5 results on '"I.A. Snegurskaya"'
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2. Aldosterone synthase gene polymorphism in alimentary obesity, metabolic syndrome components, some secondary forms of arterial hypertension, pathology of the adrenals glands core (literature review)
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S.N. Koval, D.K. Miloslavsky, I.A. Snegurskaya, O.V. Mysnichenko, and M.Yu. Penkova
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levels and gene polymorphism of aldosterone synthase ,obesity ,metabolic syndrome ,secondary arterial hypertension ,hyperaldosteronism ,aldosterone synthase inhibitors ,review ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Hormonal factors of adrenal origin belong to the pathophysiological mechanisms of the formation and progression of arterial hypertension (AH) and should be considered while developing differentiated approaches to the treatment and prevention of hypertensive states, their primary, secondary and resistant forms. The first thing we should point up is aldosterone (AL), enzyme aldosterone synthase (AS), which takes a direct part in the formation of this hormone, as well as gene polymorphisms of AS, which have not only molecular genetic, but also differential diagnostic and therapeutic significance for secondary forms of arterial hypertension, abdominal obesity (AO), metabolic syndrome (MS), adrenal pathology and other endocrine disorders. AL is a steroid (mineralocorticoid) hormone of the adrenal cortex, which is synthesized from cholesterol (CH), mainly in the glomerular zone of the adrenal glands, is released under the action of angiotensin II (A II) and potassium ions (K+). AL activity is mediated through the corresponding mineralocorticoid receptors (MKR). The particular importance in AH and MS development belongs to AL activation and MKR density in adipocytes, this phenomenon is accompanied by increased expression of pro-inflammatory cytokines, leptin, an adipogenic effect, and the inhibition of MCR activity is accompanied by increased production of adiponectin, which is more pronounced in patients with AH. Aldosterone synthase, a mitochondrial human enzyme encoded by the CYP11B2 gene (cytochrome P450, family 11, subfamily B, polypeptide 2) is located on the 8th chromosome. AS belongs to the superfamily of cytochrome P450 and regulates the synthesis of AL hormone. The CYP11B2 gene encodes the key enzyme for the synthesis of AL 18-hydroxylase. In scientific papers, single nucleotide polymorphism (SNP) of AS gene is often studied, such as 5312T, Intron 2, Lys-173/Arg; T-344C, 3097 C/A. 227 SNP of the AS gene were identified in different populations. Europeans, Asians, Africans and North Americans were among them and were genotyped by CYP11B2. To date, there is ample evidence that fatty tissue (FT), apart from a source of energy, is an active endocrine organ that plays a key role in maintaining homeostasis and participating in the pathogenesis of a number of diseases. Its excess is accompanied by hyperactivation of tissue renin-angiotensin-aldosterone system (RAAS), strengthening of local and systemic synthesis of AL and the emergence of secondary aldosteronism. AL, in its turn, has a direct effect on FT due to increased MKR density expressed on adipocytes surface, leading to acceleration in the maturation of the latter and a further increase in FT. Getting into the systemic blood circulation and effecting other organs, the excess AL promotes the development of insulin resistance, atherosclerosis, the progression of systemic inflammatory reactions. MKR activation in FT plays not only the key role in sodium reabsorption by kidneys and the control of BP, but also in the differentiation of preadipocytes into mature adipocytes in FT, induction of inflammation and hyperproduction of cytokines — tumor necrotic factor alpha (TNF-α), monocyte chemotactic protein (MCP-1) and interleukin 6 (IL-6) in the white FT, a decrease in the thermogenic activity and transcription of the uncoupling protein-1 (UCP-1) in brown FT. MCR hyperactivation was detected in mice with AO (obese db/db mice), associated with increased BMI in humans and contributes to the development of IR and associated with AO cardiovascular diseases. The gene polymorphism of AS may be a marker of aggravated pregnancy, the presence of gestational hypertension or pre-eclampsia. Some studies found that AS gene polymorphism can affect plasma glucose levels. AS gene polymorphism was not associated with the progression of diabetic nephropathy (DN), but is associated with