CARDIOVASCULAR DISEASES AND VITAL EXHAUSTION: LONGITUDINAL STUDY IN RUSSIA/SIBERIA (WHO MONICA — PSYCHOSOCIAL PROGRAM)

Aim. To study prevalence rates of vital exhaustion and its effects on 14-year risk of cardiovascular disease (CVD) (arterial hypertension (AH), myocardial infarction (MI), and stroke) development and genetic traits in open population of 25–64-yearold men in Russia/Siberia (West Siberia metropolis, Novosibirsk).Material and methods. Random representative sample of 25–64-year-old men was studied in a framework of WHO MONICA-Psychosocial Program (MOPSY) in 1994. Maastricht Questionnaire (MQ) was used to assess vital exhaustion. Genotyping for variable number of tandem repeats (VNTR) polymorphisms in DRD4 and DAT genes was performed. All new cases of AH, MI, and stroke were registered among people without CVD for 14 years (from 1994 to 2008). Statistical analysis was done by using software package SPSS 11.5. Cox proportional hazards regression model was used for evaluation of risk coefficient (hazard ratio (HR) taking into account time-adjusted control. Х2 test was used to assess statistical significance of differences between the groups.Results. In the study population, the vital exhaustion rate was 66,8%. Hazard ration was significantly increased (AH: HR=3,2; MI: HR=2,7; stroke: HR=3,2) in men with vital exhaustion compared with vital exhaustion-free individuals in open population during the first five years of observation. Multifactorial modeling showed that vital exhaustion together with concomitant social gradient determined development of AH, MI, and stroke in open population of 25–64-year-old men. Allele 7 of DRD4 and genotype 9/9 of DAT gene were associated with high level of vital exhaustion.Conclusion: Open population of 25–64-year-old men (Russia/Siberia, Novosibirsk) showed high level of vital exhaustion, a predictor for risk of developing CVD. Vital exhaustion is significantly associated with certain VNTR polymorphisms of DRD4 and DAT gens

Features of life situations prediction in patients with neurotic disorders

The study explores the person’s anticipatory consistency as one of the factors of neurotic disorders genesis. The research comprised 60 participants: 30 in-patients of the neurosis clinic and 30 people with no history of neurotic disorders. A comparative analysis revealed reduced personal, situational and temporal predictive competence in patients with neurotic disorders. This results in the disruption of cause-effect assessment, the diminished ability to predict everyday situations and, finally, maladjustment to interpersonal relationships.В исследовании рассматривается качество прогнозирования жизненных ситуаций пациентами с невротическими расстройствами как одного из факторов неврозогенеза. Участниками исследования стали 60 человек: 30 пациентов отделения неврозов, находящихся на стационарном лечении, и 30 человек, не имеющих в анамнезе невротических расстройств. При сравнительном анализе установлено, что у лиц с невротическими расстройствами снижена личностно-ситуативная и временная прогностическая компетентность как результат плохой оценки причинно-следственных связей и коммуникативной дезадаптации

СОЧЕТАНИЕ ТЯЖЕЛОГО ТЕЧЕНИЯ ЯЗВЕННОЙ БОЛЕЗНИ И ГЕМОФИЛИИ В У РЕБЕНКА. КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ

Gastroduodenal ulcer is less common and milder in children than in adults. Gastroduodenal ulcer complications, such as hemorrhage, penetration etc. are even less common. Recurrent ulcerous defect hemorrhage is a reason to expand diagnostic search and involve various specialists, primarily hematologists, into the diagnosis establishing process. The article presents a clinical case of a child with gastroduodenal ulcer complicated with recurrent hemorrhage not terminated with the standard therapy; thus, additional diagnostic testing was performed. This helped to detect a hematological disease and determine an optimal therapy amount.Язвенная болезнь желудка и двенадцатиперстной кишки у детей встречается реже, чем у взрослых, и отличается более легким течением. Еще реже у детей встречаются осложнения язвенной болезни, такие как кровотечение, пенетрация и др. Рецидивирующие кровотечения из язвенных дефектов являются поводом для расширения диагностического поиска и привлечения к процессу постановки диагноза различных специалистов, в первую очередь гематологов. В статье представлен клинический случай ребенка с язвенной болезнью, осложненной рецидивирующими кровотечениями, которые не купировались при применении стандартной терапии, что послужило причиной для дополнительных диагностических исследований. Это позволило выявить гематологическое заболевание и определить оптимальный объем терапии

