P P Malyshev

Russian Cardiology Research and Production Complex, Moskva, Moscow, Russia

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Publications (25)23.01 Total impact

  • Kardiologiia 08/2015; 55(3):115-20. DOI:10.18565/cardio.2015.3.115-120 · 0.12 Impact Factor
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    ABSTRACT: A new method for the analysis of blood lipid based on direct mass spectrometry of lipophilic low molecular weight fraction of blood plasma has been considered. Such technique allows quantification of hundreds of various types of lipids and this changes existing concepts on diagnostics of lipid disorders and related diseases. The versatility and quickness of the method significantly simplify its wide use. This method is applicable for diagnostics of atherosclerosis, diabetes, cancer and other diseases. Detalization of plasma lipid composition at the molecular level by means of mass spectrometry allows to assess the effectiveness of therapy and to optimize the drug treatment of cardiovascular diseases by phospholipid preparations.
    04/2015; 61(1):7-18. DOI:10.18097/pbmc20156101007
  • V N Titov · K V Ivanova · P P Malyshev · S I Kaba · Iu K Shiriaeva ·
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    ABSTRACT: The pathogenesis of non-alcoholic fatty disease of liver (steatosis) is still as unclear as a loss of hepatocytes similar to apoptosis, development of biological reaction of inflammation, its transformation into steatohepatitis with subsequent fibrosis and formation of atrophic cirrhosis. The article suggests that steatosis is developed due to higher concentration of palmitic saturated fatty acid (C 16:0) in food, intensification of its endogenic synthesis from food carbohydrates and glucose and development of insulin resistance. It is displayed in in hormone ability to activate both oxidation in cells of glucose and synthesis of oleic monoene fatty acid from palmitic saturated fatty acid (C 18:1). The insulin resistance initiates pathologic process on the level of paracrine associations of cells resulting in permanent increase of concentration of non-etherified fatty acids in intercellular medium and intensification of their passive absorption by cells. The phylogenetically ancient mitochondrions will not to oxidize glucose until non-etherified fatty acids are present in cytosol and hence there is an opportunity to oxidize them. To eliminate undesirable action of polar saturated palmitic fatty acid, the cells etherify it by spirit glyceride into triglycerides to deposit in cytosol or to secrete into blood in a form of lipoproteins of very low density. Under insulin resistance, saturated palmitic fatty acid synthesized by hepatocytes from glucose, does not further transform into oleic monoenic fatty acid. The cells are to etherify endogenic (exogenic) palmnitic saturated fatty acid into composition of aphysiologic palmitic triglycerides (saturated palmitic fatty acid in position sn-2 of spirit glyceride). At that, triglycerides of palmitat-palmitat-oleat and even tripalmitat type are formed. The melting temperature of tripalmitat is 48 degrees C and melting temperature of physiologic trioletat is 13 degrees C. The intracellular lipases factually can't hydrolyze palmitic triglycerides. So, hepatocytes, overloaded by them, are destroyed in a way similar to apoptosis. The formed corpuscles of apoptosis disorder the biologic function of endoecology and trigger biologic reaction of inflammation. At that, steatosis changes into steato-hepatitis. The prevention of steatosis consists in dramatic restriction of concentration of palmitic saturated fatty acid in food. The treatment effect is targeted to: decreasing the formation of palmitine triglycerides by force of concurrent etherification of palmitic saturated fatty acid not into triglycerides but into phosphatidylcholine (symmetric phospholipids of soya); intensification of oxidation of palmitic saturated fatty acid in peroxisomes (glytazones and fibrates); decrease of insulin resistance (binuanide metformine).
    Klinicheskaia laboratornaia diagnostika 01/2013;
  • T A Rozhkova · V A Ameliushkina · E B Iarovaia · P P Malyshev · V N Titov ·
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    ABSTRACT: The purpose of the study was to define the values of clinical and biochemical (phenotypic) differences in 2 groups of patients: 1) those with moderate (< or =4.5 mmol/l) blood triglyceride (TG) levels and 2) those with high (more than 4.5 mmol/l) blood TG levels and to reveal significant parameters of a diagnostic algorithm for primary and secondary forms of hypertriglyceridemia (HTG). Ninety-six (54%) patients females) with a TG level of more than 2.3 mmol/l were examined. The age was 12 to 71 years (median [quartiles] 50 years [41-61 years]); women accounted for 54%. The patients had the following diseases: coronary heart disease (CHD) (44.89%), myocardial infarction (13.5%), arterial hypertension (87.9%). The diagnosis of HTG included an algorithm for the clinical, biochemical, and clinicogenealogical examination of patients. Biochemical blood analysis involved lipoprotein parameters: cholesterol, triglycerides, low-density lipoprotein cholesterol, lipid electrophoresis, apolipoproteins Al, B-100, E, and C-III. The data were processed using the statistical packages STATISTICA 6.0 and SPSS 17.0. Comparison revealed no age- and gender-related differences in the parameters between Groups 1 and 2 There was a significant correlation between the high levels of TG and the following indicators: total cholesterol, chylomicrones, lipoprotein(a), LP-E , LP B:E, LP C-III4, and LP C-III, smoking (a risk factor) and with the indicators of other metabolic disturbances--total C, chylomicrones, lipoprotein(a), LP-E-total, LP B:E, LP-C3-total, and LP-C3, which determined the impact of nutrition had a hereditary predisposition through the polygenic mechanisms of gene expression under the influence of a number of factors. Pancreatitis was found to be implicated in the development of HTG. Higher TG levels correlated with the parameters, the diagnosis of which reveals additional metabolic disturbances via environmental and polygenic mechanisms
    Klinicheskaia laboratornaia diagnostika 05/2011;

