Objective. The aim of the study was to evaluate the effectiveness of the hypolipidemic therapy with Rosuvastatin in patients, suffering from ischemic heart disease (IHD), II-III class stable angina, and to estimate the risk of IHD development among the inhabitants of Central Russia taking into account carriers of APOE rs7412 gene variant. Materials and methods. We participated 144 patients in pharmacogenetic study, aged 40-70 years, who were prescribed Rosuvastatin in initial dose 5 mg daily with gradual increase up to 10-20-40 mg to attain the target lipid levels in accordance with national recommendations. To estimate IHD risk we used 669 DNA samples, taken from IHD patients and relatively healthy individuals. We estimated the association between genotype and hypolipidemic effect of Rosuvastatin in IHD patients using linear regression, corrected by sex, age, body mass index (BMI), and Rosuvastatin dose. The influence of genotype on IHD risk was estimated using logistic regression. Results. The presence of APOE rs7412 C/T and T/T genotypes was associated with decreased IHD risk (OR=0.51 95% CI 0.30-0.87, P =0.013). IHD patients, being homozygotes in rs7412 had higher initial total cholesterol (TC) levels ( P =0.049) in interaction with age and BMI. T/T genotype was associated with increased response to Rosuvastatin in terms of TC in 1 month ( P =0.0022) and 12 months of therapy ( P =0.037), and in terms of low-density lipoprotein cholesterol (LDL-C) in 1 ( P =0.0018) and 6 months ( P =0.043). Conclusion. We have found the association between APOE rs7412 polymorphism and hypolipidemic effect of Rosuvastatin in IHD patients, and IHD risk in inhabitants of Central Russia.

Objective. The aim was to study the state of macrohemodynamics, microcirculatory bed and their relationship in patients with occlusive-stenotic lesions of the aorto-iliac-femoral arterial segment before and after revascularizing operations. Materials and methods. The results of the analysis of macrogemodynamic and microcirculatory bed state in 330 patients with obliterating atherosclerosis of lower limb arteries in various types of revascularizing interventions are presented: femoral-popliteal (group I, n=140), aorto-femoral (group II, n=97) bypass surgery, angioplasty with iliac artery stenting (group III, n=93). Results. There was a decrease in microcirculation in group I - 2.39 times, p<0.001, II - 3 times, p<0.001, III - 2.31 times, p<0.001, capillary blood flow reserve - in group I 1.63 times, p<0.001, II - 2.18 times, p<0.001, III - 1.77 times, p<0.001 and an increase in arterial-venular bypass regardless of the level of damage, as well as an oppression of endothelial mechanism and an increase in neurogenic mechanisms of regulation of microcirculation in all groups. Surgeries do not normalize microhemodynamics. Correlation interrelations of macrohemodynamics, changes in clinical status and microcirculation indices both in basal blood flow and under conditions of post-occlusive hyperemia were established. Changes in clinical status after surgery and bypass surgery had a negative-oriented correlation in all study groups (r=-0.2-0.3, p<0.05-0.01), and ankle-brachial index before and after surgery and RCC - the positive-oriented relationship (r=0.2-0.4, p<0.05-0.001). Conclusion. The state of microcirculation affects the change in clinical status after surgery, in this regard, it is necessary to take into account the parameters of microcirculation disorders and the mechanisms of regulation of tissue blood flow in surgical revascularization.

Spontaneous rupture of esophagus is a rare condition and is associated with a high mortality. Currently, there is no single approach in diagnosis and treatment of Boerhaave's syndrome. Objective. The aim is to analyze the world literature for seeking the most informative methods for diagnosis of Boerhaave’s syndrome and optimal methods of surgery. Materials and methods. 32 case reports with spontaneous rupture of esophagus in English and Russian articles within the last 10 years (according to “e-library” and “pubmed” databases) were analyzed. In this period we have had experienced the treatment of two patients with spontaneous rupture of esophagus. Results. Pneumohydrothorax in X-ray picture in patients with a short duration and acute attack of the disease with pleuropulmonal shock is an important complex of symptoms of spontaneous rupture of esophagus. In this case, the diagnosis must be confirmed in CT with oral contrast. The study presents the modern possibilities for non-operative management, traditional open surgery and minimally invasive methods. Advantages, disadvantages and indications of different operative approaches for operative treatment were also discussed in the study. Conclusion. It is crucial to diagnose Boerhaave’s syndrome early. CT with oral contrast is the most informative diagnostic method. Nowadays the surgical treatment of Boerhaave’s syndrome includes the early primary surgical repair of esophagus rupture with fundoplication and gastrostomy. Endoscopic techniques for the treatment of Boerhaave’s syndrome are the promising areas in management strategies.

