Get Adobe Flash player


Authors: Dudchenko I.O., Prystupa L.N.

Pages: 246-255


Introduction. Analysis of scientific studies has revealed the relationship between the T393C polymorphism of GNAS1 gene and Arg389Gly of ADRβ1 gene, and effectiveness of treatment using β1-blockers. However, these results are controversial, which may be due to ethnicity of the studied groups. In Ukraine, the study of T393C polymorphism of GNAS1 gene and its impact on the effectiveness of antihypertensive therapy using β1-blockers were not carried out.

Our aim was to determine the impact T393C polymorphisms of gene GNAS1 and Arg389Gly of ADRβ1 gene on efficiency of treatment using β1-blockers for patients with hypertension.

Materials and methods. The study involved 70 patients with verified diagnosis of hypertension. At baseline, β1‑blockers were appointed for patients at doses: metoprolol – 12.5 mg/kg per day, carvedilol – 25 mg/kg per day, and bisoprolol – 5 mg/kg per day. Efficacy of treatment was determined after 2 weeks by measuring heart rate and blood pressure. Polymorphism of gene was determined by polymerase chain reaction followed by restriction fragment analysis. Statistical analysis of the data was performed using the SPSS Statistics 21.0 program.

Discussion. It is proved that determining of T393C polymorphisms of GNAS1 gene and Arg389Gly of ADRβ1 gene plays an important role for the treatment with β1-blockers, because:

    • in patients with T393T genotype of GNAS1 gene observed higher level of reduction of systolic blood pressure and heart rate, when the treatment by β1-blocker was used, than in patients with C393C genotype;
    • in patients with Arg389Arg and Arg389Gly genotypes of ADRβ1 gene the level of reduction of heart rate and systolic blood pressure, when the treatment by β1‑blocker was used, was higher than in patients with Gly389Gly genotype.
    • in case when T393C or C393C genotypes of GNAS1 gene and Gly389Gly of ADRβ1 gene are combined, application of β1-adrenergic blockers is ineffective, even with its dose adjustment.

Key words: β1-blockers, gene polymorphism, heart rate, blood pressure.

        This email address is being protected from spambots. You need JavaScript enabled to view it.  

The full text

To view the full text


  1. Gong Y, McDonough CW, Wang Z, Hou W, Cooper-DeHoff RM, Langaee TY, Beitelshees AL, Chapman AB, Gums JG, Bailey KR, Boerwinkle E, Turner ST, Johnson JA. Hypertension susceptibility loci and blood pressure response to antihypertensives: results from the pharmacogenomic evaluation of antihypertensive responses study. G. 2012;5(6):686–691. doi: 10.1161/CIRCGENETICS.112.964080
  2. Pacanowski MA, Gong Y, Cooper-DehoffRM, Schork NJ, Shriver MD, LangaeeTY, Pepine CJ, Johnson JA. Bold beta-adrenergetic receptor gene polymorphisms and bold beta-blocker treatment outcomes in hypertension. Clinical Pharmacology and Therapeutics. 2008;84(6):715721.doi:10.1038/clpt.2008.139
  3. Leineweber К, Heusch G. β1- and β2-adrenoceptor polymorphisms and cardiovascular diseases. British Journal of Pharmacology. 2009;158(1):6169. doi:10.1111/j.1476-5381.2009.00187.x
  4. Sofowora GG, Dishy V, Muszkat M, Xie HG, Kim RB, Harris PA, Prasad HC, Byrne DW, Nair UB, Wood AJ, Stein CM. А common bold beta1-adrenergic receptor polymorphism (Arg389Gly) affects blood pressure response to bold beta-blockade. Clinical Pharmacology and Therapeutics. 2003;73(4):366371.
  5. Liu J, Liu ZQ, Tan ZR, Chen XP, Wang LS, Zhou G, Zhou HH. Gly389Arg polymorphism of bold beta1-adrenergic receptor is associated with the cardiovascular response to metoprolol. Clinical Pharmacology and Therapeutics. 2003;74(4):372379.
  6. Liu J, Liu ZQ, Yu BN, Xu FH, Mo W, ZhouG, Liu YZ, Li Q, Zhou HH. Вold beta1-adrenergic receptor polymorphisms influence the response to metoprolol monotherapy in patients with essential hypertension. Clinical Pharmacology and Therapeutics. 2006;80(1):2332.
  7. Johnson JA, Zineh I, Puckett BJ, McGorraySP, Yarandi HN, Pauly DF. Вold beta1-adrenergic receptor polymorphisms and antihypertensive response to.Clinical Pharmacology and Therapeutics. 2003;74(1):4452.
  8. Amosova KM, Sydorchuk LP, Kushnir OV. [Changes in endothelial function under the influence of combination treatment in patients with hypertension]. Bukovinian Medical Herald. 2010;14(4):36.
  9. Sydorchuk LP. [Cellular immunity of patients with hypertension, polymorphism 5 genes influence treatment]. Ukr Med Almanakh. 2008;11(3):143147.
  10. Sydorchuk LP, Amosova KM. [Indicators echocardiogram and geometric patterns of left ventricular in patients with hypertension based on five genes polymorphism]. Ukrainian Therapeutical J. 2008;2:1320.
  11. Sydorchuk LP. [Justification of antihypertensive treatment in patients with essential arterial hypertension depending on individual pharmacogenetic sensitivity]. Ukrainian Cardiology Journal. 2009;5:3551.
  12. Udovychenko MM. Оsoblyvosti perebigu sertsevoi nedostatnosti u khvorykh na tsukrovui diabet 2-ho typu v zalezhnosti vid polimorfizmu gena beta1-adrenoretheptoriv [Peculiarities of heart failure in patients with diabetes mellitus type 2, depending on the gene polymorphism of beta1-adrenergic receptors]. Kharkiv, 2012. 20 p.
  13. Karlsson J, Lind L, Hallberg P, MichaelssonK, Kurland L, Kahan T, Malmqvist K, Ohman KP, Nystrm F, MelhusClinical Cardiology. 2004;27(6):34750.
  14. Saveleva EG. Klinicheskaia i instrumentalnaia otsenka effektivnosti betaksolola u bolnykh gipertonicheskoi bolezniu [Clinical and instrumental evaluation of betaxolol in patients with essential hypertension: genetic aspects of individual sensitivity]. Moscow, 2007. 116 p.
  15. Maneshina OA. Sostoianie i modifikatsiia kletochnnoi β-adrenoretseptsii i rol polimorfizma genov β-adrenoretseptorov v terapii arterialnoi hipertonii i khronicheskoi serdechnoi nedostatochnosti [State and modification of β-cell adrenoretseptsii role of gene polymorphism and β1-adrenergic receptors in the treatment of hypertension and congestive heart failure]. Moscow, 2006. 27 p.
  16. Maneshina OA, Leonova MV, Belousov YuB, Gogolevskaia IK, Erofeeva SB. [Effect of polymorphism of β1-adrenoceptor Arg389Gly to reduce heart rate in patients with chronic heart failure during treatment with metoprolol CR/XL]. Biomedicina. 2006;3:128129.
  17. Minushkina LO. Geneticheskie factory pri gipertonicheskoy bolezni: sviaz s osobennostiami techeniia, razvitiem oslozhnenii, effektivnostiu terapii [Genetic factors in hypertension: association with features of progression, development of complications, and effectiveness of the therapy]. Moscow, 2008. 288 p.
  18. Beitelshees AL, Zineh I, Yarandi HN, PaulyDF, Johnson JA. Influence of phenotype and pharmacokinetics on beta-blocker drug target pharmacogenetics. The Pharmacogenomics J. 2006;6(3):174–178.
  19. Jia H, Hingorani AD, Sharma P, Hopper R, Dickerson C, Trutwein D, Lloyd DD, Brown MJ. Association of the Gsα gene with essential hypertension and response to β-blockade. Hypertension. 1999;34(1):834.
  20. Nieminen T, Lehtimaki T, Laiho J, Rontu R, Niemela K, Kbi T, Lehtinen R, Viik J, Turjanmaa V, Kahnen M. Effects of polymorphisms in beta1-adrenoceptor and α-subunit of G protein on heart rate and blood pressure during exercise test. The Finnish Cardiovascular Study. J Applied Physiology. 2006;100(2):507–511.


Authors: Dyachenko A.G., Gorobchenko K.M., Savinova E.V., Miroshnechenko E.A.,Shkrioba O.A.

Pages: 259-272



Permanent balance between microbiota, intestinal barrier and mucosal immune system is the basis of the normal intestinal homeostasis. HIV infection leads to significant violations of the immune status and structural damage of the intestinal mucosa that is a threat barrier function. The weakening of the immune pressure leads to disbiotic processes and microbial translocation that causes chronic activation of the immune system and the progression of HIV infection. Although the introduction of combined antiretroviral therapy is a great achievement in the treatment of HIV infection remains a need for some additional measures aimed to restorethe structure and functional integrity of the intestinal epithelium.

The hypothesis that probiotic administration protects the gut surface and can delay progression of HIV infection to the AIDS was proposed in 1995. Over the last five years, new studies have clarified the significance of HIV-1 infection of the gut associated lymphoid tissue (GALT) for subsequent alterations in the microflora and breakdown of the gut mucosal barrier leading to pathogenesis and development of AIDS. Current studies show that loss of gut CD4+ Th17 cells, which differentiate in response to normal microflora, occurs early in HIV-1 disease. Microbial translocation and suppression of the T regulatory (Treg) cell response is associated with chronic immune activation and inflammation. Combinations of probiotic bacteria, which upregulate Treg activation, have a promising effect in suppressing pro inflammatory immune response in models of autoimmunity including inflammatory bowel disease and provide a rationale for use of probiotics in HIV-1/AIDS. Disturbance of the microbiota early in HIV-1 infection leads to greater dominance of potential pathogens, reducing levels of bifidobacteria and lactobacillus species and increasing mucosal inflammation. The interaction of chronic or recurrent infections and immune activation contributes to nutritional deficiencies that have lasting consequences. As discussed here, current and emerging studies support the concept that probiotic bacteria can provide specific benefit in HIV-1 infection.

Key words: intestinal microbiota, intestinal barrier, dysbacteriosis, HIV infection.

This email address is being protected from spambots. You need JavaScript enabled to view it.   

The full text

In progress


  1. Ancuta P, Kamat A, Kunstman KJ, Kim EY, Autissier P, Wurcel A, Zaman T, et al. Microbial translocation is associated with increased monocyte activation and dementia in AIDS patients. PLoS ONE. 2008;3(6):e2516.
  2. Artis D. Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut. Nat Rev Immunol. 2008;8(6):411–20.
  3. Atarashi K, Nishimura J, Shima T, Umesaki Y, Yamamoto M, Onoue M, Yagita H, et al. ATP drives lamina propria T(H)17 cell differentiation. Nature. 2008;455(7214):808–12.
  4. Ayabe T, Satchell DP, Wilson CL, Parks WC, Selsted ME, Ouellette AJ. Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria. Nat Immunol. 2000;1(2):113–8.
  5. Baba N, Samson S, Bourdet-Sicard R, Rubio M, Sarfati M. Commensal bacteria trigger a full dendritic cell maturation program that promotes the expansion of non-Tr1 suppressor T cells. J Leukoc Biol. 2008;84(2):468–76.
  6. Backhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI. Host-bacterial mutualism in the human intestine. Science. 2005;307(5717):1915–20.
  7. Barnes MJ, Powrie F. Regulatory T cells reinforce intestinal homeostasis. Immunity. 2009;31(3):401–11.
  8. Becker Y. The changes in the T helper 1 (Th1) and T helper 2 (Th2) cytokine balance are indicative of an allergic response to viral proteins that may be reversed by Th2 cytokine inhibitors and immune response modifiers – a review and hypothesis.Virus Genes. 2004;28(1):5–18.
  9. Brenchley JM, Douek DC. HIV infection and the gastrointestinal immune system. Mucosal Immunol. 2008;1(1);23–30.
  10. Brenchley JM, Schacker TW, Ruff LE, Price DA, Taylor JH, Beilman GJ, Nguyen PL, et al. CD+4 T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med. 2004;200(6):749–59.
  11. Brenchley JM, Price DA, Douek DC. HIV disease: fallout from a mucosal catastrophe? Nat Immunol. 2006;7(3);235–239.
  12. Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, Rao S, Kazzaz Z, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med. 2006;12(12):1365–71.
  13. Buonaguro L, Tornesello ML, Gallo RC, Marincola FM, Lewis GK, Buonaguro FM. Th2 polarization in peripheral blood mononuclear cells from human immunodeficiency virus (HIV)-infected subjects, as activated by HIV virus-like particles. J Virol. 2009;83(1);304–313.
  14. Coombes JL, Powrie F. Dendritic cells in intestinal immune regulation. Nat Rev. Immunol. 2008;8(6):435–446.
  15. Douek D. HIV disease progression: immune activation, microbes, and a leaky gut. Top HIV Med. 2007;15(4);114–117.
  16. Duh EJ, Maury WJ, Folks TM, Fauci AS, Rabson AB. Tumor necrosis factor alpha activates human immunodeficiency virus type 1 through induction of nuclear factor binding to the NF-kappa B sites in the long terminal repeat. Proc Natl Acad Sci U S A. 1989;86(15):5974–8.
  17. Estes JD, Harris LD, Klatt NR, Tabb B, Pittaluga S, Paiardini M, Barclay GR, et al.. Damaged intestinal epithelial integrity linked to microbial translocation in pathogenic simian immunodeficiency virus infections. PLoS Pathog. 2010;6(8):e1001052.
  18. Ferre AL, Hunt PW, Critchfield JW, Young DH, Morris MM, Garcia JC, Pollard RB, et al. Mucosal immune responses to HIV-1 in elite controllers: a potential correlate of immune control. Blood. 2009;113(17):3978–89.
  19. George MD, Reay E, Sankaran S, Dandekar S. Early antiretroviral therapy for simian immunodeficiency virus infection leads to mucosal CD4+ T-cell restoration and enhanced gene expression regulating mucosal repair and regeneration. J Virol. 2005;79(5):2709–19.
  20. Giorgi JV, Hultin LE, McKeating JA, Johnson TD, Owens B, Jacobson LP, Shih R, et al. Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage. J Infect Dis. 1999;179(4):859–70.
  21. Gori A, Tincati C, Rizzardini G, Torti C, Quirino T, Haarman M, Ben Amor K, et al. Early impairment of gut function and gut flora supporting a role for alteration of gastrointestinal mucosa in human immunodeficiency virus pathogenesis. J Clin Microbiol. 2008;46(2):757–8.
  22. Grossman Z, Meier-Schellersheim M, Paul WE, Picker LJ. Pathogenesis of HIV infection: what the virus spares is as important as what it destroys. Nat Med. 2006;12(3):289–295.
  23. Guadalupe M, Reay E, Sankaran S, Prindiville T, Flamm J, McNeil A, Dandekar S. Severe CD4+ T-cell depletion in gut lymphoid tissue during primary human immunodeficiency virus type 1 infection and substantial delay in restoration following highly active antiretroviral therapy. J Virol. 2003;77(21):11708–17.
  24. Guadalupe M, Sankaran S, George MD, Reay E, Verhoeven D, Shacklett BL, Flamm J, et al. Viral suppression and immune restoration in the gastrointestinal mucosa of human immunodeficiency virus type 1-infected patients initiating therapy during primary or chronic infection. J Virol. 2006;80(16):8236–47.
  25. Harrer T, Harrer E, Kalams SA, Elbeik T, Staprans SI, Feinberg MB, Cao Y, et al. Strong cytotoxic T cell and weak neutralizing antibody responses in a subset of persons with stable nonprogressing HIV type 1 infection. AIDS Res Hum Retroviruses. 1996;12(7):585–92.
  26. Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, Weaver CT. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005;6(11):1123–32.
  27. Hofer U, Schlaepfer E, Baenziger S, Nischang M, Regenass S, Schwendener R, Kempf W, et al. Inadequate clearance of translocated bacterial products in HIV-infected humanized mice. PLoS Pathog. 2010;6(4):e1000867.
  28. Jiang W, Lederman MM, Hunt P, Sieg SF, Haley K, Rodriguez B, Landay A, et al. Plasma levels of bacterial DNA correlate with immune activation and the magnitude of immune restoration in persons with antiretroviral-treated HIV infection. J Infect Dis. 2009;199(8):1177–85.
  29. Johansson ME, Phillipson M, Petersson J, Velcich A, Holm L, Hansson GC. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc Natl Acad Sci U S A. 2008;105(39):15064–9.
  30. Katakura K, Lee J, Rachmilewitz D, Li G, Eckmann L, Raz E. Toll-like receptor 9-induced type I IFN protects mice from experimental colitis. J Clin Invest. 2005;115(3):695–702.
  31. Kelly D, Campbell JI, King TP, Grant G, Jansson EA, Coutts AG, Pettersson S, Conway S. Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-gamma and RelA. Nat Immunol. 2004;5(1):104–12.
  32. Kelly P, Todd J, Sianongo S, Mwansa J, Sinsungwe H, Katubulushi M, Farthing MJ, Feldman RA. Susceptibility to intestinal infection and diarrhoea in Zambian adults in relation to HIV status and CD4 count. BMC Gastroenterol. 2009;9:7.
  33. Knox TA, Spiegelman D, Skinner SC, Gorbach S. Diarrhea and abnormalities of gastrointestinal function in a cohort of men and women with HIV infection. Am J Gastroenterol. 2000;95(12):3482–9.
  34. Kraehenbuhl JP, Neutra MR. Epithelial M cells: differentiation and function.Annu Rev Cell Dev Biol. 2000;16:301–32.
  35. Lane HC, Masur H, Edgar LC, Whalen G, Rook AH, Fauci AS. Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1983;309(8):453–8.
  36. Lederman MM, Penn-Nicholson A, Cho M, Mosier D. Biology of CCR5 and its role in HIV infection and treatment. JAMA. 2006;296(7):815–26.
  37. Lim SG, Condez A, Poulter LW. Mucosal macrophage subsets of the gut in HIV: Decrease in antigen-presenting cell phenotype. Clin Exp Immunol. 1993;92(3):442–7.
  38. Macpherson AJ, Uhr T. Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science. 2004;303(5664):1662–5.
  39. Marchetti G, Bellistri GM, Borghi E, Tincati C, Ferramosca S, La Francesca M, Morace G, et al. Microbial translocation is associated with sustained failure in CD4+ T-cell reconstitution in HIV-infected patients on long-term highly active antiretroviral therapy. AIDS. 2008;22(15):2035–8.
  40. Mattapallil JJ, Douek DC, Hill B, Nishimura Y, Martin M, Roederer M. Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection. Nature. 2005;434(7037):1093–7.
  41. Mazmanian SK, Round JL, Kasper DL. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature. 2008;453(7195):620–625.
  42. McCune JM. The dynamics of CD4+ T-cell depletion in HIV disease. Nature. 2001;410(6831):974–9.
  43. McKenna P, Hoffmann C, Minkah N, Aye PP, Lackner A, Liu Z, Lozupone CA, et al. The macaque gut microbiome in health, lentiviral infection, and chronic enterocolitis. PLoS Pathog. 2008;4(2):e20.
  44. Mehandru S, Poles MA, Tenner-Racz K, Horowitz A, Hurley A, Hogan C, Boden D, et al. Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract. J Exp Med. 2004;200(6):761–70.
  45. Niess JH, Leithauser F, Adler G, Reimann J. Commensal gut flora drives the expansion of proinflammatory CD4 T cells in the colonic lamina propria under normal and inflammatory conditions. J Immunol. 2008;180(1):559–68.
  46. Nilssen DE, Muller F, Oktedalen O, Froland SS, Fausa O, Halstensen TS, Brandtzaeg P. Intraepithelial gamma/delta T cells in duodenal mucosa are related to the immune state and survival time in AIDS. J Virol. 1996;70(6):3545–50.
  47. Ouyang W, Kolls JK, Zheng Y. The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity. 2008;28(4):454–67.
  48. Paiardini M, Cervasi B, Sumpter B, McClure HM, Sodora DL, Magnani M, Staprans SI, et al. Perturbations of cell cycle control in T cells contribute to the different outcomes of simian immunodeficiency virus infection in rhesus macaques and sooty mangabeys. J Virol. 2006;80(2):634–42.
  49. Picker LJ. Immunopathogenesis of acute AIDS virus infection. Curr Opin Immunol. 2006;18(4):399–405.
  50. Piconi S, Trabattoni D, Gori A, Parisotto S, Magni C, Meraviglia P, Bandera A, et al. Immune activation, apoptosis, and Treg activity are associated with persistently reduced CD4+ T-cell counts during antiretroviral therapy. AIDS. 2010;24(13):1991–2000.
  51. Poccia F, Piselli P, Vendetti S, Bach S, Amendola A, Placido R, Colizzi V. Heat-shock protein expression on the membrane of T cells undergoing apoptosis. Immunology. 1996;88(1):6–12.
  52. Rajasuriar R, Booth D, Solomon A, Chua K, Spelman T, Gouillou M, Schlub TE, et al. Biological determinants of immune reconstitution in HIV-infected patients receiving antiretroviral therapy: The role of interleukin 7 and interleukin 7 receptor alpha and microbial translocation. J Infect Dis. 2010;202(8):1254–64.
  53. Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, Edberg S, Medzhitov R. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell. 2004;118(2):229–41.
  54. Rancinan C, Morlat P, Chene G, Saillour F, Guez S, Lacoste D, Bernard N, et al. Prevalence of clinical manifestations of allergic reactions in HIV infection. Cross sectional study of 115 subjects. Rev Med Interne. 1997;18(9):691–4.
  55. Rescigno M, Urbano M, Valzasina B, Francolini M, Rotta G, Bonasio R, Granucci F, et al. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol. 2001;2(4):361–7.
  56. Rook GA, Brunet LR. Microbes, immunoregulation, and the gut. Gut. 2005;54(3):317–320.
  57. Sato A, Iwasaki A. Peyer’s patch dendritic cells as regulators of mucosal adaptive immunity. Cell Mol Life Sci. 2005;62(12):1333–8.
  58. Smith K, McCoy KD, Macpherson AJ. Use of axenic animals in studying the adaptation of mammals to their commensal intestinal microbiota. Semin Immunol. 2007;19(2):59–69.
  59. Stein TP, Koerner B, Schluter MD, Leskiw MJ, Gaprindachvilli T, Richards EW, Cope FO, Condolucci D. Weight loss, the gut and the inflammatory response in aids patients. Cytokine. 1997;9(2):143–7.
  60. Strober W, Murray PJ, Kitani A, Watanabe T. Signalling pathways and molecular interactions of NOD1 and NOD2. Nat Rev Immunol. 2006;6(1):9–20.
  61. Suzuki K, Meek B, Doi Y, Muramatsu M, Chiba T, Honjo T, Fagarasan S. Aberrant expansion of segmented filamentous bacteria in IgA-deficient gut. Proc Natl Acad Sci U S A. 2004;101(7):1981–6.
  62. Tesori V, Puglisi MA, Lattanzi W. et al. Update on small intestinal stem cells. World J Gastroenterol. 2013;19(29):4671–4678.
  63. van de Veerdonk FL, Gresnigt MS, Kullberg BJ, van der Meer JW, Joosten LA, Netea MG. Th17 responses and host defense against microorganisms: an overview. BMB Rep. 2009;42(12):776–87.
  64. Vaishnava S, Behrendt CL, Ismail AS, Eckmann L, Hooper LV. Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interface. Proc Natl Acad Sci U S A. 2008;105(52):20858–63.
  65. Wells JM, Loonen LM, Karczewski JM. The role of innate signaling in the homeostasis of tolerance and immunity in the intestine. Int J Med Microbiol. 2010;300(1):41–8.
  66. Wolf BW, Wheeler KB, Ataya DG, Garleb KA. Safety and tolerance of Lactobacillus reuteri supplementation to a population infected with the human immunodeficiency virus. Food Chem Toxicol. 1998;36(12):1085–94.
  67. Yilmaz OH, Katajisto P, Lamming DW, Gultekin Y, Bauer-Rowe KE, Sengupta S, Birsoy K, et al. mTORC1 in the Paneth cell niche couples intestinal stem cell function to calorie intake. Nature. 2012;486(7404):490–5.

