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To study the relationship between vitamin D deficiency, VDR gene polymorphism rs10735810 (A G), and a missed abortion in the first trimester of gestation; to determine the predictors of its risk.178 women aged between 18 and 41 were surveyed. The main group consisted of patients with miscarriage (WE found that patients with miscarriage in the first trimester of gestation (The data obtained show that vitamin D insufficiency plays a pathogenetically significant role in early reproductive losses associated with miscarriages, both first and recurrent.

Relevance. Currently, the number of percutaneous coronary interventions continues to increase, which leads to an increase in the absolute number of restenosis cases, which is the main complication of the long-term postoperative period. The search for risk factors responsible for restenosis and artery re-narrowing mechanisms in order to prevent this complication is an important goal in interventional cardiology. Risk factors for the restenosis development include clinical, angiographic and genetic factors. An active search for biomolecular markers associated with the coronary artery restenosis is currently underway. Objective: to study the role of polymorphic variants C-174G of the IL6 gene and C-819T of the IL10 gene as a risk factor for the development of restenosis in patients after stent implantation. Materials and Methods : The study included 113 patients with stable coronary artery disease, who had previously undergone balloon angioplasty and implantation of drug-eluting stents, and 62 patients with intact arteries that were included to the control group. Statistical data processing was carried out using the R-language program and the SPSS Statistics 20 software package. Results: GG genotype for IL6 gene was associated with the development of coronary artery disease. In the subgroup of patients over 65 years of age and instent restenosis, the GG genotype was significantly less frequent. The homozygous CC genotype for IL10 gene was associated with rapid angiographic in-stent restenosis progression.

Loss of cardiomyocytes due to apoptotic or necrotic death is an important component of the pathogenesis of heart failure. Initiation of apoptosis by the mitochondrial pathway depends on the balance between proapoptotic and antiapoptotic factors, in particular, Bax and Bcl-2. Cardiomyocyte apoptosis in essential hypertension is studied in sufficient details. At the same time, apoptotic processes in the myocardium in diabetes mellitus alone and in combination with essential hypertension remain poorly understood. Here we studied the expression of Bax and Bcl-2 in the left ventricular cardiomyocytes of 38-week-old male Wistar-Kyoto rats and 38- and 57-week-old SHR rats with essential hypertension, diabetes mellitus, and a combination of these pathologies. Insulin-dependent diabetes mellitus was modelled by a single parenteral administration of streptozotocin in a dose 65 mg/kg. Expression of Bax and Bcl-2 was assessed by the immunohistochemical method. In essential hypertension and diabetes mellitus, the apoptotic processes in the ventricular myocardium were enhanced, as is seen from the increase in the content of the proapoptotic factor Bax and a decrease in the expression of the antiapoptotic factor Bcl-2. However, in case of combined pathology, Bax content increased less markedly, while the expression of antiapoptotic Bcl-2 was significantly increased.

A clinical-genetic study using ABPM (24-hour BP monitoring) and Holter’s ECG methods in 49 pa-tients with essential arterial hypertension (group 1: 17 patients without sufficient nocturnal BP de-crease СI≤10%, and group 2: 32 patients with suf-ficient nocturnal BP decrease СI≥10%,) was per-formed for comparative analysis of the genotype frequencies of ACE, AGT, AGTR1, ITGB3, and PPARG. The study was conducted in order to clari-fy the pathogenetic mechanisms of the implementa-tion of different dynamics of nocturnal blood pres-sure in patients with hypertension without metabol-ic syndrome. It was found that in group 1, protec-tive genotype II of the ACE gene was more com-mon (p ≤ 0.025) than in the population data. A sig-nificant increase (p ≤ 0.025) in the frequency of the CC genotype of the AGTR1 gene responsible for the formation of insulin resistance compared to the population data was combined with a significant increase in the frequency of autonomic dysfunction in patients of group 1 - 83.4% vs. 64.5% group 2 respectively. The results obtained indicate the pos-sible pathogenetic links between genetically deter-mined insulin resistance and autonomic nervous system dysfunction and allows us to determine therapeutic approaches for correcting the noctur-nal blood pressure profile.