  • Artery Research 12/2010; 4(4):165-165. DOI:10.1016/j.artres.2010.10.069
  • P P Malyshev · Z Iu Mal'makova · A N Meshkov · V V Kukharchuk ·
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    ABSTRACT: Statins are widely used in clinical practice for lowering of levels of atherogenic blood plasma lipids and treatment of atherosclerosis. Variability of response of the body to these drugs might be determined by genetic factors (gene polymorphisms) related to metabolism of drugs. Among them central place belongs to enzymes of subfamily 3A of cytochrome P450 (CYP). In this review we present results of studies assessing effect of various allele variants of CYP3A4 and CYP3A5 on efficacy and tolerability of atorvastatin, lovastatin,, and simvastatin in different populations of patients. We also present data on populational frequency of genetic polymorphisms under study. In addition we cover the problem of possible influence of apoE genotype on efficacy of statins. The available data do not allow yet to recommend pharmacogenetic testing for wide clinical practice.
    Kardiologiia 01/2010; 50(8):69-75. · 0.12 Impact Factor
  • A Meshkov · D Stambolsky · P Malyshev · T Kotkina · S Boitsov · V Kukharchuk ·

    Atherosclerosis Supplements 06/2009; 10(2). DOI:10.1016/S1567-5688(09)70968-7 · 2.29 Impact Factor
  • V V Kukharchuk · P P Malyshev · A N Meshkov ·

