[Non-alcoholic fatty liver disease and type 2 diabetes mellitus: general approaches to the choice of therapy].

Currently, there is a growing interest in one of the most common diseases in hepatology - non-alcoholic fatty liver disease (NAFLD). There is evidence that approximately 75% of cases of NAFLD occur against the background of obesity, dyslipidemia or type 2 diabetes mellitus (T2DM). At the present stage, a persistent pathophysiological interaction between NAFLD and T2DM has been demonstrated. Insulin resistance is one of the main pathogenetic causes of the development of T2DM and NAFLD. At the same time, it is necessary to highlight the role of the intestinal microbiota and epigenome in the manifestation and progression of NAFLD. Therefore, treatment approaches should be comprehensive. Diet therapy should be aimed at calorie restriction. However, in real clinical practice, phisicians face a low commitment to appropriate and long-term dietary recommendations necessary for weight loss. At the same time, use of dietary fibers, which are part of the preparation Mucofalk, helps to slow down the passage of food through the digestive tract, increase the saturation period. Use of a low-calorie diet with a significant fat restriction may increase the risk of gallstones. Ursodeoxycholic acid preparations (Ursofalk) can be recommended for the prevention of cholelithiasis. Considering the role of intestinal microflora in the pathogenesis of NAFLD, it is necessary to correct dysbiotic changes as well as basic pharmacotherapy. Thus, a comprehensive approach to the management of patients with NAFLD and T2DM should be aimed not only at therapy, but also at the prevention of associated metabolic disorders.

[Historical aspects of diagnosis and control of diabetes mellitus].

Diabetes mellitus is a group of metabolic diseases affecting carbohydrate, lipid, and protein metabolism. This pathology has a long history, and it was considered a disease of the kidneys until the middle of the 19th century. Descriptions have been found in Egyptian papyri, in ancient Indian and Chinese medical literature, in the writings of ancient Greek and Arab doctors. Aretaeus of Cappadocia gave the first accurate description of the disease, coining the term "diabetes". Thomas Willis first differentiated diabetes from other causes of polyuria by the sweet taste of urine. Matthew Dobson proved the presence of glucose in urine by evaporation. Claude Bernard demonstrated that hyperglycemia contributes to glucosuria. This is how the concept of the renal threshold appeared. In domestic practice, the term "renal threshold" was introduced by endocrinologist V.G. Baranov. The development of qualitative tests for determining glucose in the urine, the creation of test strips and glucometers has significantly improved the quality of life of patients with diabetes. The current stage of development of glucometry includes the determination of fasting plasma glucose, postprandial glycemia, glycated hemoglobin, as well as continuous glucose monitoring. Continuous glucose monitoring systems make it possible to estimate the time in target range, show the rate of rise or fall of glucose levels. It affects the rate and degree of carbohydrate metabolism compensation and allows for maximum control of the disease.

[The influence of weight loss interventions on psycho-emotional state of young men with obesity].

AIM: To assess the relationship of psychoemotional changes with obesity in young men, depending on the age of manifestation of the disease and against the background of the program of weight loss. MATERIALS AND METHODS: The study included 48 young men with obesity, aged 17 to 24 years. The subjects were divided into two groups. Group A consisted of 26 men with manifestation of obesity since childhood, group B 22 patients with onset of the disease from puberty. Subsequently, the study patients were subdivided depending on the type of obesity treatment (complex and non-pharmacological). The psychological status and anthropometric parameters were assessed on screening and after 12 weeks of treatment. RESULTS: Depressive disorders were initially observed in 40.9% of patients in group B and in 19.2% of patients in group A. In young men who underwent complex treatment of obesity, regardless of the time of manifestation of the disease, a clinically significant decrease in symptoms of depression was revealed. All types of eating behavior were revealed in the subjects, and these manifestations are more common in patients with manifestation of the disease since childhood. In group A, the restrained eating was in 50% of young men, external eating in 42.3%, and emotional eating in 30.7%. In group B, emotional eating in 9% of patients, external eating in 40.9%, and restrained eating in 31.8% of young obese men. CONCLUSION: In the group of patients with manifestation of obesity since puberty, the frequency of depressive disorders was higher than in the group of young men with onset of obesity since childhood.

Early diagnosis of cardiotoxic complications of chemotherapy: the possibility of radiation research methods.

