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The Cretaceous/Paleogene (K/T) boundary interval was studied in the Okhli and Gubden sections, northeastern Caucasus. Two sediment successions represented in these sections were accumulated in different zones of the paleobasin and distinguished by their lithological and geochemical characteristics. The high-resolution study of nannofossils revealed very gradual changes in nannoplankton community at the Cretaceous/Paleogene transition. The nannofossil assemblage becomes poor from the level ca. 4 m below K/T boundary and it is very scarce in the last 2.5 m of uppermost Maastrichtian. The significant sea-level fall is evidenced in the beginning of the K/T event. It led to erosion and redeposition of Maastrichtian calcareous sediments within the thin layer of clay, covering erosional surface in the Okhli section. The clay mineral assemblage, starting from this surface contains palygorskite. The concentrations of coprolites (Decapoda?) and microspherulas (diagenetic microconcretions) with higher content of some trace elements were found within the small red lenses at the base of the clay layer overlying the Maastrichtian erosional surface. The reliable evidence of impact event are not recognized. The evolutional trends which are recorded within the Cretaceous/Paleogene transitional interval in the Okhli and Gubden sections are similar to trends recognized in studied sections of the K/T event on the adjacent territories of the North-Eastern Peri-Tethys (e.g., southern Turkmenistan and Mangyshlak Peninsula).

The results of integrated study of the Cretaceous/Paleogene transition in the northeastern Caucasus are reported. The lithological, geochemical and micropaleontological characteristics of the sediments from two sections (Okhli and Gubden, Mountainous Dagestan) accumulated in different parts of paleobasin are displayed. An analysis of nannofossil distribution at the Cretaceous/Paleogene transition allowed to define the stratigraphic position of the stage boundary and reveal the interval of sediments (1–2 m thick transitional zone) accumulated under stress conditions. The large-scale sea-level fall occurred at the onset of the Cretaceous/Paleogene boundary event is evidenced. It led to the erosion and redeposition of the Maastrichtian calcareous sediments. In Okhli section, the occurrence of palygorskite is detected in the clay mineral assemblage of the transitional zone. The local concentrations of coprolites (Decapoda?) and spherical nodules of different composition (more likely, concretions) are found in the clay layer onlapping the erosional surface at the top of Maastrichtian. There is no reliable evidence of the impact nature of these nodules. The lithological record at the Cretaceous/Paleogene transition of the studied sections is similar to those exposed in other areas of the NE Peri-Tethys (e.g., southern Turkmenistan and Mangyshlak Peninsula).

This paper presents a new model of the distinct formation of groundwater of the aquifer system of the Northern Near-Caspian Region. The absence of sedimentary water displacement in plane is shown. An increase in mineralization and a wide range of characteristics of the composition and properties of rocks and waters are explained by processes of the mass-exchange in the water-rock system under conditions of low groundwater flow. The complex of the factors and conditions responsible for the integrity or displacement of sedimentary waters is determined, and it is suggested that it should be used to study the current and ancient sedimentary basins.

The paper reports lithological and geochemical data on the stratigraphic interval corresponding to the Paleocene/Eocene Thermal Maximum (PETM) event in the Paleogene section of Eastern Crimea (Nasypnoe section). The section is located on the western continuation of the sublatitudinal profile consisting of 15 PETM sections spanning the area from Crimea to Tajikistan (over 2500 km). It is shown that PETM sediments have the negative δ13C and δ18O isotope excursions and are enriched in kaolinite, which is typical of most sections of this interval around the world. At the same time, the extremely low content of organic matter (OM) in sediments of the Nasypnoe section makes them sharply different from the highly carbonaceous rocks of the PETM interval in Central and Eastern Caucasus, and Central Asian regions. This is correlated with the low contents of many chemical elements in the studied rocks, and their extremely high contents in the highly carbonaceous rocks of the easterly sections. Thus, Eastern Crimea in the end of the Paleocene‒beginning of the Eocene was occupied by the low-bioproductive marine paleobasin, whereas the coeval paleobasin in Central Asia was characterized by extremely high bioproductivity owing to the presence of significant amount of phosphorus.

