[Comparative analysis of informative-diagnostic properties of mucosa immune-reactivity parameters].

AIM: Study the features of immune-reactivity expression in mucosa depending on their topicity and etiopathogenesis of the pathological process. MATERIALS AND METHODS: Data from 30 clinically healthy children and 77 children with acute and recurrent diseases of respiratory tract: 51--with acute and 15--with chronic bronchitis; as well as 132 women: 41--with active stage of acute urogenital chlamydia infection, 29--with recurrent chronic process, 30--with non-recurrent form and 32 clinically healthy women were analyzed. Saline and urogenital tract mucosa discharge was analyzed for IgG, sIgA and secretory component, IL-1beta, 4, 6, 8, 9, 10, 12, IFNgamma, TNFalpha and GM-CSF, TLR-2, TLR-3, TLR-4, TLR-8 gene expression levels as well as content of lysozyme, total protein and leucocytes. RESULTS: Solidity, universality and practically single-stage triggering of mucosa immune reaction mechanisms to intervention by foreign agents regardless of their localization was confirmed. A dependence of immune-reactivity expression on the form of pathologic process, its localization and qualitative and quantitative characteristics of the infectious agents was clearly seen. The highest level of clinical-laboratory and immunological parameters is inherent for patients with acute processes in urogenital tract (cervical canal and urethra), especially cause by mixed infections. CONCLUSION: Immune diagnostic parameters of mucosa among which TLR system is especially notable have high information properties allowing not only diagnostics of inflammatory process but also differentiating its form and character our course.

[Trans isomers of unsaturated fatty acids increase the risk of atherosclerosis-related circulatory system diseases].

The paper provides a review of the literature on a relevant non-drug prevention problem, namely the negative effect of trans isomers of unsaturated fatty acids (trans-UFA) on the risk of circulatory system diseases (CSD) and other chronic noncommunicable diseases. It gives data on the specific features of the structure and ability of trans-UFA to elevate the plasma levels of atherogenic low-density lipoproteins and to lower those of non/antiatherogenic high-density lipoproteins. The natural sources of their moderate content in the animal fats from ruminants and those of their redundant content in the margarines manufactured by hydrogenation of liquid vegetable oils are described. A new technology for preparing soft margarines (spreads) is presented, which can produce fatty products that do not virtually contain trans-UFA. There is evidence that trans-UFA can considerably raise the risk of CSD and their acute complications. It is concluded that the manufacture of fatty products with low and even no trans-UFA levels should be expanded in Russia to improve its population's health.

[Molecular-genetic and phylogenetic characteristic of Streptococcus pneumoniae strains isolated from patients with meningitis and carriers].

AIM: Analyze genetic and phylogenetic interrelations between S. pneumoniae strains isolated from meningitis patients and carriers. MATERIALS AND METHODS: 23 S. pneumoniae isolates (9 from bacterial meningitis patients, 9 from nasopharynx of bacterial carriers, 5 strains from museum collection of Gabrichevsky Moscow Research Institute of Epidemiology and Microbiology) were studied. S. pneumoniae ATCC 49619, S. mitis ATCC 49456 served as control strains. S. pneumoniae serotype determination was carried out in latex-agglutination reaction and quelling reaction. Multiplex PCR according to WHO protocols was used for molecular-genetic study and pneumolysin (ply), autolysin (lytA), surface cellular adhesin A (psaA) and capsule polysaccharide (cpsA) gene determination. Multilocus sequence-typing was carried out according to WHO scheme for 7 "housekeeping" segments--aroE, gdh, gki, recP, spi, xpt and ddl. Computer programs from available internet resources were used for data processing and dendrogram building. RESULTS; The S. pneumoniae isolates analyzed were established to belong to 19 sequence types that may be combined into 4 subclusters. Results of molecular-genetic and serologic typing were completely comparable. CONCLUSION: Attribution of isolates from the same serotype and serogroup to different sequence-types gives evidence on the ongoing changes within serotype and as a result changes in allele profile of circulating S. pneumoniae isolates. Membership of isolates in separate subclusters gives evidence on close evolution relationship between isolates obtained from patients with bacterial meningitis and carriers. Certain isolates had not previously been registered in Russia and were probably imported from the territories of other countries.