About 30% of male infertility is associated with genetic abnormalities. Genetic polymorphisms increase the level of individual susceptibility to adverse environmental factors and affect human reproductive function. Aim To study associations of glutathione S-transferase GSTP1(Ile/Val) gene polymorphisms (A313G; rs1695) with the risk of pathospermia in men of the Moscow region. Materials and methods We examined 138 men in the Moscow region (n=70 - proven pathospermia, n=68 - fertile men). We obtained genomic DNA from blood leukocytes and studied the gene polymorphisms of glutathione-S-transferase GSTP1 (Ile/Val) (A313G; rs1695) in real time. Results In the analysis of the distribution frequencies of polymorphisms GSTP1 (Ile/Val) (A>G rs1695), we revealed the predominance of the AA genotype in fertile men and the predominance of the GG genotype (homozygous minor allele) in men with pathospermia. However, we found no significant difference in these parameters between the compared groups of patients (p=0.344). For GSTP1 (Ile/Val) polymorphism (A313G, rs1695), significant differences in the distribution of genotype frequencies in the subgroup of men with teratospermia (2=7.00; p=0.03) were revealed. The frequency of allele G in the subgroup of men with teratospermia is statistically significantly different from the frequencies of alleles in the control group: 52% versus 30% (2=10,004; p=0.0015). In subgroups of men with azoospermia and asthenospermia, we did not find significant differences in the distribution of genotypes of GSTP1 polymorphism (rs1695) (p>0.05). Discussion Glutathione-S-transferase (GSTP1) is a multifunctional protein that protects sperm cells from the damaging effects of reactive oxygen species and xenobiotics. The Association of GSTP1 polymorphism (Ile/Val) (A313G, rs1695) with teratospermia explains the main stages of the pathogenesis of male infertility in this category of patients. Conclusion Gene polymorphism GSTP1 (A313G, rs1695) can be considered a genetic marker of susceptibility to pathospermia in men.

Restenosis remains the main complication after percutaneous coronary interventions in patients with coronary heart disease. The causes of its development include, in particular, genetic factors. We studied polymorphic loci of genes encoding endothelin-1 (EDN1 rs5370), endothelin-1 receptor (EDNRA rs5333), endothelin-converting enzyme (ECE1 rs1076669), and endothelial NO synthase (eNOS rs1549758, eNOS rs1799983, and eNOS rs2070244) in the context of in-stent restenosis development. It was found that the analyzed polymorphisms of the endothelin system genes were more significant for patients aged ≥ 65 years, while the polymorphic loci of the endothelial NO synthase gene (eNOS rs1799983 and eNOS rs1549758) were predominantly associated with time of in-stent restenosis. The obtained results can be useful for comprehensive assessment of the restenosis risk factors and the choice of optimal treatment for patients with coronary heart disease before elective surgical intervention.

DNA methyltransferase DNMT3A and DMNT1 are required for de novo and maintenance methyltransferase activities that catalyze the establishment of methylation patterns during embryogenesis and gametogenesis. Inactivation of their genes may cause embryonic lethality. We conducted a case-control study to explore the association between DNMT3A rs7590760, DNMT1 rs2228611, and DNMT1 rs8101626 polymorphisms and early pregnancy loss susceptibility in Russian women. 100 women with early pregnancy loss (EPL) were involved and divided into two subgroups consisting of 50 women: sporadic pregnancy loss (SPL) and recurrent pregnancy loss (RPL). The control group included 56 women with full term pregnancies. Genotyping was performed using PCR-RFLP methods. GG genotype and allele G of DNMT1 rs2228611 were significantly associated with EPL and RPL, and GG genotype of DNMT1rs8101626 with EPL, SPL and RPL. Our findings have shown that women carrying GG genotype of DNMT1 rs2228611 had a higher risk of EPL and RPL (OR = 3.0, 95% CI: 1.44–6.23; OR = 3.94, 95% CI: 1.92–8.09 respectively) as well as that carrying GG genotype of DNMT1 rs8101626 are at higher risk of EPL and RPL (OR = 2.64, 95% CI: 1.2– 5.76). Conclusion: our results suggest that DNMT1 rs2228611 and DNMT1 rs8101626 gene polymorphisms are associated with early pregnancy loss and can be a genetic risk factor for recurrent pregnancy loss.

