[Characteristics of the Renin-Angiotensin-Aldosterone System in Carriers of Polymorphic Variants of the VDR Gene With Arterial Hypertension and Obesity].

AIM: to study the renin-angiotensin-aldosterone-system (RAAS) in patients with polymorphic variants of the vitamin D receptor gene (VDR), arterial hypertension (AH) and obesity. MATERIALS AND METHODS: We included in this study 98 patients with stage II-III AH and obesity (33 men, 65 women, mean age 61.1±9.9 years and BMI 43.3±5.0 kg/m2). The VDR gene study included genotypes TaqI, BsmI, FokI. After identification of TaqI, BsmI, FokI VDR gene sites we carried out measurements of levels of RAAS markers. RESULTS: We revealed an associative relationship between the presence of allele G of the BsmI site, C/C homozygosity of FokI site of VDR gene and presence of AH in patients with obesity. An increase of renin level was noted only in the homozygous T/T genotype of FokI, no differences in the concentration of aldosterone and angiotensin were detected between any of the studied genotypes. CONCLUSION: Polymorphic alleles and genotypes of the VDR gene can be used as predictors of AH development in obese patients with subsequent characterization of the state of the RAAS system.

[Alternative food for рatients with allergу to the egg].

Patients suffering from food allergy/food intolerance of eggs need alternative products that do not cause allergic reactions. The purpose of the research: to evaluate guinea fowl egg and meat tolerance among children with chicken egg allergy. There has been conducted single-centre prospective research into intolerance of the products. Appearance or increase in skin or gastrointestinal allergic symptoms was registered; the concentration of specific IgE antibodies against chicken egg and meat in blood serum was assessed. As alternative products, the children were offered guinea fowl egg and meat; these products were given to them during 14 days. In the research 40 children (23 girls and 17 boys) from the age of 8 months to 1.5 years old took part; all children were diagnosed with atopic dermatitis, one of its triggers was chicken egg. Exacerbation of skin allergy was connected with eating chicken egg, which was confirmed by the results of the allergy examination. 28 (70.0%) children were diagnosed as having the mild form of atomic dermatitis, while 12 (30.0%) patients had the moderate form of atomic dermatitis. At the beginning of the research the patients were divided into 2 equal groups (each group of 20 patients). The first group consisted of the children aged 8 moths - 1.5 years old who received 1/2 guinea fowl egg every other day. The second group consisted of the patients aged 1.5-3 years old who received 60-90 grams fowl egg meat per day. The research has revealed that the children showed tolerance of guinea fowl egg and meat, the majority of the patients did not experience any skin or gastrointestinal allergic reactions. It has also been shown that at the end of the research the majority of the children (73.3%) had a decrease in concentration of specific IgE antibodies against chicken egg and meat in blood serum. According to the allergy examination, 8 (26.7%) children experienced an increase in skin sensitization to chicken egg and meat, which coincided with exacerbation of skin allergy. Thus, the examined products can be used as alternative products for those children who suffer from food allergy/food intolerance of chicken egg and meat.

[Toxicological evaluation of colloidal nano-sized silver stabilized polyvinylpyrrolidone. III. Enzymological, biochemical markers, state of antioxidant defense system].

Nanosized colloidal silver (NCS) with primary nanoparticles (NPs) size in the range of 10-80 nm in aqueous suspension was administered to rats with initial weight 80±10 gfor the first 30 day intragastrically and for lasting 62 days with the diet consumed in doses of 0.1; 1.0 and 10 mg/kg of body weight b.w) per day based on silver (Ag). The control animals received deionized water and carrier of NPs - aqueous solution of stabilizer polyvinylpyrrolidone. Activity (Vmax) was determined in liver of microsomal mixed function monooxygenase isoforms CYP 1A1, 1A2 and 2B1 against their specific substrates, the activity of liver conjugating enzymes (glutathione-S-transferase and UDP-glucuronosyltransferase) in the microsomal fraction and a cytosol, and the overall and non-sedimentable activities of lysosomal hydrolases. In blood plasma there were evaluated malonic dialdehyde, PUFA diene conjugates, in erythrocytes - the activity of antioxidant enzymes. A set of standard biochemical indicators of blood serum was also determined. The studies revealed changes in a number of molecular markers of toxic action. Among them - the increase in the activity of key enzymes I and II stages of detoxification of xenobiotics, indicating its functional overvoltage; reducing the activity of glutathione peroxidase (GP), the total arylsulfatase A and B, ß-galactosidase (in the absence of changes in their non-sedimentable activity), levels of uric acid, increased alkaline phosphatase activity. These changes occurred mainly at the dose Ag of 10 mg/kg b.w., except for the GP to which the threshold dose was 1 mg/kg b.w. No significant changes in the studied markers in a dose Ag 0,1 mg/kg b.w. were identified. Possible mechanisms of the toxic action of silver NPs are discussed.