[Clinical value of insulin resistance in fasting normoglycemia].

Aim of the study was to clarify the question of the presence of manifestations of insulin resistance (IR) in fasting normoglycemia and to assess their association with risk of development and presence of clinically overt cardiovascular diseases (CVD) caused by atherosclerosis. We included into this study 1127 men and women older than 55 years with normal blood serum level of glucose in fasting state (<6.1 mmol/l) without diabetes mellitus selected from a random sample of Moscow inhabitants (n=1186). In participants selected for this study we determined risk factors, calculated indexes of IR (HOMA-IR) and functional capacity of pancreatic -cells (HOMA-%B) using fasting levels of glucose and insulin. The examined subsample was divided into quartiles according to values of HOMA-IR. It was shown that in the 4-th quartile HOMA-%B was substantially higher than in other quartiles. With this values of body mass index and waist circumference were also highest in the 4-th quartile. Fasting insulin level compared with glucose level contributed more to determination of values of indexes of both IR and functional capacity of pancreatic -cells. In the upper 4-th quartile signs of atherogenic dyslipidemia appearing as higher concentration of triglycerides and lowered concentration of high density lipoprotein cholesterol manifested to the greatest degree. At statistical analysis of probability of CVD with clinical manifestations it was shown that in the 4-th quartile of distribution of HOMA-IR (>2.7) values of odds ratio (OR) of development of arterial hypertension (AH), total CVD, angina pectoris, history of brain stroke were elevated. With that in the 3-rd quartile of distribution i.e. at HOMA-IR >1.9 there were higher ORs of development of AH, CVD, angina pectoris. Thus even in the range of normal fasting glucose concentrations in subjects older than 55 years we detected IR associated with elevated risk of development of atherosclerosis related CVD. For detection of IR it is appropriate to measure in blood serum not only concentration of glucose but also fasting insulin level with subsequent calculation of HOMA-IR and HOMA-%B indexes.

[The phylogenetic position of Chlamydia strains isolated from monkeys and humans with Chlamydial pathology in the family Chiamydiaceae. Genotypic and phenotypic properties of this pathogen].

Based on the results of the comparative analysis concerning relatedness and evolutional difference of the 16S - 23S nucleotide sequences of the middle ribosomal cluster and 23S rRNA I domain, and based on identification of phylogenetic position for Chlamydophila pneumoniae and Chlamydia trichomatis strains released from monkeys, relatedness of the above stated isolates with similar strains released from humans and with strains having nucleotide sequences presented in the GenBank electronic database has been detected for the first time ever. Position of these isolates in the Chlamydiaceae family phylogenetic tree has been identified. The evolutional position of the investigated original Chlamydia and Chlamydophila strains close to analogous strains from the GenBank electronic database has been demonstrated. Differences in the 16S - 23S nucleotide sequence of the middle ribosomal cluster and 23S rRNA I domain of plasmid and non-plasmid Chlamydia trachomatis strains released from humans and monkeys relative to different genotype groups (group B- B, Ba, D, Da, E, L1, L2, L2a; intermediate group - F, G, Ga) have been revealed for the first time ever. Abnormality in incA chromosomal gene expression resulting in Chlamydia life and development cycle disorder and decrease of Chlamydia virulence can be related to probable changes in the nucleotide sequence of the gene under consideration.

[Level of nitrous oxide in peripheral blood serum in patients with various severity of arterial hypertension].