Yin L, Rodriguez CA, Hou W, Potter O, Caplan MJ, Goodenow MM, Sleasman JW. Antiretroviral therapy corrects HIV-1-induced expansion of CD8+ CD45RA+ CD27− CD11a(bright) activated T cells. J Allergy Clin Immunol. 2008;122(1):166–172.



Authors: ZhyliukV.I., MamchurV.I., LievykhA.E., Petruk N.S.

Pages: 273-282



The paper presents the results of research of piracetam cerebroprotective activity under coadministration with hypoglycemic, antioxidant or antiplatelet drugs in rats with hyperglycemia.

Research was carried out on 70 white rats weighing 250–300 g. Experimental diabetes was initiated by subcutaneous injection of alloxan monohydrate. On the 11th day after administration of alloxan the animals were randomized in 7 groups : I – intact (distilled water); II – diabetes (distilled water); III – diabetes + piracetam (500 mg/kg); IV – diabetes + piracetam (400 mg/kg) + metformin (500 mg/kg); V – diabetes + piracetam (400 mg/kg) + pioglitazone (10 mg/kg); VI – diabetes + piracetam (400 mg/kg) + thiotriazoline (100 mg/kg); VII – diabetes + piracetam (400 mg/kg) + acetylsalicylic acid (50 mg/kg). Experimental combinations and distilled water were administered intragastrically for 20 days.

We assessed content of protein oxidative modification markers and total level of nitrates/nitrites in homogenates of neocortex using spectrophotometric analysis. Ultrastructural studies of neocortical tissue were performed using a transmission electron microscope TEM-100-01 according to the standard plan.

We found that experimental model of diabetes was accompanied by the development of carbonyl stress and led to overproduction of nitric oxide in neocortex. Piracetam, when used with metformin, thiotriazoline or acetylsalicylic acid, significantly reduced content of early and late markers of protein molecules degradation (aldehydephenylhydrazones and ketonephenylhydrazones) and decreased level of nitric oxide stable metabolites. Coadministration of piracetam with pioglitazone did not result in considerable effect on content of these substances. We established that the use of all experimental drug combinations did not provide full recovery of ultrastructural changes in the neocortex; however, coadministration of piracetam with thiotriazolin, acetylsalicylic acid and metformin, but not with pioglitazone, led to a significant limitation of destructive changes in neurons and synaptic mechanism. Cerebroprotective activity of the combinations did not depend on the presence of hypoglycemic properties.

Key words: piracetam, metformin, pioglitazone, thiotriazoline, acetylsalicylic acid, protein oxidative modification, nitric oxide, diabetes, neocortex.

This email address is being protected from spambots. You need JavaScript enabled to view it.   

The full text

In progress


  1. Boulton AJ, Vinik AI, Arezzo JC, Bril V, Feldman EL, Freeman R, Malik RA, et al.Diabetic Neuropathies: a statement by the American Diabetes Association. Diabetes Care. 2005; 28(4):956–962.
  2. Mironenko TV, Mironenko MO, EvtushenkoUkrainian Neurological Journal. 2011;3:101–108.
  3. Pankiv VI. [Efficacy of Tiocetam medication for treatment diabetic patients with with diabetic encephalopathy].Mezhdunarodnyj NevrologicheskyiZ2007;4(14).
  4. Markin SP. [Neurological manifestation of diabetes mellitus].  Nevrologiia i Revmatologiia. 2011;1.
  5. Tomlinson DR, Gardiner NJ. Glucose neurotoxicity. Nature Reviews Neuroscience. 2008; 9(1):36–45.
  6. Morozova OG. [Metabolic aspects of pathogenetic therapy for cerebral complications at diabetes mellitus].Liky Ukrainy. 2011;2:50–57.
  7. Liu Y, Tian X, Gou L, Sun L, Ling X, Yin X. Luteolin attenuates diabetes-associated cognitive decline in rats. Brain Res Bull. 2013; 94:23–29.
  8. Umegaki H, Hayashi T, Nomura H, YanagawaM, Nonogaki Z, Nakshima H, Kuzuya M. Cognitive dysfunction: an emerging concept of a new diabetic complication in the elderly. Geriatr Gerontol Int. 2013;13(1):28–34.
  9. Dave KR, Katyare SS. Effect of alloxan-induced diabetes on serum and cardiac butyrylcholinesterases in the rat. J Endocrinol. 2002;175(1):241–250.
  10. Lenzen S. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia. 2008;51:216–226.
  11. Belenichev IF, Pavlov SV. [RoleZaporozhskiyMedicinskiyZ 2005;3:125.
  12. Solodkov AP. Fotometricheskij metod opredelenija nitratov i nitritov v biologicheskih zhidkostjah (instrukcija po primeneniju). [The photometric method to assess nitrates and nitrites in biological fluids (manual)]. Vitebsk State Medical University Publ., 2001. 9 p.
  13. Green LC, Wagner DA, Glogowski J, SkipperPL, Wishnok JS, TannenbaumAnalysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Analytical Biochemistry. 1982;126(1):131–138.
  14. Kamyshnikov VS. Spravochnik po kliniko-biokhimicheskim issledovanijam i laboratornoj diagnostike [Guidelines on clinical and biochemical research and laboratory diagnostics].Moscow: MEDpress–inform, 2004. pp. 425–427.
  15. [Ethics of a doctor and human rights: statements on using animals for biomedical research]. Eksperymentalna ta Klinichna Fiziologija i Biokhimii 2003;2:108–109.
  16. Zanozina OV, Borovkov NN, Shherbatjuk TG. [Free-radical oxidation in diabetes type 2: formation sources and components of pathogenetic mechanisms of toxicity].  2010;3:104–112.
  17. Fatehi-Hassanabad Z, Chan CB, Furman BL. Reactive oxygen species and endothelial function in diabetes. Eur J Pharmacol. 2010;636(1:8–17.
  18. Sosunov AA. [Nitrogen oxide as a intacellulra mediator]. SorosovskiyObrazovatelnyiZ 2000;6(12):27–34.
  19. Luo F, Guo NN, Li SH, Tang H, Liu Y, Zhang
  20. Reynolds ES. The use of lead citrate at high ph an electronopaque stain in electron microscopy. J Cell Biol. 1963;17:208–212.
  21. Sarkisov DS, Perova Yia tehnika.[Microscopic technique]. Moscow:Meditcina, 1996. 542 p.

Uikli B. Elektronnaia mikroskopija dlia nachinaiushhih [Electron microscopy for beginners]. Moscow:Mir Publ., 1975. 324 p.


Authors: Kucheriavchenko M.A.

Pages: 283-291



Introduction. The investigatedxenobiotics are employed to produce plastic, epoxide resins, varnishes, enamels, paints, foam plastic and et cetera. The study of pathophysiological mechanisms triggering structural and metabolic disorders in response to prolonged subtoxic exposure on the body was commissioned by the absence of prognostic characteristics of potential danger, which laproxides can constitute for hematothermal animals and humans. The study showed that determination of integral intensity of blood serum phosphorescence would become a promising methodological approach in early diagnosis of blood serum protein capacity. Considering its high sensitivity and informative value, phosphorescence enables to detect abnormalities when studying electron excitation states of molecules, photochemical reactions, fast molecular transition dynamics, structures and properties of chemical and biological systems. Properties and differences of protein exchange and their conformational compact structure tend to develop with the progression of the impairment. Previous studies have confirmed that alteration of qualitative properties of proteins is always associated with the impairment of their main functions, such as enzyme, hormone, receptor, transport, structural, mechanical, supporting, reserve, substrate-energetic, contractile, electro-osmotic, energy transforming, cogenic, gene regulating, immunologic, anti-toxic, neutralizing and hemostatic functions.

The aim was to determine the effect of laproxides in response to prolonged subtoxic exposure on the indices of blood serum phosphorescence in white rats and assess its prognostic value.

Material and Methods. The study implied determination of blood serum phosphorescence intensity in animals exposed to peroral exposure to epoxide-containing oligo-ethers in dosages of 1/10; 1/100 and 1/1000 DL50 during 45 days. New substances (the trade name “Laproxides”) were employed, namely triglycidyl ether of polyoxypropylene triol with molecular mass 303 (L-303) and ethylene glycol propylene epoxide with molecular mass 500 (L-500). Aqueous solutions of the substances at the above mentioned doses were administered endogastrically with a metal feeding tube on an empty stomach in the morning. The control group received corresponding doses of drinking water.

Discussion. The study of laproxides L-303 and L-500 effect showed a significant increase in blood serum phosphorescence intensity in the group of animals in response to peroral exposure to xenobiotics in 1/10 and 1/100 DL50 dosages in spectral lines of excitation light 297; 313; 334; 365; 404 and 434 nm. In 1/1000 DL50 the substances did not exert any effect on blood serum phosphorescence intensity rate. Thus, high levels of phosphorescence intensity indicate that laproxides at subtoxic doses of 1/10 and 1/100 DL50 induce the development of significant amount of reactive molecules, capable to condition chain reactions of lipids, proteins, nucleic acids and other biological substrates oxidation. The results show that these compounds are capable of changing conformational properties of proteins, nucleic acids and nucleotides, as well as their functional activity, resulted from the formation of free radical membrane pathology.

Key words: xenobiotics, laproxides, blood serum phosphorescence.

This email address is being protected from spambots. You need JavaScript enabled to view it.">  

The full text

In progress


  1. Bagnich SA, Melnichenko IM, Poddenezhnyiy EN. [The effect of matrix on aromatic compounds phosphorescence in porous sol-gel glasses]. Optics and Spectrum. 1995;79(6):936–941.
  2. Zaytseva OV, Zhukov VI, Perepadya SV, Moiseenko AS, Vinnik Yu.A. [Investigation of phosphorescence in patients with colorectal cancer and its diagnostic significance]. Visnyk Problem Biolohii i Medytsyny. 2010;3:136–141.
  3. Levshin LV, Saletskiy AM. Lyuminestsentsiya i ee izmereniya. Molekulyarnaya lyuminestsentsiya [Luminescence and its dimensions. Molecular luminescence]. Moscow: Moscow State University Publ., 1989. 272 p.
  4. Letuta SN, Maryahina VS. [Kinetics of delayed fluorescence as a method of breast cancer diagnosis]. VI Mezhdunarodnaia. nauchno-tehnicheskaia konferentsiia. “Aktualnyie voprosyi teoreticheskoy i prikladnoy biofiziki, fiziki i himii” [Proceedings of the 6th International scientific technical conference “Relevant issues of theoretical and applied biophysics, physics and chemistry”]. Sevastopol, 2010, pp. 222-224. (In Russian).
  5. Mazhul VM, Zaitseva EM, Shavlovsky MM, Povarova OI, Kuznetsova IM, Turoverov KK. [Room temperature phosphorescence of amorphous aggregates and amyloid fibrils resulting from protein misfolding]. Tsitologiya. 2005;47(11):978–987.
  6. Mironov AF. [Photodynamic cancer therapy: a novel effective method for the malignant tumors diagnostics and treatment]. Sorosovskiy Obrazovatelnyiy Zhurnal. 1996;8:32–39.
  7. RekharskyEM, Polenova TV, Borzenko AG. [Phosphorescence of some naphthalene derivative drugs in water media]. Vestnik Moskovskogo Universiteta. Khimia. 2004;45(2):112–116.