Primary hyperoxaluria is a group of rare inherited diseases characterized by impaired oxalate metabolism with the early manifestation of urolithiasis and the development of the chronic kidney disease. The mutations in the AGXT, GRHPR, HOGA1 genes are attributable for different types of primary hyperoxaluria leading to the dysfunction of specific enzymes involved in the oxalate metabolism. The article summary the current data on the epidemiology, genetic and biochemical aspects of pathogenesis of the primary hyperoxaluria types 1-3. The variety of clinical signs and disease severity depend on the type of hyperoxaluria.

Primary hyperoxaluria is a group of inherited metabolic diseases characterized by increased formation of calcium-oxalate stones in kidneys with development of nephrolithiasis and chronic kidney disease. The article summarizes the modern information on the diagnostics and treatment of the disorder depending on genotype of the patient (AGXT, GRHPR, HOGA1 genes). The evaluation of the molecular genetic aetiology of the kidney stone disease contributes to the personalized treatment and prevention of the pathology in the patients and their relatives.

A total of 100 women with early pregnancy loss were recruited and further classified into two subgroups: sporadic pregnancy loss and recurrent pregnancy loss; each subgroup consisted of 50 women. The control group included 56 women with normal pregnancies. Genotyping was performed by PCR with restriction fragment length polymorphism analysis. A statistically significant increase in the frequencies of TT genotype and T allele for DNMT3B rs2424913 polymorphism was found in the total patient group and in both patient subgroups in comparison with the control. Moreover, homozygous TT genotype was associated with increased risk of early pregnancy loss (both sporadic and recurrent). DNMT3B rs2424913 gene polymorphism in women can be used a marker of predisposition to early pregnancy loss and recurrent pregnancy loss.

The study included pregnant women aged 23-41 years with preeclampsia and gestation-associated arterial hypertension at weeks 27-40 and patients with essential arterial hypertension developing under conditions of the metabolic syndrome and without it. Frequency analysis of polymorphisms of the renin-angiotensin system genes (ACE, AGT, and AGTR1), ITGB3, FTO and their associations confirmed the syndrome nature of hypertensive disorders in pregnancy. The presence allele T of AGT gene and/or allele C of AGTR1 gene in the genotype of patients with preeclampsia was associated with higher BP and pressure load over 24 h. Allele D of ACE gene was also essential for BP parameters (pressure load) in patients with preeclampsia and gestation-associated arterial hypertension. Due to high genetic heterogeneity of the preeclampsia syndrome and genetic differences in the incidence of the studied gene polymorphisms in preeclampsia and gestation-associated arterial hypertension, no direct associations between these gestation disorders and polymorphic markers of the renin-angiotensin system genes can be established. However, polymorphisms of the renin-angiotensin system genes are essential for the 24-h dynamics of BP and pressure load under conditions of hypertensive disorders in pregnancy.

