Comprehensive analysis of the 5-HTTLPR allelic polymorphism effect on behavioral and neurophysiological indicators of executive control in people from different ethnic groups in Siberia.

The allelic polymorphism of the serotonin transporter's gene 5-HTTLPR is considered as one of the factors determining an individual genetic predisposition to the development of a wide range of affective disorders, including depression. Many studies have shown that the climatic and social conditions of people's life can have a significant impact on the connections of 5-HTTLPR with the risk of depression. The stop-signal paradigm (SSP) is an experimental method allowing evaluating an individual ability to the self-control of behavior in a changing environment. In the SSP experiment, a subject should either press one of several buttons quickly after the appearance of the target stimuli or suppress the already started movement if an inhibitory signal follows the target stimulus. The aim of this study is a research of associations between the allelic the 5-HTTLPR polymorphism and the individual scores of the personal anxiety level, as well as the behavioral and neurophysiological indicators of the ability to self-control over motor reactions in the SSP. The study was conducted among people from three ethno-regional groups: healthy Caucasoids from Novosibirsk, the Mongoloid groups of the indigenous population of the Tuva Republic and Sakha Republic (Yakutia). Genetic, ethnographic, and psychological influences on an individual's ability to control motor responses were compared. The amplitude of the premotor peak of the evoked brain potential was used as a neurophysiological marker of the person's readiness to the execution of target-directed activity. It was revealed that the frequency of the S-allele polymorphism 5-HTTLPR was significantly higher for both mongoloid groups compared to the Caucasoids. The S/S genotype was associated with an increased level of personal anxiety and at the same time with a better ability to the self-control of behavior in the SSP experiment. Anxiety level, participants' sex, ethnicity, and allelic polymorphism 5-HTTLPR had a statistically significant effect on the amplitude of the premotor readiness potential recorded under the SSP conditions in the frontal and parietal-occipital cortical regions. Our data support the hypothesis that the S/S genotype of the 5-HTTLPR polymorphism may be associated with more success in adapting to the climatic conditions connected with high life risk in comparison to L/L and L/S genotypes.

THE ROLE OF VIRAL HEPATITIS IN THE MECHANISM OF LIVER CANCER FORMATION AMONG THE FAR NORTH INDIGENOUS INHABITANTS.

INTRODUCTION: Yakutia is a region of high prevalence of viral hepatitis B, C and D. The rating and ranking of risk factors for the formation of cirrhosis and primary liver cancer in patients with chronic viral hepatitis (CVH) B, C and D in the Republic of Sakha (Yakutia) (R S(Y)), it is a serious medical problem. AIM: Studying of the main reasons for the progression of chronic viral hepatitis B, C and D to cirrhosis and liver cancer in the Far North. MATERIALS AND METHODS: Materials of official statistics of theTerritorial Rospotrebnadzor and official registration of the Ministry of Health of RS (Y); serological and molecular biological research methods to the studying of HCV genotype B, C, D. RESULTS: On the basis of long-term morbidity of chronic viral hepatitis B, C and D and their outcomes in Yakutia defined a role in the progression to cirrhosis and primary liver cancer, ethnicity and genotype of HBV and HDV. Established fact of viral replication in cirrhosis and primary liver cancer under adverse social and environmental factors, genetically determined increased concentration of acetaldehyde due to impaired activity of alcohol dehydrogenases (ADH) and aldegiddegirogenases (AIDG) at the indigenous inhabitants of the republic proves the need for targeted therapy of complex events. CONCLUSIONS: The regions of Yakutia are the most affected by the virus of hepatitis B, C and D with progressive course of the disease to cirrhosis and cirrhosis liver cancer, defined by genotype hepatitis B & D, in which significantly usually occurs primary liver cancer, also noted that the combined mixed-replicating virus hepatitis is a risk factor for primary liver cancer.

ADAPTIVE REACTIONS OF INDIGENOUS POPULATION OF YAKUTIA.

INTRODUCTION: The researches of organism's adaptive possibilities of indigenous population of the Arctic region are extremely important in modern conditions of the development of northern territories. The functional reserve of basic physiological systems and their interaction define "the health's resources", its potential level. AIM: This research has substantiated the adaptive reactions of organism of the North inhabitants on the basis of medical-physiological results. MATERIALS AND METHODS: Physical development was estimated by the standard anthopometrical method: the height and body mass were measured, index of body mass (BM), Quetelet's index, Rohrer's index were defined, area of body surface was calculated. Carbon dioxide in the air was defined by portable infra-red gas analyzer of firm "Fudji" for measurements indoors and outdoors. The parametres of blood acid-base state (ABS) were analyzed by standard procedures with microevaluator application ABL-330 (Denmark). Computer spirometry was done on the hardware-software diagnostic complex (HSDC) for analyses of external respiration function (NSRIMT - Russia) and "Pneumoscrin-2" of Erih Eger company (Germany). Arterial pressure was measured by Korotkov's method. RESULTS: The inhabitants of the North irrespective of ethnicity have conditions for more effective lung ventilation to satisfaction of the high metabolic requirements of the organism. CONCLUSIONS: Stability of arterial pressure among indigenous population, microcirculation optimisation and transcapillary tissues exchange, conserves steady level of metabolism that testifies a high level of adaptation of the person to severe climate- geographic North conditions.

