[Common Carotid Intima-Media Thickness, Levels of Total and High-Molecular Weight Adiponectin in Women With Abdominal Obesity].

OBJECTIVE: to investigate influence of different forms of adiponectin on carotid intima-media thickness (CIMT) in women with abdominal obesity (AO) in St.­Petersburg. It has been recognized before that AO is associated with cardiovascular diseases, including atherosclerosis, but mechanism of this association remains unclear. AO leads to imbalance of adipokines, in particularly decrease of adiponectin, which may lead to atherosclerotic lesion of carotid arteries. MATERIALS AND METHODS: We investigated 81 women with AO (IDF criteria, 2005) and 21 women with normal waist circumference. СIMT was evaluated by an ultrasound scanner. RESULTS: Among patients with AO 54.9 % had CIMT >0.9 mm and 38.5 % had atherosclerotic plaques in common carotid arteries. The total adiponectin level (TA) was lower in women with CIMT> 0.9 mm, than in women with normal CIMT (23.20 [2.55; 40.65] and 18.09 [1.60; 38.92] µg/ml, respectively; р0.9 mm, than in women with normal CIMT (2.21 [0.50; 6.85] and 2.88 [1.29; 15.45] µg/ml, respectively; р0.9 mm, than in women with CIMT >0.9 mm and atherosclerotic plaques in carotid arteries (3.09 [1.34; 6.85] and1.82 [0.50; 2.94] mcg/ml, respectively; р0.9 mm depended on waist circumference, diastolic blood pressure and level of C-reactive protein (CRP), while presence of atherosclerotic plaques was associated with levels of HMWA and CRP. CONCLUSIONS: Factors that make the greatest contribution at early stages of atherosclerosis development in carotid arteries in women with AO can be increased waist circumference, high diastolic blood pressure, and high level of CRP. At later stages of atherosclerosis development lowered HMWA level can contribute to the formation of atherosclerotic plaques.

ITLN1, PPARg AND TNFa GENE EXPRESSION IN VISCERAL ADIPOSE TISSUE.

The adipose tissue is considered today as an endocrine organ in which tissue-specific regulation of gene expression plays a key role in the processes of development of obesity and comorbidities, such as diabetes and cardiovascular disease. The present study is focused on ITLN1, PPARã and TNFá gene expression in intra-abdominal adipose tissue and its effect on the serum levels of omentin 1 and TNFa in individuals with different body mass. It has been shown that serum TNFa level is significantly higher in the subgroup of patients with overweight and obesity (BMI ≥ 25 kg/m2) as compared to individuals with normal body weight (BMI < 25 kg/m2)( p < 0.03). We have demonstrated that the expression level of the PPARã gene is positively correlated with the ITLN1 gene expression level in the intra-abdominal adipose tissue (r = 0.516, p = 0.020). Serum level of omentin 1 positively correlates with PPARã mRNA and protein levels in intra-abdominal adipose tissue (r = 0.550, p < 0.05 and r = 0.581, p < 0.03, respectively). For the subgroup of patients with overweight and obesity, we have shown negative correlation of the level of TNFá mRNA with PPARã and ITLN1 mRNA levels was shown (r = ­0.549, p < 0.05 and r = ­0.475, p < 0.05, respectively). This study is the first to show a correlation relationship between PPARã gene expression level in the intra-abdominal adipose tissue and the expression and secretion levels of omentin 1.

[Regulation of ABCA1 and ABCG1 gene expression in the intraabdominal adipose tissue]. / Reguliatsiia ékspressii genov transporterov ABCA1 i ABCG1 v intraabdominal'noi zhirovoi tkani.