Oncological diseases are the main causes of death in the world. Modern treatment of cancer patients contributes to an increase in survival rate due to strong chemotherapeutic drugs, the use of which is accompanied by toxic effects on cardiomyocytes. The main manifestations of cardiotoxicity are left ventricular dysfunction, myocardial ischemia, thromboembolic complications, chronic heart failure. As a result, the risk of cardiovascular mortality may be higher than the risk of death from the tumor process. An important task of oncologists and cardiologists is the early diagnosis of cardiotoxic complications in order to start treatment in time and reduce mortality from cardiovascular pathology in cancer patients.

Identification of interstitial-like defects in a computer model of glassy aluminum.

Computer simulation shows that glassy aluminum produced by rapid melt quenching contains a significant number of 'defects' similar to dumbbell (split) interstitials in the crystalline state. Although these 'defects' do not have any clear topological pattern as opposed to the crystal, they can be uniquely identified with the same properties which are characteristic of these defects in the crystalline structure, i.e. strong sensitivity to applied shear stress, specific local shear strain fields and distinctive low-/high-frequency peculiarities in the vibration spectra of 'defective' atoms. This conclusion provides new support for the interstitialcy theory, which was found to give consistent and verifiable explanations for a number of relaxation phenomena in metallic glasses and their relationship with the maternal crystalline state.

STRUCTURAL AND FUNCTIONAL CHARACT ERISTICS OF THE LMP1 ONCOGENE IN PATIENTS WITH TUMORS ASSOCIATED AND NOT ASSOCIATED WITH THE EPSTEIN-BARR VIRUS.

Epstein-Barr virus (EBV) - the etiological agent of a number of human benign and malignant tumors including infectious mononucleosis (IM), Burkitt lymphoma (BL), Hodgkin (HL) and non-Hodgkin (NLH) lymphomas, nasopharyngeal carcinoma (NPC), and many other tumors. Latent membrane protein 1 (LMPl) encoded by the gene of the same name (LMP I) is the main oncoprotein of EBV. LMP1 is a transmembrane protein capable of activating many signaling pathways and transcription factors of the cells, which leads to its transformation. Molecular analysis of LMP1 of various clinical origins identified many variants with different types of amino acid mutations that influence its biological activity. Since the role of LMPl in the development of NPC is still not fully understood, it is important to find out how LMPl samples from patients with EBV-associated form of NPC differ from those of patients with other tumors also located in the oral cavity (OTOC), but not associated with this virus. Unlike most investigations conducted in endemic regions, the present work is intended to compare the genetic structure and the transforming activity of LMPl variants from NPC and OTOC patients has been carried out in a non-endemic region of Russia, where NPC is rarely diagnosed. The obtained data show structural and functional similarities of LMP1 variants in the two groups of patients and, accordingly, a genetic relationship of EBV strains persisting in these patients. Our work suggests that in non-endemic regions any EBV strain with any structure of LMP1 may become the etiologic agent of NPC. However, based on modem concepts, the cancer can occur only if EBV-infected persons have a unique pattern of HLA associated with a high sensitivity to the development of NPC combined with exposure to harmful environmental factors (chemical or physical carcinogens) and lifestyle.

[Epstein-Barr Virus LMP1 oncogene variants in cell lines of different origin].

It is well known that the Epstein-Barr virus (EBV) is a widespread infection in the human population. Typically, infection occurs in early childhood without serious consequences for infected people. At the same time, a secondary infection with an additional EBV strain occurs quite often. During the in vitro cultivation of peripheral blood lymphocytes from persons infected with multiple strains of the virus, only one of these strains with higher transforming potential becomes dominant, while the others are eliminated. Under certain conditions, such a highly transforming EBV strain apparently is able to be the etiologic agent of EBVassociated diseases. To find out the range of highly transforming EBV strains prevalent among Russians, cell lines from patients with EBV-associated and non-associated tumors, as well as healthy individuals, were established. The structural analysis of the latent membrane protein 1 gene (LMP1), a key oncogene of the virus, isolated from established cell lines and peripheral blood lymphocytes of blood donors was carried out, and data obtained were compared with the respective data for LMP1 isolates, amplified from cell lines established from African and Japanese patients with Burkitt's lymphoma. The data obtained show a genetic relationship between Russian LMP1 isolates regardless the fact whether they come from patients with tumors or healthy individuals and differ significantly from LMP1 isolates from Burkitt's lymphoma patients. Thus, the results of the study suggest that in nonendemic region for EBV-associated pathology, Russia, any strain of EBV with any structure of LMP1 with concomitant effect of additional factors may become an etiologic agent for EBV-associated neoplasia.