[Modern trends in study of polymorphism of genes encoding goat's milk proteins].

This review emphasises the genotypical heterogeneity of the population of goats, which at the molecular level is manifested in the form of gene polymorphism in the milk proteins. Polymorphic genes, represented in the population of heterogeneous alleles, cause a wide variance in the chemical composition and processing properties of goat milk. We summarized the literature about the main features of genes encoding proteins of goat milk. It is stressed that goat's milk, due to genetic polymorphism has a great value when creating a new functional food product for children.

[THE CLINICAL COURSE OF HEPATITIS C IN CHILDREN WITH DIFFERENT VARIANTS OF THE GENE POLYMORPHISM IL28B].

Aim of investigation: The aim of the research is to study the clinical course of hepatitis C in children with different variants of the gene polymorphism of IL-28B. Materials and methods: We observed 94 children (46 girls and 48 boys) with chronic hepatitis C (CHC) in age from 3 to 17 years (mean age 10 years). There were significant differences in the distribution of allele frequencies in children with chronic hepatitis C and in the population. In children with chronic hepatitis C significantly increased the incidence of the T allele at the locus of the gene IL-28B rs12979860 C>T, which makes it possible to consider it as a predictor of antiviral therapy ineffective. Results: When analyzing the frequency of occurrence of a polymorphic variant T>G [rs8099917] IL-28B gene in children with chronic hepatitis C and healthy children revealed no differences in the distribution of alleles. Conclusion: Personalized approach to the appointment of HCV antiviral therapy in children is to carry out genetic studies to determine on the basis of predictive features of the course of HCV in children during the treatment.

Criteria of Glycemic Control in Type 2 Diabetes Mellitus.

The paper presents the basic criteria for glycemic control in type 2 diabetes mellitus, the data on the relationship between postprandial glycemia and the development of the late vascular complications, and methods for evaluating the glycemic index of foodstuffs and dishes in order to optimize the diets and improve the efficiency of therapeutic measures in this disease.

[Genomic, proteomic and metabolomic predictors of atherosclerosis in obese patients. Part II].

Currently there is no extensive research of metabolic disorders in obese patients with atherosclerosis, including the study of genomic, biochemical, immune and other markers. Therefore, the aim of the study was to identify the genomic, proteomic and metabolic predictors of atherosclerosis in obese patients. We evaluated condition of the cardiovascular system of the 100 obese patients aged 18 to 66 years, which were divided in two groups of patients: Group 1 consisted of 50 obese patients without vascular pathology, 2nd group consisted of 50 patients with obesity, complicated by atherosclerosis. We carried out a study of the lipid metabolism and analysis of polymorphic alleles ε2, ε3, ε4 of the ApoE gene by PCR. Our data showed that clinically significant predictors of atherosclerosis in obese patients are homozygous genotypes ε2/ε2 of the ApoE gene, increased blood serum level of triglycerides, oxidated LDL, interleukin-6, adhesion molecules SICAM, L-FABP and adiponectin reduction.

[Genomic, proteomic and metabolomic predictors of nonalcoholic fatty liver disease development in obese patients. Part I].