About 30% of male infertility is associated with genetic abnormalities. Genetic polymorphisms increase the level of individual susceptibility to adverse environmental factors and affect human reproductive function.To study associations of glutathione S-transferase GSTP1(Ile/Val) gene polymorphisms (A313G; rs1695) with the risk of pathospermia in men of the Moscow region.We examined 138 men in the Moscow region (n=70 - proven pathospermia, n=68 - fertile men). We obtained genomic DNA from blood leukocytes and studied the gene polymorphisms of glutathione-S-transferase GSTP1 (Ile/Val) (A313G; rs1695) in real time.In the analysis of the distribution frequencies of polymorphisms GSTP1 (Ile/Val) (AG rs1695), we revealed the predominance of the AA genotype in fertile men and the predominance of the GG genotype (homozygous minor allele) in men with pathospermia. However, we found no significant difference in these parameters between the compared groups of patients (p=0.344). For GSTP1 (Ile/Val) polymorphism (A313G, rs1695), significant differences in the distribution of genotype frequencies in the subgroup of men with teratospermia (2=7.00; p=0.03) were revealed. The frequency of allele G in the subgroup of men with teratospermia is statistically significantly different from the frequencies of alleles in the control group: 52% versus 30% (2=10,004; p=0.0015). In subgroups of men with azoospermia and asthenospermia, we did not find significant differences in the distribution of genotypes of GSTP1 polymorphism (rs1695) (p0.05).Glutathione-S-transferase (GSTP1) is a multifunctional protein that protects sperm cells from the damaging effects of reactive oxygen species and xenobiotics. The Association of GSTP1 polymorphism (Ile/Val) (A313G, rs1695) with teratospermia explains the main stages of the pathogenesis of male infertility in this category of patients.Gene polymorphism GSTP1 (A313G, rs1695) can be considered a genetic marker of susceptibility to pathospermia in men.

This study investigated the renin-angiotensin-aldosterone system (RAAS) gene polymorphisms as possible genetic risk factors for the restenosis development in patients with drug-eluting stents. 113 participants had coronary artery disease and underwent stenting. The control group consisted of 62 individuals with intact coronary arteries. Patients were divided into two groups: with in-stent restenosis (ISR) and without it. The patients with ISR were classified into subgroups by the terms of the restenosis development and age. Real-time PCR and Restriction Fragment Length Polymorphism-PCR were used to genotype the study participants for RAAS gene polymorphisms. We found that the development of restenosis is generally associated with the minor A allele for renin (REN) rs2368564 and the major TT genotype for angiotensinogen (AGT) rs699. The heterozygous genotype for AGT rs4762 acts as a protective marker. A minor A allele for angiotensin II type 2 receptor (AGTR2) rs1403543 is associated with a risk of restenosis in people under 65 years old. Among patients with the early ISR, heterozygotes for angiotensin II type 1 receptor (AGTR1) rs5186 are more frequent, as well as A allele carriers for AGTR2 rs1403543. A minor homozygous genotype for REN rs41317140 and heterozygous genotype for aldosterone synthase (CYP11B2) rs1799998 are predisposed to the late restenosis. Thus, to choose the effective treatment tactics for patients with coronary artery disease, it is necessary to genotype patients for the RAAS polymorphisms, which, along with age and clinical characteristics, will allow a comprehensive assessment of the risk of the restenosis development after stenting.

Restenosis remains the main complication after percutaneous coronary interventions in patients with coronary heart disease. The causes of its development include, in particular, genetic factors. We studied polymorphic loci of genes encoding endothelin-1 (EDN1 rs5370), endothelin-1 receptor (EDNRA rs5333), endothelin-converting enzyme (ECE1 rs1076669), and endothelial NO synthase (eNOS rs1549758, eNOS rs1799983, and eNOS rs2070244) in the context of in-stent restenosis development. It was found that the analyzed polymorphisms of the endothelin system genes were more significant for patients aged ≥ 65 years, while the polymorphic loci of the endothelial NO synthase gene (eNOS rs1799983 and eNOS rs1549758) were predominantly associated with time of in-stent restenosis. The obtained results can be useful for comprehensive assessment of the restenosis risk factors and the choice of optimal treatment for patients with coronary heart disease before elective surgical intervention.