AIM: To elucidate the role of nitrous oxide (NO) in development of severe primary arterial hypertension (AH) including malignant hypertension and concomitant ischemic heart disease (IHD). MATERIAL AND METHOD: Patients with diagnosis of primary 1-3 degree AH (n=62, 21 men, 41 women aged 39-87 years, mean age 63.7+/-2.7 years) and 28 subjects with normal arterial pressure (AP) (n=28, 13 men, 15 women aged 30-85 years, mean age 57.5+/-7.8 years). Blood serum levels of NO stable metabolites (nitrates and nitrites) were measured by reaction of their reduction in the presence of vanadium chloride and by reaction of diazotization of sulfanilamide by generated nitrite (modification by R.M.Miranda et al., 2001). RESULTS: NO level (level of its stable metabolites) was substantially elevated in patients with various severity of AH compared with subjects with normal AP. Severe and malignant course of AH was not associated with substantial lowering of NO level in blood serum. Relation between NO level and age found in subjects with normal AP, was not observed in patients with labile and stable course of AH. In patients with AH, normal serum NO level and signs of chronic involvement of cardiovascular system the disease was several times more often associated with atrial fibrillation and class II-III angina than in patients with high NO levels. Patients with AH combined with IHD more often had signs of heart failure and history of myocardial infarction.

[Colonization resistance and immunological reactivity of children's oropharyngeal mucosa in health and bronchopulmonary pathology].

The study group was comprised of 27 practically healthy children, 51 patients with acute bronchitis, 15 with chronic bronchitis and 11 with pneumonia. It was shown that changes of microbiocoenosis in back of the throat (BOT) were related to increased mucosal contamination with normal microflora and opportunistic microorganisms. The highest degree of contamination was observed in children with acute bronchitis. Normocoenosis was detected only in 13 practically healthy children. The disorders of microbiocoenosis took the form of disbiosis and acute inflammatory processes in patients with acute and chronic bronchitis and pneumonia. However, the large amount of normal flora together with the high Ig level ensured marked colonization resistance as evidenced by the values of natural colonization coefficient of nasopharyngeal epithelium (NCCNE) and balance coefficient (BC). These data suggested development of compensated secondary immunodeficiencies. In patients with acute bronchitis and pneumonia, local synthesis of Ig prevailed. It is shown that BC can be used to screen children for disorders of mucosal immunity. The presence of increased saliva IgE levels in patients with acute and chronic bronchitis supports the generally accepted concept of bronchi as a "shock organ" in allergic condition. It was demonstrated that IgE levels in saliva increase earlier than in serum and may be used as a prognostic criterion in patients with bronchopulmonary pathology.

[Relationship between activity of fibrinolysis, parameters of lipid spectrum and carbohydrate metabolism].

In this work analysis of results of a prospective populational cohort study "Stress and health in Russia" is presented. We included in the study inhabitants of Moscow randomly sampled from the population of men and women aged > or =55 years. Aim of the present work consisted in the study of relationship of activity of fibrinolysis and main parameters of the system of lipoproteines providing transport of lipids in blood serum and system controlling utilization of glucose by tissues. In dependence on fibrinolytic activity all examined persons were divided into 3 groups: with hypofibrinolysis (group 1, n=41.5%), with normofybrinolysis (group 2, n=41.9%), and hyperfibrinolysis (group 3, n=16.6%). In persons of group 1 low fibrinolytic activity and high level of fibrinogen were combined with atherogenic spectrum of blood serum lipids and elevated level of insulin at normal level of glucose. In patients of group 3 elevated fibrinolytic activity was combined with more favorable composition of blood lipids, lower levels of insulin and glucose and absence of obesity. At study of relation between fibrinoltic activity and a row of clinical states by the method of logistic regression a tendency to elevation of prevalence of myocardial infarction in persons with hypofibrinolysis was found while in persons with hyperfibrinolysis a significant lowering of prevalence of arterial hypertension, ischemic heart disease, and angina pectoris was observed.

[Molecular mechanisms of induction of innate immunity].

Cellular and molecular mechanisms of congenital immunity at different levels are discussed including single cell expression patterns and intracellular localization of individual TLR, the use of adapter molecules for generation of activation signals in response to microbial and non-microbial pathogens, soluble trap receptors, and intracellular negative regulators.