    Kardiologiia 02/2009; 49(1):76-83. · 0.12 Impact Factor
  • A N Meshkov · P P Malyshev · V V Kukharchuk ·
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    ABSTRACT: To make qualitative and quantitative analyses of phenotypical characteristics and to study a spectrum and frequency of mutations in LDLR and APOB genes in patients with familial heterozygous hypercholesterolemia (FHHC). Clinical symptoms of FHHC were studied in males and females. Mutations were detected with PCR, analysis of SSCP of all the exones of LDLR gene and a fragment of exone 26 of APOB gene with subsequent sequestration of DNA fragments with anomalous electrophoretic motility, analysis of restriction fragments length polymorphism. LDLR gene mutations were detected in 50%, of APOB gene in 2.6% patients with FHHC, 70% of LDLR gene mutations have never been discovered before. Three known mutations were detected in the APOB gene: R3500Q (1.9% cases), H3543Y (0.55%), R3531C (0.15%). Incidence of coronary heart disease in untreated FHHC patients is 61.5%, of myocardial infarction--31%. Life span of both males and females with FHHC was subnormal, especially of men (median: 53 years in 95% CI, 49.2-56.8 years and 62 years in 95% CI 59.2-64.8 years, respectively). Incidence rate of basic clinical symptoms increased with age and significantly correlated with LDLP cholesterol. Frequency and severity of clinical symptoms and complications in FHHC and in Russian population agree with those of the European countries. The same occurs with frequency and mutations of the APOB gene, while mutations of the LDLR gene in 70% cases are unique for Russian population and are not described in other countries. This makes impossible to use foreign test kits for FHHC diagnosis in Russia.
    Terapevticheskii arkhiv 01/2009; 81(9):23-8. · 0.05 Impact Factor
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    ABSTRACT: To assess a hypolipidemic effect and tolerance of phenofibrate (lipantil 200M) in different variants of treatment in patients with combined hyperlipidemia having moderate and high levels of triglycerides (TG). A total of 26 patients (16 males, 10 females; age 32-67, mean age 55.1 years) received lipantil 200M (phenofibrate) in a dose 200 mg for 12 weeks either as monotherapy or in combination with statins (or fibrate) or plasmapheresis. Clinical, biochemical and blood lipid parameters were studied at baseline and after 12-week treatment. Baseline mean value and standard deviation of a blood cholesterol level was 8.3 (15.4) mmol/l, TG--7.2 (70.5) mmol/l). A mean cholesterol level decreased by 26.1%, TG--by 64.4%. Correlation with initial values was found. Systolic and diastolic blood pressure diminished significantly. No significant changes were found in the levels of AST, ALT, GGT, CPK, alkaline phosphotase, total bilirubin, creatinine. Before the treatment blood glucose was elevated in 14 patients, after 12-week therapy it remained elevated in 10 patients. Lipantil 200M (phenofibrate) had a good hypolipidemic effect in patients with combined hyperlipidemia in different baseline levels of cholesterol and TG elevation and in different variants of treatment. Significant side effects were not registered.
    Terapevticheskii arkhiv 01/2009; 81(9):29-33. · 0.05 Impact Factor

  • Atherosclerosis Supplements 06/2007; 8(1):53-53. DOI:10.1016/S1567-5688(07)71155-8 · 2.29 Impact Factor
  • T. V. Chepetova · A. N. Meshkov · P. P. Malyshev · V. V. Kukharchuk ·

    Atherosclerosis Supplements 06/2007; 8(1):180-180. DOI:10.1016/S1567-5688(07)71680-X · 2.29 Impact Factor
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    ABSTRACT: To conduct a quantitative and qualitative analysis of phenotypical manifestations in patients with a heterozygous form of familial hypercholesterolemia (FHC) and to reveal factors involved in their development. A total of 247 patients with a clinical diagnosis of heterozygous FHC participated in the trial. Clinical manifestations of the disease in men and women were analysed and compared. Blood lipids were compared to those in the controls. A correlation analysis was used to reveal correlations between symptoms of the disease and lipid levels in the blood. Tendon xanthomas were most frequent (79%) clinical sign with location primarily in Achilles' tendon. Incidence of basic clinical manifestations increased with age and significantly correlated with LDLP cholesterol. Two clinical signs were seen in 1/3 of the patients, three--in 13% (sex differences were insignificant). Mean levels of total cholesterol and LDLP serum cholesterol in heterozygous patients were 1.9 and 2.5 times higher than in the controls. Total cholesterol was significantly higher in women. A mean level of HDLP cholesterol was significantly lower while triglycerides were higher than in the control group. The disease symptoms manifested in men 5 years earlier than in women, FHC was diagnosed in men 7.5 years earlier. Patients with heterozygous FHC are characterized by higher levels of LDLP cholesterol, lower level of HDLP cholesterol and higher triglycerides in the serum than in healthy controls. Sex-related differences by severity and prevalence of basic symptoms in heterozygous FHC patients were not found. The time of clinical symptoms appearance and diagnosis evidences for more rapid progression of the disease in men.
    Terapevticheskii arkhiv 02/2007; 79(9):34-8. · 0.05 Impact Factor