The prevention, diagnosis and treatment of diseases associated to obesity require a qualitative increase of efficiency. There are still disputable questions about diagnostic significance of some molecules, including genomic, proteomic and metabolomic biomarkers. We observed 72 obese patients (20 men and 52 women, mean age--41.3 +/- 2.5) and performed ultrasound elastography and ultrasound of liver. We have identified two groups of patients: Group 1 consisted of 50 obese patients without complications (BMI 43.2 +/- 0.6), group 2 consisted of 22 patients with obesity complicated with nonalcoholic fatty liver disease (BMI 45.8 +/- 2.3). Determination of the adipokines (adiponectin, ghrelin, resistin, visfatin, and apelin), cytokine (interleukin--6, TNFalpha) oxidized lipoproteins (oxLDL), adhesion molecule sICAM (soluble intercellular cell adhesion molecule), fatty acid transporter L-FABP in serum was performed by ELISA. The study of the lipid metabolism involved determination of the concentration of total cholesterols, triglycerides, low and high density lipoproteins (LDL and HDL) by turbidimetry and spectrophotometry by analyzer. In addition, we conducted analysis of polymorphic alleles epsilon2, epsilon3, episolon4 of ApoE gene using polymerase chain reaction. Our data indicate that reducing the concentration of adiponectin (0.46-1.71 mcg/ml), increasing the level of glucose (5.57-6.25 mmol/l), triglycerides (2.06-3.94 mmol/l), TNFalpha (5.07-16.68 pg/ml) and L-FABP (11.62-23.76 pg/ml) are predictors of nonalcoholic fatty liver disease in obese patients, and the presence of genotype epsilon3/epsilon4 of ApoE gene is a poor prognostic marker of severity of nonalcoholic fatty liver disease.

[Selenium metabolism in patients with severe multiple trauma].

GOAL OF THE STUDY: To define a relation between the selenium level and the risk of the development of nosocomial pneumonia in patients with severe multiple trauma depending on the trauma severity and the volume of blood loss. MATERIALS AND METHODS: We measured serum selenium concentration in 40 patients with severe multiple trauma. The ISS score was used to estimate the trauma severity. Patients were divided into 2 groups: group I--25 patients without pneumonia, group II--15 patients with pneumonia. The volume of blood loss was estimated in each group. The oxidative stress was estimated by means of the antioxidant index. RESULTS: For selected groups the significant difference (P < 0.05) in the volume of blood loss was detected. It was shown the significant decrease of selenium concentration (P < 0.05) in both groups in comparison with control for all testing time points (the 6-12 hrs, 24 hrs, 3 and 5-7 days). The mean of selenium concentration in group II was significantly lower in comparison to the group I. A significant difference of selenium concentrations (P < 0.05) between groups were detected on the 6-12 hrs and day 3 from the trauma onset. The antioxidant index was significantly lower in the group II within the 6-12 hrs, 12-24 hrs and 5-7 days (P < 0.05) in comparison to group I. CONCLUSIONS: The severe multiple trauma and severe blood loss lead to a selenium deficiency in the blood serum starting with the first hours from the trauma onset, which leads to the critical level of selenium concentration by the Ist day's end after trauma. It also leads to a pronounced oxidative stress that is reflected in the antioxidant index dynamics. Thus serum selenium concentration may be included in the set of the early prognostic detectors to detect infectious pulmonary complications development at severe multiple trauma, and it could be the basis for the decision to take early prophylaxis using selenium medications.

[Soluble apoptosis markers in obese patients with food intolerance].

For the soluble apoptosis markers study 151 patients with obesity (92 women and 59 men) aged between 18 and 63 years were examined. Diagnosis and degree of obesity was based on the body mass index (38.2 +/- 5.4 kg/m2). Generally food intolerance was identified in 36.4% of obese patients. Four groups of patients were formed: three groups of patients with obesity stage I (15 patients), II (18 patients) and III (22 patients), respectively, and with food intolerance, and a group of obese patients without food intolerance (control group, n = 31). Obese patients with food intolerance received standard version of hypocaloric diet with the exception of specific food allergens. Duration of observation was 39-43 days. Such soluble apoptosis markers as sFas-L, Caspase-9, Caspase-8 and sCD153 were significantly higher in stage III obesity patients compared obese patients without food allergy (0.120 +/- 0.030 vs 0.035 +/- 0.010; 13.2 +/- 3.2 vs 5.9 +/- 0.4; 1.4 +/- 0.18 vs 0.6 +/- 0.24; 0.123 +/- 0.010 vs 0.025 +/- 0.002 ng/ml respectively). Positive dynamic of sFas-L, Caspase-9 and Caspase-8 (decrease to 0.052 +/- 0.030; 7.7 +/- 2.2 and 0.4 +/- 0.18 ng/ml respectively) in patients with obesity stage III and intactness sCD153 during diet therapy course were revealed. Significant differences for only Caspase-9 in patients with obesity stage II were obtained. The data obtained are considered as normalization of apoptosis due to nutritional correction of immunological disorders. Study of sFas-L, Caspase-9 and Caspase-8 allows to predict the course of disease, as immunological research for early detection of food allergy makes possible to implement the principles of personalized diet therapy.