[Metabolic peculiarities of dyslipoproteinemias unrelated to high level of blood cholesterol].

The aim of this study was to reveal whether atherogenic or nonatherogenic properties of dyslipoproteinemias (DLP) not related to high level of blood total cholesterol (C) and low density lipoprotein C (LDL C) are determined only by shifts in serum triglycerides (TG) and/or high density lipoprotein cholesterol (HDL C) levels, or by other lipoprotein system alterations, if any. Biochemical factors regulating both lipid and carbohydrate metabolism were analyzed in two subsamples of Moscow residents aged 55 years with DLP: "high TG and low HDL C" and "normal TG and high HDL C" in comparison with randomly selected subsample assumed as "normal". Specific biochemical indexes of atherogenicity of DLP "high TG and low HDL C" were found, namely: increased apo B/AI ratio; disturbed functional activity of HDL in promoting reverse cholesterol transport expressed as elevated apo AII/AI ratio, decreased apo AI and phospholipids (PL) levels, decreased ratios of C/apo AI and C/PL in HDL, and decreased cholesterol-accepting capacity of HDL. Moreover, while fasting glucose level in subjects from this group remained unchanged, their fasting insulin level and HOMA-IR index were increased. Thus, DLP "high TG and low HDL C" is characterized by some specific metabolic features underlying its involvement into pathogenesis of atherosclerosis and type 2 diabetes mellitus. On the other hand, differences in biochemical parameters of antiatherogenic DLP "normal TG and high HDL C" from random subsample appeared to be opposite to differences from random subsample found for DLP "high TG and low HDL C", being in line with the present concept about their role in determining the antiatherogenicity of this kind of DLP.

[Modern methods of laboratory diagnostics of Chlamydia infections].

Need for further improvement of methods for verification of etiological agent of urogenital and respiratory chlamydiosis on the basis of increased biotechnological requirements to antigens for serological reactions, primers for PCR assay (refinement of connection of primers with microorganism's zones of genome most significant for its life activity or formation of most diagnostically significant complexes of primers), and selection of cultivating conditions considering the predicted features of clinical strains of the agent was substantiated.

[The microflora of vaginal, gutter, and intestinal bioptats of women with a threat of early miscarriage].

A complex simultaneous assessment of the microbiota (the aerobic and anaerobic links as well as the parietal and lumen components) of the gutter, vagina, and intestines of women with a pathological pregnancy was performed. In 30% of women the study revealed system dysbiotic changes. Local immune reactivity was decreased, which may be considered a provoking factor. In conclusion, complex microbiological examination makes it possible to objectivize the picture of the pathological process and its outcome. A criterion for the administration of correcting measures is offered.

[The role and biological significance of toll-like receptors in the anti-infectious resistance of the organism].

Modem conceptions of the role of toll-like receptors (TLR) in the innante immunity mechanisms realization and data on the interaction between TLR and pattern-associated molecular proteins of microbial or endogenic origin are presented in the review.

[Hormonal regulation of lipoprotein metabolism: the role in pathogenesis of coronary heart disease].

The character and role of hormonal dysregulation of lipoprotein metabolism during postprandial hyperlipemia were studied in patients with coronary heart disease (CHD) and hyperthyroidism as compared with healthy subjects. Pronounced hypertriglyceridemia alongside with the decreased high density lipoprotein cholesterol (HDL C) after standard fat load were associated with increased level of insulin and decreased level of cortisol. Moreover, in CHD patients fasting hyperinsulinemia becoming even stronger postprandially resulted in prevalence of antilipolytic action of insulin over lipid-mobilizing effect of cortisol; and an extended postprandial hypertriglyceridemia took place. Patients with hyperthyroidism and low cholesterol level both in atherogenic LDL and antiatherogenic HDL, demonstrated decreased level of apo AI (as in CHD patients) and apo B (three times lower than in CHD patients). Very low ratio of apo B/AI in patients with hyperthyroidism both in fasting and postprandial state was a clear indication of their lipoprotein profile antiatherogeneity. Thus, in patients with hyperthyroidism despite of low HDL C and apo AI levels, antiatherogenic properties of lipoprotein profile are probably determined by very low apo B/AI ratio induced by thyroid hormones, and might be explained by the influence of thyroid hormones on the expression of genes coding these apoproteins.