Authors: Doroshenko A.M., Dybkova S.M., Rieznichenko L.S., Gruzina T.G., UlbergZ.R., Chekman I.S.

Pages: 292-299



According to the WHO data, iron deficiency anemia (IDA) is one of the most widespread pathological states as well as social problem. IDA is also one of the most important causes of intestinal dysbacteriosis. Varieties of oral iron preparations are widely prescribed as a part of medical care for patients with IDA. However, iron of existing oral antianemic drugs is not usually effectively absorbed. It may lead to elevation of intestinal iron content. The excess of iron in intestine can also result in dysbacteriosis. Moreover, existing antianemic drugs are not usually effective and safe. Thus, either IDA or oral iron supplementation may cause intestinal dysbacteriosis. Therefore, synthesis and development of new classes of biosafe and biocompatible antianemic drugs is an urgent task. Iron nanoparticles are promising in this direction. Due to high biological activity of iron nanoparticles, preclinical study of their effectiveness and safety for IDA treatment should include determining of their impact on intestinal microflora. The aim of this work was to study the influence of iron nanoparticles on intestinal microflora under conditions of oral administration to rats with IDA.

Substance of 40 nm sized spherical zero-valent iron nanoparticles (FeNPs) used in this study have been synthesized according to the original protocol of chemical condensation in water medium by iron (III) chloride reduction. We studied biological activity of FeNPs, as potential pharmacological substance with antianemic properties, on the model of IDA using Wistar female rats. IDA in experimental animals was modelled using iron deficiency diet. The experimental treatment course of rats with IDA included 10 days oral administration of FeNPs at/in therapeutic (12 mg/kg) dose. Commercial preparation based on pharmacological substance ferri (III) hydroxydi polymaltosum complexus was used as comparison drug in therapeutic dose. The status of microflora in lower part of rats’ gastrointestinal tract after experimental treatment course has been determined using standard microbiological protocols.

According to microbiological tests, rats fed with iron deficient diet demonstrated intestinal dysbiosis. In this case, there was a significant reduction of the protective microflora (bifidobacteria and lactobacilli). After 10 days of experimental treatment course (either with FeNPs or comparison drug), we observed normalization of quantitative parameters of protective and transient intestinal microorganisms in rats with IDA up to a level of healthy animals. However, recovery of number of sulphite-reductive clostridia in anemic animals’ gut, which had been receiving FeNPs, was more effective than in the case of comparison drug administration. FeNPs are possessed by favourable effect on the gastrointestinal tract microflora in case of IDA. Therefore, FeNPs are perspective as biosafe and biocompatible pharmacological substance for development of new class antianemic preparations.

Key words: iron nanoparticles, anemia, iron deficiency, dysbacteriosis, intestinal microflora, normalization.

This email address is being protected from spambots. You need JavaScript enabled to view it. 

The full text

In progress


  1. Nissenson AR, Goodnough LT, Dubois RW. Anemia: not just an innocent bystander? Arch Intern Med. 2003;163(12):1400–1404.
  2. Tompkins GR, O'Dell NL, Bryson IT, Pennington CB. The effects of dietary ferric iron and iron deprivation on the bacterial composition of the mouse intestine. Curr Microbiol. 2001;43(1):38–42.
  3. Balamurugan R, Mary RR, Chittaranjan S, Jancy H, Shobana Devi R, Ramakrishna BS. Low levels of faecal lactobacilli in women with iron-deficiency anaemia in south India. Br J Nutr. 2010;104(7):931–934.
  4. Dostal A, Chassard C, Hilty FM, Zimmermann MB, Jaeggi T, Rossi S, Lacroix C. Iron depletion and repletion with ferrous sulfate or electrolytic iron modifies the composition and metabolic activity of the gut microbiota in rats. J Nutr. 2012;142(2):271–277.
  5. Dostal A, Fehlbaum S, Chassard C, Zimmermann MB, Lacroix C. Low iron availability in continuous in vitro colonic fermentations induces strong dysbiosis of the child gut microbial consortium and a decrease of main metabolites. FEMS Microbiol Ecol. 2013;83(1):161–175.
  6. Hamer HM, Jonkers D, Venema K, Vanhoutvin S, Troost FJ, Brummer RJ. Review article: the role of butyrate on colonic function. Aliment Pharmacol Ther. 2008;27(2):104–119.
  7. Stecher B, Hardt WD. The role of microbiota in infectious disease. Trends Microbiol. 2008;16(3):107–114.
  8. Andrews SC, Robinson AK, Rodriguez-Quinones F. Bacterial iron homeostasis. FEMS Microbiol Rev. 2003;27(2–3):215–237.
  9. Santiago P. Ferrous versus ferric oral iron formulations for the treatment of iron deficiency: a clinical overview. Scientific World Journal. 2012;2012:846824.
  10. Zimmermann MB, Chassard C, Rohner F, N'goran EK, Nindjin C, Dostal A, Utzinger J, et al. The effects of iron fortification on the gut microbiota in African children: a randomized controlled trial in Cote d'Ivoire. Am J Clin Nutr. 2010;92(6):1406–1415.
  11. Mevissen-Verhage EA, Marcelis JH, Harmsen-Van Amerongen WC, de Vos NM, Verhoef J. Effect of iron on neonatal gut flora during the first three months of life. Eur J Clin Microbiol. 1985;4(3):273–278.
  12. Lee SH, Shinde P, Choi J, Park M, Ohh S, Kwon IK, Pak SI, Chae BJ. Effects of dietary iron levels on growth performance, hematological status, liver mineral concentration, fecal microflora, and diarrhea incidence in weanling pigs. Biol Trace Elem Res. 2008;126(1)S57–68.
  13. Geisser P, Burckhardt S. The pharmacokinetics and pharmacodynamics of iron preparations. Pharmaceutics. 2011;3(1):12–33.
  14. Chekman IS. Nanofarmakologiia [Nanopharmacology]. Kyiv: Zadruha Publ., 2011. 424 p.
  15. Chekman IS, Ulberg ZR, Malanchuk VO, Gorchakova NO, Zupanets IO. Nanonauka, nanobiologiia, nanofarmatsiia [Nanoscience, nanobiology, nanopharmacy]. Kyiv: Poligraf plius Publ., 2012. 328 p.
  16. Rieznichenko LS, Dybkova SM, Doroshenko AM, Chekman IS, Ulberg ZR. [Synthesis of iron nanoparticles and characterization of their biosafety]. Visnyk Problem Biologii i Medytsyny. 2014;2(3):319–324.
  17. Guidelines “Safety assessment of medical nanopreparations” approved by the Scientific Expert Council of the State Expert Centre of the Ministry of Health of Ukraine (protocol 8, dated
  18. Stefanov O, editors.Doklinichni doslidzhennia likarskykh zasobiv (metodychni rekomendatsii) [Preclinical studies of drugs (Guidelines)]. Kyiv: Avitsenna Publ., 2002. 527 p.
  19. Labinskaia AS. Mikrobiologiia s tekhnikoi mikrobiologicheskikh issledovanii [Microbiology with technique of microbiological studies]. Moscow: Meditsina Publ., 1978. 394 p.

Lakin GF. Biometriia: uchebnoe posobie dlia biologicheskikh spetsialnostei VUZov [Biometrics: a training manual for biological specialties of universities]. Moscow: Vysshaia Shkola Publ., 1990. 352 p.



Authors: Zilfyan A.V., Avagyan S.A. 

Pages: 300-307



We studied the influence of exogenously administered putrescine on morphofunctional state of the central and peripheral organs of immunogenesis of experimental animals. White mice were exposed to single intravascular administration of putrescine (Sigma, USA) at a concentration of 10-9 mg/mL per 100 g animal body weight. Animals were euthanized in 2 and 8 hours after putrescine administration observing all standards set forth by the Yerevan State Medical University (YSMU) Committee on Bioethics for investigations involving laboratory animals.

Structural changes corresponding to the notion of “accidental involution” occurred in the cortical layer of thymus in experimental animals 8 hours after putrescine administration. Structural shifts manifested as a targeted activation of B-dependent zones and layers were observed in spleen and lymph nodes. The performed immunomorphological studies revealed that activation of B-dependent zones expresses a marked increase in number of B-lymphocytes containing IgG, as well as an increase of IL-1α content in these cells. It is not excluded that putrescine at rather low concentrations (similar to those determined in blood serum of intact mammals) in spleen and lymph nodes exerts targeted immunomodulating action and selectively activates B-lymphocytes populations, which, in turn, are responsible for activation of humoral immunity reactions.

Key words: putrescine, organs of immunogenesis, structural shifts, B-lymphocytes, interleukin 1 α, immunomodulation.

This email address is being protected from spambots. You need JavaScript enabled to view it. 

The full text

In progress


  1. Avagyan SA, Zilfyan AV, Yeramyan DG, Nersisyan SS, Avagyan TS. Role of putrescine in processes of increased heart contractile activity formation (Experimental Research: First Communication). The New Armenian Medical Journal. 2008;2(3):83–102.
  2. Bagdade JD, Subbaiah PV, Bartos D, Bartos F, Campbell RA. Polyamines: an unrecognized cardiovascular risk factor in chronic dialysis? Lancet. 1979;13(8113):412–413.
  3. Hakovirta H, Keiski A, Toppari J, Halmekyto M, Alhonen L, Janne J, Parvinen M. Polyamines and regulation of spermatogenesis: selective stimulation of late spermatogonia in transgenic mice overexpressing the human ornithine decarboxylase gene. Mol Endocrinol. 1993;7(11):1430–1436.
  4. Manni A., Badger B, Glikman P, Bartholomew M, Santner S, Demers L. Individual and combined effects of a-difluoromethylornithine and ovariectomy on the growth and polyamine milieu of experimental breast cancer in rats. Cancer Res. 1989;49(13):3529–3534.
  5. Nesher G, Moore TL, Dorner RW. In vitro effects of methotrexate on peripheral blood monocytes: modulation by folinic acid and S-adenosylmethionine. Ann Rheum Dis. 1991;50(9):637–641.
  6. Corona-de-la-Pena N, Uribe-Carvajal S, Barrientos-Rios R, Matias-Aguilar L, Montiel-Manzano G, Majluf-Cruz A. Polyamines inhibit both platelet aggregation and glycoprotein IIb/IIIa activation. J Cardiovasc Pharmacol. 2005;46(2):216–21.
  7. Schipper RG, Penning LC, Verhofstad AAJ. Involvement of polyamines in apoptosis. Facts and controversies: effectors or protectors? Semin Cancer Biol. 2000;10(1):55–68.
  8. Seiler N, Raul F. Polyamines and apoptosis. J Cell Mol Med. 2005;9(3):623–642.
  9. Sjoholm A, Arkhammar P, Berggren PO, Andersson A. Polyamines in pancreatic islets of obese-hyperglycemic (ob/ob) mice of different ages. Am J Physiol Cell Physiol. 2001;280(2):C317–23.
  10. Soulet D, Rivest S. Polyamines play a critical role in the control of the innate immune response in the mouse central nervous system. J Cell Biol. 2003;162(2):257–268.

Yu H, Yoo PK, Aguirre CC, Tsoa RW, Kern RM, Grody WW, Cederbaum SD, Iyer RK. Widespread expression of arginase I in mouse tissues. Biochemical and physiological implications. J Histochem Cytochem. 2003;51(9):1151–1160.



Authors: Tsulun O.V. 

Pages: 308-315



Introduction. Burn can be defined as a tissue damage caused by a variety of agents such as heat, chemicals, electricity, sunlight, or nuclear radiation. Treatment of burns has an important medico-social significance in order to speed up the recovery of injured people and return them working ability. One of perspective directions is to create preparations that possess antioxidant properties, have sufficient reparative anti-inflammatory effect, and are safe.

My aim is to assess the effect of a topical ointment with licorice extract, coenzyme Q10 and dihydroquercetin (further mentioned as LCD ointment) on healing of partial thickness burn wounds in rats.

Material and Methods. Burns were modeled on 20 albino rats, weighting 260–300 g under ketamine (100 mg/kg) anesthesia by pouring hot molten wax at 80°C into pattern of 4 cm2 placed on depilated skin on one side of the animals. Rats were divided into four groups: group 1 – control group; group 2 – treated with LCD ointment; group 3 – treated with methyluracil ointment (reference-drug); group 4 – treated with ointment containing rutin, coenzyme Q10 and licorice extract (further mentioned as LCR ointment). Ointments were applied topically once a day. I performed evaluation by measuring wound contraction and recording the period of epithelialization.

Results and Discussion. Topical application of ointments LCD and LCR enhanced significantly healing of burn wounds. The mean period of epithelialization was significantly reduced in topical LCD ointment (by 31.5%) group and LCR ointment (by 20.4%) group as compared to the control.

Conclusion. I established that ointments LCD and LCR promoted healing of burns and exhibited evident reparative activity on the model of wax-induced burn wounds in rats. Ointments LCD and LCR reduced epithelialization period by 6.8 and 4.4 days respectively, compared to the control group. Planimetric parameters showed that burn area decreased by 63.5% on day 5 and by 98.2% on day 15 in LCD treated group; in LCR ointment group percentages of wound contraction were 44.6% and 94% respectively, which exceeded reference-drug. Therefore, ointments LCD and LCR have expressed reparative activity; they can become promising drugs for further pharmacological studies to use in clinical practice.

Key words: dihydroquercetin, licorice extract, thermal burn, reparative properties, ointment.

This email address is being protected from spambots. You need JavaScript enabled to view it.  

The full text

In progress


  1. Gerych ID, Makar DA, Sachin VS. Termichni opiky [Thermal burns]. Lutsk: Galitska spilka Publ., 2000. 32 p.
  2. Fistal YeYa, Kozinets GP, Samoylenko GYe. Kombustologiya [Combustology]. Donetsk.
  3. Tkacheva OV, Butko YO. The dynamics of the level cytokines and inflammatory markers in rats third-degree burn trauma under influenced by wound-healing medications. European Applied Sciences. 2013;3:61–64.
  4. Velnar T, Bailey T, Smrkolj V. The wound healing process: an overview of the cellular and molecular mechanisms. JIntMed 2009;37(5):32–39.
  5. Hunt TK, Hopf H, Hussain Z. Physiology of wound healing. Adv Skin Wound Care. 2000;13(2 Suppl):6–11
  6. Griendling KK, Sorescu D, Ushio-Fukai M. NAD(P)H oxidase: role in cardiovascular biology and diseases. Circ Res. 2000;86(5):494–501.
  7. Tolstykh MP, Akhmedov BA, Ataev AR, Shin FYe, Parfenov AP. Lechenie ran antioksidantami [Treatmnt of wounds with antioxidants]. Makhachkala: Epokha Publ.,
  8. Gaman DV, Kononenko NN, Altukhov AA. [Antiradical activity of inacsoril]. Chelovek i lekarstvo: materialy XVIII Ros. naz. congressa. [Proceeding of XVIII Russian National Congress human and drug].Moscow, 2011, pp. 428–429.
  9. Rhee M-H, Endale M, Kamruzzaman SM, Lee W-M, Park H-J, Yoo M-J, Cho J-Y.Taxifolin inhibited the nitric oxide production and expression of pro-inflammatory cytokine mRNA in lipopolysaccharide-stimulated RAW264.7 cells. Journal of experimental and biomedical sciences. 2008;14(3):147–155.
  10. Cakir B, Yegen BC. Systemic responses to burn injury. Turk J Med Sci. 2004;34:215226.
  11. Diegelmann RF, Evans MC. Wound healing: an overview of acute, fibrotic and delayed healing. Frontiers in Bioscience. 2004;9:2839.
  12. Kataranovski M, Magic Z, Penjnovic N. Early inflammatory cytokine and acute phase protein response under the stress of thermal injury in rats. Physiol Res. 1999;48(6):473–82.
  13. Ravage ZB, Gomez HF, Czermak BJ, Watkins SA. Mediators of microvascular injury in dermal burn wounds. Inflammation. 1998; 22(6):619-629
  14. Plotnikov MB, Tiukavkina NA. Lekarstvennye sredstva na osnove dikverina [Diquerin-based medications]. Tomsk: Tomsk University
  15. Tsulun OV, Gaman DV, Derymedvid LV. [Efficacy of a new combined ointment with dihydroquercetin, coenzyme Q10 and licorice extract on UV-erythema in rats]. Problems of Ecological and Medical Genetics and Clinical Immunology. 2013;5(119):262–272.
  16. Bairy KL, Rao CM. An experimental model to produce partial thickness burn wound. Indian J Exp Biol. 1997;35(1):7072.
  17. Stefanov OV. Doklinichne doslidzhennia likarskikh zasobiv: metodychni rekomendatsii [Preclinical study of drugs: methodological recommendations]. Kyiv: Avitsena Publ., 2001. 528
  18. Halafian AA. STATISTICA 6. Statisticheskiy analiz dannych [STATISTICA 6. Statistical analysis of data]. Moscow: Binom-Press, 2007. 512 p.
  19. Bodet C, Gafner S, Bergeron C. A licorice extract reduces lipopolysaccharide-induced proinflammatory cytokine secretion by macrophages and whole blood. J Periodontol. 2008;79(9):5261.
  20. Mellors A, Tappel A. The inhibition of mitochondrial peroxidation by ubiquinone and ubiquinol. J Biol Chem. 1966;241(19):4353–6.