Upper Eocene and Lower Oligocene rocks in the northeastern Caucasus were examined in the most representative Chirkei section (Sulak River basin). Sharp lithogeochemical distinctions between them were revealed. The results of the study of nannoplankton demonstrated that the Eocene/Oligocene interface occurs slightly below the boundary between the Belaya Glina and Khadum formations. The studied section revealed a series of nannoplankton bioevents facilitating its stratigraphic subdivision. It has been established that organic matter (OM) in rocks of the Khadum Formation is characterized by a relatively high degree of maturity. Probably, the material of mainly marine genesis contains a terrigenous OM admixture. Positive oxygen isotope anomaly in the upper part of the Belaya Glina Formation reflects global climate changes (cooling) near the Eocene/Oligocene interface. Limitation of the anomaly by the upper boundary of the Belaya Glina Formation is likely related to changes in water salinity variations in the Early Oligocene basin and intense early diagenetic processes in rocks therein. Lithological, geochemical, and paleoecological data suggest that the Khadum paleobasin was depleted in oxygen. Such environment was unstable with periodic intensification or attenuation. Paleoecology in the Belaya Glina basin was typical of normally aerated basins.

An additional very important and, possibly, unique feature of the Caspian sedimentary basin—the retention of sedimentary water in the Pleistocene aquifer system of the North Caspian and Near-Caspian regions—is discussed. It is shown that increase of the groundwater mineralization was caused by its metamorphization during diagenesis. Under conditions of the integrity of sedimentary water during geological history, hydromicaceous clays serve as the main source providing a significant increase of mineralization in the interstitial water of marine sediments and groundwater. The comprehensive examination of sedimentary processes in the Neopleistocene Caspian Basin and groundwater formation in the Pleistocene aquifer system of the northern Near-Caspian region made it possible to determine (and, frequently, to quantify) a system of specific natural factors and conditions (at the quantitative level in many cases). They can be used for the assessment of retention or displacement of sedimentary water from the sedimentary basin with a high degree of confidence. This is of great importance for the study of present-day sedimentary basins and geological reconstructions.

Water contained in marine sediments is of great significance in evolution process of sedimentatry basin. Transformation of sediments at all stages of lithogenesis occurs through interaction with water of different genetic types, as well as with organic matter and gases. Our attention was focused on the proportions of sedimentary and infiltration water in basin. The possibility and degree of displacement of sedimentary water by waters of other genetic types, first of all, infiltration water, are considered. In this communication, we consider specific natural conditions that provided the integrity of sedimentary water at least during the entire Pleistocene-Holocene. It was convincingly demonstrated for the first time that infiltration water, evaporation, and deep factors have a minimum or local influence on the total balance of the Pleistocene aquifer system of the North Caspian and near-Caspian regions. The water balance is mainly determined by the following principal factors: extremely low Darcy velocity of regional groundwater flow and insignificant contribution of local recharge of atmospheric precipitation, evaporation, and vertical water exchange between aquiferous strata.

Presented herein are the results of the Russian part of the International Research Programme 'VEIN ACT' aimed at studying approaches to conservative treatment of chronic vein diseases in the Russian Federation, assessing its efficacy and safety, as well as monitoring the patient compliance. Also discussed are the regimen and results of conservative therapy, depending on patients' gender, age and body mass index, as well as the level of adherence to various methods of treatment in the cohorts concerned. High efficacy of conservative therapy in all patients was confirmed. However, the regimen of drug therapy needs to be adjusted depending on the disease severity, especially in patients of a more advanced age and those with obesity. The lowest patient compliance was observed in relation to compression treatment. The existing situation may be improved by be means of appropriate recommendations and a possible decrease of the level and degree of compression. This should of course be done carefully and attentively, with obligatorily taking into consideration the patients' age and body mass index.Представлены результаты российской части международной исследовательской программы 'VEIN ACT', направленной на изучение подходов к консервативному лечению хронических заболеваний вен в Российской Федерации, оценку его эффективности и безопасности, а также мониторинг приверженности пациента лечению. Рассмотрены регламент и результаты консервативной терапии в зависимости от пола, возраста и индекса массы тела пациентов, а также уровень комплаентности к различным методам лечения в данных группах. Объективно доказана высокая эффективность консервативной терапии у всех групп пациентов. Однако регламент фармакотерапии нуждается в регулировании в зависимости от степени тяжести заболевания, особенно у пациентов более старшего возраста и больных с ожирением. Наименьшая приверженность отмечается в отношении компрессионного лечения. Рациональные рекомендации и возможное уменьшение уровня и степени компрессии, могут улучшить сложившуюся ситуацию. При этом также нужно учитывать возраст и индекс массы тела пациентов.