In cardiomyocytes, high molecular ATP-dependent HSP70 and HSP90 play an important role in protecting the myocardium from abnormal proteins that appear, in particular, due to activation of oxidative stress. Molecular chaperone HSP60 is of particular importance for cardiomyocytes as it is responsible for assembly of mitochondrial matrix proteins. We studied the peculiarities of expression of HSP60 in left ventricular cardiomyocytes in hypertension, insulin-dependent diabetes mellitus, and their combination. The experiment was performed on 38-week-old male Wistar-Kyoto and SHR (spontaneously hypertensive) rats aged 38-57 weeks. Insulin-dependent diabetes mellitus was modeled by a single parenteral administration of 65 mg/kg streptozotocin. Expression of HSP60 in left ventricular cardiomyocytes was evaluated by immunohistochemical methods. It was found that hypertension, diabetes mellitus, and their combination are associated with a significant decrease in the content of HSP60 in left ventricular cardiomyocytes in comparison with the control. This finding can be considered as a pathogenetic mechanism of myocardial damage induced by hypertension and diabetes mellitus.

Primary hyperoxaluria is a group of rare inherited diseases characterized by impaired oxalate metabolism with the early manifestation of urolithiasis and the development of the chronic kidney disease. The mutations in the AGXT, GRHPR, HOGA1 genes are attributable for different types of primary hyperoxaluria leading to the dysfunction of specific enzymes involved in the oxalate metabolism. The article summary the current data on the epidemiology, genetic and biochemical aspects of pathogenesis of the primary hyperoxaluria types 1-3. The variety of clinical signs and disease severity depend on the type of hyperoxaluria.

Chromosomes of embryos of couples with reduced number of morphologically normal sperm cells (less than 4%) and couples with a normal level of morphologically normal sperm cells (over 4%) has revealed significant differences. In the group with a low level of normal spermatozoa, the frequency of embryos with normal chromosomes is significantly reduced and incidence of sex chromosome trisomies and autosomal monosomies and trisomies is increased; a tendency to decrease has been found for the frequency of male embryos. The obtained data may be useful to establish additional criteria for preimplantation genetic screening in the case of male infertility.

Aim. To study the anti-inflammatory effects of intensive lipid-lowering therapy and genetic predictors of its effectiveness in patients with very high cardiovascular risk.Material and methods. 58 patients with a history of cardiovascular disease and low-density lipoprotein cholesterol (LDL-C)>1.8 mmol/l or non-highdensity lipoprotein cholesterol (non-HDL-C)>2.6 mmol/l (mean age 61.9±8.6 (M±SD) years, 62.1% of men) were included into the study. Polymorphism Phe189Ser of the CYP3A4 (gene encoding cytochrome P4503A4, CYP3A4*17, rs4987161) and APOA1 (gene encoding apolipoprotein A): -75G/A in the promoter region (rs670) and +83C/T in the 5'-untranslated region (rs5069) was determined in all patients. Inflammatory status (high-sensitivity C-reactive protein (hsCRP), monocyte chemoattractant protein (MCP-1) and soluble vascular adhesion molecule (sVCAM-1)) was assessed initially and after 4 weeks of treatment with atorvastatin 80 mg/day. The results were considered statistically significant at p

According to the literature, arterial hypertension is a multifactorial disease with a significant genetic component; therefore, the study of pathogenic mechanisms of this disease depending on gene polymorphism of the angiotensin system, in particular AGTR1, is of special interest. This study involved 30 patients, in 15 of whom arterial hypertension was diagnosed as a component of metabolic syndrome while the remaining 15 ones had isolated arterial hypertension. The genotyping of patients was performed using the polymerase chain reaction and detection of amplification products by horizontal agarose gel electrophoresis. DNA was extracted from blood samples. All patients underwent 24-hour BP monitoring (ABPM). Two groups were formed according to the results of PCR: one consisted of patients with the AGTR1А1166А genotype (n=16) and the other included patients with the AGTR1А1166СorAGTR1С1166С genotypes (n=14). The groups were matched for age, sex, body-weight index (BWI), and waist circumference (WC). We studied the features of arterial hypertension, the clinical course including duration of AH, maximum and minimum values of systolic and diastolic blood pressure during 24 hours, the degree of night-time drop in BP, and effects of antihypertensive therapy. It was shown that systolic blood pressure, duration of the disease, comorbidity, effects of the treatment, the frequency of metabolic syndrome were significantly different in the two groups. It was concluded that hypertension and metabolic syndrome may develop synchronously in patients with the C allele of the AGTR1 gene.