[Epstein-Barr virus (EBV) in Russia: infection of the population and analysis of the LMP1 gene variants in patients with EBV-associated pathologies and healthy individuals].

The Epstein-Barr virus, widespread herpesvirus among the population of the planet, is also the etiologic agent for a number of malignancies. One of the oncoproteins encoded by the virus, the latent membrane protein 1 (LMP1I), through activation of the complex signaling pathways is involved in the processes of cell immortalization and transformation. The goal of this work was to study the level of the EBV infection in Russian population and LMP1 polymorphism in patients with benign and malignant EBV-associated diseases and healthy virus carriers. Studies have shown that by the age of 5-9 years the percentage of the infected persons and the level of antibody titers reaches almost the maximum values. With the age, virus specific antibody titers are decreased (with a high percentage of infected persons) and increased again in groups of older persons. The analysis of the nucleotide sequences of the gene LMP1 translated in amino acid (aa) sequences unexpectedly revealed the dominance a low divergent variant LMP1 B95.8A not only in healthy individuals but also in patients with all forms of EBV-associated diseases. Highly divergent variants Ch1 and Med +, containing a deletion of 10 aa, and characterized by elevated transforming activity more often were detected in the tumor tissue samples than in the blood samples/mouth washes of the same patients. Detection of highly transforming variant LMP1 Ch1 in blood samples of healthy individuals indicates that this analog of Chinese variant Cao may persist in any population and is not necessarily associated with the occurrence of the EBV-associated disorders.

[The dynamics of indicators of selenium, glutathione and anti-oxidant defense of blood in patients with anemic cardiomyopathy against the background of treatment with preparations of iron and selenium].

The study was carried out on samplings of 46 patients with asiderotic anemia of severe degree and complicated by cardiomyopathy and 16 healthy persons. The content of selenium was analyzed using I.I. Nazarenko technique of detection of mass concentration GOST 19413-89. The content of glutathione in blood was detected using the technique based on capacity of acid-soluble thiol aggregations at interaction with 5,5-dithio-bis(2-nitrobenzene) acid to form a colored compound--thio-2-nitrobenzene acid. The principle of technique of measurement of activity of glutathione peroxidase of blood ervthrocvtes is in capacity of peroxide hydrogen to form a resistant colored complex with molybdenum salts. The technique of detection of activity of glutathione peroxidase is based on its capacity to catalyze reaction of interaction of reduced glutathione with tretbutyl hydro peroxide and on capacity of glutathione reductase to catalyze NADFN-dependent reduction of oxidated glutathione. The principle of technique of detection of activity of superoxiddismutase is based on capacity of enzyme to suppress reaction of reduction of nitro blue tetrazolium with superoxide anion-radical generated in vitro in the system xanthine-xanthineoxidase. The study established decreasing of content of selenium in blood of patients with anemic cardiomyopathy up to 1.8 times as compared with control group. The content of total glutathione in blood of patients was decreased up to 17.7% at the expense of decreasing of level of reduced glutathione up to 18.5%. The study established decreasing of activity of catalase in erythrocytes up to 1.3 times, glutathione peroxidase up to 2.5 times, glutathione reductase up to 2.1 times and superoxiddismutase up to 1.5 times as compared with control group. After the preparations of iron and selenium ware applied to patients with anemic cardiomyopathy the increase of level of selenium in blood up to 80.4% was established. The level of total glutathione increased up to 54.5% at the expense of increase of content of reduced glutathione up to 59.5%. The activity of blood erythrocytes in patients against the background of treatment increased up to 9.1%, the activity of glutathione peroxidase, glutathione reductase and superoxiddismutase of blood erythrocytes increased up to 3, 2.1 and 2 times respectively.

[The LMP1 oncogene sequence variations in patients with oral tumours associated or not associated with the Epstein Barr].

