Experimental Study of the Effects of Nanodispersed Ceria on Wound Repair.

We studied the effects of nanodispersed ceria on wound healing in vitro and in vivo. It was found that cerium dioxide stimulated wound healing, which manifested in shrinkage of burn wound area (by 1.5 times) and intensification (by 2.4 times) marginal epithelialization.

[The application of lipoprint-system for analysis of sub-fractional spectrum of lipoproteins of blood serum.]

The lipoproteins of low and high density are presented by heterogeneous specter of particles differing by size, density, charge, composition and functional characteristics. The prevalence of small dense particles of lipoproteins of low and high density in blood plasma is associated with higher risk of development of coronary heart disease. The identification of subfractional spectrum of lipoproteins in clinical purposes is complicated because of requirement of expensive equipment and reagents and extended time of implementation. The lipoprint-system (Quantimetrix Lipoprint LDL/HDL System, USA) based on the vertical electrophoresis using 3% polyacrilamid gel, permits shortening time of sub-fractioning of lipoproteins up to three hours. In the spectrum of apoB-containing lipoproteins of very low density, intermediate density, C, B, A, lipoproteins of low density 1 and 2, small dense (lipoproteins of low density 3-7) are singled out. In the spectrum of lipoproteins of high density up to 10 sub-fractions associated in three groups and represented by large (lipoproteins of high density 1-3), intermediate (lipoproteins of high density 4-7) and small (lipoproteins of high density 8-10) particles are singled out. The article describes technique of identification of spectrum of particles of lipoproteins of low and high density in human blood serum. The conditions of implementation of experiments are presented. The advantages and limitations of technique are indicated. The number of examples of application of indices of sub-fractional spectrum of lipoproteins as additional markers of evaluation of aterogenity of lipid profile are presented. The conclusion is made concerning possibility of application of technique in clinical laboratory diagnostic.

[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.

[Correction of cronic liver failure by transplantation of liver cells suspension and cell-engineering designs (experimental investigation)].

On an experimental model of chronic fibrotic liver damage (male rats Wistar (n-60), damage of CCl4, the duration of the experiment 90 days) it was studied the effectiveness of cell therapy for the correction of chronic liver failure. These rats were divided into 3 experimental groups: in the Ist-group (control, n=10) isotonic saline (650 mkl.) was injected; in the IInd-group (n=20) suspension of liver cells was applicated in a dose 8 - l0 x 10(6) cells; in the IIIrd-group (n=30) suspension of liver cells and bone marrow cells (mesenchymal stromal cells) in ratio 5:1 were used as cell associates on microparticles intjectable heterogeneous biopolymer hydrogel "SpheroGEL" (cell-engineering design) in common dose 8 - l0 x 10(6) It was ascertained that in the 2nd and in the 3rd groups the accelerated normalization of disturbed liver functional indices (ALT, AST, ALP) took place - to 30 days, but in the control group only to 90 days. The reliable differences in rats ofnormalization offunctional indices were absent between the IInd and the IIIrd groups. But in 90 days by using special histological dyeing it was found out that defibrotic processes in liver tissue were more expressed in the IIIrd group in comparison with the IIIrd group. Received results were consequence of prolonged vital activity of cells (liver cells and mesenchymal stromal bone marrow cells) into cell-engineering designs, which were transplanted in the IIIrd group. The obtained effect can be explained by that the developed cell-engineering designs provide adequate conditions for prolonged vital activity of the transplanted cells.

[The antiaggregant action of 2-morpholino-5-(thienyl-2)-6-H-1,3,4-thiadiazine in in vitro and ex vivo experiments].

The influence of 2-morpholino-5-(thienyl-2)-6-H-1,3,4-thiadiazine (H-29) on the platelet aggregation has been studied in experiments on donor plasma in vitro. It is established that H-29 causes a decrease in the platelet interaction induced by ADP and arachidonic acid. The influence of H-29 on platelet aggregation was also studied in ex vivo experiments with intravenous and oral administration, and some parameters of plasmatic hemostasis were evaluated.

[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.

[Influence of new 1,3,4-thiadiazines on platelet aggregation in vitro and ex vivo].