The purpose of our study was to evaluate both clinical and laboratory efficacy of sulodexide given at a daily dose of 500 lipasemic units (LSU) in patients presenting with class C3-C4 chronic venous insufficiency (CVI) according to the CEAP classification.The study included a total of 25 patients diagnosed with C3-C4 CVI and prescribed to receive sulodexide at a daily dose of 500 LSU for 90 days. Efficacy was comprehensively controlled by the following tools: the disease-specific Chronic Venous Insufficiency Quality of Life Questionnaire (CIVIQ), visual-analogue methods of assessment separate symptoms; the Venous Clinical Severity Score (VCSS), as well as ultrasonographic determination of the thickness of subcutaneous fat and crural fascia. Amongst the key laboratory indices determined by means of the ELISA test were the levels of interleukin-1 alpha (IL-1α), interleukin-1 beta (IL-1β), matrix metalloproteinases-2 and -9 (MMP-2, MMP-9), vascular endothelial growth factor A (VEGF-A), vasopressin and endothelin.Of the initially enrolled 25 subjects, twenty-two patients completed the study and were taken as 100%. The 90-day treatment yielded favourable results manifesting themselves in complete disappearance of convulsions in the calf muscles detected at the first visit in 22.7% of patients (p=0.0485), a significant reduction in the frequency of complaints of decreased tolerance to static loads from 27.3 to 9.1% (p=0.2404). The volume of the crus of the control lower extremity decreased from 134.18±14. 92 to 128.42±12.46 cm3 (p=0.0006), subcutaneous fat thickness at the fixed point decreased from 1.50±0.53 to 1.32±0.46 cm (p=0.0007), and fascial thickness decreased from 0.14±0.7 to 0.11±0.04 (p=0.0359). Pain syndrome according to the visual analogue scale (VAS) decreased from 36.45±25.60 to 17.50±19.27 mm (p=0.0002). The global index of quality of life (GIQoL) according to the CIVIQ-20 increased by 27.7% compared with the baseline level (p = 0.0001), the VCSS index decreased from 6.00±1.83 to 4.86±2.05 points (p=0.0002). as for the laboratory markers of endothelial dysfunction, there was a significant decrease in the levels of MMP-2 - from 178.53±36.30 to 176.35±36.67 ng/ml (p=0.0152), MMP-9 - from 90.84±20.41 to 89.78±20.32 ng/ml (p=0.0394), and that of endothelin - from 0.42±0.10 to 0.39±0.10 fmol/ml.Sulodexide exerting a statistically significant clinical and endothelium-protecting effect turned out to be an effective drug for treatment of initial forms of chronic venous insufficiency of lower limbs.Цель – оценить клиническую и лабораторную эффективность сулодексида в суточной дозе 500 ЛЕ у пациентов с хронической венозной недостаточностью (ХВН) С3–С4 по СЕАР. Материалы и методы. В исследование включены 25 пациентов с ХВН С3–С4, которым на 90 дней был назначен сулодексид в суточной дозе 500 ЛЕ. Для контроля эффективности были использованы: болезнь-специфический опросник CIVIQ; визуально-аналоговые методы оценки отдельных симптомов; шкала VCSS; ультразвуковое определение толщины подкожно-жировой клетчатки и фасции голени. Среди ключевых лабораторных показателей определяли (тест ELISA) уровни интерлейкина-1 альфа (IL-1α), интерлейкина-1 бета (IL-1β), матриксных металлопротеиназ-2 и -9 (MMP-2, MMP-9), сосудистого эндотелиального фактора роста А (VEGF-A), вазопрессина и эндотеллина. Результаты и обсуждение. Исследование завершили 22 пациента, принятые за 100%. На фоне проведенного лечения произошло полное исчезновение судорог в икроножных мышцах, выявленных на первом визите у 22,7% пациентов (p=0,0485), уменьшилась частота жалоб на снижение толерантности к статическим нагрузкам с 27,3 до 9,1% (p=0,2404). Объем голени контрольной нижней конечности снизился с 134,18±14,92 до 128,42±12,46 см3 (p=0,0006), толщина подкожно-жировой клетчатки в фиксированной точке уменьшилась с 1,50±0,53 до 1,32±0,46 см (p=0,0007), а также фасции – с 0,14±0,07 до 0,11±0,04 см (p=0,0359). Болевой синдром согласно визуально-аналоговой шкале (ВАШ) снизился с 36,45±25,60 до 17,50±19,27 мм (p=0,0002). Глобальный индекс качества жизни (ГИКЖ) по CIVIQ-20 возрос на 27,7% в сравнении с исходным уровнем (p=0,0001), индекс VCSS снизился с 6,00±1,83 до 4,86±2,05 баллов (p=0,0002). Из лабораторных маркеров эндотелиальной дисфункции достоверно снизились показатели уровня: ММP-2 – со 178,53±36,30 до 176,35±36,67 нг/мл (p=0,0152), MMP-9 – с 90,84±20,41 до 89,78±20,32 нг/мл (p=0,0394), а также эндотелина – с 0,42±0,10 до 0,39±0,10 фмоль/мл. Заключение. Сулодексид, оказывая достоверное клиническое и эндотелиопротективное действие, является эффективным препаратом для лечения начальных форм хронической венозной недостаточности нижних конечностей.