Background ― Genetic polymorphisms analysis of metabolic and antioxidant systems pathway genes are associated with male infertility is the most perspective and developed field in andrology. Purpose ― the aim of the research is to reveal the association of the glutathione S-transferase gene GSTP1 polymorphism C/T (rs1138272) with risk of pathospermia in Russian men in Moscow region. Material and Methods ― Case control study was conducted on 68 fertile men and 70 infertile men with various forms of pathospermia. Sperm analysis was performed according to WHO guidelines (WHO, 2010). DNA was extracted from peripheral blood leukocytes. Genotyping of the GSTP1 gene polymorphisms was carried out by generated amplicons from melting curve analysis after real time PCR. Results ― statistically significant association of polymorphism GSTP1 C/T (Ala/Val; rs1138272) with asthenozoospermia (χ2=8.58, p=0.003) and teratospermia (χ2=6.81, p=0.009) risk was found. The frequencies of homozygous and heterozygous carries (CT+TT genotypes) for polymorphic locus GSTP1 gene (rs1138272) are 3 times higher for men with disturbance of motility of spermatozoa and 2.5 times higher for men with abnormalities in morphology of spermatozoa, then for men with normozoospermia. Conclusion ― The GSTP1 C>T polymorphism (rs1138272) associated with risk of teratospermia and asthenozoospermia in male of reproductive age.

Primary hyperoxaluria is a group of inherited metabolic diseases characterized by increased formation of calcium-oxalate stones in kidneys with development of nephrolithiasis and chronic kidney disease. The article summarizes the modern information on the diagnostics and treatment of the disorder depending on genotype of the patient (AGXT, GRHPR, HOGA1 genes). The evaluation of the molecular genetic aetiology of the kidney stone disease contributes to the personalized treatment and prevention of the pathology in the patients and their relatives.

We investigated the distribution of the AGT T174M and AGTR1 A1166C polymorphisms, which predispose to cardiovascular diseases, among Algerians, Syrians and Russians from Central Russia. The genotypes were determined with the use ofallele-specific PCR. A significant difference between the studied samples was revealed in the T174M genotype distribution, whereas no significant difference was found in case of the A1166C polymorphism.

Changes in the frequencies of genotypes and mutant alleles of ACE, AGTR1, AGT, and ITGB3 genes were analyzed in patients with arterial hypertension coupled with metabolic syndrome (N=15) and compared with population data and corresponding parameters in patients with isolated hypertension (N=15). Increased frequency of genotype ID of ACE gene (hypertension predictor) was confirmed for both groups. In case of isolated hypertension, M235M genotype (gene AGT) was more frequent, in case of hypertension combined with metabolic syndrome, the frequency of genotypes A1166C and C1166C of the gene AGTR1 was higher in comparison with population data. Comparison of mutant allele frequencies in the two groups showed that at the 90% significance level allele T of the AGT gene was more frequent in hypertension coupled with metabolic syndrome (OR=1.26) and genotype A1166A of the AGTR1 gene was more frequent in the group with isolated hypertension.

The expression of Bax protein, marker of intracellular pathway of apoptosis initiation, in viable left ventricular cardiomyocytes and morphological changes in the myocardium in acute pressure overload of the left ventricle were studied in experiment on male rabbits. The content of Bax protein in the cardiomyocyte cytoplasm decreased, this indicating that the mitochondrial pathway was not involved in the realization of the apoptotic program. This decrease was associated with manifest destructive changes in the left ventricular myocardium.