Objective. The aim of the research was a comparative experimental study of the effect of vitamin C and potassium orotate preparations on the formation of a connective tissue capsule around a mesh implant. Materials and methods. The experiment was performed on 150 white mice. The first group of animals received a standard diet after surgery. The diet of second and third animal groups was supplemented with vitamin C and potassium orotate, respectively. Histological sections obtained from the animals were placed on glass slides and stained with hematoxylin and eosin. The morphometry was performed afterwards in the capsule around the implant threads. Results. Being compared the cellular composition of the connective tissue regenerating around the hernia implant in the studied groups of animals showed that in both experimental groups, on the 7th day after implantation, fibroblastic cells predominated over non-resident cells. In the early postoperative period (7-30 days), the introduction of vitamin C into the diet contributed to a more rapid increase in the fibroblast population. A similar effect of potassium orotate is realized later, already at the stage of modeling and remodeling the capsule around the implant threads, on 60 and 90 days after the experimental surgical intervention. Conclusion. In the experiment, the effect of drugs in the zone of implantation of a hernioimplant was determined, which was manifested itself by a significantly more pronounced proliferation of fibroblast cells.

Objective. The purpose of the study was to assess the integral indicators of the functional state (FS) of the body, the parameters of central and intracardiac hemodynamics in patients with acute myocardial infarction in the process of hospital and post-hospital rehabilitation, and to study the relationships between the received data. Materials and methods. An open, randomized study included 111 people (76 men and 35 women) aged 40 to 65 years (57.2±0.6). The study of the body FS was carried out using the Dynamic-Omega-M hardware-software complex on the 3rd, 8th, and 14th days and by the 6th and 12th months. Doppler echocardiography was performed on the 3rd and 14th days of treatment, 6 and 12 months after discharge. Results. The obtained results allowed to establish a decrease in the values of integral indices of FS at the stages of hospital and post-hospital rehabilitation, the presence of myocardial hypertrophy, disorders of diastolic function of the heart and local contractility. Against the background of rehabilitation, positive dynamics of FS parameters and indices characterizing intracardiac hemodynamics was established. Significant correlations were established between the values of FS parameters and echocardiographic parameters and their dynamics during the study. Conclusion. The research justified the expediency of using the integrated parameters of FS for a comprehensive assessment of the status of patients with acute myocardial infarction and as prognostic criteria for the effectiveness of rehabilitation.

Objective: to analyze the influence of Indolicidin analogues N7 and N8 on the prooxidant-antioxidant balance in animals with acute periodontitis. Materials and methods. Acute periodontitis was simulated according to the method supposed by Volozhin A.I. and Vinogradova S.I. (1990). Indolicidins N 7 and N 8 were injected intraperitoneally at the dose 500 mcg/kg daily for 7 days after periodontitis modeling had been over. The animals were withdrawn from the experiment on the 7^th, 14^th and 21^st days after periodontitis modeling. The concentration of malonic aldehyde and acylhydroperoxides, as well as the catalase and superoxide dismutase activity in plasma were determined by traditional methods. Results. The modeling of acute periodontitis to Wistar rats is accompanied with the activation of lipid peroxidation, which manifests itself by the accumulation of malonic dialdehyde and acylhydroperoxides. The decrease in the activity of antioxidant enzymes - superoxide dismutase and catalase - was shown in the blood of experimental animals throughout the whole experiment. The administration of Indolicidin analogues stimulated the lipid peroxidation only in the beginning (7 days) of periodontitis. Indolicidins N 7 and N8 activated the action of superoxide dismutase and catalase. Conclusion. The stimulatory influence of investigated Indolicidins on the antioxidant enzyme activity in plasma was established in rats with periodontitis. No significant differences of the activity of the investigated Indolicidin analogues on the prooxidant-antioxidant balance in acute parodontitis were established compared to Indolicidin N 7 and Indolicidin N 8 effects.

