The Impact of Hypoglycemic Therapy on the Prognosis for Acute Coronary Syndrome in Patients with Type 2 Diabetes.

The article discusses particular circumstances of acute coronary syndrome (ACS) in patients with type 2 diabetes (T2D). In addition, the available literature data and clinical guidelines reflecting the role of hypoglycemic therapy as a cardioprotection factor in ACS are analyzed. The article considers possible protective molecular mechanisms of various groups of drugs in ischemic cardiomyocytes.

[Atrial fibrillation and cognitive impairment: features of the relationship, developmental and prevention mechanisms].

The article discusses the development of cognitive deficit in patients with atrial fibrillation (AF) and provides data on mechanisms of the development of cognitive disorders in AF. Under discussion are a possibility of reducing the risk of cognitive disorders with the anticoagulant therapy for prevention of stroke in AF and different properties of different anticoagulants, which may be important for patients. Thus, patients with cognitive disorders are more prone to missing the dose, which may entail serious, possibly fatal consequences. Therefore, the convenience of dosing may be essential. The drug rivaroxaban that has once-a-day dosing schedule and a calendar package, may help the patient better adhere to the doctor's recommendations. Therefore, rivaroxaban may help improving the compliance, which is the major condition for comprehensive, necessary protection of an elderly patient with AF, including the protection, with high safety, from stroke, from the risk of coronary complications, and from the impairment of kidney function.

[Algorithm for selection of individual therapy with clopidogrel in vascular surgical practice]. / Algoritm podbora individual'noi terapii klopidogrelom v praktike sosudistogo khirurga.

For treatment of patients with diseases of lower limb arteries and prevention of cardiovascular complications in high-risk patients (those with diabetes mellitus, arterial hypertension, dyslipidemia, obesity) permanent antiplatelet therapy is indicated. A problem is variable individual sensitivity to therapeutic agents. For antiplatelet therapy in patients with atherosclerosis of lower limb arteries there has been obtained an evidence-supported base concerning efficacy of long-term administration of clopidogrel preparations, unlike patients with acute coronary syndrome, for whom there has been accumulated an evidence-confirmed base of administering clopidogrel preparations, as well as ticagrelor and prasugrel in various clinical situations. Clopidogrel is currently the best known representative from the group of thienopyridines. It is a pro-drug and has complicated metabolism: two-stage oxidation under the effect of isoforms of cytochrome 2C19. Its active form irreversibly inhibits binding of ADP with P2Y12 receptors of thrombocytes. This is followed by inhibition of binding of fibrinogen with the glycoprotein IIb/IIIa receptor and a decrease of aggregation. Determining blood platelet aggregation with ADP, collagen and arachidonic acid forms the basis of clinical assessment of the functional state of thrombocytic activity and may be a marker of efficacy of treatment with antiaggregants. A complicated mechanism of action of clopidogrel implies individual policy of the attending physician in making a decision concerning the duration of therapy and selection of the dose. These prerequisites resulted in working out a recommended algorithm of individual dosing of clopidogrel (based on the analysis of case histories of patients with atherosclerosis of lower limb arteries by the level of platelet aggregation to a series of inducers) and correction of the dose of the drug based on the results of molecular-genetic testing of the cytochrome CYPC19 gene. The algorithm makes it possible to achieve a maximum level of efficacy and safety of treatment with antiaggregants.

[Comparison of Empiric and Pharmacogenetic Approaches in Assessment of Efficacy of Anticoagulant Therapy].

We compared pharmacogenetic (PG) and standard approaches to selection of individual dose of warfarin on 2 groups of patients each comprising 17 persons. In the group with PG selection we took into consideration the result of preliminary genotyping of polymorphisms of VKORC1 and CYP2C9 genes known to be associated with individual warfarin dose. Control of warfarin therapy was carried out during 6 months, number of measurements of international normalized ratio (INR) exceeded 500. Dosing based on knowledge of genotype allowed to achieve therapeutic effect 5 days earlier than with traditional selection of individual dose (=0.023). Number of INR values above 3.5 indicative of increased risk of bleeding was lower at PG compared with standard approach (3.1 and 7.7%, respectively, =0.03). Carriers of *2 and/or *3 of CYP2C9 associated with lowering of activity of this cytochrome had greater lability of INR values during course of therapy with warfarin.