The Cretaceous sections of the eastern Caucasus contain rich in organic matter (OM) sediments corresponding to the late Cenomanian Oceanic Anoxic Event 2. They are marked by positive δ13C and negative δ18O isotopic anomalies, which are characteristic for this level in many areas of the world. The sediments exhibit distinct cyclic patterns reflected in an alternation of black OM-rich and gray more calcareous layers. The rocks are enriched with many chemical elements, although concentrations of some of them (Mo, Se) are lower than in typical sediments of anoxic basins. It is inferred that anoxic environments in the paleobasin were unstable and locally developed. Nannofossil assemblages from OAE 2 sediments are dominated by the highly resistant eurytropic taxon Watznaueria accompanied by common cool-water Eprolithus and rare warm-water Rhagodiscus representatives, which implies the development of environments unfavorable for the normal marine nannoflora and short-term cooling in the basin during OAE 2. The OM-rich sediments were deposited against the background of the rapid eustatic transgression due to a significant increase in productivity of phytoplankton in the paleobasin. The OAE 2 duration is estimated to be approximately 400 ka.

Based on population analysis of the DRB1, DQA1, DQB1 and TNFA allele frequency distribution patterns, regional features of immunogenetic structure of the population of West Siberia were investigated. Statistically significant linkage disequilibrium within the HLA class II region, as well as between the TNFA and DRB1, DQA1, and DQB1 was demonstrated. Population frequency distribution patterns of two- and multilocus haplotypes were examined.

Presented herein are the results of the Russian part of the International Research Program "VEIN ACT" aimed at studying the structure of variants of conservative treatment for chronic venous diseases in the Russian Federation, assessing its efficacy and safety, as well as monitoring of patient compliance. The obtained findings demonstrated high popularity, among both physicians and patients, of phlebotrophic drugs, determining high patient's adherence thereto. Recommendations on correction of the lifestyle were complied with by more than 80% of patients, however frequently not in the full scale. Noted was sufficiently low compliance to compression therapy, manifesting itself as a decrease in the class of compression and irregular use thereof in more than 30% of patients. Usefulness of conservative therapy was objectively proved, consisting in satisfaction with treatment and a statistically significant decrease in severity of symptoms of chronic venous diseases in the overwhelming majority of patients.

The aim of the study was to analyze the results of the electrical muscle stimulation (EMS) usage in patients with venous ulcers developed on top of a post-thrombotic syndrome (PTS).Sixty patients (60 legs) with active venous ulcer (C6EsAsdpPr according to CEAP classification) were divided into two groups. In addition to the background therapy consisting of a standardized compression with ULCER X and intake of micronized purified flavonoid fraction (MPFF 1000 mg daily), all the patients in the main group underwent EMS with Veinoplus® V.I. for at least 3 times a day. Follow-up examinations were performed on days 30, 60 and 90. These included pain severity assessment with 100-mm Visual Analogue Scale (VAS), disease severity measurement with VCSS (Venous Clinical Severity Score) and ankle circumference above malleolus, as well as recording number of healed venous ulcers.At day 90 pain severity was reduced in both main and control groups. However, according to VAS pain reduction rates were significantly higher in patients of the main group (from 8.7 ± 0.6 to 1.9 ± 0.3 in the main group and 8.4 ± 0.6 to 3.9 ± 0.5 in the control group). At the end of the study, ankle circumference decreased from 270.9 ± 4.6 mm to 257.1 ± 4.2 mm in the main and from 269.7 ± 5.3 mm to 263.4 ± 5.2 in the control group. VCSS before treatment was 7.3 ± 0.6 in the main group and 6.8 ± 0.5 in the control group. By day 90 VCSS significantly decreased to 2.3 ± 0.4 and 4.6 ± 0.5 in the main and control groups respectively. Healing rates were significantly higher in the main group. On day 90, the number of open venous ulcers in the main group was 3 times lower than in the control group (4 vs. 12).EMS demonstrated high efficacy and good tolerability and provided significant reduction in pain severity, VCSS score and ankle edema, as well as a 3-fold increase in the number of healed venous ulcers.