Objective. The study of morphometric parameters of thymus of immature white rats exposed to inhalation of formaldehyde. Materials and methods. It was studied the formaldehyde inhalation effects at concentration of 2.766 mg/m³ on the structure of the thymus of white male rats with an initial body weight of 40-50 g. Formaldehyde exposures were carried out for 1 h/day daily for 10, 20, 30, 60 and 90 days. We studied separately the morphogenesis of thymus of rats that after 60 days of exposure to formaldehyde for 30 days were under standard vivarium conditions. Results. It has been established that the inhalation effect of formaldehyde leads to a decrease in the organometric parameters of the thymus gland in comparison with the control. In animals that were exposed to formaldehyde for 10 and 20 days, the average of the cortex area was lower than the control by 8.06% (p <0.05) and 11.48% (p <0.01), respectively. After 30 and 60 days of exposure to formaldehyde, this difference with control data was 13.60% (p <0.02) and 13.98% (p <0.001), respectively. A decrease in the area occupied by the cortex resulted in an increase in the area of the medulla. Conclusion. Inhalation of formaldehyde causes a decrease in the area of the cortex of the thymus, an increase in the number of apoptotic bodies, which is manifested in the “starry sky” pattern. Reducing the severity of changes in the thymus of animals that were removed from the experiment 30 days after exposure to formaldehyde indicates that the changes in the thymus are reversible.

Objective. The aim of the work was to compare the content of α-defensins (HNP 1-3), pro- and anti-inflammatory cytokines in plasma and cerebrospinal fluid (CSF) and their role in the development of a systemic inflammatory response in the post-traumatic period in patients with severe traumatic brain injury (TBI). Materials and methods. Under the supervision there were 20 patients with severe traumatic brain injury aged 18 to 78 years (mean age 38.3 ± 11.5 years). In the first 24 hours and 7 days after the injury, the patients underwent lumbar puncture with cerebrospinal fluid and peripheral blood sampling from the central vein. The quantitative contents of α-defensins in plasma and cerebrospinal fluid, cytokines in serum and CSF were determined by ELISA with a kit for determining human α-defensins and cytokines. Results. The results of the studies showed that severe head injury is accompanied by increased production of antimicrobial peptides (α-defensins - HNP 1-3), pro- and anti-inflammatory cytokines, whose products have a number of features in the dynamics of the inflammatory process in the brain. On the first day after TBI in plasma and CSF, there is a significant increase in the concentration of HNP 1-3. The level in the blood plasma significantly exceeds their content in CSF by 9.7 times. In the dynamics on the seventh day after injury there was a decrease in the content of HNP 1-3 in the blood plasma and CSF, more pronounced in the cerebrospinal fluid. Between the level of HNP 1-3 and IL-1β in plasma, HNP 1-3 and protein content, cytosis in the cerebrospinal fluid on the 1st day, and also between HNP 1-3 and the anti-inflammatory cytokine IL-10, both in blood plasma and in the cerebrospinal fluid on the 7th day a direct correlation dependence was revealed, reflecting the dynamics of the inflammatory process in the brain. Conclusion: The level of HNP 1-3 in plasma and CSF can serve as a prognostic criterion for the severity, course, and outcome of TBI.