The role of the Epstein-Barr virus (EBV), a ubiquitous lymphotropic human herpesvirus type 4, in the etiology of nasopharyngeal carcinoma (NPC) is not fully understood. The mechanism of NPC carcinogenesis, associated with the virus, is also not clear. The objective of present investigation was to carry out comparative analysis of the structure of an LMP1 oncogene of EBV in viral isolates obtained from patients with two types of tumors of the oral cavity: (a) associated (i.e., NPC) and (b) not associated (other tumors of the same anatomical region, OTOC) with EBV. Comparative analysis of C-terminal regions of LMP1 variants that was based on a sequence analysis of LMP1 from tumor, blood and throat washing samples of NPC and OTOC patients showed that all structural characteristics of LMP1 in both groups of patients were genetically similar, and differences found between compared parameters were statistically insignificant. Thus, for the first time it has been revealed that in NPC and OTOC patients in Russia genetically related EBV strains with structurally similar LMP1 variants are persisting that are likely to reflect a polymorphism of the virus circulating in population. The findings allow us to suggest that in non-NPC-endemic regions of the world, which include Russia, the risk of NPC development does not depend on the EBVstrain and its variant of LMP1 so much, but mostly from the genetic predisposition of infected persons to the disease and the exposure to other, as yet unknown agents.

[LMP1 gene polymorphism in patients with Epstein-Barr virus-negative gastric carcinomas in Russia].

The investigation was undertaken to study the molecular characteristics of Epstein-Barr virus (EBV) LMP1 gene samples amplified from the tumor and intact tissues of patients with EBV-negative forms of gastric carcinoma (GC). The genetic structure of these samples determined by their sequencing was compared with that of the gene samples isolated from the cells of oropharyngeal washing specimens from the same patients with GC, as well as peripheral blood lymphocytes of patients with infectious mononucleosis (IM) and blood donors. The findings suggest that the samples of tumor tissue LMP1 from patients with GC have higher divergence than those from patients with IM and blood donors although no specific variants of the gene for GC were found. Comparison of LMP1 sequences from tumor tissue and cells of oropharyngeal washing specimens from the same patients with EBV-negative GC revealed the common LMP1 variant in 2 cases while they differed in 3 cases. The findings are an initial step in studying the role of EBV in the carcinogenesis of EBV-negative GC that is likely to be established by investigations on representative clinical material, by applying the up-to-date technologies.

[HERV-K-associated carcinogenesis: co-expression of viral and cellular proteins in the development of human germ-cell tumors].

To elucidate the role of some viral and cellular proteins in the occurrence and development of HERV-K-associated germ-cell tumors (GCT), reverse-transcription polymerase chain reaction using specific primers has been employed to study the transcription of the protein Rec HERV-K and the possible interaction of the protein Rec(cORF), that has transforming properties, and the cellular protein PLZF, that is a negative regulator of cell division, in human GCT tissues, in the testicular parenchyma adjacent to a tumor, and in the normal testicular tissues. It was shown that there was expression of Rec(cORF) of mRNA, rather than cellular PLZF in all malignant GCT tissues, this led to the conclusion that no interaction occured between the Rec HERV-K and PLZF proteins in the GCT cells. At the same time co-expression of Rec and PLZF protein was first revealed at the level of transcription in the testicular parenchyma adjacent to a tumor that exhibited carcinoma in situ cells. By taking into account that the protein Rec HERV-K has transforming activity and it is presumed to be Implicated in the development of GCT, the authors discuss a possible role in the Rec HERV-K/HTDV and cellular PLZF interaction in the pathogenesis of GST at the early stages of its genesis.

[Fatty acid composition of red blood cells in patients with iron-deficiency anemia in relation to the presence of cardiomyopathy].

The purpose of the investigation was to study the fractional composition of fatty acids (FA) of red blood cell membrane lipids in 51 patients with chronic posthemorrhagic iron-deficiency anemia (IDA) of first-third grade in relation to the presence or absence of anemic cardiomyopathy and in 15 healthy individuals. In IDA patients without cardiomyopathy, there was an increase in the sum of saturated FA at the expense of a palmitic acid fraction and a decrease in the sum of unsaturated FA at the expense of arachidonate as compared with these in healthy individuals. In patients with cardiomyopathy-complicated IDA, fatty acid impairments were greater pronounced: the concentrations of myristic and pentadecanoic FAs raised and the relative content of omega 3-polyunsaturated FA reduced.

[Changes in fatty acids content in blood red cells of patients with iron-deficiency anemia treated with sorbifer and mildronate].