[Adipokines and the metabolism of key nutrients in patients with obesity].

AIM: To study the effect of adipokines on the metabolism of key nutrients in patients with obesity. SUBJECTS AND METHODS: Ninety patients aged 18 to 66 years old who were treated at the Department of Preventive and Rehabilitative Nutrition, Research Institute of Nutrition, Russian Academy of Medical Sciences, were examined. Carbohydrate and lipid metabolisms were assessed by turbidimetry and spectrophotometry. The levels of adipokines, insulin, and oxidized low-density lipoproteins (LDL) were measured by ELISA. Insulin resistance was assessed with HOMA-IR in all the patients. RESULTS: It was found that there were discoordinated changes in the content of adipokines. The patients with Grade 1 obesity, as compared to the control group, had a statistically significant decrease in the serum concentrations of adiponectin (5.94 +/- 0.90 and 15.34 +/- 0.45 microg/ml; p < 0.05) and ghrelin (215.50 +/- 104.50 and 540.67 +/- 0.76 pg/ml; (p < 0.05) and resistin levels above the normal values (7.34 +/- 1.24 and 5.12 +/- 0.22 ng/ml; p < 0.05; respectively). There was an inverse correlation between the content of adiponectin and ghrelin, and body mass index in obese patients (r1 = -0.25, r2 = -0.15; p < 0.05). There was evidence that there was also an inverse correlation between the levels of adiponectin, triglycerides, LDL, particularly oxidized LDL (p < 0.05). Adipokine-induced insulin resistance appeared as increases in the concentrations of glucose, insulin, and HOMA-IR, as compared to those in the control group. CONCLUSION: A comprehensive approach to evaluating metabolic disorders and adipokine synthesis in obese patients makes it possible to optimize the diagnosis of type 2 diabetes mellitus and cardiovascular diseases and to personalize diet therapy.

[Toxicological assessment of nanostructured silica. II. Enzymatic, biochemical indices, state of antioxidative defence].

Nanostructured silica (SiO2) "Aerosil" with the size of the primary nanoparticles (NPs) of 5-30 nm, in the form of ultrasound treated water suspension was administered to rats of 80 ± 4 g initial body weight for the first 30 days by intragastric gavage and then for 62 days with diets consumed in doses of 0.1; 1.0; 10 and 100 mg/kg body weight per day. The control group received vehicle of nanomaterial (NM)--deionized water. There were measured in liver of ani- mals the content of total cytochromes P450 and b5 in the microsomal fraction of liver, activity (Vmax) of microsomal monooxygenases with the mixed func- tion of isoforms CYP1A1, 1A2 and 2B1 on their specific substrates, the activity of conjugating liver enzymes glutathione-S-transferase and UDP-glucuronosyl-transferase in microsomal fraction and cytosol, the total and non sedimentable activity of lysosomal hydrolases (ß-glucuronidase, ß-galactozydase, arylsulphatase A, B). The content of PUFA's diene conjugates and TBA-reactive substances in the blood plasma and the activity of antioxidative enzymes (glutathionperoxidase, superoxidedismutase, glutathionreductase, katalase) in erytrocytes were estimated. A set of standard biochemical parameters of blood serum was also examined (total protein, albumin, glucose, creatinine, urea, uric acid, activities of hepatic transaminases). The studies revealed changes of a number of molecu lar markers that could be interpreted as unfavorable. These include isoforms of CYP2B1 activity decrease at a dose HM 1-10 mg/kg of body weight, decrease in the serum content of total protein, albumin and glucose levels in a dose range of 0.1-10 mg/kg. These changes were absent at the maximum dose of NM, which did not allow to clearly establish the dose-response. The remaining studied fig ures resided in the normal range or experienced changes that could not be interpreted as toxic.