[Informativeness of genetic factors for optimization of personalized therapy with clopidogrel].

We studied occurrence of allele variants *1, *2, *3, and *17 of CYP2C19 gene and polymorphic variants of ABCB1 gene in clopidogrel treated patients from West Siberian and Far Eastern regions and determined contribution of these polymorphisms to laboratory efficacy of clopidogrel. In dependence on magnitude of change of platelet aggregation we distinguished groups of patients with different sensitivity to clopidogrel. We found association between polymorphic variant CYP2C19*2 with changes of platelet aggregation after administration of clopidogrel. An additional group of patients with augmented platelet aggregation after administration of clopidogrel was detected. There was no correlation between the latter effect and any of studied polymorphisms.

[Association of chromosome 8q24 variants with prostate cancer risk in the Siberian region of Russia and meta-analysis].

Compelling evidence demonstrates chromosome 8q24 as a prostate cancer susceptibility locus. In present work we studied whether the common variants of 8q24 region, rs6983267 and rs1447295, were associated with the sporadic prostate cancer risk in the Russian population. Polymorphisms were genotyped in 393 case and 384 control Russian Caucasian men from Siberia region. The A allele of rs1447295 was significantly associated with the risk of prostate cancer (OR[CI 95%] = 1.74 [1.26-2.4], p = 7.8 x 10(-4)). A common G-A haplotype for rs6983267 - rs1447295 also showed an association with prostate cancer risk in Russian population (OR[CI 95%] = 2.03 [1.1 - 3.75], p = 0.02). We performed a meta-analysis combining our results with previous studies to evaluate the association between studied SNPs and prostate cancer risk. Meta-analysis has strongly supported the association for these SNPs (p < 10(-6)). Accordingly our study confirms the association between chromosome 8q24 and prostate cancer risk.

Polymorphic locus rs10492972 of the KIF1B gene association with multiple sclerosis in Russia: case control study.

Axonal degeneration is responsible for the progression of the irreversible destruction caused by multiple sclerosis (MS) resulting ultimately in permanent disability. The KIF1B protein, a member of the kinesin family, is necessary for axon growth and myelination in vertebrates. In the recent paper, Aulchenko et al. suggested that the rs10492972[C] variant of KIF1B increases susceptibility to MS, but three following replication study didn't confirm this association. We studied the association of the polymorphic locus rs10492972 present in the KIF1B gene with genetic predisposition and its occurrence in clinical presentations of MS patients resident in western Siberia and the Sakha Republic (Yakutia), Russia. rs10492972 has been genotype in 833 samples of MS patient and 689 healthy controls. Distribution of rs10492972 genotypes corresponded with a Hardy-Weinberg distribution in both the MS patient and control groups, with the frequency of the C allele being the same in both groups (33%). Frequencies of occurrence of the genotypes were not shown to be associated with different disease courses or other characteristics of the disease, such as age at onset or duration. A complete meta-analysis of all analogous studies published to date showed that the protective effect of the rs10492972[C] allele is statistically significant (OR=0.95, C.I.95% [0.90-0.99], p=0.02).

[Vegetovascular dysfunction as an integral parameter of high risk for cardiovascular diseases development in young subjects]. / Sindrom vegetososudistoi disfunktsii kak integral'nyi pokazatel' vysokogo riska razvitiia serdechno-sosudistykh zabolevanii u lits molodogo vozrasta s otiagoshchennoi nasledstvennost'iu.

AIM: To study manifestations of vegetative dystonia in children of probands from families with hereditary IHD load regarding the main risk factors. MATERIALS AND METHODS: 44 individuals aged 21 +/- 0.7 years were selected out of 111 children from 103 examined families the fathers of which had transmural or macrofocal myocardial infarction at the age under 50. 22 of 44 examinees had syndrome of vegetovascular dystonia (VVD). RESULTS: Children of probands with family history of cardiovascular disease and having VVD had levels of cholesterol, triglycerides and apoB higher, but HDLP cholesterol lower than those free of VVD. In daughters of the probands insulin and hydrocortisone levels were high whereas sons with VVD had only insulin levels higher. CONCLUSION: Children of probands of both sexes had high coefficients of hormonal and metabolic adaptation dependent on the severity of VVD syndrome.

