjustment of dietary and regime measures. Statistical analysis of our data showed a positive correlation between the assessed parameters of insulin resistance and metabolic compensation of diabetes with a Pearson correlation coefficient of 0.3156, and a decrease in glycated hemoglobin and insulin resistance after adjustment of dietary and regimen measures in 73.58 % of patients. Based on the above results, it is shown that non-drug measures are able to significantly improve the parameters of metabolic compensation of diabetes mellitus as well as those of insulin resistance (Tab. 4, Fig. 1, Ref. 18) Keywords: insulin resistance, TAG/HDL ratio, diabetes mellitus.

Mitoxantrone in combination with a DNA-PK inhibitor: possible therapy of promyelocytic leukaemia resistant forms.

The aim of the study was to sensitize cells of human promyelocytic leukaemia HL-60/MX2 (resistant to mitoxantrone and further substances interacting with topoisomerase II) to the effect of mitoxantrone (MTX). We demonstrated that the main mechanism of the HL-60/MX2 cell atypical multiple drug resistance is not only their altered activity of topoisomerase II and reduced levels of topoisomerase II α and ß proteins. The resistance of the HL-60/ MX2 cells to MTX is associated with their increased ability to repair DNA double-strand breaks (DSBs) in these cells. The HL-60/MX2 cells, compared to HL-60 cells (which are sensitive to MTX effects), contain large amounts of DNA-PK, which is responsible for the main pathway of the DSB repair, nonhomogenous end joining (NHEJ), and they also contain large amounts of further repair proteins Rad50 and Nbs1, which are important in both types of the repair processes (NHEJ as well as homologous recombination). We demonstrated that specific DNAPK inhibitor NU7026 reduced the amount of DNAPK in HL60/MX2, thus preventing the DSB repair through the NHEJ pathway after the incubation with MTX and in this way essentially abolished the resistance of these cells to MTX.