[Immune status estimation algorithm in irritable bowel syndrome patients with food intolerance].

OBJECTIVE: To develop an algorithm for evaluation of the immune status in IBS patients with food intolerance. MATERIALS AND METHODS: 42 patients with IBS were observed. The diagnosis is based Rome III criteria. Determination of the concentration of serum allergen-IgG-antibodies to food allergens, IgG, IgA, IgM, IgE and immunoregulatory substances IL-5, TGF ß1, IL-10, IL-4 IL-2, IL-13 were determined by enzyme immunoassay. All the patients received rotational diet therapy based on immunoassay data in addition to medical treatment of the basis disease. The control group comprised 15 healthy individuals. RESULTS: Food intolerances basically to foods proteinaceous was diagnosed in 25 patients with IBS (59.5% of cases). The effectiveness of diet therapy was 68% (17 patients). Analysis of clinical and laboratory data revealed that the implementation of food intolerance in patients with IBS reducing the levels of IL-10 and TGFß1. An effective rotational diet of food intolerance in IBS patients had significantly (p < 0.05) increase IgA levels. CONCLUSION: Food intolerance in IBS patients characterized an increased synthesis of allergen-specific IgG antibodies, insufficient production of anti-inflammatory immunoregulatory substances IL-10 and TGFß1, and intact cytokines IL-2, - 4, - 5, - 13, IgG and IgM in serum. Efficiency rotary diet in patients with IBS is accompanied by positive clinical dynamics, increase levels of anti-inflammatory substances and serum IgA.

[Polymorphisms Ser447Ter of lipoprotein-lipase gene, Cys112Arg and Arg158Cys of apolipoprotein E gene in patients with obesity].

The distribution of allele Ser447Ter of lipoprotein lipase gene (LPL) and polymorphic markers E2 and E4 of the apolipoprotein E gene (ApoE) were examined in 100 obese patients at the age of 18-66 years (28 men and 72 women, 40.6 +/- 2.1 years old). The first group included patients with I degree of obesity (n = 26, BMI = 32.5 +/- 0.2), the second group--patients with II degree of obesity (n = 33, BMI = 37.1 +/- 0.2), the third group--patients with grade III obesity (n = 41, BMI = 46.3-1.1) and control group were 18 healthy individuals aged from 22 to 55 years (7 men and 11 women, 36.5 +/- 0.9 years old, BMI = 22.4 +/- 1.8). Maximal frequency of allelic polymorphism epsilon2 has been revealed in patients with I degree of obesity, and allele epsilon4--in patients with III degree of obesity. The most common genotype of ApoE gene was epsilon3/epsilon3 in all three groups of patients with obesity. In a comparative analysis of allelic variants of the Apo E gene occurrence it has been found that the frequency of a polymorphic variant epsilon2/epsilon2 tended to decrease with BMI increasing, whereas a higher rate of detection of genotypes epsilon4/epsilon3, epsilon4/epsilon4 and epsilon2/epsilon4 was found in patients with III degree of obesity. The data obtained suggest that the epsilon4 allele of the Apo E gene is associated with the development of morbid obesity, rather than allele epsilon2. This phenomenon can be explained by the fact that apoE4 isoform has reduced affinity for LDL in comparison with apolipoprotein E3. The maximum concentration of cholesterol, triglycerides and LDL cholesterol has been observed in patients with epsilon2/epsilon4 genotype of ApoE gene, and it was significantly higher than in the control group (p < 0.05). The content of blood lipid fractions in patients with epsilon3/epsilon4 genotype of ApoE gene, in contrast, was the lowest among obese and did not exceed the values of the control group (p > 0.05). These data indicates a small contribution of epsilon4 polymorphism in heterozygous form to the development of dyslipidemia in obesity. The most positive effect of diet treatment was achieved in patients with genotype epsilon3/epsilon3 and epsilon3/epsilon4. An integrated approach to the assessment of lipid metabolism in patients with obesity, including the analysis of polymorphic genetic loci, can optimize and personalize the diet therapy.