[Ischemic heart disease and metabolic syndrome X (family study)]. / Ishemicheskaia bolezn' serdtsa i komponenty metabolicheskogo sindroma X.

AIM: To evaluate prevalence of metabolic syndrome "X" (MS) components in the families of probands and their wives regarding the presence of hyperinsulinemia and in probands' children of both sexes regarding their having vegetovascular dystonia. MATERIAL AND METHODS: 92 families were selected by the proband who survived acute myocardial infarction (MI) at the age under 50: 92 probands (mean age 47 +/- 1.1 years), 57 probands' wives (mean age 47 +/- 0.7 years), 20 sons (mean age 18.3 +/- 0.8 years), 24 daughters (mean age 19.1 +/- 1.0 years). Two groups were formed: group 1 of 48 probands and 25 wives (the presence of hyperinsulinemia in the proband); group 2 of 44 probands and 32 their wives (controls with normal insulin levels). Anthropometric, arterial pressure and lipid-hormonal measurements were made by standard techniques. Nutrition was studied by random reproduction of 24-h diet. RESULTS: More factors of risk to develop atherosclerosis and MS"X" components in probands and their wives were found in group 1. More frequent in the parents were the following MS components: hypoalphacholesterolemia, overweight, arterial hypertension, hyperapolipoprotein-B-emia. Vegetovascular asthenia in the probands' children predisposed to cardiovascular diseases is closely linked with the presence of hypoalphacholesterolemia, hypertriglyceridemia, overweight and arterial hypertension. CONCLUSION: MS "X" for probands and their wives is a "malignant" risk factor for cardiovascular diseases; in the presence of IHD in father, vegetovascular asthenia in children is a risk factor of cardiovascular disease.

[The characteristics of neuroendocrine regulatory disorders in acute myocardial infarct in relation to the severity of the course of the disease]. / Osobennosti neiroéndokrinnykh narushenii reguliatsii pri ostrom infarkte miokarda v zavisimosti ot tiazhesti techeniia zabolevaniia.

A total of 45 patients aged 35 to 73 years who had sustained acute myocardial infarction (MI) were studied in a special cardiological unit. On days 1, 5, 14, 28 of hospital stay, each patient underwent measurements of cortisol, insulin, T3 and T4 and calculations of the mathematical clinic severity index after G.I. Marchuk et al. In acute MI, there were elevated plasma levels of cortisol depending on the MI severity with a small repeated peak of its increase on day 14 and its subsequent decrease, except deaths. In severe acute MI there were impairments of reciprocal cortisol/insulin ratios. This was particularly pronounced in patients with lethal outcomes. By the end of hospital rehabilitation, patients with acute MI displayed lower levels of thyroidal hormones. The maximum decrease in T3 and T4 was found in patients with lethal outcomes. There was a direct correlation between the mathematical clinical severity index of the natural history of acute MI and the levels of cortisole triidothyronine at the hospital stage of observation. In the course of the study it was found that the Marchuk clinical severity index serves as an informative severity index of MI course whose determination in its acute period allows one to predict the course of acute MI and to choose a differential therapy of and to make a diagnosis of possible complications.

[Prognostic evaluation of vascular reactivity to vasoactive drugs and the clinical index of disease severity in patients with myocardial infarction]. / Prognosticheskaia otsenka sosudistoi reaktivnosti k vazoaktivnym veshchestvam i klinicheskogo indeksa tiazhesti u bol'nykh ostrym infarktom miokarda.

The parameters of vascular responsiveness to vasopressors and vasodilators and the clinical severity index were determined in 45 patients with various acute myocardial infarction (AMI) extents in the hospital period. In a group of patients with small AMI foci, the responsiveness to vasopressors normalized on day 14 with normal parameters to vasodilators throughout the study. The mean clinical severe index was the highest. In a group of patients with gross and transmural AMI there was a high responsiveness to norepinephrine in the whole hospital period and a high clinical severity index. Patients with fatal AMI outcomes showed an extremely low responsiveness to norepinephrine in the whole hospital period and a low abnormal response to histamine. The clinical severity index corresponded to the most grave course leading to an unpredictable outcome without any trends to decrease.