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

ASSOCIATION OF PSYCHOSOCIAL FACTORS WITH DOPAMINE RECEPTOR D4 (DRD4), DAT GENE POLYMORPHISM AND CARDIOVASCULAR INCIDENCE RISK

Anxiety is considered as an independent risk factor for cardiovascular diseases (CVD). Relationships between genetic markers of anxiety and risk of developing CVD remain unknown.Aim. The objectives of the study were to determine trait anxiety prevalence; to find associations between trait anxiety and VNTR polymorphisms in the DRD4 and DAT genes; and to calculate Hazard retio (HR) for developing arterial hypertension (AH), myocardial infarction (MI), and stroke.Material and methods. Representative sample of 25-64-year-old males (n=2149) was examined in three screening studies in a framework of the WHO MONICA program and MONICA-psychosocial subprogram in Novosibirsk in 1984, 1988, and 1994. All first time MI, AH, and stroke events were registered from 1984 to 2008. Genotyping of VNTR polymorphism was performed for DRD4 and DAT genes. Anxiety levels were evaluated by using the Spielberger’s test. Stratified Cox proportional regression model was used for Hazard ratio (HR) estimation.Results. High level of anxiety (HLA) in an open male population was 50,9%. The DRD4 genotype 4/6 and DAT genotype 9/9 were significantly associated with HLA. HLA increased CVD risk. HR for developing AH and stroke was maximal during the first five years of the study, whereas maximal risk of developing MI was found for 10-year period.Conclusion. Prevalence of HLA in an open 25-64-year-old male population in Novosibirsk was high. Rates of HLA were significantly associated with certain VNTR polymorphisms in the DRD4 and DAT genes. HLA were associated with increased risk of developing CVD

Association of the dopamine receptor (DRD4, DAT) gene polymorphisms with vital exhaustion in an open population among 25—64-year-old men (Novosibirsk): Epidemiological study according to the WHO MONICA-psychosocial program

Objective: to study the association of the DRD4, DAT genes with vital exhaustion in an open 25—64-old-year male population. A random representative sample of 657 men aged 25—64 years, living in one of the Novosibirsk districts was examined within the WHO MONICA project in 1994. The MONICA-MOPSY test was used to estimate the level of vital exhaustion. The examined DRD4, DAT gene Polymorphisms were genotypes in the Laboratory of Molecular Genetic Studies, Therapy Research Institute, Siberian Branch, Russian Academy of Medical Sciences (Novosibirsk). Results. The genotype containing allele 7 in the dopamine receptor subtype 4 (DRD4) gene, as well as genotype 9/9 in the dopamine-transporter protein (DAT) gene are significantly associated with the high level of vital exhaustion. Conclusion. The vital exhaustion is significantly associated with certain DRD4, DAT gene polymorphisms in the open 25—64-year-old male population of Novosibirsk

COMBINATION OF SEVERE GASTRODUODENAL ULCER AND HEMOPHILIA B IN A CHILD. CLINICAL CASE

Gastroduodenal ulcer is less common and milder in children than in adults. Gastroduodenal ulcer complications, such as hemorrhage, penetration etc. are even less common. Recurrent ulcerous defect hemorrhage is a reason to expand diagnostic search and involve various specialists, primarily hematologists, into the diagnosis establishing process. The article presents a clinical case of a child with gastroduodenal ulcer complicated with recurrent hemorrhage not terminated with the standard therapy; thus, additional diagnostic testing was performed. This helped to detect a hematological disease and determine an optimal therapy amount