Authors: Absettarova A.I., Kakura S.I., Oleynikova O.K.Pikaluk V.S.Bessalova Ye.Yu. 

Pages: 316-322



Our aim is to analyze a xenogenic cerebrospinal fluid as radioprotectivebiological substrate. The article is devoted to revealing and studying of the morphological changes of the irradiated Wistar rats' bone marrow, blood, hypophysis and peripheral glands after parenteral injection of xenogenic cerebrospinal fluid in different periods of postnatal development (newborn, immature, mature). Lactating cows aged 4–6 years were taken as cerebrospinal fluid donors. We studied the effect of cerebrospinal fluid using certain anatomical and histological methods.

It was found out that cerebrospinal fluid preparation caused different inhibiting effects on destructive processes in cells of some organs; it is associated with the presence of broad spectrum of biological active substances in mammalian cerebrospinal fluid. The evident radioprotective effect was proved by the analyses of the destructive processes degree in red bone marrow cells of the rats exposed to total body radiation at 5 Gr and 3- and 10-times infusions of cerebrospinal fluid. Findings testify to activating of regenerator and strengthening processes of all sprouts of red marrow at the correction of consequences of irradiation by introduction of cerebrospinal fluid. However, the least degree of expression of these processes is noticed in the old age group: there is, probably, cerebrospinal fluid with the decline of activity of adaptation mechanisms. Morphofunctional indexes and age-dependent dynamics were revealed using white rats after xenogenic CSF parenteral injections at various ontogenetic periods.

Nowadays, cerebrospinal fluid is considered to be a morphological substrate at the homeostasis anatomophysiological component; it also participates in the intersystemic nervous and endocrine regulation. These facts allow us to formulate a new scientific conception of xenogenic cerebrospinal fluid morphophysiological regulatory effects. That provides their systemic cognition at leading intention to disclose liquor’s regulatory physiological role at an organism. Considering none immunopathological response onto injection of cerebrospinal fluid and the complex assessment of its anatomophysiological effects, we set up challenging perspectives to develop a directional bioactive drug based on cow’s cerebrospinal fluid. This drug can be applied in fields of medical and veterinary science, animal breeding and experimental morphology.

Key words: cerebrospinal fluid, radiation, bone marrow, nervous, endocrine, immune regulation.

This email address is being protected from spambots. You need JavaScript enabled to view it.  

The full text

In progress


  1. Tkach VV, Kubishkin AV, Tkach VV Jr. [Estimation of biological activity level in cattle cerebrospinal fluid on different pharmaceutical tests]. Tavricheski medikobiologicheski vestnik. 2002;5(3):154–155.
  2. Paltsev MA, Kvetnoi IM. Rukovodstvo po neiroimmunoendokrinologii [Guidance on neuroimmunoendicrinology]. 2nd ed. Moscow: Medicine Publ., 2008. 512 p.
  3. Bessalova YeYu, Barsukov NP, Ivahnenko VN. [Changes of dehydrogenase activity in organs of the reproductive system of female pigs at xenogenic cerebrospinal fluid parenterally injection (cytochemical research)]. Morphology. 2006;129(1):80–84.
  4. Bessalova YeYu, Korolov VA. [Indexes of estral cycles of white rats in a norm and at parenteral introduction of xenogenic cerebrospinal fluid]. Bulletin of Experimental Biology and Medicine. 2007;144(8):213–215.
  5. Blanco AI, Chao KS, El Naqa I, Franklin GE, Zakarian K, Vicic M, Deasy JO. Dose-volume modeling of salivary function in patients with head-and-neck cancer receiving radiotherapy. Int J Radiat Oncol Biol Phys. 2005;62(4):1055–69.
  6. Merkulov Kurs patogistologicheskoi tekhniki [Course of pathohistological technique]. 5th ed. Saint Petersburg: Medicine Publ., 1969. 423 p.
  7. Bessalova YeYu. Behavioral activity and anxiety of rats under open field conditions in the norm and after parenteral introductions of xenogenic cerebrospinal fluid. Neurophysiology. 2012;43(5):369–376.



Authors: Zilfyan A. V.,Avagyan S. A. 

Pages: 323-330



Method of immune enzyme assay (ELISA) was employed to study the shifts in content of immunocytokines, prolactin, and insulin-like growth factor-1 in the central and peripheral organs of immunogenesis in mice. Single intravascular administration of putrescine was performed at rather low doses similar to levels determined in blood serum of small laboratory animals (rats and mice). Animals were euthanized by decapitation under the Nembutal narcosis in accordance with the strict requirements of Yerevan State Medical University (YSMU) Committee on Bioethics for investigations involving laboratory animals.

Shifts revealed in thymus of experimental animals signified putrescine-dependent immune-suppressive effect regarding the selective inhibition of IL-2, IL-6 and γ-IFN synthesis in the central organs of immunity. High indices of IL-1a, IL-6 and prolactin were recorded in the spleen and nodes of experimental animals 8 hours after the putrescine administration. It is not excluded that under conditions of our experiment, IL-6 high levels in spleen and lymph nodes were also conditioned by stimulant effect of prolactin towards B-lymphocytes populations (this effect is induced by relatively high levels of prolactin); besides that, similar mechanism of prolactin direct stimulating influence on B-lymphocytes in the aspect of IL-1a synthesis by B-lymphocytes is described in the literature.

It is also known that the enhanced synthesis of γ-IFN in immunocompetent cells is accompanied with the marked activation of specific T-lymphocytes sub-populations: T-suppressors and T-killers possessing the cytotoxic activity. Therefore, we might make an assumption: exogenous putrescine administered by us to the animal organism at rather low concentrations directly and/or indirectly inhibits the activity of cytotoxic T-lymphocytes sub-populations.

Key words: putrescine, organs of immunogenesis, B-lymphocytes, immunocytokines, prolactin, immunomodulation.

This email address is being protected from spambots. You need JavaScript enabled to view it.

The full text

In progress


  1. Berczi I, Nagy E, Kovacs K, Horvath E. Regulation of humoral immunity in rats by pituitary hormones. Acta Endocrinol (Copenh). 1981;98(4):506–13.
  2. Bowlin TL, McKown BJ, Babcock GF, Sunkara PS. Intracellular polyamine biosynthesis is required for interleukin 2 responsiveness during lymphocyte mitogenesis. Cell Immunol. 1987;106(2):260–72.
  3. Bowlin TL, McKown BJ, Sunkara PS. The effect of a-difluoromethylornthine an inhibitor of polyamine biosynthesis, on mitogen induced interleukin 2 production. Immunopharmacology. 1987;13(2):143–7.
  4. Byrd WJ, Jacbos DM, Amoss MS. Synthetic polyamines added to cultures containing bovine sera reversibly inhibit in vitro parameters of immunity. Nature. 1977;267(5612):621–3.
  5. Endo Y, Kikuchi T, Nakamura M. Ornithine and histidine decarboxylase activities in mice sensitized to endotoxin, interleukin-1 or tumour necrosis factor by D-galactosamine. Br J Pharmacol. 1992;107(3):888–94.
  6. Endo Y, Kikuchi T, Takeda Y, Nitta Y, Rikiishi H, Kumagai K. GM-CSF and G-CSF stimulate the synthesis of histamine and putrescine in the hematopoietic organs in vivo. Immunol Lett. 1992;33(1):9–13.
  7. Flescher E, Bowlin TL, Ballester A, Houk R, Talal N. Increased polyamines may downregulate interleukin 2 production in rheumatoid arthritis. J Clin Invest. 1989;83(4):1356–62.
  8. Flescher E, Bowlin TL, Talal N. Regulation of IL-2 production by mononuclear cells from rheumatoid arthritis synovial fluids. Clin Exp Immunol. 1992;87(3):435–7.
  9. Flescher E, Bowlin TL, Talal N. Polyamine oxidation down-regulates interleukin-2 production by human peripheral blood mononuclear cells. J Immunol. 1989;142(3):907–12.
  10. Flescher E, Ledbetter JA, Schieven GL, Vela-Roch N, Fossum D, Dang H, Ogawa N, Talal N. Longitudinal exposure of human T lymphocytes to weak oxidative stress suppresses transmembrane and nuclear signal transduction. J Immunol. 1994;153(11):4880–9.
  11. Lahat N, Miller A, Shtiller R, Touby E. Differential effects of prolactin upon activation and differentiation of human B lymphocytes. J Neuroimmunol. 1993;47(1):35–40.
  12. McMurray R, Keisler D, Kanuckel K, Izui S, Walker SE. Prolactin influences autoimmune disease activity in the female B/W mouse. J Immunol. 1991;147(11):3780–7.
  13. Stefanelli C, Carati D, Rossoni C, Flamigni F, Caldarera CM. Accumulation of N1-acetylspermidine in heart and spleen of isoprenaline-treated rats. Biochem J. 1986;237(3):931–4.
  14. Stefanelli C, Flamigni F, Carati D, Rossoni C, Caldarera CM. Effects of dexamethasone on spermidine N1-acetyltransferase and ornithine activities in rat spleen. Biochim Biophys Acta. 1987;930(1):79–86.

Til HP, Falke HE, Prinsen MK, Willems MI. Acute and subacute toxicity of tyramine, spermidine, spermine, putrescine and cadaverine in rats. Food Chem Toxicol. 1997;35(3–4):337–348.



Authors: Kravchun P.G., Mykhailova Yu.O., Lapsina L.A.

Pages: 331-338



Introduction. Renal dysfunction in patients with chronic heart failure (CHF) plays a key role as a risk factor and predictor of unfavorable prognosis, marker of increasing the frequency of hospitalizations and deaths. In recent years cystatin C as a marker of early diagnosis of glomerular functions, staging and prognosis of chronic kidney disease (CKD) is often used for assessment of renal function. There are a lot of publications about the role of cystatin C as an independent biomarker of cardiovascular events, including myocardial dysfunction in patients without primary renal impairment.

Our aim was to access the cardiorenal interactions in patients with CHF associated with CKD I–II stage by determining the levels of cystatin C.

Material and Methods. We examined 103 patients with CHF. 58 patients with CHF and CKD comprised group 1; group 2 – 45 patients with CHF without CKD. Serum creatinine was measured by Jaffe-method, the levels of cystatin C – by ELISA, glomerular filtration rate (GFR) was calculated by MDRD formula; also used echocardiography, kidneys ultrasound.

Discussion. We determined the increase of creatinine levels in patients with CHF and CKD in 58 % cases, cystatin C – in 78 % cases; the decrease of GFR – in 76.1 % cases, in patients with CHF without CKD – in 42 %, 64 % and 68.9 % cases respectively.

The increase of cystatin C levels was more significant than the classical indicators of glomerular function (creatinine and GFR) in patients with CHF and CKD and without CKD in general groups, also in such subgroups as: 1) patients with preserved systolic function (ejection fraction>45%) and systolic dysfunction (ejection fraction≤45%), 2) patients with presence of left ventricular hypertrophy, 3) with normal values of GFR (GFR ≥ 90 ml/min/1.73 m2) and a moderate decline of GFR (GFR ≤ 89 ml/min/1.73 m2). Thus, cystatin C can be considered as an earlier marker of renal function disorders. We found correlations between ejection fraction and left ventricular mass index with cystatin C. Perhaps, cystatin C contributes to formation of hemodynamic disturbances. Early stages of CKD in patients with CHF potentiate disorders of renal function and play the role as an additional risk factor forprogression of heart failure.

Assessment of cystatin C in CHF with CKD and without CKD patients can help doctors in daily practice to improve the quality of early diagnosis and prognosis.

Key words: chronic heart failure, chronic kidney disease I - II stage, cystatin C, glomerular filtration rate (MDRD), creatinine.

This email address is being protected from spambots. You need JavaScript enabled to view it.

The full text

In progress


  1. Ronco C, McCullough P, Anker SD, Anand I, Aspromonte N, Bagshaw SM, Bellomo R. Cardiorenal syndromes: report from the consensus conference of the Acute Dialysis Quality Initiative. Eur Heart J. 2010;31(6):703–711.
  2. Bongartz LG, Cramer MJ, Doevendans PA, Joles JA, Braam B. The severe cardiorenal syndrome: Guyton revisited. Eur Heart J. 2005;26(1):11–17.
  3. Arutiunov GP. [Pathophysiological processes in the kidneys in patients with chronic heart failure]. Serdechnaya nedostatochnost. 2008;5:234–249.
  4. Reznik EV, Gendlin GE, Guschina VM, Storozhakov GI. [Chronic kidney disease in patients with chronic heart failure (Review)]. Nephrologia i Dialis. 2010;12(1):13–24.
  5. Berezin AE. [Cardiorenal syndrome]. Novosti Mediciny i Farmacii. 2011;359:24–31.
  6. McMurray J, Komajda M, Mckelvie R, Zile M, Ptaszynska A, Donovan M, Massie B, Carson P. Renal dysfunction is associated with increased risk of fatal and non-fatal cardiovascular events in patients with heart failure and preserved ejection fraction – findings from the I-PRESERVE trial. European Journal of Heart Failure Supplements. 2008;7(S1):86.
  7. Borelli G, Cellamaro T, Bellini F, Morelli I, Kardash I, Rondinini L, Mariotti R. Comparative prognostic value of glomerular filtration rate estimating formulas in chronic heart failure. European Journal of Heart Failure Supplements. 2009;8(S2):i470.
  8. Diadyk AI. [Cardiorenal and renocardial syndromes]. Sertseva Nedostatnist. 2009;2:10–19.
  9. Diadyk AI, Bagriy AE, Litvinova IA, et al.  [The defeat of the cardiovascular system in chronic renal failure: the experience of a 15-year prospective study]. Ukrainian Cardiology Journal. 2002;4:38–43.
  10. Kuzmin OB. [Chronic kidney disease and cardiovascular system]. Nefrologia. 2007;11(1):28–37.
  11. Locatelli F, Marcelli D, Conte F, D'Amico M, Del Vecchio L, Limido A, Malberti F, Spotti D. Cardiovascular disease in chronic renal failure: challenge continues. Nephrol Dial Transplant. 2000;15(Suppl 5):69–80.
  12. Velkov VV, Reznikova OI. [Modern laboratory diagnosis of renal pathologies: at the early stages to acute renal failure]. Vestnik “Laboratorii DNK Diagnostiki”. 2011;1(10):6–11.
  13. Turk V, Stoka V, Turk D. Cystatins: biochemical and structural properties, and medical relevance. Front Biosci. 2008;13:5406–20.
  14. Angelidis C, Deftereos S, Giannopoulos G, Anatoliotakis N, Bouras G, Hatzis G, Panagopoulou V, et al. Cystatin C: an emerging biomarker in cardiovascular disease. Curr Top Med Chem. 2013;13(2):164–79.
  15. Peralta CA, Katz R, Sarnak MJ, Ix J, Fried LF, De Boer I, Palmas W, et al. Cystatin C identifies chronic kidney disease patients at higher risk for complications. J Am Soc Nephrol. 2011;22(1):147–55.
  16. Reinhard M, Erlandsen EJ, Randers E. Biological variation of cystatin C and creatinine. Scand J Clin Lab Invest. 2009;69(8):831–836.
  17. Hojs R, Bevc S, Ekart R, Gorenjak M, Puklavec L. Serum cystatin C-based equation compared to serum creatinine-based equations for estimation of glomerular filtration rate in patients with chronic kidney disease. Clin Nephrol. 2008;70(1):10–17.
  18. Agarwal S, Thohan V, Shlipak MG, Lima J, Bluemke DA, Siscovick D, Gomes A, Herrington DM. Association between cystatin C and MRI measures of left ventricular structure and function: multi-ethic study of atherosclerosis. Int J Nephrol. 2011;58(14). ID 153868.
  19. Patel PC, Ayers CR, Murphy SA, Peshock R, Khera A, de Lemos JA, Balko JA, et al. Association of cystatin C with left ventricular structure and function: the Dallas Heart Study. Circ Heart Fail. 2009;2(2):98–104.
  20. Ix JH, Shlipak MG, Chertow GM, Whooley MA. Association of cystatin C with mortality, cardiovascular events, and incident heart failure among persons with coronary heart disease: data from the Heart and Soul Study. Circulation. 2007;115(2):173–9.
  21. Cepeda J, Tranche-Iparraguirre S, Marin-Iranzo R, Fernandez-Rodriguez E, Riesgo-Garcia A, Garcia-Casas J, Hevia-Rodriguez E. Cystatin C and cardiovascular risk in the general population. Rev Esp Cardiol. 2010;63(4):415–422.
  22. Shlipak MG, Katz R, Sarnak MJ, Fried LF, Newman AB, Stehman-Breen C, Seliger SL, et al. Cystatin C and prognosis for cardiovascular and kidney outcomes in elderly persons without chronic kidney disease. Ann Intern Med. 2006;145:237–246.
  23. Gao C, Zhong L, Gao Y, Li X, Zhang M, Wei S. Cystatin C levels are associated with the prognosis of systolic heart failure patients. Arch Cardiovasc Dis. 2011;104(11):565–71.
  24. Taglieri N, Koenig W, Kaski JC. Cystatin C and cardiovascular risk. Clin Chem. 2009;55(11):1932–43.
  25. McMurray JJV, Adamopolos S, Anker SD, et al. [Recommendations of the European Society of Cardiology (ESC) for the diagnosis and treatment of acute and chronic heart failure – 2012]. Novosti Mediciny i Farmatsii. 2012;432:20–29.
  26. Kovalenko VM, Lutay MI, Sirenko YM, editors. Klasificatsia, standarty diahnostiki ta likuvannia [Cardiovascular disease. Classification standards for diagnosis and treatment]. Kiyv, 2011. 96 p.
  27. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(2 Suppl 1):S1–S266.