AIM: To study fractional composition of red cell membrane (RCM) lipids in patients with severe iron-deficiency anemia (IDA) complicated by myocardiodystrophy prior to treatment and after 1-month combined treatment with sorbifer and mildronate. MATERIAL AND METHODS: Fatty acid composition of RCM lipids was studied in 12 patients with severe chronic posthemorrhagic IDA complicated by myocardiodystrophy and in 15 healthy subjects. Extraction of lipids from blood red cells and methylation of fatty acids were performed according to K.M. Sinyak et al. (1976). Relative content of fatty acids was determined at chromatography. RESULTS: The study detected increased content of saturated fatty acids, especially palmitic and decreased content of unsaturated fatty acids especially fraction of omega6-polyunsaturated fatty acids: arachidonic and gamma-linolenic. CONCLUSION: Sorbifer in combination with mildronate improved fatty acid composition of blood red cells in patients with iron-deficiency anemia.

[Structural-functional parameters of the myocardium in patients with chronic iron deficiency anemia].

Aim of the study was investigation of structural-functional parameters of the myocardium and assessment of segmental diastolic left ventricular function with myocardial tissue dopplerography in 56 patients with iron deficiency anemia (IDA). We studied parameters of structure of the myocardium, its systolodiastolic function, as well as velocities of early (Ve) and late (Va) diastolic waves, Ve/Va ratio, isovolumic relaxation times in 15 segments of the left ventricle. We revealed changes of myocardial structure appearing as LV hypertrophy, dilation of chambers of the heart, as well as disturbances of global and segmental diastolic LV function. Most pronounced changes were observed in patients with IDA of II and III degree of severity. The method of myocardial tissue Doppler echocardiography allows to diagnose LV diastolic dysfunction at early stages and can be used for detection of preclinical stage of myocardial dystrophy.

[The dynamics of left ventricular segmental diastolic function in patients with iron-deficit anemia treated within the course of treatment with sorbifer and triovit].

The parameters of segmental left ventricular (LV) diastolic function were studied by tissue myocardial Doppler echoCG in 54 patients with severe iron-deficit anemia (IDA) before treatment and after one month of treatment with sorbifer combined with triovit. The control group consisted of 16sex- and age-matched practically healthy persons. The following parameters were studied: early diastolic wave velocity (Ve), late diastolic wave velocity (Va), and Ve/Va ratio in 15 LV segments. Alterations in diastolic function were found in the majority of LV segments; they included a decrease in Ve, an increase in Va, and a decrease in Ve/Va in patients with severe IDA. Administration of sorbifer combined with triovit in this category of patients facilitated improvements in the parameters of LV segmental diastolic function.

[Mutations of the Epstein-Barr virus LMP1 gene mutations in Russian patients with lymphoid pathology and healthy individuals].

Epstein-Barr virus (EBV) is an etiological agent of a number of benign and malignant human diseases, such as infectious mononucleosis (IM), Hodgkin's lymphoma (HL), and non-Hodgkin's lymphoma (NHL). EBV latent membrane protein 1 (LMP1) gene (recognized as a viral oncoprotein) of various clinical and geographical origin was found to have different types of amino acid mutations affecting its biological activity. Since there was no information on the strain differences in LMP1 of EBV persisting in Russia, the authors made a sequence analysis of LMP1 samples amplified from the biological materials of Russian patients with IM, HL, and NHL and healthy individuals. The studies have shown that LMP1 variants of Russian origin are a mixed heterogeneous group containing both the earlier characterized and presumably new genetic variants. Among the point amino avid substitutions, the mutations S366T, F106Y, 185L, and E328Q associated with the enhanced transforming activity of a LMP1 molecule and its reduced cytotoxicity. There was no specific association between the certain Russian variants of LMP1 and the specific forms of the disease (IM, HL, and NHL).

[LMP1 gene variants of Epstein-Barr virus in patients with some lymphoproliferative malignancies].

The samples of tumor biopsy, blood, and saliva from 10 patients with Hodgkin's disease, 10 patients with non-Hodgkin's lymphoma, and the blood samples of 20 donors were tested by polymerase chain reaction (PCR) for standard (wild) B95-8 and Cao-like (deleted) variants of the LMP1 gene. The paraffin sections of most PCR-tested tumors were also investigated by immunohistochemistry using the monoclonal antibodies S12 or 7D7 to detect the expression of the standard or Cao-like variants of LMP1 protein, respectively. It is suggested that Eptein-Barr virus (EBV) that contains the above deletion is not crucial for the development of the study lymphoproliferative malignancies. The fact that in some cases there is the Cao-like variant of LMP1 in the tumor biopsy specimen and its standard variant LMP1-B95-8 in the biological fluids of the same patient is very likely to suggest that the patient is infected with both types of the virus or there is genetic mutation(s) of EBV during viral carcinogenesis preceding or accompanying the development of a tumor.