Tissue specific expression of genes encoding cholesterol transporters ABCA1 and ABCG1 as well as genes encoding the most important transcriptional regulators of adipogenesis - LXRa, LXRb, PPARg and RORa has been investigated in intraabdominal adipose tissue (IAT) samples.A direct correlation between the content of ABCA1 and ABCG1 proteins with RORa protein level (r=0.480, p<0.05; r=0.435, p<0.05, respectively) suggests the role of the transcription factor RORa in the regulation of IAT ABCA1 and ABCG1 protein levels. ABCA1 and ABCG1 gene expression positively correlated with obesity indicators such as body mass index (BMI) (r=0.522, p=0.004; r=0.594, p=0.001, respectively) and waist circumference (r=0.403, p=0.033; r=0.474, p=0.013, respectively). The development of obesity is associated with decreased IAT levels of RORa and LXRb mRNA (p=0.016 and p=0.002, respectively). These data suggest that the nuclear factor RORa can play a significant role in the regulation of cholesterol metabolism and control IAT expression of ABCA1 and ABCG1, while the level of IAT LXRb gene expression may be an important factor associated with the development of obesity.

[Anxiety/depressive disorders and vitamin D status]. / Trevozhno-depressivnye rasstroistva u lits s raznym urovnem obespechennosti vitaminom D.

OBJECTIVE: To search for the association between vitamin D status and anxiety and depression. MATERIAL AND METHODS: Authors examined 310 residents of St. Petersburg (137 men and 173 women). Anxiety and depression were measured with the HADS. RESULTS AND CONCLUSION: In people with vitamin D deficiency, anxiety and depression were noted in 32.5% and 11.0%, respectively. There were negative correlations between serum 25(OH)D level and anxiety (r= -0,11, p=0.03). Symptoms of depression were not correlated with vitamin D status (r= -0.08, p=0.09) but were correlated with the age (r=0.12, p=0.02). After excluding other risk factors for psychogenic disturbances (obesity, hypertension and impaired glucose metabolism) we concluded that serum 25(OH)D could be an independent risk factor for anxiety (R2=0.02, p=0.01) in the population studied.

[Contribution of neuraminidase of influenza viruses to the sensitivity to the serum inhibitors and reassortment efficiency].

The live attenuated influenza vaccine (LAIV) consists of reassortant viruses with hemagglutinin (HA) and neuraminidase (NA) gene segments inherited from the circulating wild-type (WT) parental and the 6 internal protein-encoding gene segments from the cold-adapted attenuated master donor viruses (genome composition 6:2). In this study, we describe the obstacles to developing LAIV vaccine strains depending on the phenotypic peculiarities of the WT viruses used for reassortment. The genomic composition analysis of 849 reassortants revealed that over 80% of the reassortants based on the inhibitor-resistant WT viruses inherited WT NA as compared to 26% of reassortants based on the inhibitor-sensitive WT viruses. In addition, the highest percentage of the vaccine genotype reassortants was achieved when WT parental viruses were resistant to the non-specific serum inhibitors. We demonstrate that NA may play a role in the influenza virus sensitivity to the non-specific serum inhibitors. Replacing NA of the inhibitor-sensitive WT virus with the NA of the inhibitor-resistant master donor virus significantly decreased the sensitivity of the resulting reassortant virus to the non-specific inhibitors.

[Peculiarity of reassortment of current wild type influenza viruses with master donor viruses for live influenza vaccine].

The live attenuated influenza vaccine (LAIV) currently licensed in Russia consists of the reassortant viruses with hemagglutinin (HA) and neuraminidase (NA) gene segments from the circulating wild-type viruses and the six internal protein-encoding gene segments from cold-adapted master donor viruses (MDV) A/Leningrad/134/17/57 (H2N2) or B/USSR/60/69. Presently, only classical reassortment technique is approved for the generation of Russian LAIV strains. In this work, we describe the obstacles to the development of LAIV 6:2 vaccine strains depending on the phenotypic properties of the wild-type viruses used for reassortment. It was demonstrated that the highest percentage of 6:2 vaccine reassortants could be achieved when wild-type parental viruses were resistant to non-specific gamma-inhibitors. It was shown that it was impossible to generate 6:2 vaccine reassortants possessing six internal genes of the AILeningrad113417/57 (H2N2) master donor virus and avian HA and NA genes from H5N1-PR8 viruses using classical reassortment technique. It was suggested that strong constellation effects between the gene segments of the parental viruses could affect the virus gene reassortment. A strong interaction between the genome segments encoding neuraminidase of avian origin and PB2 gene of PR8 virus was observed. When the PB2 gene was inherited from cold-adapted master donor virus, the neuraminidase was also found to be of MDV origin.