The influence of new original 1,3,4-thiadiazines on the human platelet aggregation in vitro was studied. All substances inhibited the platelet aggregation induced by both ADP and arachidonic acid. 1,3,4-Thiadiazines L-19, H-30 and L-37 were the most effective inhibitors. Effect of the intravenous injection of L-19 in various doses on platelet aggregation and some parameters of plasmatic hemostasis were studied ex vivo.

[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.

[Clinico-experimental basis of application of biodegradable implants in surgical treatment of peripheral nerve lesions].

Aim of this study was to provide clinico-experimental basis of application of biodegradable implants in surgical treatment of peripheral nerve lesions. Experimental investigations were performed on non-pedigree female rats with body weight of 200-250 grams. 10 animals were used, 20 sciatic nerves were operated. Morphological examinations were done on 21st and 101st days after surgery. Clinical part of the study was performed after finishing of experimental block and included 20 patients with peripheral nerve lesions. Information about patients included: sex, age, type and localization of lesion, preoperative neurological status, data of electrophysiological and ultrasonographic studies and MRI. Follow-up period varied between 3 and 12 months. The series included 13 male and 7 female patients, age was 20-63 years. Injection of "Sphero(r)Gel" in the area of nerve suture enables more effective regeneration of axons and their growth through the injury site. Application of "ElastoPOB(r)" membrane favors demarcation of peripheral nerve from surrounding scar tissues in the wound. Acquired data demonstrate decreased influence of scarring process on the nerve trunk in the postoperative period according to neurological examination, electroneuromyography, ultrasonography and MRI.

[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.

[Primary prevention of cardiovascular diseases: long term results of five year long preventive intervention in 12-year old boys (ten year prospective study)].

In a longitudinal cohort (prevention group, n=213, comparison group, n=163) of 10-year prospective follow-up we addressed efficacy of 5-year-long multifactor preventive intervention, conducted in a sample of population of 12 year old boys. Preventive intervention was carried out both at populational level and among persons with risk factors of development of cardiovascular diseases with the use of group, individual, and partly family approaches, and was directed at rationalization of nutrition, elevation of physical activity and prevention of harmful habits. During first 3 years of prevention we succeeded to achieve stable statistically significant lowering of mean levels of total cholesterol, low density lipoprotein cholesterol, triglycerides, and atherogeneity index, as well as to affect fatty component of body mass (skinfold thickness). Long term effect of 5-year long preventive intervention manifested as significantly lower level of systolic blood pressure, lower prevalence of low levels of high density lipoprotein cholesterol, smaller increment of low density lipoprotein cholesterol and index of atherogeneity in the prevention group. These results evidence that prevention of main factors of risk of development of cardiovascular diseases (obesity, arterial hypertension, disorders of lipid composition of the blood, and low physical activity) in child and adolescent age in the period of active growth and development is feasible, effective, safe and is able to lead to decrease of levels of these factors in adults, but should last uninterruptedly until formation of stable habits of healthy life style.

Parameters of high-density lipoproteins in patients with arterial hypertension in combination with other components of metabolic syndrome.

Parameters of HDL (concentrations of cholesterol, apoprotein A1, and phospholipids and phospholipid composition) determining their functional properties were studied in patients with arterial hypertension in combination with other components of metabolic syndrome (abdominal obesity, hyperlipidemia, and impaired glucose tolerance). Patients with isolated arterial hypertension did not differ from the control group by the concentration of apoprotein A1 and HDL cholesterol, but had lower content of HDL phospholipids and changed phospholipid composition: lower ratio of phosphatidylcholine and higher relative contents of lysophosphatidylcholine, sphingomyelin, and phosphatidylethanolamine. Parameters of HDL in patients with arterial hypertension associated with other components of metabolic syndrome did not differ from those in patients with isolated arterial hypertension. The observed changes in HDL in patients with arterial hypertension alone or in combination with other components of metabolic syndrome can impair functional capacity of HDL in reverse cholesterol transport, which increases the risk of atherosclerosis.

[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.

Association of serum apolipoprotein A-II concentration with combined hyperlipidemia and impaired glucose tolerance.