Daytime and nighttime systolic and diastolic BP was recorded in 23-week-old SHR and Wistar rats by telemetric monitoring. Urine concentrations of sodium, potassium, and calcium were determined in SHR rats during of light (07.00-19.00 h) and dark hours (19.00-07.00 h) at the age of 18, 19, 20, 21, 22, and 23 week; 23-week-old Wistar rats were used as the control. At early stages of the experiment, urine sodium concentration was elevated in SHR rats both at daytime and at night. Thereafter, this value declined and by 22-23 week was significantly lower than in normotensive Wistar rats, but only during daytime. Daytime potassium concentration significantly surpassed the control level during weeks 18-19 of the experiment, but later, a tendency to a decrease in this parameter was observed. Daytime calcium content in SHR rats did not significantly differ from the control throughout the experiment. At night, this value exceeded the control level by more than 2 times during weeks 18-19, but then returned to the level observed in normotensive animals.

Diphtheria is considered to be vaccine-preventable disease due to organized immunization programmes. However there are still endemic regions of diphtheria, whence reports of mortal cases are coming. Most of deaths are caused by cardiotoxic effect of diphtheria toxin. Structural changes of left ventricular myocardium were investigated on a model of acute diffuse diphtheria intoxication. It was found that the most significant inflammatory signs manifest on the 5 th day of the experiment which is confirmed by profound infiltrative-degenerative changes of the myocardium.

Prevalence and importance of hypertension in the general incidence structure determines a wide range of research problems. Chronobiological indices are of great importance in the investigatory activity concerning mechanisms of essential hypertension. Our work was focused on the dynamics of HR circadian profile at different terms in male SHR rats with the use of telemetry monitoring. The obtained data showed considerable changes of cardiac rhythm in different time intervals which was understood as inhibition of the chronotropic function of the heart.

The article presents the results of the study of the genetic polymorphism of HLA-antigens in 65 adult patients with ulcerative colitis (UC) living in Moscow region. It was found that certain groups of HLA alleles are associated with the pathogenesis of UC. Immunogenetic factors of predisposition and sustainability to this disease depending on gender and age were revealed. The relationship of immunogenetic factors with clinical forms of the disease, course of the UC and response to therapy with glucocorticoids were shown.

In SHR rats of different ages (22, 26, 30, 34, and 38 weeks), continuous 24-h telemetric monitoring of BP and HR was performed. The amplitude and power of oscillations of diastolic BP significantly decreased at the later stages of arterial hypertension (38 weeks), which was considered as a poor prognostic marker. We also observed a significant decrease in the mean daytime, nighttime, and maximum HR and mesor on weeks 30 and 34, but not on week 38, which can reflect triggering of the adaptive response followed by its exhaustion.

This study presents the genetic polymorphism of HLA-antigens in acquired aplastic anemia (AAA) in 147 children (85 boys и 62 girls) aged 1 to 18 with. The control group is consisted of 1700 umbilical cord blood samples of healthy newborns. The genetic polymorphism of HLA was studied in groups of children with AAA, divided by gender and age. Our results revealed distinction in HLA-markers of predisposition and sustainability to AAA. Possible differences in factors of immunogenetic predisposition suggest different mechanisms involved in the development of the disease in different groups of children and reconsider the existing model of the pathogenesis of AAA.

Caspase-3 and caspase-8 activity in right ventricular myocardial cells of rabbits with experimental arterial hypertension (AH) was investigated. Caspase-3 activity significantly increased at 2 and 4 weeks after modeling of AH. Obtained data demonstrated increased apoptosis in right ventricular myocardial cells in experimental arterial hypertension. Absence of significant increasing of caspase-8 activity indicates the predominance of intrinsic apoptogenic signals.