THE ANALYSIS OF MAJOR RISK FACTORS OF CARDIOVASCULAR DISEASES AMONG INHABITANTS OF THE NORTH REGION.

Last years the problem of organism's adaptation to severe climate-environmental conditions of the Far North has been intensively developed. The Republic of Sakha (Yakutia) is the most northern republic of the Russian Federation. People have created a unique way of life, language, original culture on this cold part of the earth and have carried centuries later. This unique experience has been saved up throughout many centuries and generated in natural environment of habitation and passed from generation to generation. Last years the changes of living conditions of indigenous population, urbanization and globalisation, deterioration of ecological conditions exhausted reserve possibilities of organism. Among the indigenous population health change has menacing character, especially among the children's population. The analysis of major risk factors of the development of cardiovascular diseases among the indigenous population of the north has been carried out in this research.

[Physico-chemical properties of borate derivatives of DOPA, dopamine, and their liposome forms]. / Fiziko-khimicheskie svoistva boratnykh proizvodnykh DOPA, dopamina i ikh liposomnykh form.

To increase the solubility of L-3,4-dihydroxyphenylalanine (DOPA) and dopamine (DA) incorporated in liposomes, it was suggested to convert them into ammonium and 1-adamantylammonium borate complexes. The structure of these complexes was studied by 11B and 1H NMR, IR, and mass spectrometry and conductometry. The liposomic form of the complexes is characterized by a high active compound/lipid molar ratio (0.5). Catechols in the form of complex salts are retained better within the inner volume of liposomes.

[Oxidation in liposomes from egg phosphatidylcholine loaded with L-3,4-dihydroxyphenylalanine (DOPA) and dopamine: mutual effect of components]. / Okislenie v liposomakh iz iaichnogo fosfatidilkholina, nagruzhennykh L-3,4-digidroksifenilalaninom (DOPA) i dopaminom: vzaimnoe vliianie komponentov.

Oxidation of egg phosphatidylcholine and catechols (L-3,4-dihydroxyphenylalanine or dopamine) in liposome dispersions was studied. These catechols, encapsulated in liposomes, were shown to decrease the rate of phosphatidylcholine oxidation by factors of 4.9 and 2.6, respectively, at storage in darkness at 4 degrees C. After 40 min of Fe(II)-ascorbate-induced oxidation, the level of malonaldehyde in such liposomes remained constant, while in the empty liposomes, it increased 3,4-fold. Egg phosphatidylcholine protected catechols encapsulated into liposomes from oxidation, and the rate of this oxidation was shown to be substantially lower than that in micellar solutions under the same conditions. Evidently, this can be due to the barrier function of a lipid bilayer.

[Physico-chemical properties of liposome forms of L-3,4-dihydroxyphenylalanine (DOPA) and dopamine]. / Fiziko-khimicheskie svoistva liposomnykh form L-3,4-digudroksifenilalanina (DOPA) i dofamina.

L-3,4-Dihydroxyphenylalanine (DOPA) and dopamine encapsulated in liposomes have been obtained. These preparations can be used as drugs for Parkinson's disease. The level of encapsulation of the compounds under study in liposomes and their partition coefficients have been determined. The kinetics of DOPA (or dopamine) exit from the liposomes have been studied.

Analysis of collagen hydroxypyridinium crosslinks in samples of tissues and urine of patients with inherited connective tissue disorders.

Ion paired reversed-phase high performance liquid chromatography in a gradient system on an Altex Ultrasphere ODS column (3 microns; 7.5 cm x 4.6 mm) protected by an Ultrasphere ODS guard cartrige (5 microns; 5.0 cm x 4.0 mm) was used for the analysis of mature collagen crosslinks-hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP). The content of hydroxypyridinium crosslinks in biopsy specimens of human rib cartilage, rib bone, hip joint capsule, and urine was determined. Analysis of normal tissues revealed the presence of LP (alongside with HP) in embryonal rib cartilage and of HP+LP in the hip joint capsule. The urinary content of excreted HP in children under the age of two years exceeded the HP content in urine samples from children in the 2-12 year age group (t = 2.58, p < 0.05). The pathological material was obtained, for the most part, from patients with funnel chest (FC), both isolated and combined with the Ehlers-Danlos (EDS) and Marfan syndrome (MS). Abnormalities in tissue and urinary hydroxypyridinium crosslinks were observed in patients with clinical features of EDS. LP was found in the rib cartilage of 4 out of 6 patients with FC associated with EDS; no signs of this pathology were detected in individuals with isolated FC.