[Genome composition analysis of the reassortant influenza viruses used in seasonal and pandemic live attenuated influenza vaccine].

The cold-adapted, temperature sensitive and attenuated influenza master donor viruses A/Leningrad/134/17/57 (H2N2) and B/USSR/ 60/69 were used to generate the vaccine viruses to be included in live attenuated influenza vaccine. These vaccine viruses typically are 6:2 reassortant viruses containing the surface antigens hemagglutinin and neuraminidase of current wild type influenza A and influenza B viruses with the gene segments encoding the internal viral proteins, and conferring the cold-adapted, temperature sensitive and attenuated phenotype, being inherited from the master donor viruses. The 6:2 reassortant viruses were selected from co-infections between master donor virus and wild type viruses that theoretically may yield as many as 256 combinations of gene segments and thus 256 genetically different viruses. As the time to generate and isolate vaccine viruses is limited and because only 6:2 reassortant viruses are allowed as vaccine viruses, screening needs to be both rapid and unambiguous. The screening of the reassortant viruses by RT-PCRs using master donor virus and wild type virus specific primer sets was described to select both influenza A and influenza B 6:2 reassortant viruses to be used in seasonal and pandemic live attenuated vaccine.

[Genetic variants of platelet ADP receptor P2Y12 associated with changed platelet functional activity and development of cardiovascular diseases].

The key role in platelet aggregation is played by the platelet ADP receptor P2Y12, which is the target for antiaggregant drugs, clopidogrel and ticlopidine. At present, only sporadic data on genetic variants of platelet ADP receptor P2Y12 are available from literature, and their association with thromboembolic and cardiovascular diseases still remains obscure. Analysis of the group of subjects with high platelet reactivity resulted in identification of two nucleotide substitutions, C18T and G36T, in the coding region of the P2Y12 gene. The frequency of the P2Y12 T1 8 allele was higher in control group than in the group of patients survived from myocardial infarction at the age under 45 years (39% versus 28%, respectively, P = 0.04). Moreover, in the T18 carriers, platelet aggregation activity was lower than in the carriers of the wild-type genotype (0.84 +/- 0.05% versus 1.01 +/- 0.08%, respectively, P = 0.03). In the group of patients with early myocardial infarctions, a tendency towards the increased frequency of 16T allele in comparison with control group (20 and 12%, respectively, P = 0.07) was observed. The rate of ADP-induced platelet aggregation in the carriers of 16T allele from the control group was somewhat higher than in the subjects with the GG36 genotype (1.31 +/- 0.16% versus 1.12 +/- 0.06%, respectively, P = 0.07). The nucleotide substitutions identified were in absolute disequilibrium, i.e., allele T18 conformed to allele G36. On the contrary, allele C18 conformed to allele T36. Haplotype T18G36 was found to be responsible for the decreased risk of myocardial infarction and decreased platelet reactivity. It is suggested that polymorphisms of the P2Y12 gene identified can be used for determination of the risk group for myocardial infarction in the young males.

[Genetic risk factors for development of myocardial infarction in young men living in North-West region of Russia].

With the aim to detect genetic factors of risk of development of early myocardial infarction (MI) we studied 29 allele variants of 19 genes in 206 men who had survived MI in the age before 45 years and in 195 men of similar age without cardiovascular diseases. All subjects were inhabitants of North-West region of Russia. The following factors were associated with history of myocardial infarction: genotype RR191 of paraoxonase-1 (PON1) gene (RR 2.8 [95% CI: 1.24 - 6.30]), P1A2 allele of glycoprotein (GP) IIIa subunit of platelet fibrinogen receptor GPIIb/IIIa (RR 1.8 [95% CI: 1.11 - 2.93]), and Met145 allele of GPIbalpha platelet von Willebrand factor receptor gene. Genotype CC ( - 108) PON1 was associated with lowered risk of MI development (RR 0.6 [95% CI: 0.40 - 0.91]). During 7 years of follow-up 30 men from MI group died of recurrent acute coronary syndromes. In the group of those who died we noted increased prevalence of P1A2 GPIIIa allele compared with those who survived (p < 0.03). The results allow to suggest that contribute to development of MI in young men factors associated with elevation of functional state of platelets and levels of oxidized lipids in blood plasma.