We studied the relationship of serum apolipoprotein A-II concentration with biochemical parameters of lipid and carbohydrate metabolism, type of hyperlipidemia, and insulin sensitivity in male patients with hyperlipidemia. High concentration of apolipoprotein A-II was associated with increased indices of atherogenic lipoproteins and high-density lipoprotein-mediated reverse cholesterol transport, combined hyperlipidemia, and decreased insulin sensitivity calculated with consideration for glucose and insulin levels in glucose tolerance test and body weight.

[Physical activity and atherosclerosis: effect of dynamic activity of various intensity on parameters of lipid-transport system and carbohydrate metabolism in patients with coronary heart disease and type 2 diabetes].

Effect of single bout of dynamic physical exercise on parameters of lipid-transport system and carbohydrate metabolism and hormones (insulin, cortisol) in the blood was studied in patients with coronary heart disease with class I-III angina and type 2 diabetes. Intensity of exercise was limited by severity of stable effort angina and was > 95, 80 and 70% of predicted maximum in patients with class I (n=10), II (n=12) and III (n=14) angina, respectively. High intensity exercise provoked development of atherogenic dyslipidemia: elevation of levels of total cholesterol, low density lipoprotein cholesterol, triglycerides, apolipoprotein B and apolipoprotein B/A1 ratio, and lowering of levels of high density lipoprotein cholesterol and apolipoprotein A1. Patients with diabetes responded to high intensity exercise by elevation of blood glucose and insulin levels and lowering of sensitivity of tissues of the periphery to insulin (glucose/insulin ratio). On the contrary exercise of moderate intensity did not affect negatively metabolism of blood lipids and carbohydrates. Six months course of physical training in patients with diabetes (n=10) corrected exogenous atherogenic dyslipidemia and derangements of carbohydrate metabolism, which developed after acute dynamic effort of high intensity.

[Multidirectional effects of exercise of various type and intensity on lipid transport system of blood in healthy subjects and patients with coronary heart disease].

AIM: To evaluate effects of dynamic exercise (DE) and static leg exercise (SE) varying by intensity on blood serum spectrum of lipoproteins and apolipoproteins in healthy persons and patients with coronary heart disease (CHD). MATERIAL AND METHODS: Healthy 12 men and 12 CHD patients of functional class I performed bicycle DE of maximal (for age) intensity (100%), submaximal (80, 70 and 60%), SE of maximal and submaximal intensity. Blood samples were taken before the exercise, after it and 3 hours after the exercise. RESULTS: DE of high intensity (80% and higher) and SE of maximal and moderate intensity (100 and 60%, respectively) produced atherogenic changes in the blood of both healthy subjects and CHD patients: a rise in total cholesterol, LDLP cholesterol, triglycerides, apolipoprotein (apo) B and apo B/ apo AI. Moderate (60%) DE gave rise to antiatherogenic changes in the blood: a fall in lipoproteins containing apoB and a rise in concentration of apo AI both in healthy and CHD subjects. CONCLUSION: To prevent atherosclerosis by correction of atherogenic lipid disorders, CHD patients and healthy persons should do DE of moderate intensity in addition to other prophylactic measures.

[Small dense low density lipoprotein particles: mechanisms of formation, atherogenic properties, possibilities of modification of their content in blood plasma].

Atherogenic low density lipoproteins (LDL) consist of subfractions of particles with different dimensions, density, proportion of various lipid components, affinity to apo B/E receptors, susceptibility to oxidation, and other properties. As a rule spectrum of LDL particles has one predominant central peak and several (up to 6) additional peaks containing particles which are smaller or larger than particles of the main peak. There are also smaller and bigger particles within the main peak itself. In normolipidemia average diameter of particles of the predominant main peak exceeds 25.5 hm (profile A), in combined hyperlipidemia main peak consists of smaller (<25.5 hm) particles (profile B). It has been shown in many studies that because of several characteristics (lower affinity to apo B/E receptors, prolonged presence in blood stream, susceptibility to oxidation and uncontrolled entrapment by macrophages) small dense LDL particles play significant role in atherogenesis. The authors of this review have demonstrated that in subjects with abdominal obesity and concomitant metabolic risk factors in postprandial period after standard meal LDL spectrum shifts towards small particles and this shift persists during 6 hours after meal. An apparently atherogenic subfraction of large cholesterol ester loaded particles is also described in this paper.

[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.