Authors: Tarasova I.V., Turova L.O., Kasian S.M., Shvydun K.O. 

Pages: 339-345



Our aims was to study the contents of trace elements (Co, Ni, Pb) in biological fluid of the pregnant women and newborns. The objects of investigation were 30 women with physiological pregnancy and 30 healthy full-term newborns. We measured levels of these trace elements in the serum, erythrocytes, cord blood and placenta. The content and balance of microelements were analyzed by the atomic absorption spectrophotometry method using aspectrophotometer C 15-M1 with a flame atomizer(“Selmi”, Ukraine).We also characterized the features of transplacental migration of these micronutrients to a fetus. We studied the placenta barrier function and deposition of cobalt, nickel and lead. Our research proved that lead retained less in the placenta of a pregnant woman than nickel. Thus, nickel can be more vulnerable to the fetus, because of its toxic effect during the prenatal period. We also reported that placenta plays an important role in balance of trace elements in the fetus; it performs a barrier and depot functions. Unfortunately, the placenta barrier function is relatively weak against lead, nickel and cobalt. Although, the placenta can accumulate a greater amount of nickel (accumulation index – 275.8 %) than lead (accumulation index – 204.0 %) and, especially, cobalt (accumulation index – 121.2 %).

Key words: placenta, fetus, full-term newborn.

This email address is being protected from spambots. You need JavaScript enabled to view it.

The full text

In progress


  1. Batman YuA, Ivanitskaya NF, Zykov AS, Stepanova MG. [The level of heavy metals in newborns and their mothers, in condition of ecologically unfavourable Donbass region].Neonatolohiia, khirurhiia ta perinatalna medytsyna.2012;4(6):31–36.
  2. Turova LA. Rol mikroelementiv y patogenezi ta likyvanni ditey z zatrimkou vnutrishneytrobnogo rozvitky [The role of trace elements in the pathogenesis and treatment of children with intrauterine growth retardation] [PhD thesis]. Kyiv, .
  3. Tarasova IV. Mikroelementny disbalans y novonarodzhenykh iz perinatalnoiu patolohieiu: diahnostyka ta prognoz [Microelement imbalances in newborns with perinatal pathology: diagnosis and prognosis] [MD thesis]. Kharkiv, 2013. 398 p.
  4. Ohtomo S, Nangaku M, Izuhara Y, Takizawa S, Strihou Cv, Miyata T. Cobalt ameliorates renal injury in an obese, hypertensive type 2 diabetes rat model. Nephrol Dial Transplant. 2008;23(4):1166–72.
  5. Sabolic I. Common mechanisms in nephropathy induced by toxic metals. Nephron Physiol. 2006;104(3):107–14.
  6. Valko M, Morris H, Cronin MT.Metals, toxicity and oxidative stress. Curr Med Chem. 2005;12(10):1161–208.
  7. Lapach SN. Statisticheskie metody v mediko-biologicheskikh issledovaniiakh s ispolzovaniem Excel [Statistical methods in biomedical research using Excel]. Kyiv: MORION Publ., 2001. 408 p.
  8. Yevstafieva EV, Zalata OA, Sliusarenko AE, KozlovKP. [Features of calcium, iron, manganese, molybdenum, nickel, strontium and lead levels in children with different levels of mental development]. Zdorovie Rebenka.2012;6(41):45–49.
  9. Dobrovolsky LA, BelashovaIG, Radvanska ES. [Pollution and pregnancy outcomes (review)]. Environment and Health. 2007;3(42):29–32.
  10. Rozanov VA. [Low level lead neurotoxicity in children: epidemiological, clinical and neurochemical aspects].Ukrainskyi Medychyi Chasopys.2000;5(19):9-10.
  11. MishchenkoMezhdunarodnyi Meditsynskii Zhurnal.2001;2:38–41.
  12. SyslikovTrace Elements in Medicine. 2000;1:9
  13. Vasiljevic B, Maglajlic-Djukic S, Gojnic M, Stankovic S, Ignjatovic S, Lutovac D. New insights into the pathogenesis of perinatal hypoxic-ischemic brain injury. Pediatr Int. 2011;53(4):454–62.



Authors: Tymchenko O.I., Koba O.P., Mykytenko D.O., Maksiyan O.I., Lynchak O.V.

Pages: 346-352



Introduction. In conditions of decreasing birthrate, the infertile couples as well as couples with reproductive losses could be as a reserve of increasing birthrate. These families want, but cannot have got their own children. A sequential detection and study of complex cases and mechanisms of infertility development allows us to determine the exact individual strategy of treatment. In the same time, the measures of primary prevention (based on the prevention of negative influence of different risk factors) are efficient on a population level. Even in a case of reproductive clinics activity, the prevention measures on a primary stage of pregnancy planning are necessary and urgent. Many factors, which could be important in human pathology development, should be taken into account in order to prognostication of individual reproductive health status. That is why process of regional investigation results extrapolation to the other regions without analysis of their features is inadequate and ineffective.

The aim is to determine the infertility development risk factors prevalence between people of the Chernivetsky region over time.

Material and Methods. The primary materials were 273 special registration cards for cases of infertile couples in the Chernivetsky region (in 1999–2003 and 2012–2013).The cases of healthy children birth were taken as control (1010). The risk was calculated as Odds Ratio indicator, including 95 % confidence interval. The infertility risk factors prevalence was determined by comparison of infertile couples percentage in 1999–2003 and 2012–2013. The critical level of statistical criterions was accepted as P ≤ 0.05.

Discussion. In 1999–2003 the main infertility risk factors were chronic female and male infections (OR = 4.02 95%CI:3.35–4.82 and 4.82 95%CI:4.18–5.61 accordingly). In comparison with 1999–2003 / 2012–2013, we noticed the absence of differences in prevalence of extragenital and endocrine pathology, chronic infections, professional risks as well as smoking between infertile couples. Over time between infertile women and men, we detected increasing of educational level and fraction of unemployed individuals. Moreover, 7-time increasing of fraction of couples, who used paid medical services, was shown as well as 4-time increasing of fraction of couples, whose total income allows them to use paid medical services.

Key words: infertility, married couples, risk factors.

This email address is being protected from spambots. You need JavaScript enabled to view it.">This email address is being protected from spambots. You need JavaScript enabled to view it.

The full text

In progress


  1. Nazarenko TA. [Modern approaches to infertility treatment]. In: Prilepskaia VN, editor.Poliklinicheskaya ginekologiya[Policlinic gynecology].2nd ed. enl.Moscow: Med-Press Inform Publ.,
  2. Baskakov VP. Klinika i lechenie endometrioz. [Clinic and endometriosis treatment]. Мoscow: Meditsyna Publ., 1990. 240 р.
  3. Zaporozhan VM, Sobol RV. [Basic components of multifaktorial infertility of women]. Pedіatrіia, Akusherstvo ta Hіnekolohіia. 2003;1:101–103.
  4. Yen SSC, Jaffe RB, editors. Reproductive endocrinology. 2nd ed. Philadelphia, PA:W.B.Saunders; 1986. 806 р.
  5. Konovalov OYe. [Problems of health care in a fight against infertility]. Zdravookhranenie Rossiyskoy Federatsii.1990;5:1014.
  6. Erenshtain V. [Case-control studies]. Mezhdunarodnyi Zhurnal Meditsinskoy Praktiki. 2007;1:39–50.
  7. Mikitenko DO, Linchak OV, Koba OP, Kachko GO, Timchenko OІ. [Negative factors of infertility in marriage: result of epidemiological investigation of population in some regions of Ukraine]. Aktualnі problemy akusherstva і hіnekolohіi, klіnіchnoi іmunolohіi ta medychnoi henetyki. 2014;27:156–173.
  8. Timchenko OІ, Linchak OV, Maksіian OІ, Shkrobanets ІD, Nikifor LV, Polіshchuk MІ, Vdovіchen AM. Genofond і zdorovia: reproduktivny potentsіal naselennya ta vrodzhena patologіya novonarodzhenikh v Chernіvestkіy oblastі [Genofound and health: reproductive potential of population and birth defects in the Chernivetsky region] Kiїv: Medіnform Publ., 2010. 147 p.
  9. Zіnchenko GG, Linchak OV, Kurilo ІO, Timchenko OІ. [Reproductive losses among female smokers with different levels of education]. Aktualnі problemy akusherstva і hіnekolohіi, klіnіchnoi іmunolohіi ta medychnoi henetyki. 2009;16:307–313.



Authors: Diaa Kareem Abd-Ali, Halima Yusuf Al-Rubaiyee

Pages: 353-364



Cardiovascular disease (CVD) remains a global health problem that affects millions of people worldwide. This disease affects people at all ages; it's not a disease of the elderly. Thus, this study is conducted to establish a data base for the patient adherence to medications and the impact of social and economic factors on such adherence after ischemic heart disease in Al-Najaf City.

Our aim was to assess patients’ adherence to medications after ischemic heart disease (IHD), to assess the social and economic factors of the patients, which may affect their adherence to medications, and to find out the impact of social and economic factors on patients’ adherence to medications.

Material and Method. We carried out a cross-sectional study in Al-Najaf Health Directorate, Al-Sadder Medical City and Al-Najaf Center for Heart Diseases and Surgery from June 5, 2013 to April 10, 2014. A non-probability sampling (purposive sample) of 102 patients diagnosed medically as the ischemic heart disease patients (angina and myocardial infarction) were included in the study. We collected the data using the semi-structured questionnaire, which consisted of three parts: 1) socio-demographic and clinical data form; 2) patient adherence to medications scale; 3) socioeconomic factors of a patient. The data were described statistically and analyzed using the descriptive and inferential statistical analyses.

Results and Discussion. Our results reveled a deficient in the patients’ adherence to medications. Moreover, there was a significant impact of the social and economic factors on the patients’ adherence to medications after ischemic heart disease.

Conclusion. We found a deficient in the patients’ adherence to therapeutic recommendations, specifically to medications use. Certain defects were with the social and economic factors, which could enhance the patient adherence to medications. The intensive comprehensive wide population-based studies should be conducted to assess the factors, which affect the patient adherence to medications after the IHD suggesting a suitable solution for these factors to improve the level of patient adherence. The health education program should be implemented to increase patients’ knowledge about importance of adherence to medications, certain factors that may affect their adherence, and possible ways to solve this problem.

Key words: impact, patient adherence, ischemic heart disease.

This email address is being protected from spambots. You need JavaScript enabled to view it.

The full text

In progress


  1. Al-Jubouri M. Assessment of stressful life events of adult patients with ischemic heart disease in Baghdad City [PhD thesis]. Baghadad: University of Baghdad Publ. pp. 2–11.
  2. Ngiap-Chuan T, Wei S, Seng-Lian C. Lifestyle modifications of patients with coronary heart disease on follow up in public primary care centres in Singapore: assessment of perception and behavior. The Singapore Family Physician. 2011;37(1):67–72.
  3. Jin J, Sklar E, Sen M, Li C. Factors affecting therapeutic compliance: a review from the patient’s perspective. Ther Clin Risk Manag. 2008;4(1):269–286.
  4. Sabate E. WHO adherence to long-term therapies evidence for action. 6th ed. Geneva: World Health Organization, 2003. 209 p.
  5. van Dulmen S, Sluijs E, van Dijk L, de Ridder D, Heerdink R, Bensing J. Patient adherence to medical treatment: a review of reviews. BMC Health Serv Res. 2007;7:55.
  6. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353(5):487–497.
  7. Grahame-Smith DG, Aronson JK. Oxford textbook of clinical pharmacology and drug therapy. 3rd ed. USA: Oxford University Press, 2002. 641 p.
  8. World Health Organization. Adherence to long-term therapies: evidence for action. Retrieved from:
  9. Sokol MC, McGuigan KA, Verbrugge RR, Epstein RS. Impact of medication adherence on hospitalization risk and healthcare cost. Med Care. 2005;43(6):521–530.
  10. Lawson VL, Lyne PA, Harvey JN, Bundy CE. Understanding why people with type 1 diabetes do not attend for specialist advice: a qualitative analysis of the views of people with insulin-dependent diabetes who do not attend diabetes clinic. J Health Psychol. 2005;10(3):409–23.
  11. Kaplan RC, Bhalodkar NC, Brown EJ Jr, White J, Brown DL. Race, ethnicity, and sociocultural characteristics predict noncompliance with lipid-lowering medications. Prev Med. 2004;39(6):1249–55.
  12. Mishra P, Hansen EH, Sabroe S, Kafle KK. Socio-economic status and adherence to tuberculosis treatment: a case-control study in a district of Nepal. Int J Tuberc Lung Dis. 2005;9(10):1134–9.
  13. Okoro R, Ngong C. Assessment of patient’s antihypertensive medication adherence level in non-comorbid hypertension in a tertiary hospital in Nigeria. Int J Pharm Biomed Sci. 2012;3(2):47–54.
  14. Saleem F, Hassali MA, Shafie AA, Awad AG, Bashir S. Association between knowledge and drug adherence in patients with hypertension in Quetta, Pakistan. Tropical Journal of Pharmaceutical Research. April 2011; 10 (2): 125-132.
  15. Mehta RH, Montoye CK, Faul J, Nagle DJ, Kure J, Raj E, Fattal P, et al. Enhancing quality of care for acute myocardial infarction: shifting the focus of improvement from key indicators to process of care and tool use: the American College of Cardiology Acute Myocardial Infarction Guidelines Applied in Practice Project in Michigan: Flint and Saginaw Expansion. J Am Coll Cardiol. 2004;43(12):2166–73.
  16. Oliveira-Filho AD, Barreto-Filho JA, Neves SJ, Lyra Junior DP. Association between the 8-item Morisky Medication Adherence Scale (MMAS-8) and blood pressure control. Arq Bras Cardiol. 2012;99(1):649–58.
  17. Iestra JA, Kromhout D, van der Schouw YT, Grobbee DE, Boshuizen HC, van Staveren WA. Effect size estimates of lifestyle and dietary changes on all-cause mortality in coronary artery disease patients: a systematic review. Circulation. 2005;112(6):924–3.
  18. Bisiriyu G. Non-adherence to lifestyle modification recommendations (diet and exercise) amongst type 2 diabetes mellitus patients attending extension II clinic in Gaborone, Botswana [PhD thesis]. Republic of South Africa: University of Limpopo, 2008. pp. 1–3.
  19. Brown JR, Malenka DJ, DeVries JT, Robb JF, Jayne JE, Friedman BJ, Hettleman BD, et al. Transient and persistent renal dysfunction are predictors of survival after percutaneous coronary intervention: insights from the Dartmouth Dynamic Registry. Catheter Cardiovasc Interv. 2008;72(3):347–54.
  20. Desai NR, Choudhry NK. Impediments to adherence to post myocardial infarction medications. Curr Cardiol Rep. 2013;15(1):322.
  21. Viswanathan M, Golin CE, Jones CD, Ashok M, Blalock SJ, Wines RC, Coker-Schwimmer EJ, et al. Interventions to improve adherence to self-administered medications for chronic diseases in the United States: a systematic review. Ann Intern Med. 2012;157(11):785–95.



Authors: Kasianova A.Yu., Lebid I.G.

Pages: 365-372


Modern cardiosurgery opportunities of highly qualified specialists can help patients with congenital heart disease (CHD) to improve significantly their health and life longevity, but at the same time, many patients still complain of weakness, fast tiredness, bad mood and low quality of life.

Our aims was to identify medical and psychological features of low quality of life of adult patients of younger age after congenital heart surgery.

Material and Methods. The study involved patients (aged 19 ± 2.8 years) with surgically corrected inborn congenital heart disease. The psychodiagnostics included the study of the quality of life and the identification of signs of anxiety and depression in the patients.
Discussion. We identified gender differences in the quality of life of young adult patients with CHD: namely, every day activities of men were significantly limited due to their physical condition, – it either precedes or follows the worsening of their emotional status – but women had rather high indices of life quality. However, both men and women displayed a dramatic limitation of social contacts. Young adult patients with surgically corrected CHD displayed significant limitation of social contacts, decrease in communication levels due to the worsening of their physical and emotional condition. 42 % of male and 50 % of female patients displayed the symptoms of anxiety and/or depressive disorders.

Conclusion. Having analyzed practical advantages and possible disadvantages of different foreign questionnaires, which are adapted in Russian to assess the quality of life, we found out that MHFLQ (Minnesota Living with Heart Failure Questionnaire) is very simple and easy to use in individual analysis. However, it does not allow us to differentiate the calculation of component parts of mental, physical and social functioning for a specific group of patients. At the same time, the MOS SF-36 (36-Item Short Form Health Survey) and WHOQoL-bref (World Health Organization Quality of Life) methods allow us to assess a specific influence of physical, mental and social components on the quality of life. Unfortunately, these surveys have displayed different results. The HADS (Hospital Anxiety Depression Scale) method provides an opportunity to single out a patients’ risk group characterized by a clinical level of depression and anxiety. The implementation of active and timely psychodiagnostics and psychocorrection measures will help adult patients with the inborn congenital heart disease after the surgery to improve their quality of life.