The review based on analysing the results of epidemiological studies, as well as international guidelines and consensuses published in 2011-2012 reflects the present-day data concerning prevalence, principles of diagnosis and treatment of chronic venous oedema. This is followed by determining the role of compression and drug therapy in treatment thereof from the positions of evidence-based medicine.

The article deals with historical information dedicated to the discovery of bioflavonoids and their effect on the human cardiovascular system, also considering the modern classification of phlebotrophic agents, followed by generalization and analysis of their mechanisms of action, as well as detailed discussion of different forms of diosmin. Summing up contains generalization of the Russian, European, and American guidelines on using phlebotrophic drugs for various forms and stages of chronic venous diseases.

Presented in the article are the results of the DECISION multicenter study dedicated io assessment of efficacy and feasibility of using the phlebotropbic drug detralex in the perioperative period in patients undergoing endovascular treatment of lower limb varicose discase. The study comprised a total of 230 patients presenting with chronic venous disease. (CVD) C2-4s according the CEAP classification, each of these had not less than three CVD- related symptoms. All patients were randomly assigned to the Study Group (126 people) and the Control Group (104 subjects). The Study Group patients 2 weeks prior to endovascular treatment and during 4 weeks thereafter took the phlebotrophic drug detralex at a standard daily dose of 1,000 mg. The Control Group patients received conventional compression thernpy using compression bandages or medicinal knitted fabric. The findings of the statistically processed results in the both groups demonstrated a significant decrease in the CVD severity score according to the VCSS scale and an increase in the quality of life parameters according to the disease-specilic questionnaire CIVIQ-14. While so doing, more pronounced dynamics was observed in patients taking detralex during the perioperative period. Besides, there was synergism between the results of the endovascular intervention and therapeutic effects from detralex. Based on the findings obtained in the present study, the authors made a conclusion on feasibility of using the drug detralex as an agent for nonspecific pharmacological protection in endovascular treatment of varicose disease.

Electromuscular stimulation (EMS) with VEINOPLUS® has recently emerged as a new technique to activate the calf muscle pump, improving the symptoms of venous disease. The aim of the study was to evaluate efficacy of EMS and its impact on evening edema, venous pain, venous outflow and patients quality of life.Thirty patients (32 legs) aged 19-50 (mean 45.2±1.3) classified CEAP C3 with chronic evening venous edema took part in the study (22 limbs: C3, S, Ep, Asp, Pr and 10 limbs: C3, S, Es, Aspd, Pr). All patients were treated with CE-registered VEINOPLUS® neuromuscular stimulator for 30 days. 3 sessions per day (each session lasted for 20 minutes) for the first 10 days, the next 10 days 2 sessions per day and one session per day for the last 10 days. The main evaluated criteria for venous edema was the circumference of the supramaleoal shin segment, measured twice with a tape measure; in the evening the day before and then 5 days after the treatment. All measurements were taken during the interval between 6 and 8 o'clock P.M. All the patients were asked to evaluate venous pain using the Visual Analog Scale, and to fill in a CIVIQ questionnaire (validated for Russian patients) for the Quality Of Life (QOL) measurement. Also venous refilling time (RT) was measured by digital PPG. That was also made twice - before the treatment and in 35 days after the treatment. No other treatments were used.The EMS treatment was well tolerated by patients. There were no drop outs and patients had no need to change their lifestyles. After the treatment, total or partial reduction of evening edema was shown in 93.8% of limbs, the circumference of the lower leg diminished by 20.3mm (P0.001), the number of painful legs reduced from 28 to 12 and the severity score of venous pain was cut from 8.3 ±1.1 to 3.8 points ±0.9 (P0.001), QOL improved significantly as the score dropped from 34.5 ±7.8 to 17.2 points ±4.6 (P0.001) and RT increased from 17.3 ±0.9 to 21.5 seconds ±1.1 (P0.001). Three months after VEINOPLUS® treatment, total remission of symptoms was observed in 50% of legs, despite there being no other treatments.VEINOPLUS® stimulation is an effective and well-tolerated therapeutic method for the treatment of chronic venous disease. The introduced scheme of EMS application was shown to be useful for treatment of chronic edema, for reducing pain and improving quality of life. It can be used as an additional mean in treatment and to prevent symptoms of CVI. This study also reveals that stimulation of calf muscles with VEINOPLUS® can improve venous outflow and symptoms of CVI. This finding should be investigated and confirmed in further studies.