Aim. To investigate the effects of phosphocreatine and ethylmethylhydroxypyridine succinate on cardiomyocyte apoptosis intensity and degree of ventricular cardiomyocytes hypertrophy in rabbits with vasorenal hypertension (VH) model. Methods. VH was modeled on rabbits by artificial abdominal aortic stenosis by one-third of the diameter just above the renal arteries arising. Rabbits were divided to 4 groups: rabbits with 4-week VH without treatment, rabbits with 4-week VH treated with phosphocreatine, rabbits with 4-week VH treated with ethylmethylhydroxypyridine succinate, and healthy rabbits (control group). Cardiomyocyte apoptosis intensity and degree of ventricular cardiomyocytes hypertrophy was assessed in all of the rabbits by evaluation of nuclear-cytoplasmic ratio. Results. Use of phosphocreatine or ethylmethylhydroxypyridine succinate led to a significant reduction of the apoptotic index in the left ventricular myocardium, whereas the similar effect on the right ventricle was only typical for phosphocreatine. None of these drugs had an effect on myocardial hypertrophy degree, which remained on the same level as in the untreated hypertensive animals. Conclusions. Energy deficiency is one of the factors inducing cardiomyocyte apoptosis, so administration of phosphocreatine or ethylmethylhydroxypyridine succinate might be an important component of heart failure prevention and treatment in hypertension. Myocardial hypertrophy has no effect on the cardiomyocyte apoptosis intensity in case of proper energy supply.

We studied the effect of phosphocreatine and ethylmethylhydroxypyridine succinate on the expression of Bax and Bcl-2 proteins in left-ventricular cardiomyocytes of spontaneously hypertensive rats (SHR). Both drugs have no effect on the expression of Bcl-2, but significantly reduce the level of Bax protein (phosphocreatine produces more pronounced effect). These data attest to an important role of energy deficit and oxidative stress in the induction of cardiomyocyte apoptosis in genetically determined arterial hypertension.

Cardiomyocyte apoptosis and hypertrophy have been studied in the left and right ventricular myocardium of spontaneously hypertensive rats without treatment and after 10-day administration of the ETA-receptor antagonist BQ-123. It is established that BQ-123 prevents the activation of cardiomyocyte apoptosis and significantly decreases the extent of hypertrophy development in the left ventricular myocardium, but does not influence the same mechanisms in the right ventricular myocardium.

Numerous experiments on simulation of acute coronary failure in initially intact rabbits showed that under the same experimental conditions irreversible ventricular fibrillation developed in some animals and did not develop anothers. We hypothesize that the probability of fibrillation development was determined by the time of the day, during which acute coronary failure developed. The study was carried out on 2 groups of rabbits in winter in Moscow. In group 1, the failure was induced by ligation of the left descending coronary artery at the interface between its middle and lower thirds at 11.00-18.00 with 30-min intervals. In group 2, the microcirculatory status of the left-ventricular myocardium was studied by light microscopy and morphometry at 12.00 and 18.00. Induction of coronary failure during the period from 15.30 to 18.00 led to irreversible ventricular fibrillation and death in 100% cases. Modeling of the condition from 11.00 to 15.00 caused no ventricular fibrillation in 89% cases, and the animals survived. The area of left-ventricular myocardial capillaries at 12.00 virtually 2-fold surpassed that at 18.00. Presumably, the electrolyte balance and metabolic characteristics of the myocardium switch over to the nocturnal mode of functioning at 15.30 due to changes in blood filling of the myocardium. The appearance of an ischemic focus in the myocardium during this period inevitably leads to the development of irreversible ventricular fibrillation.

Activities of caspase-3 and caspase-8 in the left ventricular myocardium of Chinchilla rabbits with renovascular arterial hypertension and spontaneously hypertensive rats were measured after 10-day administration of a macroergic compound phosphocreatine. Treatment with phosphocreatine prevented activation of caspase-3, but had no effect on caspase-8 during secondary and genetically determined arterial hypertension. Our results indicate that the intrinsic mechanism of the induction of the caspase cascade in myocardial cells dominates over the extrinsic pathway during both types of arterial hypertension. Energy deficit is one of the inducing factors of these processes.