Objective. The aim of the study was the investigation of the effects of a new Thymogen analogue modified with D-alanine from the C-terminus of the peptide and having the formula H₂N-L-Glu-L-Trp-D-Ala-COOH under conditions of skin wounds. Materials and methods. The peptide was administered once a day, parenterally (intraperitoneally) in an single dose of 1.2 μg / kg which is tenfold equimolar to Thymogen (1 μg / kg). The values of phagocytic and oxygen-dependent activities of blood neutrophils and levels of superoxide dismutase and malonic dialdehyde were detected. Also the histological investigation of skin wounds was carried out. Results. It has been established that an analogue of Thymogen does not impair the indicators of the absorption stage of blood neutrophils phagocytosis, the activity of superoxide dismutase and the number of lymphocytes in the skin in comparison with Thymogen and those are comparable to it. The Thymogen analogue, modified with D-alanine, has a more pronounced stimulation of oxygen-dependent neutrophil activity (NBT-test) and an increase in the number of fibroblasts in the skin, indicating a more pronounced immunotropic and reparative effects of this analogue. Conclusion. Thus, due to its introduction of the amino acid D-Ala (D-alanine) from the C-terminus into the Thymogen molecule , its stimulating effect on the oxygen-dependent function of neutrophils and wound-healing activity increases.

Objective. The main aim of the research is to discover regularities and specific features of systemic structural organization of the human humeral and femoral bones according to the functions of extremities and their belonging to the side of the body. Materials and methods. By the classic osteometry with some authors’ modifications 35 anatomical structures on 308 of humerus and femur have been measured. All the bones had no pathological symptoms, with complete synostosis of epiphyses. To access the somatotype effect on the dimensions of human bone structures all the values obtained were normalized. As a unit for measurement normalization the transverse diameter of the shaft in the middle of the bone length was chosen. The values obtained were processed by the methods of factor analysis Maximum Maximum Likelihood Factor with rotation Equamax normalized, and four groups were generated according to the limb girdle and the side of the body. Results. The asymmetry of the structural organization of bones and vertical differentiation of their epiphyses are determined by the presence of unstable parameters. The asymmetry of the structural organization of the femur is more pronounced. Unstable parameters were found in the proximal epiphysis of the right femur - 4, in the distal epiphysis - 1; in the proximal epiphysis of the left femur - 1, in the distal epiphysis - 3. Unstable parameters of the proximal epiphysis of the right humerus made up 3, distal epiphysis - 2; in the structural organization of the epiphysis of the left humerus 6 unstable parameters were identified. Conclusion. The basis of the structural organization of the bone proximal segments of the human limbs regardless of belonging to the extremity or the side of the body is formed by anatomical objects which are responsible for conveying the power loads along the axis of the limb. Functional differentiation of human limbs is shown in the structural organization of both bones by asymmetric vertical differentiation of their epiphysis.

Objective. The aim of the research is to study the characteristics of the morphometric parameters of the abdominal part of the aorta and its unpaired branches in adult women with different body types. Materials and methods. 152 computer tomograms of the abdominal part of the aorta and its unpaired branches were analyzed in adult women with different body types. According to the classification by V.N. Shevkunenko, all women studied were divided into groups with dolichomorphic, mesomorphic and brachymorphic body types. According to Pignet index, asthenic, normosthenic, and hypersthenic body types in women are distinguished. Results. It is established that body types according to V.N. Shevkunenko have fewer statistically significant parameters in the abdominal part of the aorta and its unpaired branches, but there are statistically significant differences between constitutional types identified using the Pignet index in the vast majority of the morphometric parameters studied. Conclusion. Due to the fact that the classification by V.N. Shevkunenko reflects to a greater degree the linear parameters of the body, and the Pignet index is also voluminous (chest girth, body weight), the latter provides a greater number of differences in the compared parameters of the abdominal aorta and its unpaired branches, including those depending on the type and degree of development of the abdominal fat fiber.