The purpose of the study was to test the hypothesis on participation of WBCs in damaging the venous wall in patients presenting with primary forms of lower limb chronic venous diseases LLCVD .The study included a total of fifteen consecutively selected patients (13 women and 2 men) diagnosed as having grade C2-C-4 LLCVD according to the CEAP classification. Static loading (30 minutes in the sitting position) was followed by simultaneous sampling of blood from the varicose vein of the cms and ulnar vein. The total blood count including determination of both the absolute values and percentage of blood formed elements was performed using the automated haematological counter «Advia 7» («Bayer», USA). The obtained findings were statistically processed using the Microsoft Office Excel software by means of the pared two-sample τ-test for the average values.The number of leukocytes and their subpopulations in blood samples obtained from the crural varicose veins turned out to be significantly less as compared with that in blood sampled from the ulnar vein. Thus, blood sampled from the crural varicose veins demonstrated a decrease in the counts of WBC by 9.6% in fourteen (93.3%) patients, that of neutrophils by 4.9% in twelve (80%) patients, that of lymphocytes by 16,8% in fifteen (100%) patients, and that oi monocytes by 24% in twelve (80%) patients. The mentioned differences were statistically significant at a = 0.05. The eosinophilic counts in blood sampled from the upper and lower extremities appeared similar in 66.7% of the examined subjects. In 33.3% of cases the eosinophilic count in blood samples from crural varicose vein was by 16.7% lower than that for blood samples form the ulnar vein. No differences for the rest parameters of the clinical blood count were revealed.The absolute lymphocytic count in the blood samples taken after the 30-minute static loading from the crural varicose veins was significantly lower as compared with that in blood sampled form the cubital vein. The counts for RBCs and blood platelets, as well as other qualitative haematological indices (haemoglobin, haematocrit, average volume of the RBC, erythrocytic diameter, etc.) in blood sampled form crural and ulnar veins in the same patient were identical, thus strongly suggesting the lack of either haemodynamic or haemorheological phenomena capable of leading to redistribution of the blood formed elements in varicose veins. Hence a decrease in the counts of leukocytes and their subpopulations in blood sampled from crural varicose veins might be associated with the «leukocytic trap» phenomenon.

To analyze the prognostic value of detection of allelic variants of the promoter regions of cytokine genes in patients with rheumatoid arthritis (RA) with varying efficiency of basic anti-inflammatory therapy (BAIT).Eighty-nine patients with a valid diagnosis of RA, of them there were 79 females and 10 males (mean age 52.5 +/- 13.1 years), were examined. The patients received BAIT with methotrexate in a dose of 10.0-17.5 mg/week (77.5%) or with sulfasalazine in a dose of 2.0 g/day (22.5%) for 24 weeks. The efficiency of BAIT was evaluated using the European League Against Rheumatism (EULAR) criteria (DAS28) following 24 weeks. A high therapeutic effect was stated when DAS28 decreased by more than 1.2 scores. Changes in DAS28 by less than 0.6 scores were regarded as ineffective BAIT. Cytokine gene polymorphisms were studied by restriction analysis of amplification products. The following polymorphic sites in the interleukin genes: FNOA at positions C-863A, G-308A, G-238A, IL-1BT-31C, IL-4 C-590T, IL-6 G-174C, and IL-10 C-592A, were explored.The IL-6 G-174G genotype associated with the high production of this proinflammatory cytokine and the IL-IB C-31C genotype associated with the low production of interleukin-1beta (IL-1beta) were most frequently encountered in a group of patients with the high efficiency of BAIT (22 and 24.7%). At the same time the C allele associated with the low production of IL-6 and the IL1B T-31C genotype associated with the high production of this cytokine were most frequently detected at position of G-174C of the promoter regions in the IL-6 gene in patients unresponsive to BAIT (32 and 36%).The allelic variants of the promoter regions of the IL-6 G-174G, IL-1B C-31C, IL-4 C-590T, and IL-10 C-592A can be genetically prognostic factors of formation of the high efficiency of BAIT.

The article reports results of the first study of cytokine gene polymorphic sites and analysis of distribution of their complexes among healthy subjects and patients with rheumatoid arthritis (RA) representative of the Russian Europeoid population; their possible prognostic significance is evaluated. Comprehensive analysis of the frequency of allelic variants of cytokine genes IL1B C-31T, IL6 G-174C, TNFA A-238G, TNFA A-308G, TNFA A-863C, IL4 C-590T, IL10 A-592C and VEGF C-2578A was performed for 513 residents of the Novosibirsk region showing no obvious signs of any diseases and 125 RA patients. The results suggest association of RA with certain alleles of pro- and anti-inflammatory cytokine genes. Complex indices reflecting combinations of genotypes of two, three, four, five, six and seven loci of the explored cytokine genes found in individual patient demonstrate their high specificity for RA. It is supposed that these findings can be used in further clinical studies for the development of algorithm designed to detect risk groups among clinically healthy subjects.