AH in persons with type 2 diabetes mellitus. National authors conclude about the association of the genotype TT(-344) of the gene CYP11B2 with the risk of MS among residents of the North-West region of Russia. The carrier of 344T allele of AS gene in patients with AO was associated with an increased risk of hypertension development. The features of AS gene polymorphism and blood levels in acromegaly have been studied, and the allelic polymorphism of AS and chymase genes (CMA) has been analyzed to identify the possible association of alleles of these genes with secondary hypertension and hyperaldosteronism in Russians. The congenital defects of the enzymatic activity of AS are of undoubted interest. AS gene is a promising candidate gene in the European and Asian populations for a number of secondary forms of hypertension, MS, diabetes mellitus, abdominal obesity, renal pathology, diabetic nephropathy, gestational hypertension. Genotyping of AS gene polymorphisms can be useful in differential diagnostic in patients with secondary forms of arterial hypertension, hypertension with low plasma renin activity, renovascular and resistant hypertension, adrenal tumors, primary and secondary hyperaldosteronism, aldosteromas, imaginary excess of mineralcorticoids syndrome, congenital hyperplasia of adrenal cortex. The advantages and disadvantages of the therapeutic use of MCR antagonists and the prospects for the administration of aldosterone synthase inhibitors among various categories of patients are considered. Carrying out the genotyping of patients by the CYP11B2 gene before therapy starting will allow take into account the genetic factors of sensitivity to drug in patients with the phenomenon of arterial hypertension and endocrine disorders. New AS inhibitors will not only effectively reduce blood pressure, but also will be able to prevent the development of adverse humoral and hormonal changes, what will prolong the life of patients and will help to reduce the level of total mortality from this pathology.
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- 2017
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3. Альдостеронсинтаза, поліморфізм її гена CYP11B2 при артеріальній гіпертензії і асоційованих з нею кардіоваскулярних захворюваннях (огляд літератури)
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D.K. Miloslavsky, E.N. Shchenyavskaya, V.V. Bozhko, I.A. Snegurskaya, and S.N. Koval
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Aldosterone synthase ,medicine.medical_specialty ,Aldosterone ,biology ,business.industry ,medicine.disease ,Left ventricular hypertrophy ,Hyperaldosteronism ,Angiotensin II ,chemistry.chemical_compound ,Mineralocorticoid receptor ,Endocrinology ,chemistry ,Internal medicine ,medicine ,biology.protein ,Apparent mineralocorticoid excess syndrome ,Gene polymorphism ,business - Abstract
The article presents the data of foreign and national literature on the pathogenetic role of aldosterone (AL), levels of aldosterone synthase (AS) and gene polymorphisms of this enzyme in patients with various forms of arterial hypertension, associated with diseases of the heart and vessels, such as hypertrophic cardiomyopathy, atrial fibrillation, brain pathology etc. The activation of circulating and local renin-angiotensin system results in increased secretion of the powerful vasoconstrictor angiotensin II, which stimulates AL production in an auto- and paracrine way. Angiotensin II and AL have independent regulatory effect on the function and structure of the heart and blood vessels, kidneys and brain. Both hormones stimulate hypertrophy of cardiomyocytes and vascular smooth muscle cells, hyperplasia of myocardial fibroblasts, synthesis of connective tissue matrix. As a result, the left ventricular hypertrophy is formed, cardiac remodeling is progressing, in which processes AL is involved. The main humoral, metabolic, cellular, immune-inflammatory and profibrogenic effects of aldosterone are considered. The AS gene CYP11B2 catalyzes the last stage of the synthesis of AL from desoxycorticosterone. The gene is located in the g21 region of chromosome 8, and consists of nine exons and eight introns. Single nucleotide polymorphisms are known in the promoter region of AL and in the AS gene. The polymorphism of the 5th section of this gene, which manifests itself by replacing cytosine (C) with thymine (T) at the 344th position of the 344 T/C nucleotide sequence, rs1799998, has been most fully investigated. MiR-766 can be used to suppress the expression of the AS gene in an experiment, as