Breast cancer (BC) is the prevailing malignancy and major cause of cancer-related death in females. Doxorubicin is a part of BC neoadjuvant and adjuvant chemotherapy regimens. The administration of anthracycline derivates, such as doxorubicin, may cause several side effects, including hematological disfunction, gastrointestinal toxicity, hepatotoxicity, nephrotoxicity, and cardiotoxicity. Cardiotoxicity is a major adverse reaction to anthracyclines, and it may vary depending on individual differences in doxorubicin pharmacokinetics. Determination of specific polymorphisms of genes that can alter doxorubicin metabolism was shown to reduce the risk of adverse reactions and improve the safety and efficacy of doxorubicin. Genes which encode cytochrome P450 enzymes (CYP3A4 and CYP2D6), p-glycoproteins (ATP-binding cassette (ABC) family members such as Multi-Drug Resistance 1 (MDR1) protein), and other detoxifying enzymes were shown to control the metabolism and pharmacokinetics of doxorubicin. The effectiveness of doxorubicin is defined by the polymorphism of cytochrome p450 and p-glycoprotein-encoding genes. This study critically discusses the latest data about the role of gene polymorphisms in the regulation of doxorubicin’s anti-BC effects. The correlation of genetic differences with the efficacy and safety of doxorubicin may provide insights for the development of personalized medical treatment for BC patients.

Возможности применения пробиотика БИФИФОРМ КИДС с целью профилактики заболеваемости острыми респираторными вирусными инфекциями у детей

About 187 million couples worldwide suffer from infertility, with the male factor being diagnosed in 2070% of cases. The main cause of idiopathic infertility has been recognized as the adverse effects of reactive oxygen species. On the one hand, the cellular antioxidant defense is a highly efficient multilevel system; therefore, the pharmacological targets may vary. On the other hand, antioxidant enzymes (superoxide dismutase, catalase, peroxidase) have high activity and specificity, which limits the pharmacological capabilities of direct antioxidants. Indirect methods, such as the normalization of mitochondrial function, are more promising. Mitochondria play a key role in providing energy for sperm motility (one of the main factors of male fertility). Myo-inositol (MI) derivatives involved in cell signaling regulate intracellular Ca2+ ion levels affecting mitochondrial oxidative metabolism and adenosine triphosphate production. Thus, mitochondrial antioxidants are of particular interest for therapeutic strategies. Currently, various routes and regimens of MI use in the treatment of males with oligo-astheno-teratozoospermia (OAT) are being considered in clinical practice. MI-based oral nutraceutical complexes for the treatment of male factor infertility contain both direct and indirect antioxidants. In vitro studies revealed damage to mitochondrial cristae in the sperm intermediate tract in patients with OAT. Experimental studies have demonstrated that mitochondrial structure is restored when sperm are incubated in an MI-containing medium. Clinical studies confirmed that sperm incubation in such an environment leads to increased sperm motility and viability in patients with OAT. Intravaginal administration of MI showed increased total sperm motility and an increased proportion of progressively motile sperm. It is the progressive motility that is considered the best marker for identifying quality and healthy sperm. This type of sperm is usually used for in vitro fertilization techniques. In addition, intravaginal MI administration improved the quality of cervical mucus and reduced its viscosity and crystallization. The effect of intravaginal MI on cervical mucus can be considered as an additional independent factor in increasing fertility.

BACKGROUND: High prevalence of type 2 diabetes mellitus (T2DM) and its input to the increase of mortality indicate that social and economic value of this disease and financial burden are great. Testosterone replacement therapy (TRT) enhances the effectiveness of T2DM treatment. A research was conducted to assess if Androgel therapy in diabetic men is cost-effective. OBJECTIVES: Defining of economic benefit of adding Androgel to the T2DM treatment in men with testosterone deficiency. MATERIALS AND METHODS: Economic modeling and results of other clinical studies were used in the analysis. A guildeline of The Scottish Intercollegiate Guidelines Network (SIGN) was used for clinical study selection, development of economic modelling and study design, assessment of study quality. The study analyzed clinical effects (fasting morning glycemia, glycosylated hemoglobin, HOMA index) and mortality reduce. RESULTS: It was shown that TRT can help to reduce costs of glycemic control, to increase efficiency in terms of cost-effectiveness analysis. Target HbA1c value can be reached by additional cost of 569.39 roubles for every patient. There is a possible additional income from 454.100 to 8.896.186 rubles though reduced mortality. CONCLUSION: Thus, testosterone replacement therapy was shown as cost effective due to reduced costs. The analysis demonstrated HbA1c target achievement and, as a result, reduction of the T2DM outcomes and reduced mortality. There is a possible additional income from 454.100 to 8.896.186 rubles per year.

The basis of modern strategies for the treatment of oncological diseases is the use of pharmaceutical products. A high frequency of refractoriness and formation of tumor cells' resistance to anti-EGFR drugs dictates the need to develop new active inhibitors of this intracellular kinase. The aim of this work was to study the antitumor effect of a new compound – a derivative of 9-Dihydroacridone on in vitro models of EGFR-expressing tumor cells. Material and methods. The compound of 9-aminium-3,3-dimethyl-3,4-dihydroacridine-1(2H)-one L-2-hydroxy-butandiovate (laboratory cipher of the developer institution LHT-17-19) was studied. Three cultures of human stomach cancer were used for the study. The analysis of tumor cell growth suppression was performed in a test with 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide, intracellular identification of the phosphorylated form of receptor tyrosine kinase – by Western blotting. Study results. The compound of 9-dihydroacridone dose-dependently suppresses the growth of EGFR-expressing tumor cells of human gastric cancer. Hs746T culture cells have the greatest sensitivity to the compound, MKN1 has the least. The antitumor activity of the substance is based on the ability to reduce the intracellular pool of the activated form of receptor tyrosine kinase EGFR. Conclusions. The obtained results allow enable to consider the compound LHT-17-19 as a promising compound for the subsequent preclinical study of its antitumor properties in animal systems.