Key words: congenital heart disease, adult patients, cardiosurgery, quality of life, anxiety, depression.

This email address is being protected from spambots. You need JavaScript enabled to view it.

The full text

In progress


  1. Sommerville J. Management of adults with congenital heart disease: an increasing problem. Annu Rev Med. 1997;48:283–93.
  2. Webb GD. Care of adults with congenital heart disease – a challenge for the new millennium. Thorac Cardiovasc Surg. 2001;49(1):30–4.
  3. Longmuir PE, Brothers JA, Ferranti SD, Hayman LL, Hare GF, Matherne P, Davis CK, et al. Promotion of physical activity for children and adults with congenital heart disease: a scientific statement from the American Heart Association. Circulation. 2013;127(21):2147–59.
  4. Sable C, Foster E, Uzark K, Bjornsen K, Canobio MM, Connolly HM, Graham TP, et al. Best practices in managing transition to adulthood for adolescents with congenital heart disease: the transition process and medical and psychosocial issues: a scientific statement from the American Heart A Circulation. 2011;123(13):1454–85.
  5. Callus E, Quadri E, Chessa M. Elements of psychocardiology in the psychosocial handling of adults with congenital heart disease. Front Psychol. 2010;1(34):1–6.
  6. Kovacs AH, Saidi AS, Kuhl EA, Sears SF, Silversides C, Harrison JL, Ong L, et al. Depression and anxiety in adult congenital heart disease: predictors and prevalence. Int J Cardiol. 2009;137(2):158–64.
  7. Voronkov LG, Parascheniuk LP. [Quality of life in patients with chronic heart failure: topical aspects]. Sertseva Nedostatnist. 2010;2:12–16.
  8. Novik AA, Ionova TI. Rukovodstvo po issledovaniiu kachestva zhizni v meditsine. [Guidelines on the study of quality of life in medicine]. 2nd edition.Мoscow: OLMA Media Group Publ., 2007. 320p.
  9. The World Health Organization Quality of Life (WHOQOL)-bref. Retrieved from:
  10. Akarachkova OS. [On the question of diagnosis and treatment of psycho-vegetative disorders in somatic practice]. Lechashchiy Vrach. 2010;10.
  11. Kasianova A, Revenko K, Babliak O. [Emotional disorders as a cause of poor quality of life in patients after cardiac surgery]. Meditsinskaya P 2013;8(20):66–68.
  12. Bang JS, Jo S, Kim GB, Kwon BS, Bae EJ, Noh CI, Choi JY. The mental health and quality of life of adult patients with congenital heart disease. Int J Cardiol. 2013;170(1):49–53.
  13. Horner T, Liberthson R, Jellinek MS. Psychosocial profile of adults with complex congenital heart disease. Mayo Clin Proc. 2000;75(1):31–6.
  14. Bromberg JI, Beasley PJ, D'Angelo EJ, Landzberg M, DeMaso DR. Depression and anxiety in adults with congenital heart disease: a pilot study. Heart Lung. 2003;32(2):105–10.
  15. Freitas IR, Castro M, Sarmento SL, Moura C, Viana V, Areias JC, Areias ME. A cohort study on psychosocial adjustment and psychopathology in adolescents and young adults with congenital heart disease. BMJ Open. 2013;3(1):e001138.
  16. Wang Q, Hay M, Clarke D, Menahem S. The prevalence and predictors of anxiety and depression in adolescents with heart disease. J Pediatr. 2012;161(5):943–6.



Authors: Orlovskyi V.F, Hordina M.A., Orlovskyi O.V., Skoropad Yu.I.

Pages: 373-380


Introduction. Metabolic syndrome(MS) is a problem of the 21st century in industrialized countries. Hypovitaminosis D is a risk factor, which may cause development of metabolic disorders. D-deficiency is usually registered in obese patients. Our aim was to find the association between metabolic syndrome and vitamin D levels in obese patients.

Material and Methods. We examined 62 obese patients with coronary heart disease: 33 patients with MS (aged 63.9 ± 1.69 years with BMI 35.1 ± 0.59 kg/m2) and 29 without MS (aged 66.9± 2.25, (p >0,05); with BMI 34.9 ± 0.57kg/m2). 25(OH) vitamin D3 levels were measured by the immunoassay analysis. Insulin resistance was estimated by fasting blood insulin, HOMA-IRQUCKI and НОМА%S.

Discussion. Serum 25(OH)D3 levels were significantly lower in MS obese patients than in obese patients without MS (39.2 ± 2.11 vs 46.5 ± 2.97, p < 0.05). The low 25(OH)D3 levels correlated with BMI, total cholesterol, triglycerides, high and low density lipoproteins, insulin, and HOMA-IR (p<0.05). After stratifying the study population according to 25(OH)D3 concentrations, patients in the lowest quartile showed a markedly increased prevalence of MS compared with those in the highest quartile (68.8 vs 25 %). Using the one way analysis of variance (ANOVA), we revealed that patients in quartile IV (with the highest 25(OH)D plasma level (53.9–70.7 nmol/l)) had significantly lower blood glucose (p = 0,007) and fasting insulin (p < 0.001). Moreover, there was better performance sensitivity of peripheral tissues insulin that is likely to lower the level of HOMA-IR index and raise the QUCKI index (p < 0.001). They also maintained a more favorable performance lipids levels: significantly lower concentrations of total cholesterol (p < 0.001), triglycerides (p < 0.001), but higher HDL levels (p = 0.020). We did not find any significant difference between quartiles I and IV for anthropometric indicators, as well as HOMA%S.

Conclusion. A strong association exists between hypovitaminosis D and MS in obese patients independently/disregarding / from BMI and waist circumference. This indicates that the association between low 25(OH)D levels and MS is not merely induced by vitamin D deposition in fat tissue and hypovitaminosis D in patients with obesity may contribute to the development of metabolic changes, such as atherogenic dyslipidemia and insulin resistance that are components of MS.

Key words: vitamin D, obesity, metabolic syndrome, insulin resistance.

The full text

In progress


  1. Christakos S, Ajibade DV, Dhawan P, Fechner AJ, Mady LJ.Vitamin D: metabolism. Rheum Dis Clin North Am. 2012;38:1–1.
  2. Krasowski MD, Ni A, Hagey LR, Ekins S. Evolution of promiscuous nuclear hormone receptors: LXR, FXR, VDR, PXR, and CAR. Mol Cell Endocrinol. 2011;334(1–2):39–48.
  3. Verhave G, Siegert CE. Role of vitamin D in cardiovascular disease. Neth J Med. 2010;68(3):113–8.
  4. Zittermann A, Gummert JF.Nonclassical vitamin D action. 2010;2(4):408
  5. Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2007;92(6):2017–29.
  6. Holick MF. The vitamin D deficiency pandemic and consequences for nonskeletal health: mechanisms of action. Mol Aspects Med. 2008;29(6):361–8.
  7. Hypponen E, Power C. Vitamin D status and glucose homeostasis in the 1958 British birth cohort: the role of obesity. Diabetes Care. 2006;29(10):2244–6.
  8. McGill AT, Stewart JM, Lithander FE, Strik CM, Poppitt SD. Relationships of low serum vitamin D3 with anthropometry and markers of the metabolic syndrome and diabetes in overweight and obesity. Nutr J. 2008;7:4.
  9. Esteghamati A, Aryan Z, Esteghamati A, Nakhjavani M. Differences in vitamin D concentration between metabolically healthy and unhealthy obese adults: Associations with inflammatory and cardiometabolic markers in 4391 subjects. Diabetes Metab. 2014. doi:10.1016/j.diabet.2014.02.007.
  10. Cheng S, Massaro JM, Fox CS, Larson MG, Keyes MJ, McCabe EL, Robins SJ, et al.Adiposity, cardiometabolic risk, and vitamin D status: the Framingham Heart Study. 2010;59(1):242–8.
  11. Barchetta I, De Bernardinis M, Capoccia D, Baroni MG, Fontana M, Fraioli A, Morini S, et al. Hypovitaminosis D is independently associated with metabolic syndrome in obese patients. PLoS ONE. 2013;8(7):e68689.
  12. Bershtein LM, Kovalenko I.G. [Metabolically healthy obese subjects and metabolic signs of obesity in subjects with normal body weight: what is behind?]. Problemy 2010;3:47–51.
  13. Park K, Lee DH, Erickson DJ, Himes JH, Shikany JM, Jacobs DR Jr. Association of long-term change in waist circumference with insulin resistance. Obesity. 2010;18(2):370–6.
  14. Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, Quon MJ. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. 2000;85(7):240210.



Authors: Yazykov O.V., Leonov V.V.

Pages: 381-389


Introduction. Up to 70 % of the female population of Ukraine has benign breast diseases, so it is extremely important to treat these patients. We know that sector resection of breast is aimed at the elimination of pathologically altered focus, but this method does not provide satisfactory aesthetic results. Scar deformation of the breast, the loss of its natural appearance after surgery significantly reduces the quality of life of patients, which can be a convincing evidence of the low efficiency of sector resection.

Our aim is to analyze the effectiveness of breast benign surgery using traditional and modified techniques.

Material  and Methods. We studied the results of treatment of 151 patients with benign breast diseases: 106 women were operated using the developed methods, sector resection of the breast was performed on 45 patients performed. We used the instruments SF-36v2TM to assess quality of life; we used BEQ before surgery, in 3 and 12 months after surgery to assess the aesthetic satisfaction tool. We estimated radicality and validity of operations from the results of histological examination of removed tissue.

Discussion. The analysis of questionnaires for three observation periods revealed that sector resection of the breast did not change the health-related quality of life of patients (51.9 and 46.08 vs. 50.8 and 47.75 points before surgery for PCS and MCS, respectively (MID ˂ 2). At the same time, a significant negative impact on the aesthetic component of quality of life made the results of surgical treatment unsatisfactory. However, the developed operations enhanced health-related quality of life of patients in a year (53.7 and 53.8 vs. 51.01 and 43.57 points before surgery for PCS and MCS respectively, p = 0.01; MID ˃ 2). For instance, significantly increased the satisfaction of the aesthetic state of breast (3.82 and 3.78 vs. 3.58 and 3.53 points before surgery for satisfaction with attributes level of self-confidence, p ˂ 0.05). Polycystic breast lesions in more than 20 % of cases expressed proliferative and degenerative changes. Therefore, the maximum removal of tissue is the prevention of breast cancer. Due to the high probability of dysplastic changes in fibroadenomas in patients older than 35 years (10 %), we believe that observation and conservative treatment is unacceptable.

Key words: breast benign lesions, mini-invasive operations, plastic and reconstructive surgery, quality of life.

The full text

In progress


  1. Pristash YuYa. [Nonhormonal rehabilitation of reproductive system in women after surgical treatment of fibrocystic mastopathy]. Taking Care of a W 2014;(6):8–10.
  2. Chuhrienko DP, Lyulko AV. Atlas operatsiy na molochnoy zheleze [Atlas of breast surgery]. Кyiv: Zdorovie Publ., 1971.146
  3. Andruschenko VV, Leonov VV, Yazykov OV, Lukavenko IM. [Oncoplastic operations in treatment of polycystic disease of mammary gland]. Kharkiv Surgical School. 2012;54(3):39–41.
  4. Druzhkov OB, Gataullin IG, Druzhkov BK, Druzhkov MO. [Optimization of the principles of surgical treatment of benign mammary disease]. Kazan Medical J.2010;91(1);120–121.
  5. Egiev VN, Rudakova MN, Zori EA. [The evolution of benign nodular lesions of mammary gland]. Endoscopic Surgery. 2007;4:58–62.
  6. Hermans BJ, Boeckx WD, de Lorenzi F, van der Hulst RR. Quality of life after breast reduction. Ann Plast Surg. 2005;55(3):227
  7. Anderson RC, Cunningham B, Tafesse E, Lenderking WR. Validation of the breast evaluation questionnaire for use with breast surgery patients. Plast Reconstr Surg. 2006;118(3):597–602.
  8. Teplyi VV. [The impact of surgical correction on body cosmetic defects on health-related quality of life]. Plastychna ta Rekonstruktyvna Khirirhiia. 2012;18(1):20–30.
  9. Alderman AK, Bauer J, Fardo D, Abrahamse P, Pusic A. Understanding the effect of breast augmentation on quality of life: prospective analysis using the BREAST-Q. Plast Reconstr Surg. 2014;133(4):787–795.
  10. Ciatto S, Biggeri A, Rosselli M, Bartoli D. Risk of breast cancer subsequent to proven gross cystic disease. Eur J Cancer. 1990;26(5):555–7.
  11. Dixon JM, McDonald C, Elton RA, Miller WR. Risk of breast cancer in women with palpable breast cysts: a prospective study. Lancet. 1999;353(9166):1742–5.
  12. Chen CM, Disa JJ, Sacchini V, Pusic AL, Mehrara BJ, Garcia-Etienne CA, Cordeiro PG. Nipple-sparing mastectomy and immediate tissue expander/implant breast reconstruction. Plast Reconstr Surg. 2009;124(6):1772–80.



Authors: Sokolenko A.A., Sydorchuk L.P., Sokolenko M.O.

Pages: s1-s12



Introduction. Abdominal obesity (AO) is one of the major independent risk factors of arterial hypertension (AH). AH and AO are multifactorial polygenic diseases. The peroxisome proliferator activated by gamma 2 receptor (PPAR-g2) plays a pivotal role in the lipid metabolism. PPAR receptors modulate the activity of the renin-angiotensin-aldosterone system (RAAS) through transcriptional control of the synthesis of renin, angiotensin, angiotensin-converting enzyme (ACE) and angiotensin II receptor type 1, linking biological effects of RAAS and PPARs. Therefore, the study of genes polymorphism PPAR-γ2 receptor and ACE allows us to explore in detail their role in the pathogenesis of AH and AO.

Our aim was to analyze the frequency of alleles and genotypes of Pro12Ala polymorphism of PPAR--g2 gene (rs1801282) and I/D polymorphism of ACE gene (rs4646994) in patients with essential AH (EAH) combined with overweight or AO.

Material and Methods. 110 screened patients with EAH I–III stages participated in a prospective study: 56.4 % women, 43.6 % men; mean age – 53.3 ± 6.05 years. Among them we revealed EAH I in 22.7 % cases, EAH II – in 45.45 %, EAG III – 31.8 %; overweight persons – 38.2 %, with AO – 53.6 %. The control group included 50 healthy individuals. Alleles of polymorphic locus were studied by polymerase chain reaction based method. Statistical processing was performed usingthe Statistica® 7.0 software. The differences were considered significant at p < 0.05.

Results. The DD-genotype of ACE gene in EAH patients is observed in 39.1 % cases, which is 2.2 times more than in the control group. In patients with EAH dominated "unfavorable" D allele. DD-genotype is associated with a greater frequency of concomitant coronary artery disease, cerebrovascular disease, left ventricle hypertrophy (LVH) in women, higher levels of systolic blood pressure (SBP), and obliterative arterial disease of lower extremities (OADVE).

ProPro-genotype of PPAR-g2 gene was found in 63.6 % cases, which generally does not differ from the control group (60.0 %). Among patients with EAH dominates Pro-allele by 3.9 times (79.5 % vs. 20.4 % Ala-allele carriers), likewise in the control group by 3.5 times (78.0 % vs. 22.0 %), respectively. ProPro-genotype in patients with EAH associated with significantly more frequent cases of diabetes mellitus type 2, AO, LVH in men, OADVE, inherited AO, higher SBP, diastolic BP, and waist circumferences in men. In patients with EAH I dominates I-allele of ACE gene by 3.8 and 3.23 times and ProPro-genotype of PPAR-g2 gene over AlaAla-genotype by 4.67 and 14 times. Exclusively D-allele and Pro-allele carriers were available among patients with EAH III stage. In patients with EAH with normal body weight and AO 1st degree II genotype prevails over DD-option by 2 and 4 times, respectively. In those with overweight, AO 2nd degree the ProPro-genotype dominated the AlaAla-genotype by 12–17 times; among those with overweight available only D-allele carriers; in patients with EAH AO 3rd degree – there are only ProPro-carriers.

Conclusion. DD-genotype or D-allele of ACE gene is a risk factor for EAH II and III stages (OR = 2.33–4.45, p ≤ 0.014–0.013), excess body weight (OR = 4.10–4.45, p < 0.001), AO (OR = 4.45, p < 0.001) with the lowest probability of EAH I stage (OR = 0.22, p = 0.007).

Key words: arterial hypertension, abdominal obesity, АСЕ gene (I/D), PPAR-g2 (Pro12Ala).

This email address is being protected from spambots. You need JavaScript enabled to view it. 