To analyze the gene polymorphisms of matrix metalloproteinase-2 and -9 in patients with coronary heart disease (CHD).The influence of single nucleotide polymorphism in the promoter region of the gene of matrix metalloproteinase (MMP)-2 at position -1306 and that of MMP-9 at position -1562 on the development of complications was studied in 181patients with atherosclerosis by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of amplification products.A significant genotype increase with enhanced MMP-9 gene transcriptional activity was found in the patients aged 55 years inclusively who had been diagnosed as having myocardial infarction as compared with an older age group and, on the contrary, a rise in the MMP-2 genotype with a high promoter activity in the older age group.The findings suggest that the functional polymorphism in the promoter region of the MMP-2 and MMP-9 genes plays a certain role in the development of acute coronary events.

We studied polymorphism of three positions of promoter region of TNF alpha gene in patients with ischemic heart disease (IHD), development of unstable angina (UA) and acute myocardial infarction (MI). Analysis of frequencies of genotypes in position A308 showed that heterozygotness in patients with cardiovascular diseases significantly decreased. Lowering of risk of development of MI in carriers of heterozygous variant of the gene in position A308 was shown. In the group of patients with Q wave MI frequency of A308 AA genotype rose.

Based on population analysis of the DRB1, DQA1, DQB1 and TNFA allele frequency distribution patterns, regional features of immunogenetic structure of the population of West Siberia were investigated. Statistically significant linkage disequilibrium within the HLA class II region, as well as between the TNFA and DRB1, DQA1, and DQB1 was demonstrated. Population frequency distribution patterns of two- and multilocus haplotypes were examined.

The study was held to assess clinical effectiveness of coaggregated semisynthetic Diosmin (Phlebodia 600) for patients with II-III CEAP classes of chronic venous insufficiency (CVI), caused by lower limb variceal diseases. In 30 cases Phlebodia 600 demonstrated positive effect on CVI symptoms, edematous and convulsive syndromes. The authors conclude that Phlebodia 600 is highly effective and safe for patients with CVI.

This paper describes the results of the study into the prevalence of chronic venous diseases among industrial workers of Moscow. It has been established that chronic venous diseases are fairly prevalent among industrial workers. They affect the people of both sexes (67.5% of women and 50.4% of men), varying age and occupation. With age their incidence rises. The most significant risk factors of the onset of chronic venous diseases include hereditary predisposition, pregnancy and birth, overweight, and intake of hormonal contraceptives. The study has demonstrated that in most cases, such patients are not rendered medical assistance.

We have carried out a prevalence analysis of IL6 (-174 G/C) gene promoter polymorphism and traditional cardiovascular risk factors in male patients living in the West Siberia that survived myocardial infarction (MI) in their anamnesis. Analysis of genotype frequencies have shown decrease of *-174 GG genotype in the patients with MI. Frequency of the same genotype is decreased among smoking patients as compared to healthy non-smokers. On other hand, an increased body weight and arterial pressure indexes increase is found in IL6*-174 G patients, versus healthy population. Hence, the analyzed IL6 (-174 G/C) polymorphism may be considered as an additional predisposition factor for development of vascular damage.

We have performed analysis of associations between IL-1β gene promoter polymorphism (-511C/T and -31 T/C variants), and conventional cardiovascular risk factors in the patients living in the West Siberia who had previously a history of myocardial infarction (MI). We are shown a strong linkage disequilibrium between IL-1β -31C/T (rs1143627), and IL-1β-511T/C (rs16944). Significant differences in frequency distributions of some compound genotypes were observed between healthy and patients with a history of MI. E.g., frequency of IL-1β-31CC/-511CT genotype was detected in 5.5 % of healthy population, while being absent among MI patients. A frequency of IL-1β (-31/-511) CC/CT genotype showed significant differences between MI patients under 55 years, as compared to healthy persons. Hence, the analyzed IL-1β promoter polymorphisms may be considered as an additional constitutional factor predisposing for vascular alterations.