[Markers of immune inflammation in patients with type 2 diabetes and obesity].

AIM: to investigate cytokine profile in patients with type 2 diabetes mellitus (DM) with different degree of obesity. 154 patients with type 2 DM were examined (55.2% women, 44.8% men). All patients received standard antihyperglycemic therapy; mean age was 46.1 +/- 0.82 years, mean duration of disease was 7.2 +/- 1.43 years. The patients were divided into the following groups according to their degree of obesity: grade I obesity (n = 50), grade II obesity (n = 51), grade III obesity (n = 53). 18 healthy volunteers (38.9% men, 61.1% women, mean age 41.2 +/- 3.2 years, BMI - 22.1 +/- 1.8 kg/m2). The patients and healthy volunteers were underwent biochemical analysis, determination of the cytokine profile and estimation of TNF-alpha, IL-1, IL-4, TGF-beta1 by enzyme-linked immunosorbent assay. It has been shown that increase of the body weight excess in patients with type 2 DM and obesity is accompanied with elevation of proinflammatory cytokines (TNF-alpha, IL-1, TGF-beta1) along with the reduction of inflammatory cytokines (IL-4). The TNF-alpha concentration in patients with grade I obesity was 2,8 fold higher than in the comparison group, in patients with grade II and III - 4 and 5,7 fold respectively. A similar trend occurred in TGF-beta1 level: 2 fold increase--when I obesity, 3,3 and 4 fold--respectively for grade II and III. Unidirectional dynamic changes of IL-1 in patients with type 2 diabetes reflects 1,3 fold increase in its level under obesity I grade, 1,7 fold--under II degree and 2,2 fold--under III degree compared to the level in the comparison group. IL-4 level in patients with diabetes and obesity is strikingly contrasted with the index of the comparison group and progressively reduced: 1,7 fold--when grade I obesity, 3,6 fold- with grade II, 7,7 fold--in the grade III. The data obtained indicates that cytokine profile play a critical part in pathogenesis of type 2 DM in association with obesity.

[Features of hormone metabolism in reproductive age women with metabolic syndrome].

Aim of this study was the investigation of feature of hormonal status in patients with metabolic syndrome (MetS). 111 reproductive age women were included in the study. According to diagnostic criteria for MetS of Society of Cardiology of the Russian Federation (2009) they were divided into two groups--study group (n=52) and control group (n=59). It was studied composition of body (fat mass, skeletal mass, lean mass, total, intracellular and extracellular fluid), parameter of lipid and carbohydrate metabolism, parameter of hormonal status. Study of hormonal status in reproductive age women with MetS showed a higher level of fasting and postprandial levels of insulin and C-peptide, hyperleptinemia and a reduced level of sex hormone-binding globulinn (SHBG). We suggest that serum leptin and SHBG levels may be used as an additional diagnostic criteria in these patients.

[The clinical and immunological manifestations of food intolerance in obese patients].

The clinical and immunological manifestations of food intolerance in obese patients were studied. Food intolerance was diagnosed in 32.6 and 33.4% in obese patients stage 2 and stage 3 respectively, and was basically determined by 13 proteinaceous food products. The changes in immune status in obese patients created conditions for development of food intolerance. The timely diagnose food intolerance allows to personalize the diet therapy.

[Definite of nutritional status in patients with metabolic syndrome with the use of modern methods of nutrimetabolomica].

A comprehensive assessment of nutritional status in 73 patients with metabolic syndrome was assessed. The consumption food pattern of the majority of examined patients have had increased energy intake with excessive fat consumption inadequate intake of complex carbohydrates. In patients with type 2 diabetes inadequate compensation of carbohydrate and lipid metabolism was marked. When assessing body composition method bioelectrical impedance analysis increased content of adipose tissue was revealed are positively correlated with insulin and tumor necrosis factor-alpha. According to indirect calorimetry, increase in the level of resting energy expenditure, reducing the rate of oxidation of fat, increase the rate of oxidation of protein and carbohydrates was noted.