The full text

To view the full text



  1. KovalenkoVM, TalayevaTV, KozliukAS.[Metabolic syndrome: mechanisms, value as a predictor of cardiovascular diseases, approaches in diagnosis and treatment]. Ukr J 2013;5:80–87.
  2. Mitchenko OІ, Romanov VYu, Kulyk OYu, Shkroba GO.[Leptin resistance in patients with essential hypertension and metabolic syndrome].Ukr J2014;2:31–35.
  3. Ataman AV, Garbusova VY, Ataman YuA, Matlaj OI, Obuchova OA. Investigation of the MGP promoter and exon 4 polymorphisms in patients with ischemic stroke in the Ukrainian population. J Cell and Molecular Biology. 2012;10(1):19–26.
  4. Sydorchuk LP, Gaborets IY, Sydorchuk AR, Ursulyak YuV, Sokolenko AA, Ivashchuk SI et al. Combined effects of ACE (I/D) and eNOS (894T>G) genes polymorphism in patients with arterial hypertension in the realization of molecular mechanisms of left ventricular hypertrophy. The New Armenian Medical J. 2013;7(2):44–54.
  5. SydorchukLP, GaboretsIY, SydorchukAR, BukachOP, SokolenkoAA, UrsuliakJV, etal. Value of angiotensin-cenzyme and mnitrogen in pathogenesis of myocardium remodeling depending on genes' ppatients with arterial h Intern J of Collabor Research on Int Med & Public Health. 2013;5(3):168
  6. SydorchukLP, AmosovaKM. Influencepharmacogeneticallydeterminedtreatmentparametersperipheralhemodynamicsinpatientswitharterialhypertension.TheNewArmenianMedicalJ. 2011;5(2):35–43.
  7. Ye X, Yu Z, Li H, Franco OH, Liu Y, Lin X. Distribution of C-reactive protein in its association with metabolic syndrome in middle-aged and older Chinese people. J Am Coll Cardiol. 2007;49(17):1798–1805.
  8. Tsuchida A, Yamauchi T, Takekawa S. Hada Y, Ito Y, Maki T, Kadowaki T. Peroxisome proliferator-activated receptor (PPRAα) activation increases adiponectin receptor and reduces obesity-related inflammation in adipose tissue. Comparison of activation of PPRAα, γ, and their combination. Diabetes. 2005;54(12):3358–3370.
  9. Roszer T, Ricote M. PPARs in the renal regulation of systemic blood p PPAR Res. 2010;2010:698730.
  10. Vergotine Z, Yako YY, Kengne AP, ErasmusRT, Matsha TE.Proliferator-activated receptor gamma Pro12Ala interacts with the insulin receptor substrate 1 Gly972Arg and increase the risk of insulin resistance and diabetes in the mixed ancestry population from South Africa. BMC Genet 2014;15:
  11. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, etal.2013 ESC/ESH guideline for the management of arterial hypertension. The task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertension. 2013;31(10):1281–1357.
  12. Ministry of Health of Ukraine Order № 384 dated 24.05.2012 [Guidelines and clinical protocols of medical care "Hypertension".On approval and implementation of medical and technical documents on standardization of medical care in patients with arterial hypertension]. Kyiv: Ministry of Health Crae of Ukraine Publ., 2012.
  13. Jensen MD, Ryan DH, Apovian CM, Ard JD, Comuzzie AG, Donato KA,etal. 2013 AHA/ACC/TOS guideline for the management of verweight and besity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society.2014;129(25 Suppl. 2):S102–38.
  14. Entrez Gene. Sequence analysis 2014. National Center for Biotechnology Information. Retrieved from:
  15. Sekerli E, Katsanidis D, Papadopoulou V, Makedou A, Vavatsi N, Gatzola M.Angiotensin-I converting enzyme gene and I/D polymorphism distribution in the Greek population and a comparison with other European populations. J Genetics. 2008;87(1):91–93.
  16. Topal NP, Ozben B, Hancer VS, Tanrikulu AM, Diz-Kucukkaya R, Fak AS, Basaran Y, Yesildag O. Polymorphisms of the angiotensin-converting enzyme and angiotensinogen gene in patients with atrial fibrillation. J RAAS. 2011;12(4):549–556.
  17. Kaydashev IP, Rasine AM, Shlykova OA, Gorbas IM, Smirnov IP, Petrushov AV, etal. Frequency Pro12Ala PPARγ2 gene polymorphism in Ukrainian population and its possible connection with the development of metabolic syndrome.Cytology and Genetics. 2007;5:43–47.
  18. Stumvoll M, Haring H.The peroxisome proliferator-activated receptor-γ2 Pro12Ala p.Diabetes. 2002;51(8):2341234.
  19. Pinterova D, Cerna M, Kolostova K, NovotaP, Cimburova M, Romzova M, Kubena A, Andel M.The frequency of alleles of the Pro12Ala polymorphism in PPARgamma2 is different between healthy controls and patients with type 2 diabetes. Folia Biol (Praha). 2004;50(5):1536.



Authors: Ancheva I.A. 

Pages: s13-s19


Introduction. One ofthe mosturgent problemsof modern obstetricsis the occurrenceof iron deficiencyin pregnant women. The experts assess its prevalence in 20–30 % ofcasesin economicallydeveloped countriesand50–80 % – in developing countries.InUkrainein the recent years,the incidenceof iron deficiency anemia during pregnancy increased from15.0 to 22.6 %. The interest ofresearchersto the problemof IDAdue to the factthat inthispathological conditionincidenceof preeclampsia,preterm labor, polyhydramnios, prematurerupture of membranes,weakness of laborforces and otherpregnancy complicationssignificantly increased.According toexperts, theincrease in the amountof blood lossduring laboris in 10 % ofpregnant women withIDA.This populationof pregnant womenhasalsopostpartumseptic complicationsandhypogalactia. Iron deficiency significantly worsensoverall condition of mother and fetus.

Our aim was to evaluate the gene expression of eNOS in placental tissue of the pregnant women with iron deficiency anemia.

Material and Methods. Research performed at the maternity hospital № 2 (Odessa), Genetic Laboratories "Nadiaya" and pathomorphological department of State Institution "IPOG NAMSU" (Head, Professor, MD Zadorozhna TD, Kyiv). The study involved 100 women in labor; we took placenta samples from them. Thus, the following clinical groups were designed: group 1 – the placenta samples of women with physiological pregnancy and childbirth (n = 20), group 2 – the placenta samples of pregnant women with a history of anemia (n = 40), group 3 – the placenta of women with placental dysfunction and a history of anemia (n = 40). In addition to the general clinical research methods, we used current clinical protocol approved by the order № 782 dated 29.12.2005 “On approval of clinical protocols for obstetric and gynecological care”, further research was conducted analysis of immunohistochemical expression of endothelial nitric synthase (eNOS) in placental tissue. Age of pregnant women ranged from 20 to 35 years (28.5 ± 2.8 years).

Discussion. As a result the level of eNOS gene expression increased by 1.4 folds in patients with IDA, while the combination of IDA and placental dysfunction eNOS gene expression level reduced by 10 folds. We discuss the adaptive nature of changes in eNOS gene expression in iron deficiency amongst pregnant women. There were compared genetic and phenotypic characteristics of the enzyme activity of endothelial nitric oxide synthase in decidual tissue. When comparing detected changes of eNOS gene expression with the phenotypic manifestations we found that the expression of endothelial nitric oxide synthase in patients with dysfunction of the placenta in the cytoplasm synticia villi and fetal capillary endothelium and vascular decidua reduced, and the presence of a combination of placental dysfunction and iron deficiency anemia occured with the paradoxical increase expression of the enzyme. Thus, inhibition of eNOS gene expression is a reflection of the exhaustion of the adaptive capacity of the organism. This circumstance suggests that routine administration of nitric oxide precursor (L-arginine medication) in women with gestational endoteliopatiyi manifestations may not give the desired effect due to the presence of a genetically determined deficiency of endothelial nitric oxide synthase and its products. Besides, when isolated iron deficiency anemia occurs than changes in eNOS gene expression is less evident.

Key words: iron deficiency anemia, pregnancy, nitric oxide synthase, genetics.

This email address is being protected from spambots. You need JavaScript enabled to view it. 

The full text

To view the full text



  1. Blackburn S. Maternal, fetal, andneonatal p 4th ed.NY: Saunders; 2012. 768
  2. Salomon C, Kobayashi M, Ashman K, Sobrevia L, Mitchell MD, RiceHypoxia-induced changes in the bioactivity of cytotrophoblast-derived exosomes. PLoS One. 2013;8(11):
  3. Ancheva IA. [Clinical epidemiology of anemia during pregnancy in the Southern Ukraine: retrospective study].Visnyk Problem Biologii i Medytsyny. 2013;2(3):112–114.
  4. O'Farrill-Santoscoy F, O'Farrill-Cadena M, Fragoso-Morales LE. Evaluacion del tratamiento a mujeres embarazadas con anemia ferropenica. Ginecol Obstet Mex. 2013;81(7):377381
  5. Goldman-Wohl D, Yagel S. United we stand not dividing: the syncytiotrophoblast and cell senescence. Placenta. 2014;35(6):341–4.
  6. Zaporozhan VM, Konkov DG, Galich SR, Lutsker OL, inventors;І. Pіrogov Vіnnitsa National Medical Unіversity. Sposib neinvazyvnoi diahnostyky funktsionalnoho stanu endoteliiu pry vahitnosti [The method of non-invasive diagnostics of the functional state of endotelium in the pregnancy]. Ukrainian patent, no. 77984 (2013) A61V 10/00, 2013.
  7. Koskenkorva-Frank TS, Weiss G, KoppenolWH, Burckhardt S. The complex interplay of iron metabolism, reactive oxygen species, and reactive nitrogen species: insights into the potential of various iron therapies to induce oxidative and nitrosative stress. Free Radic Biol Med. 2013;65:1174–94.
  8. Petruk AA, Vergara A, Estrin D, Merlino A. Molecular basis of the NO trans influence in quaternary T-state human hemoglobin: a computational study. FEBS Lett. 2013;587(15):2393–8.
  9. ENOS gene. Retrieved from:
  10. Kapustin RV, Arzhanova ON, Polyakova[Vascular tropic signaling molecules expression in the placental tissue samples from puerperae with gestational diabetes mellitus].Molecular Medicine. 2012;5:4549.
  11. Nakaz 782 Prozatverdzhenniaklinichnykhprotokolivzakusherskoitahihienichoidopomohy [Orderno. 782 datedOn approvement of clinical protocols on the obstetrics and gynecology care]. Kyiv: Ministry of Health Care of Ukraine Publ., 2005.
  12. Yau C. R tutorial.Retrived from:



Authors: Garbuzova V.Yu. 

Pages: s20-s28



Introduction. BMP-2, like other bone morphogenetic proteins, plays an important role in the development of bone and cartilage, in osteoblast differentiation. As the calcification of the atherosclerotic plaque is an untoward prognostic factor of the acute coronary syndrome, the polymorphism of gene BMP-2 can be associated with the disease progression.

The aim isto establish the association of allelic variants of BMP-2 gene Ser37Ala polymorphism on some characteristics of the acute coronary syndrome (clinical variants, ECG manifestations, development of complications).

Material and Methods. We used venous blood of 118 patients with ACS (22 % women and 78 % men) aged 40 to 73 years (mean age 55.9 ± 0.89 years) hospitalized in the cardiology department of Sumy City Clinical Hospital № 1. The control group consisted of 234 patients. I performed definition of Ser37Ala polymorphism (rs2273073) of BMP-2 gene using PCR with the following restriction fragment length analysis of the allocation of them by electrophoresis in agarose gel. Restriction endonuclease Hpy99I was used for restriction analysis. Statistical analysis was performed by using the software package SPSS-17. Thus, the significance of differences was determined by the χ2-criterion. The value of P < 0.05 was considered as significant.

Results. There isn’t significant difference in the ratio of genotypes (Ser/Ser, Ser/Ala, Ala/Ala) between patients with anginal form of acute coronary syndrome (ACS) and patients with other forms of ACS (аsthmatic, abdominal, arhythmic and painless). It accounted for 51.5; 30.1 and 18.4 % in the group with anginal form of ACS; and 40.0, 46.7 and 13.3 % – in the group with other forms of ACS. Using the χ2-Pearson criterion, it did not reveal association between the Ser37Ala polymorphism of ВМР-2 gene and the clinical variants of ACS (χ= 1.652, Р = 0.438). Analysis of the data about correlation Ser37Ala polymorphism of BMP-2 gene with different clinical variants of ACS showed no association of investigated SNP with different clinical manifestations of this disease (unstable angina, non-Q-myocardial infarction, Q-and QS-myocardial infarction). There is no veracity in the distribution of genotypes considering such risk factors as gender, BMI, hypertension, lipid composition and blood hypercoagulation, diabetes, and obesity. The difference of allelic variants frequency was statistically significant (P = 0.033) in groups with different clinical forms of ACS only in patients, who smoke. Smokers with Ser/Ser genotype were significantly more likely to develop anginal form of ACS. Significant difference in the distribution of patients with unstable angina, non-Q-myocardial infarction, Q-and QS-myocardial infarction was found only in patients with obesity (P = 0.018). I did not find significant difference in the distribution of genotypes between patients with complications and those who have had the disease without complications. However, the association with the development of complications of ACS was for male patients, smokers, patients without DAC and without obesity.

Ambiguity and deficiency of data about relationship Ser37Ala and other polymorphisms of BMP-2 gene with the development of ACS requires further research in this area.

Conclusion: Smoking patients with Ser/Ser genotype BMP-2 gene Ser37Ala polymorphism are significantly more likely to develop anginal form of ACS.

There is significant difference in the distribution of genotypes among individuals with unstable angina, non-Q-myocardial infarction, Q-and QS-myocardial infarction in the group without obesity.

There is a link with the development of complications of ACS for male patients, smokers, patients without atherogenic dislipoproteinemia and without obesity.

Key words: allelic polymorphism, bone morphogenetic protein-2, acute coronary syndrome. 

The full text

To view the full text



  1. Urist MR. Bone: formation by autoinduction. Science. 1965;150:893–899.
  2. Urist MR, Strates BS. Bone morphogenic protein. J. Dental. Res. 1971;50(6):1392–1406.
  3. Gosselet FP, Magnaldo T, Culerrier RM, Sarasin A, Ehrhart JC. BMP2 and BMP6 control p57Kip2 expression and cell growth arrest/terminal differentiation in normal primary human epidermal keratinocytes. Cell. Signal. 2007;19:731–739.
  4. Kang MH, Kim JS, Seo JE, Oh SC,Yoo YA. BMP2 accelerates the motility and invasiveness of gastric cancer cells via activation of the phosphatidylinositol 3-kinase (PI3K). Exp Cell Res. 2010;316,(1):24–37.
  5. Langenfeld E, Langenfeld J. Bone mprotein-2 stimulates angiogenesis in developing t Mol Cancer Res. 2004;2:141–149.
  6. Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS, JonesRH, et al. ACC/AHA guidelinesfor the management of patients with unstable angina and non ST-elevation myocardial infarction: executive summary and recommendations. A report of the american college of cardiology. Circulation. 2000;102:1193–1209.
  7. Bertrand ME, Simoons ML, Fox KA, Wallentin LC, Hamm CW, McFadden E, DeFeyter PJ, et al. Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2002;23:1809–1840.
  8. Nomenclature and criteria for diagnosis of ischemic heart disease. Report of the Joint International Society and Federation of Cardiology/World Health Organization task force on standardization of clinical nomenclature.
  9. Styrkarsdottir U, Cazier J-B, Kong A, Rolfsson O, Larsen H, Bjarnadottir E, Johannsdottir V, et al. Linkage of osteoporosis to chromosome 20p12 and association to BMP2. PLoS Biol. 2003;11(3):351–360.
  10. Ichikawa S, Johnson ML, Koller DL, Lai D, Xuei X, Edenberg HJ, Hui SL, et al. Polymorphisms in the bone morphogenetic protein 2 (BMP2) gene do not affect bone mineral density in white men or women. Osteoporos Int. 2006;17(4):587–592.
  11. Varanasi SS, Tuck SP, Mastana SS, Dennison E, Cooper C, Vila J, Francis RM, Datta HK. Lack of association of bone morphogenetic protein 2 gene haplotypes with bone mineral density, bone loss or risk of fractures in men. J Osteoporos. 2011;2011:243465.
  12. Freedman BI, Bowden DW, Ziegler JT, Langefeld CD, Lehtinen AB, Rudock ME, Lenchik L, et al. Bone morphogenetic protein 7 (BMP7) gene polymorphisms are associated with inverse relationships between vascular calcification and BMD: The Diabetes Heart Study. J Bone Miner Res. 2009;24(10):1719–1727.



Authors: Piddubna A.I., Chemych M.D.

Pages: s29-s37


Our aim was to study distribution character of the allelic variants of cytokines genes in HIV-infected Ukrainians.

Data for the study were DNA samples, received from 200 inhabitants of Ukraine: 78 HIV-infected, 22 HIV-negative individuals from the group of high risk of contamination, 100 healthy blood donors. IL-4 (-590C/T), IL-10 (-592C/A) andTNF-α (-308G/A) genes polymorphisms detection was made with the PCR-RLFP method.

By analysis of frequency of IL-4 gene allelic variants, we discovered that homozygotes by the main allel were the dominant variant. Among people with HIV T/T minor gene carriers were 4.5 more often met in comparison with the control group (p < 0.05) that can prove the tendency to association of the mentioned genotype with infection. Distribution of allelic variants of IL-10 gene promoter region in position -592 is characterized by homozygote dominance by the main gene. Among the individuals with HIV A/A minor allel carriers were 3.4 more often than in the control group (p < 0.05). Individuals with A/A genotype were not identified in group of high risk of virus infection. The abovementioned proves the tendency to association of minor allel carrier state with HIV infection. Theoccurrenceofthehomozygouscombinationoftheallelicvariant G/GofthepromoterofTNF-αis provedtoprevailalmosttwofoldovertheoccurrenceofthevariantG/Aamong all groups. High frequency of heterozygote by the main allel was recorded among the individuals with HIV. Thus, G/A genotype frequency in group of HIV-infected people by 2 and 1.5 times exceeded the appropriate indices of group of high risk of infection and comparison group correspondingly (p < 0.05) that points on the tendency to association of the mentioned variant with infection. We concluded that cytokines genes variationsmaycontributetotheacquisitionofHIVinfectionin the Ukrainians andencourages carrying out further populations studies in this sphere of HIV-infection immunogenetics.