well as in humans, and reduce blood pressure level in people having the –344T allele. The determination of the single nucleotide replacement of T by C at position 344 of the CYP11B2 gene is carried out by polymerase chain reaction with polymorphism of the length of restriction fragment analysis. Currently, a list of forward and reverse primers, which are used in the amplification of the CYP11B2 gene, has been compiled. In the number of studies, the relationship between AS gene polymorphism and risk factors of cardiovascular and endocrine pathology were studied, the sex, gender and ethnic characteristics of AS gene polymorphism were considered, and the results of population studies of gene polymorphism of AS in several European and Asian countries were received. The information is provided on the AS levels and gene polymorphisms of this enzyme in arterial hypertension, including its resistant form, in the combination of ischemic heart disease, postinfarction cardiosclerosis, their participation in cardiovascular remodeling, the formation of left ventricular hypertrophy, in hypertensive nephropathy, cerebral stroke, heart failure. The levels of AL and gene polymorphism of AS also can be used as differential diagnostic criteria for hypertension with low plasma renin activity, with renovascular and resistant hypertension, at hyperaldosteronism types 1 and 2, aldosteromas, apparent mineralocorticoid excess syndrome, congenital adrenal hyperplasia. The congenital defects of enzymatic activity of AS, insufficiency of AS and aldosteronism (arterial hypertension), which are cured by glucocorticoids, are described. The results of several studies provide conflicting data on the degree of response to antihypertensive therapy by various first-line drugs and mineralocorticoid receptor antagonists, depending on the haplotype CYP11B2, are presented. The prospects of therapeutic use of a new class of drugs — aldosterone synthase inhibitors among various categories of patients with symptoms of arterial hypertension are considered.
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- 2022
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4. Сравнительная эффективность и переносимость лерканидипина и левовращающего амлодипина у больных гипертонической болезнью в сочетании с абдоминальным ожирением
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L.A. Resnik, V.V. Bozhko, I.A. Snegurskaya, S.N. Koval, and S.V. Salnikova
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medicine.medical_specialty ,business.industry ,Lercanidipine ,Pharmacology ,medicine.disease ,Essential hypertension ,Gastroenterology ,Blood pressure ,Tolerability ,Internal medicine ,medicine ,Microalbuminuria ,Amlodipine ,medicine.symptom ,business ,Adverse effect ,Abdominal obesity ,medicine.drug - Abstract
The aim of the work was a comparative study of the clinical efficacy and tolerability of S-isomer of amlodipine and lercanidipine in patients with essential hypertension (EH) and abdominal obesity (AO). It was shown that monotherapy with S-amlodipine and lercanidipine are effective types in treating mild and moderate forms of EH, including that of associated with AO. However, treatment with lercanidipine in significantly greater number of cases leads to achievement of target blood pressure as compared to S-amlodipine. Lercanidipine monotherapy resulted in a significant decrease in the level of insulin resistance and microalbuminuria in the examined patients, while the S-amlodipine monotherapy did not lead to significant positive changes in these indicators. We revealed a reliable lower incidence of any adverse events in patients with EH and AO under the influence of lercanidipine monotherapy as compared with S-amlodipine. Treatment with lercanidipine caused significantly lower incidence of edema of the lower limbs in patients with EH and AO than racemic amlodipine and S-amlodipine.
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- 2013
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5. EFFECT OF AMLODIPINE AND ORLISTAT COMBINATION ON METABOLIC AND ENDOTHEUUM-DEPENDEND VASOACTIVE FACTORS IN HYPERTENSIVE PATIENTS WITH OBESITY
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V.V. Bozhko, S. Koval, and I.A. Snegurskaya
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Orlistat ,Physiology ,business.industry ,Vasoactive ,Internal Medicine ,medicine ,Amlodipine ,Pharmacology ,Cardiology and Cardiovascular Medicine ,business ,medicine.disease ,Obesity ,medicine.drug - Published
- 2004
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