Objective. The aim of the study was to establish the effectiveness of the culture fluid of allogeneic hepatocytes (CFAH) and proteins isolated from them in correcting metabolic and immune disorders in acute ischemic liver damage. Material and methods. The study has been conducted on 105 healthy mature Wistar rats. Acute ischemic liver damage (AILD) was induced by cross clamping of the hepatoduodenal ligament for 20 minutes. Isolated allogeneic hepatocytes from newborn animals were used to prepare a culture fluid from which proteins were isolated. The culture fluid of allogeneic hepatocytes (CFAH) and their proteins obtained were administered with the start of modeling acute liver ischemia five times (with a 24-hour interval) intraperitoneally to rats with AILD at the rate of 5 mg/kg. Results. Acute liver ischemia causes the development of biochemical syndromes of the liver damage (cytolysis, intra- and extrahepatic cholestasis, toxic damage, insufficiency of synthetic processes) activates the processes of lipid peroxidation, disturbs intra-erythrocyte metabolism, and causes the development of oxidative stress and suppression of forming the adaptive and innate immunity. Introduction of CFAH, undivided CFAH proteins or CFAH proteins with molecular mass (MM) less than 130 kDa to animals with AILD normalizes or corrects the studied biochemical and immunological parameters. CFAH proteins with MM more than 130 kDa do not have such effects. Conclusion. During the analysis of CFAH or CFAH proteins corrective activity on the dynamics of biochemical markers of AILD, formation of humoral and cellular immunity, impaired functional and metabolic activity of peripheral blood neutrophils, intraerythrocyte metabolism, activation of free radical oxidation, the following sequence has been established (according to increasing the effectiveness): the lack of this activity in CFAH proteins with MM more than 130 kDa; the presence of normalizing and correcting activity of: CFAH - CFAH undivided proteins - CFAH proteins less than 130 kDa.

The literature review includes the data of modern experiments on the mechanisms of development of various gestational complications in rats. It is generally accepted that rats, similar to pregnant women, have the hemochorial type of placentation and 3-week gestation which is identical to the three trimesters of pregnancy. This allows studying the mechanisms of placental disorders more profoundly in experiments in the dynamics of ultra-short pregnancy, and justifying the methods of their prevention pathogenically. The necessity to evaluate morphological and functional changes of rat placenta is emphasized. It is noted that giant Kashchenko - Gofbauer cells or fetal placental macrophages are visualized in healthy pregnancy in rats, by analogy to pregnant women, and the presence of these cells indicates the proper function of the placenta. In experiments on rats, risk factors for placental disorders were studied in details; ways of prevention and correction were developed. Currently, the special attention is paid to pilot studies of pathogenetic mechanisms of developing gestational disorders in pregnancy complicated by hypertensive disorders. Spontaneously hypertensive rats (SHR) are used in experiments related to the study of the mechanisms of hypertension, as well as the aspects of developing metabolic syndrome, insulin resistance, abdominal obesity, hypertriglyceridemia. This line of rats has the similar symptoms of primary hypertension in humans, while experimental modeling clarifies not only the pathogenesis of hypertension, but also the formation of the pathological state of the target organs. The possibility for a more detailed study of the mechanism of hypertensive disorders in the dynamics of pregnancy using rats of inbred lines, including spontaneously hypertensive and control - normotensive ones.

The flora of European countries has 3 species of the Lunaria L. genus, all of which belong to the Brassicaceae family. 2 species grow on the territory of Russia, including the most common one - Lunaria annua L. This species is widely cultivated as an ornamental plant in Russia and abroad. In scientific medicine, the Lunaria annua L. is not currently used. The pharmacopeial article is not approved for this plant. However, for its introduction into official medicine, it is necessary to develop indicators of authenticity and to investigate the morphological and anatomical signs of the above-ground structure of vegetative organs of the Lunaria annua L. Objective - to study the anatomical features of the structure of the above-ground vegetative organs of the Lunaria annua L. of Central Chernozem flora and to identify their microdiagnostic signs. Materials and methods. Microscopic analysis was performed on freshly harvested, dried and fixed plant material. The samples of raw materials have been used to prepare temporary micropreparations according to the requirements of Pharmacopoeia articles of the State Pharmacopoeia of the Russian Federation (XIII-th edition). Results. The studies revealed microdiagnostic signs of leaves and stems, which are indicators of the authenticity of the Lunaria annua L. Conclusion. These microscopic studies can be used in the preparation of Pharmacopoeia article (section «Microscopic signs»). The anatomical characteristics of above-ground vegetative organs of Lunaria annua L. were studied for the first time.