HLA-B27 gene frequencies and allelic polymorphism were studied in two Siberian ethnic groups: Russians from Novosibirsk (western Siberia) and Tuvinians from Kyzyl (southern Siberia). The HLA-B27 frequencies were determined by means of serologic typing of HLA antigens in 198 Tuvinians and 288 Russians. Molecular typing was performed via hybridization of oligonucleotide probes with amplified DNAs obtained from 30 HLA-B27-positive Russians and 11 HLA-B27-positive Tuvinians. The HLA-B27 gene frequencies in Tuvinians and Russians were 5.5 and 10.4%, respectively. Molecular variants of the HLA-B27 gene were studied in Tuvinians for the first time. The proportions of the HLA-B2705 and HLA-B2704 alleles were found to be 64 and 36%, respectively, in the population studied. The presence of the HLA-B2704 allele indicates a Mongoloid origin of Tuvinians. In the Russian population of Novosibirsk, the HLA-B2704 allele was not found, whereas the proportions of the HLA-B2705 and HLA-B2702 alleles were 76.2 and 23.8%, respectively, which is characteristic of Caucasoid populations.

To detect C. trachomatis DNA, the polymerase chain reaction (PCR) with the use of primers corresponding to variable sites of rRNA gene 16S was carried out. As the positive control of the reaction, the amplification fragment of gene 16S of rRNA, cloned in the plasmid vector and having the length of 530 nucleotide pairs (n.p.), was used. On its basis 2 kinds of the internal control of the reaction were obtained with the deletion of 110 n.p. (pMOS-Chl420) and the insertion of 930 n.p. (pMOS-Chl1460) within the cloned amplification fragment. The study revealed that the addition of the DNA of pMOS-Chl420 or pMOS-Chl1460 into the reaction mixture did not affect the sensitivity of PCR (0.02 pg of bacterial DNA in the sample) in the detection of C. trachomatis DNA isolated both from the culture of bacterial cells and from clinical samples. But in some cases of the amplification of the DNA of internal control pMOS-Chl420, but not pMOS-Chl1460, was observed in the presence of DNA obtained from clinical samples. It was supposedly linked with a higher sensitivity of Taq DNA-polymerase to the action of inhibitors in the synthesis of high-molecular DNA fragments. The observed high frequency of the inhibition (17%) of PCR makes it expedient to carry out this reaction with the use of the internal control.

To study association of TAP1/TAP2 gene polymorphism with urogenital infections combined with joint lesions.Of 139 patients examined 45 ones had inflammation caused by Chlamydia trachomatis (17 had joint disease), 42 had Mycoplasma hominis infection (joint lesions in 17 cases). Method of amplification was used on the basis of specific primers (ARMS).Patients infected with C. trachomatis significantly more frequently had allele TAP1-02011 and TAP2-0201 (RR = 18.5, p0.01 and RR = 4.61, p0.05, respectively). Joint lesion in patients with chlamydial infection was associated with allele TAP1-02011 (RR = 11.92, p0.05). In mycoplasmosis association with joint lesions there is a significant link of joint syndrome with heterogeneous combination threonine/alanine in gene TAP2 position 565 (RR = 4.22, p0.05).The findings can be used for predicting the joint syndrome development in patients with urogenital infection.

Objective. To reveal the genetic markers that may predict the efficiency of therapy for rheumatoid arthritis (RA). Subjects and methods. The study enrolled 104 patients (93 women and 11 men) (mean age 53.38+13.55 years). The duration of RA averaged 9.18+8.97 years. The patients were treated with basic anti-inflammatory drugs (BAIDs): 69.23% took methotrexate (MT), 10-17.5 mg/week; 30.77% received sulfasalazine, 2 g/day. Therapeutic effectiveness was evaluated using the European League Against Rheumatism (EULAR) criteria following 24 weeks. Clinical and laboratory parameters were similar in MT- and sulfasalazine-treated patients. The patients groups showing the varying efficacy of BAIDs were analyzed from the similar cutoffs of polymorphisms of the same cytokine genes. Results. The study indicated that some patients with certain combinations of allelic variants of promoter regions of cytokine genes had no benefits from BAID therapy. There was a preponderance of alleles in the genes associated with the high production of IL-1, the low generation of IL-6, and the low elaboration of cytokines with anti-inflammatory activity in the group of patients unresponsive to the basic therapy. The patients having many benefits from the performed treatment showed a predominance of alleles associated with the high production of IL-6 and the low generation of IL-1, with a tendency towards an increase in the frequency of alleles in the IL-1 and IL-10 genes that ensured a high elaboration of anti-inflammatory cytokines. Conclusion. The findings suggest that the effect of basic anti-rheumatic therapy with methotrexate or sulfasalazine largely depends on the cytokine genotype of a patient. Analysis of appropriate factors is likely to be used in rheumatological care.