[Analysis of hydroxypyridine cross-links of collagen from human rib cartilage]. / Analiz gidroksipiridinovykh sshivok kollagena rebernogo khriashcha cheloveka.

Ion-paired reversed-phase high performance liquid chromatography (HPLC) has been used for the analysis of the content of mature collagen crosslinks--hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) in biopsy specimens of human rib cartilage from healthy donors (n = 14) and patients with inherited diseases of the connective tissue complicated with funnel chest (n = 17). Analysis of normal tissues reveal the presence of LP (alongside with HP) in embryonal rib cartilage. LP has been found in the rib cartilage of 4 out of 6 patients with funnel chest (FC) associated with Ehlers-Danlos syndrome (EDS); with no signs of this pathology detected in individuals with isolated FC. In rib cartilage of 2 patients with recurrent isolated FC LP has been discovered alongside with the presence of type I collagen. A significant increase of LP content in rib cartilage in a child with clinical phenotype of EDS type VI has been discovered.

[The determination of fragments of the N-terminal propeptide of collagen type III in human blood serum by sandwich immunoenzyme solid-phase analysis]. / Opredelenie fragmentov N-terminal'nogo propeptida kollagena III tipa v syvorotke krovi cheloveka metodom séndvich-immunofermentnogo tverdofaznogo analiza.

Solid-phase sandwich enzyme immunoassay has been developed to determine Col1+Col2 fragments of a N-terminal propeptide of Type III collagen in human serum, using polyclonal antibodies. The procedure allows one to obtain a sensitivity of 0.5 ng of native antigen and a linearity in the range of 0.5 = 50 ng of native antigen per ml. The intra- and interassay variation coefficients were less than 2.5 and 22.6%, respectively, in the linear part of the curve. Measurement of Col1+Col2 fragments in the serum of 97 normal subjects of different ages has revealed significantly higher levels of antigen in the serum of children under 3 years of age than in that of adult subjects (p < 0.05).

Characteristics of the macromolecular components of the extracellular matrix in human hyaline cartilage at different stages of ontogenesis.

The composition of the collagen and proteoglycan components of the extracellular matrix in human rib cartilage under normal conditions at different stages of ontogenesis (from 7 weeks of intrauterine development to 60 years of age) has been analysed. Polyacrylamide gel electrophoresis of collagen CNBr-peptides has shown the presence of type I collagen in embryonal cartilage and a gradual decrease in the quantity of this component relative to type II collagen with increasing age. Analysis of reducible and mature collagen cross-links revealed traces of lysylpyridinoline in addition to hydroxylysylpyridinoline in human rib cartilage. The increase in the content of mature cross-links during ontogenesis was accompanied by a decrease in the content of dihydroxylysinonorleucine. Electrophoretic analysis of proteoglycan monomers revealed four fractions of different mobility and the ratio of these fractions altered in the course of ontogenesis. An increase in the glucosamine/galactosamine ratio in the core proteins was observed with increase in age of the donors. During electrophoretic analysis of the link protein fraction a protein of molecular mass 200 kDa was found. This protein first appeared after 9 weeks of intrauterine development and was present in the rib cartilage at all subsequent stages of embryogenesis. This protein has been identified as tenascin by immunoblotting.

Enzyme-linked immunoassay and electrophoretic separation of collagens secreted by cultured skin fibroblasts of patients with Ehlers-Danlos and Marfan syndromes.

A method for the quantitation of the collagen types I, III, IV, and V, synthesized by cultured dermal fibroblasts is described. Collagens precipitated from the culture medium and intracellular collagens were detected by enzyme-linked immunosorbent assays with rabbit polyclonal monospecific antibodies. The assay could detect 10 ng protein per well, and intraassay coefficients of variation were less than 5%. Secreted collagens types I and III were also analysed by electrophoretic separation of [3H]-labelled alpha-chains under nonreducing and reducing conditions. These methods revealed a structural abnormality in one patient with clinical features of Marfan syndrome, and led to the postulation that the abnormality resulted from substitution of cysteine for another amino acid in collagen type I. In other patients an increase in the ratio of collagen type III:type I was detected, which may be secondary to an unknown biochemical defect.