[Effect of phenofibrate treatment on endothelial dysfunction in patients with history of myocardial infarction in young age]. / Vliianie terapii fenofibratom na éndotelial'nuiu disfunktsiiu u bol'nykh, perenesshikh infarkt miokarda v molodom vozraste.

AIM: To evaluate the severity of endothelial dysfunction in patients with a history of myocardial infarction in young age and its changes during therapy with lipantil 200 M. MATERIAL AND METHODS: The percentage of dilatation of the brachial artery during reactive hyperemia test, number of circulating desquamated endotheliocytes, and lipid metabolism parameters were evaluated in 40 men with a history of myocardial infarction before the age of 45 years and 40 healthy men. RESULTS: Endothelial dysfunction was detected in coronary patients: the percentage of dilatation of the brachial artery was decreased, the number of circulating endotheliocytes increased, and lipid metabolism disordered. After 3-month lipantil 200 M therapy the severity of endothelial dysfunction significantly decreased and lipid metabolism parameters improved. CONCLUSION: Patients with a history of myocardial infarction in young age develop endothelial dysfunction, whose severity decreases after hypolipidemic therapy.

[Effects of hypolipidemic therapy on the endothelial dysfunction in patients with myocardial infarction at young age]. / Vliianie gipolipidemicheskoi terapii na éndotelial'nuiu disfunktsiiu u bol'nykh, perenesshikh infarkt miokarda v molodom vozraste.

AIM: To evaluate the degree of endothelial dysfunction in patients who survived myocardial infarction (MI) at young age, its response to therapy with lipantil. MATERIAL AND METHODS: Dilation of the brachial artery in response to reactive hyperemia, number of circulating desquamated endotheliocytes, lipid metabolism were assessed in 40 males who had survived MI at the age under 45 years and in 40 healthy males. RESULTS: Patients with ischemic heart disease had endothelial dysfunction: decreased dilation of the brachial artery, increased count of circulating endotheliocytes, defective lipid metabolism. A 3-month lipantil therapy resulted in a significant reduction of endothelial dysfunction, improvement of lipid metabolism. CONCLUSION: Patients who survived MI at young age have endothelial dysfunction the severity of which diminish in hypolipidemic therapy.

[I/D polymorphism in the angiotensin-converting enzyme gene in men with myocardial infarction at young age]. / I/D polimorfizm gena angiotenzinprevrashchaiushchego fermenta u muzhchin, perenesshikh infarkt miokarda v molodom vozraste.

The rate of D allele did not differ between patients with ischemic heart disease (IHD) who had myocardial infarction before the age 45, and healthy males. The DD genotype of the ACE gene was much more frequently encountered in the patients than in healthy males. The findings suggest that the DD genotype is an independent risk factor of the IHD and myocardial infarction in young patients.

[Endothelium disfunction in patients with myocardial infarction at the younger age]. / Disfunktsiia éndoteliia u bol'nykh, perenesshikh infarkt miokarda v molodom vozraste.

The endothelium was studied in males who had sustained myocardial infarction (MI) at young age (under 45 years). The parameters of endothelium-dependent dilatation of the brachial artery were estimated during a reactive hyperemia test and the blood count of circulating (desquamated) endotheliocytes was measured. The values obtained in patients groups randomized by different parameters were compared with each other and with control values. The patients who had experienced in youth were found to have endothelial dysfunction, as appeared as both a larger number of circulating blood endotheliocytes and an altered vascular response during the reactive hyperemia test. It was found that endothelial function was not clearly related to the risk factors of atherosclerosis though the association was more marked when coronary heart disease is concurrent with arterial hypertension and hypercholesterolemia.