[Signs of metabolic syndrome in combinations of hypertension with coronary risk factors].

Anthropometric data, parameters of lipoprotein spectrum and carbohydrate metabolism were obtained from 115 men aged 34-67 years with hypertension. Hypertension combined with any other criterion of metabolic syndrome was associated with deviations of parameters of insulin resistance, blood pressure, body mass index, waist circumference, levels of cholesterol, low density lipoproteins and lipoprotein (a) similar to those observed in complete metabolic syndrome. Combinations of hypertension with hypercholesterolemia and/or excessive body mass were not associated with signs of insulin resistance in the presence of higher then in isolated hypertension values of body mass index, cholesterol, low density lipoprotein cholesterol.

[Screening as a method for determining the serum level of nitric oxide metabolites].

The paper describes a modified method for determining stable nitric oxide (NO) metabolites, which permits one-stage assay of total nitrates and nitrites after blood serum deproteinization. The assay is based on the simultaneous reduction of nitrates and nitrites by vanadium chloride and by diazotization with subsequent stimulation of tinting whose rate is spectrophotometrically estimated at 540 nm. Assay of 100 microl of the deproteinized serum is made, by using a flat-bottomed 96-well plate. The sensitivity of the method is 1.7 microM. The concentration of total NO metabolites detected by the assay in the sera of volunteers ranged from 37.2 to 87.2 microM. It is suggested that the above modified assay may be used in clinical practice for the measurement of the concentrations of terminal NO metabolites since they are early markers of vascular endothelial NO-forming dysfunction.

[Effect of long-term physical training on hemostasis in patients with coronary heart disease and non-insulin dependent diabetes]. / Vliianie dlitel'nykh fizicheskikh trenirovok na parametry sistemy gemostaza u bol'nykh ishemicheskoi bolezn'iu serdtsa v sochetanii s sakharnym diabetom 2-go tipa.

AIM: To study effects of 6-month physical training on some parameters of hemostasis in patients with coronary heart disease and non-insulin dependent diabetes (NIDDM). RESULTS: Long-term physical training resulted in lowering of fibrinogen level and increase of fibrinolytic activity assessed as euglobulin fraction clot lysis time, while factor VII activity remained unchanged. These changes were accompanied with elevation of total and high density lipoprotein cholesterol levels without any shifts in low density lipoprotein cholesterol and triglycerides. Most pronounced positive effect physical training exerted on results of a test with standard single fat load, which was used as a model of postprandial lipemia. Serum cortisol level significantly decreased after 6-month training, especially after fat load and subsequent physical exertion. CONCLUSION: In patients with combination of coronary heart disease and NIDDM long-term physical training was associated with decreased thrombogenicity of blood.

[Lowering of antiatherogenic significance of high density lipoproteins in obese persons]. / Snizhenie antiaterogennoi znachimosti lipoproteidov vysokoi plotnosti u lits s ozhireniem.

Protein and lipid components of blood serum high density lipoproteins (HDL) responsible for their functional activity were studied before and after fat load in subjects with normal body mass and various types of obesity. Subjects with abdominal obesity compared with those with gluteo-femoral obesity and normal body mass initially had pronounced disturbances in components of HDL and their acceptor capacity. Fat load caused changes of HDL composition in all study groups. Postprandial effect in persons with normal body mass became obvious 6 hours after load while in those with excess mass it occurred earlier - 3 hours after fatty meal. In subjects with gluteo-femoral obesity this effect remained on the same level while in those with abdominal obesity it became more pronounced by hour 6. Contrary to subjects with normal body mass and gluteo-femoral obesity fat load induced changes of HDL components in persons with abdominal obesity were not associated with augmented acceptor capacity of HDL what could be considered as proatherogenic effect.