  • Atherosclerosis Supplements - ATHEROSCLER SUPPL; 06/2006

  • Atherosclerosis Supplements 04/2005; 6(1):173-173. DOI:10.1016/S1567-5688(05)80675-0 · 2.29 Impact Factor
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    ABSTRACT: Ischemic heart disease (IHD) develops in patients with familial hypercholesterolemia (FHC) 15-20 years earlier than in general population. However age of onset of the disease, its clinical manifestations are variable and not completely determined by cholesterol level and class of low density lipoprotein receptor mutations. To elucidate associations of some auxiliary genetic factors -- such as C151565T, C677T, R353Q polymorphisms of glycoprotein IIIa (GPIIIa), methylenetetrahydrofolate reductase (MTHFR) and coagulation factor VII genes, respectively, -- with the presence of IHD in patients with FHC. Patients with clinical diagnosis of heterozygous FHC (n=198) with (n=106) and without (n=92) IHD. Patients with compared with those without IHD had similar frequency of T-allele of MTHFR gene (p=0.519), more often had T-allele of GPIIIa gene (23 and 12.5%, respectively, p=0.009), and less often -- Q-allele of factor VII gene (13 and 21%, respectively, p=0.048). Multifactorial analysis showed that risk of IHD was higher in patients with TT compared with CC genotype of the GPIIIa gene (OR 1.53, 95%CI 1.12-2.3), and lower in patients with RQ and QQ compared with RR genotype of factor VII gene (OR 0.41, 95%CI 0.19-0.75). In patients with FHC polymorphisms in factor VII and GPIIIa genes but not C677T polymorphism of MTHFR gene were associated with the presence of IHD.
    Kardiologiia 02/2005; 45(7):10-4. · 0.12 Impact Factor
  • P. Malyshev · A. Meshkov · D. Stambolsky · V. Kukharchuk ·

    Atherosclerosis Supplements 04/2004; 5(1). DOI:10.1016/S1567-5688(04)90371-1 · 2.29 Impact Factor
  • A Meshkov · D Stambolsky · V Kukharchuk · P Malyshev ·

    74th Congress of the European-Atherosclerosis-Society; 04/2004
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    ABSTRACT: Low density lipoprotein receptor (LDLR) gene mutations cause familial hypercholesterolemia which is associated with elevated risk of ischemic heart disease. To define LDLR gene mutations in unrelated patients with heterozygous familial hypercholesterolemia in Russia. PCR- single-strand conformation polymorphism analysis, automated DNA sequencing, and test for the presence of the apolipoprotein (apo) B-3500 mutation known to induce hereditary defect in apo-B-100. We found 6 novel mutations of LDLR gene designated E8X, 230insG, 671_679dupGACAAATCT, W422R, D461Y, and V698L. We also identified three missense mutations - C139G, E207K and R395W, which were previously described in FH patients from western populations. None of the studied persons had apo-B-3500 mutation. These findings broaden knowledge on mutations responsible for development of familial hypercholesterolemia and confirm molecular heterogeneity of this disease in Russia.
    Kardiologiia 02/2004; 44(9):58-61. · 0.12 Impact Factor
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    ABSTRACT: Analysis of genes of apolipoprotein E (apoE), LDLP receptor and methylentetrahydrofolate reductase (MTHFR) in a female patient with mixed hyperlipoproteinemia (HLP) and early ischemic heart disease (IHD). A patient with a mixed form of HLP and 5 her relatives were examined genetically. The genotype of apoE and MTHFR was determined using a restrictive analysis of PCR fragments. Conformation of one chain DNA was used to analyse gene of LDLP-receptor with following sequencing of anomalous DNA. The proband had changes in all examined genes: nucleotide replacement of A370T gene of LDLP receptor, nucleotide replacement of MTHFR gene C677T and epsilon 2/epsilon 2-genotype of apoE. None of the relatives carried more than one polymorphism by the studied genes. Early IHD in females can be caused by combination of polymorphisms of genes associated with development of atherosclerosis.
    Terapevticheskii arkhiv 02/2003; 75(10):71-4. · 0.05 Impact Factor