Key words: HIV infection, cytokines, allelic polymorphism.

The full text

To view the full text



  1. UNAIDS. Global report: UNAIDS report on the global AIDS epidemic 2010. WHO Library. 2010. 364 p.
  2. UNAIDS. Progress report 2011: Global HIV/AIDS response. WHO Library. 2011. 229 p.
  3. Cashin K, Roche M, Sterjovski J, Ellett A, Gray LR, Cunningham AL, Ramsland PA, et alAlternative crequirements for efficient CCR5- and CXCR4-mediated HIV-1 entry into macrophages. J Virol. 2011;85(20):10699–709.
  4. Gorry PR, Ancuta P. Coreceptors and HIV-1 pathogenesis. Curr HIV/AIDS Rep. 2011;8(1):45–53.
  5. Fellay J, Ge D, Shianna KV, Colombo S, Ledergerber B, Cirulli ET, Urban TJ, et al. Vaccine Immunology (CHAVI). Common genetic variations and the control of HIV-1 in humans. PLoS Genet. 2009;5(12):e1000791.
  6. Smolnikova М. V. Polimorfizm henov tsitokinov v norme i pri VICH-infektsii: [Polymorphism of cytokine genes at normal condition and HIV-infection]. [PhD thesis]. Novosibirsk, 2002. 22 p.
  7. Yamamoto T, Price DA, Casazza JP, Ferrari G, Nason M, Chattopadhyay PK, Roederer M, et al. Surface expression patterns of negative regulatory molecules identify determinants of virus-specific CD8+ T-cell exhaustion in HIV infection.(18): 4805–4815.
  8. Blackburn SD, Wherry EJ. IL-10, T cell exhaustion and viral persistence. Trends Microbiol. 2007;15(4):143–6.
  9. Wang Y, Rice AP. IL-10 inhibits HIV-1 LTR-directed gene expression in human macrophages through the induction of cyclin T1 proteolysis. Virology. 2006;352(2):485–92.
  10. Ketlinskyi SАSimbirtsev ASTsyitokini [Cytokines]. Saint Petersburg: Fp.
  11. Wang C, Song W, Lobashevsky E, WilsonCM, Douglas SD, Mytilineos J, Schoenbaum EE, et alCytokine and chemokine gene polymorphisms among ethnically diverse North Americans with HIV-1 infection. J Acquir Immune Defic Syndr. 2004;35(5):446–54.
  12. Biktagirova EM, Sattarova LI, Vagapova GR, Kravtsova OA[Association of IL-1β, IL-4 and IL-6 genes polymorphisms with genetic predisposition for autoimmune thyroiditis].Meditsinskaya Immunologi 2011;6:603–608.
  13. Jun TY, Lee KU, Pae CU, Chae JH, BahkWM, Kim KS, Han H. Polymorphisms of interleukin-4 promoter and receptor gene for schizophrenia in the Korean population. Psychiatry Clin Neurosci. 2003;57(3):283–8.
  14. Gatlin MR, Black CL, Mwinzi PN,Secor WE,Karanja DM, ColleyAssociation of the gene p patterns of reinfection with Schistosoma mansoni. PLoS Negl Trop Dis. 2009;3(2):e375.
  15. Saxena M, Agrawal CC, Bid HK, Banerjee M. An interleukin-10 gene promoter polymorphism (-592A/C) associated with type 2 diabetes: a North Indian study. Biochem Genet. 2012;50(7–59.
  16. Lee YT, Tsai YC, Yang YK, Hsu KT, LiaoSC, Wu CH, Cheng BC, et alAssociation between interleukin-10 gene polymorphism −592 (A/C) and peritoneal transport in patients undergoing peritoneal dialysis. Nephrology (Carlton). 2011;16(7):663–71.
  17. Helmig S, Aliahmadi N, Stephan P, Dhrel J, SchneiderTNF-α -308 genotypes are associated with TNF-α and TGF-β mRNA expression in blood leucocytes of humans.;53(3):306–310.
  18. Lpez-Hernandez R, Valdes M, Campillo JA, Martinez-Garcia P, Salama H, Salgado G, Boix F, Moya-Quiles MR, et alGenetic polymorphisms of tumour necrosis factor alpha (TNF-α) promoter gene and response to TNF-α inhibitors in Spanish patients with inflammatory bowel disease. Int J Immunogenet. 2014;41(1):63–8.
  19. Sobti RC, Berhane N, Mahedi SA, Kler R, Hosseini SA, Kuttiat V, WanchuPolymorphisms of IL-6 174 G/C, IL-10 -592 C/A and risk of HIV/AIDS among North Indian population. Mol Cell Biochem. 2010;337(1–2):145152.




Authors: Rozymenko I.A. 

Pages: s38-s44


Introduction. Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 is an enzyme, which is encoded by the ENPP1 gene in humans. This gene is a member of the ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP) family. The encoded protein is a type II transmembrane glycoprotein comprising two identical disulfide-bonded subunits. This protein has broad specificity and cleaves a variety of substrates, including phosphodiester bonds of nucleotides and nucleotide sugars and pyrophosphate bonds of nucleotides and nucleotide sugars. This protein may function to hydrolyze nucleoside 5' triphosphates to their corresponding monophosphates and may also hydrolyze diadenosine polyphosphates. Mutations in this gene have been associated with іdiopathic infantile arterial calcification, ossification of the posterior longitudinal ligament of the spine, insulin resistance. As the calcification of the atherosclerotic plaque is an untoward prognostic factor of the acute coronary syndrome, the polymorphism of gene ENPP1 can be associated with the disease progression.

The aim was to establish the frequency of allelic variants of the ENPPI gene for K121Q polymorphism in patients of different sexes with acute coronary syndrome (ACS).

Material and Methods. We used venous blood of 118 patients with ACS (22 % women and 78 % men) aged 40 to 73 years (mean age 55.9 ± 0.89 years) who were hospitalized in the cardiology department of Sumy City Clinical Hospital № 1. The control group consisted of 110 patients. Definition of K121Q polymorphism (rs1044498) of ENPPI gene was performed using PCR with the following restriction fragment length analysis of the allocation of them by electrophoresis in agarose gel. Restriction endonuclease Eco47I (AvaII) was used for restriction analysis. Statistical analysis was performed using the software package SPSS-17. Thus, the significance of differences was determined by the χ2-criterion. The value of P < 0.05 was considered as significant.

Results. Using the χ2-Pearson criterion, I did not reveal association between the K121Q polymorphism of ENPPI gene and the development of ACS. Distribution of different types of genotype between patients with ACS and healthy patients did not differ statistically significantly. I pointed out that in patients with ACS value homozygotes for the major allele (K/K) and minor allele carriers (K/Q + Q/Q) were 66.9 and 33.1 %, while in the control group –75.5 and 24.5 %, respectively. Factor P, defined by χ2-Pearson criterion, was equal to 0.157 and indicated a lack of significant difference in the distribution of allelic variants of the gene ENPP1 K121Q polymorphism in patients with ACS and the controls.

The value of the given options polymorphism in females was unreliable in patients with ACS and controls (P = 0.280). The distribution of allelic potions K121Q polymorphism in males also did not differ in comparison to patients with ACS and controls (P = 0.320).

Conclusion. There is no link between the polymorphism K121Q of gene ENPP1 and the acute coronary syndrome in males and females.

Key words: ectonucleotide pyrophosphatase/phosphodiesterase, acute coronary syndrome, allelic polymorphism.

This email address is being protected from spambots. You need JavaScript enabled to view it.

The full text

To view the full text



  1. Johnson K, Goding J, Van Etten D, Sali A, Hu SI, Farley D, Krug H, et alLinked deficiencies in extracellular PP(i) and osteopontin mediate pathologic calcification associated with defective PC-1 and ANK expression. J Bone Miner Res.2003;18(6):994–1004.
  2. Ruf N, Uhlenberg B, Terkeltaub R, NurnbergP, Rutsch F. The mutational spectrum of ENPP1 as arising after the analysis of 23 unrelated patients with Generalized Arterial Calcification of Infancy (GACI). Human Mutation. 2005;26(5):495–496.
  3. Rutsch F, Vaingankar S, Johnson K, GoldfineI, Maddux B, Schauerte P, KalhoffH, et alPC-1 nucleoside triphosphate pyrophosphohydrolase deficiency in idiopathic infantile arterial сalcification. American Journal of Pathology. 2001;158(2):543–554.
  4. Glatz AC, Pawel BR, Hsu DT, Weinberg P, Chrisant MRK. Idiopathic infantile arterial calcification: two case reports, a review of the literature and a role for cardiac transplantation. Pediat Transplant. 2006; 10:225–233.
  5. Nakamura I, Ikegawa S, Okawa A, Okuda S, Koshizuka Y, Kawaguchi H, Nakamura K, et alAssociation of the human NPPS gene with ossification of the posterior longitudinal ligament of the spine (OPLL). Hum Genet. 1999;104(6):492–497.
  6. Pizzuti A, Frittitta L, Argiolas A, Baratta R,. Goldfine ID, Bozzali M, Ercolino T, et alA p Diabetеs. 1999; 48(9):1881–1884.
  7. Bacci S, Ludovico O, Prudente S, Zhang Y-Y, Di Paola R, Mangiacotti D, Rauseo A, et alThe K121Q polymorphism of the ENPP1/PC-1 gene is associated with insulin resistance/atherogenic phenotypes, including earlier оnset of type 2 diabetes and myocardial infarction. Diabetеs. 2005; 54(10):3021–3025.
  8. Meyre D, Bouatia-Naji N, Vatin V, Veslot J, Samson C, Tichet J, Marre M, et alENPP1 K121Q polymorphism and obesity, hyperglycaemia and type 2 diabetes in the prospective DESIR Study. Diabetologia. 2007;50:2090–2096.
  9. El Achhab Y, Meyre D, Bouatia-Naji N, Berraho M, Deweirder M, Vatin V, Delplanque J, et alAssociation of the ENPP1 K121Q polymorphism with type 2 diabetes and obesity in the Moroccan population. Diabetes Metab. 2009;35(1):37–42.
  10. Lee JE, Choi YK, Seo HA, Jeon JH, Jeong JY, Moon SS, Kim JG, et alImpact of ENPP1 and MMP3 gene polymorphisms on aortic calcification in patients with type 2 diabetes in a Korean population.Diabetes Res Clin Pract. 2010;88(1):87–96.
  11. Cte N, El Husseini D, Pepin A, Guauque-Olarte S, Ducharme V, Bouchard-Cannon P, Audet A, Fournier D, et al.ATP acts as a survival signal and prevents the mineralization of aortic valve. J Mol Cell Cardiol. 2012;52(5):1191–202.
  12. Moehlecke M, Kramer KC, Cristiane B, KraheAL, Balbosco I, de Azevedo JM, Gross JL, Canani LH. ENPP1 K121Q polymorphism and ischemic heart disease in diabetic patients. Arq Bras Cardiol. 2010;94(2):157–161.
  13. Eller P, Schgoer W, Mueller T, Tancevski I, Demetz E, Duwensee K, Ritsch A, et alThe K121Q polymorphism of ENPP1 and peripheral arterial disease. Heart Vessels. 2008;23(2):104–107.
  14. Wang RQ, Zhou DH, Xi B, Ge XS, Zhu P, Wang B, Zhou MA, etalENPP1/PC-1 gene K121Q рolymorphism іs аssociated with оbesity in European аdult p Biomed Environ Sci. 2011;24(2):200–206.
  15. Gonzalez-Sanchez JL, Zabena C, Martinez-Larrad MT, Martinez-Calatrava MJ, Perez-Barba M, Serrano-Ríos M. Association of ENPP1 (PC-1) K121Q polymorphism with obesity-related parameters in subjects with metabolic syndrome. Clin Endocrinol. 2008;68(5):724
  16. Suk EK, Malkin I, Dahm S, Kalichman L, RufN, Kobyliansky E, Toliat M, et alAssociation of ENPP1 gene polymorphisms with hand osteoarthritis in a Chuvasha population. Arthritis Res Ther. 2005;7(5): R1082–1090.
  17. Baba T, Endo T, Sata F, Honnma H, KitajimaY, Hayashi T, Manase K, et alPolycystic ovary syndrome is associated with genetic polymorphism in the insulin signaling gene IRS-1 but not ENPP1 in a Japanese population. Life Sci. 2007;81(10):850–854.
  18. Takahama Y, Uto H, Kanmura S, Oketani M, Ido A, Kusumoto K, Hasuike S, et alAssociation of a genetic polymorphism in ectonucleotide pyrophosphatase/phosphodiesterase 1 with hepatitis C virus infection and hepatitis C virus core antigen levels in subjects in a hyperendemic area of Japan. J Gastroenterol. 2008;43(12):942–950.
  19. Levy-Litan V, Hershkovitz E, Avizov L, Leventhal N, Bercovich D, Chalifa-Caspi V, Manor E, et alAutosomal-recessive hypophosphatemic rickets is associated with an inactivation mutation in the ENPP1 g Am J Hum Genet. 2010;86(2):273–8.
  20. Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS, Jones RH, et alACC/AHA guidelinesfor the management of patients with unstable angina and non ST-elevation myocardial infarction: executive summary and recommendations. A report of the american college of cardiology. Circulation. 2000;102:1193–1209.
  21. Bertrand ME, Simoons ML, Fox KA, Wallentin LC, Hamm CW, McFadden E, De Feyter PJ, Specchia G, Ruzyllo W. Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2002;23:1809–1840.
  22. Chen MP, Chung FM, Chang DM, Tsai J, Huang HF, Shin SJ, Lee YJ. ENPP1 K121Q Polymorphism is not related to type 2 diabetes mellitus, features of metabolic syndrome, and diabetic cardiovascular complications in a Chinese Population. Rev Diabet Stud. 2006;3(1):2130.




Authors: Kmyta V.V.

Pages: s45-s51


The purpose of our investigation was study the connection between Bcl1 polymorphism of glucocorticoids receptor gene (GR) with severity of course of disease and obesity patients with bronchial asthma (BA).

188 patients with BA and 95 almost healthy patients were examined. Body mass index, the pulmonary function test (PFT)were investigated. Determination of Bcl1 polymorphism of 2d glucocorticoids receptor exongene (GR) performed with FleuryI. etal. method with modifications. Statistically results processing were done with using of the SPSS-17programs.

The results of analyses of the genotype distribution by Bcl1 polymorphism GR gene dependingon severity of BA course showed that C/C genotype associated with easy course of disease, meanwhile, G/G with severe course. The analyzes of distributing allelic variations GR depending onforced expiratory volume in 1 second (FEV1)  showed more expressed obstructive changes in minor allele carries (C/G+G/G) comparing with homozygotes by main allele. We pointed out that patients with BA with C/C genotype index FEV1 showed 68.6 (95% CI 64.9–7.3), and with G/G genotype – 59.9(95% CI 57.02–62.7).

The analysis of genotype distribution by Bcl1 polymorphism GR gene depending on the level FEV1 with consideration BMI showed that genotype C/C mostly occured in patients with normal body mass and FEV1 in normal limits and in range of 60–80% from appropriate values, and genotype G/G –in patients with obesity and severe disorders FEV1.

Obtained results proved the availability of connection between genotypes by Bcl1 polymorphism GR gene, BMI and degree of disorder PFT in patients with BA.

Key words: bronchial asthma, Bcl1 polymorphism, body mass index, the degree of severity.

This email address is being protected from spambots. You need JavaScript enabled to view it.

The full text

To view the full text



  1. Belevskii АS. Globalnaya strategiia lecheniia i profilaktitki bronkhialnoi astmy (peresmotr  2011 g.) [Global strategy for the treatment and prevention of bronchial asthma (Review 2011)]. М: Rosiiskoe respiratornoie obshchestvo Publ., 2012. 108 p.
  2. Lenzer J. Obesity related illness consumes a sixth of US health care budget. BMJ. 2010;341:c
  3. Boulet LP. Asthma and obesity. Clin Exp Allergy. 2013 Jan;43(1):8–21.
  4. Ford ES. The epidemiology of obesity and asthma. J Allergy Clin Immunol. 2005;115(5):897–909.
  5. Kajbaf TZ, Asar S, Alipoor MR. Relationship between obesity and asthma symptoms among childrenin Ahvaz, Iran: a crosssectional study. Italian Journal of Pediatrics2011;37:1.
  6. Saint-Pierre P, Bourdin A, Chanez P, DauresJP, Godard P.Are overweight asthmatics more difficult to control? 2006;61(1):79–84.
  7. Peters-Golden M, Swern A, Bird SS, HustadCM, Grant E, Edelman JM.Influence of body mass index on the response to asthma controller agents. Eur Respir J. 2006;27(3):495–503.
  8. Sutherland ER, Goleva E, Strand M, BeutherDA, Leung DY.Body mass and glucocorticoid response in asthma. Am J Respir Crit Care Med. 2008;178(7):682–7.
  9. Hallstrand TS, Fischer ME, Wurfel MM, AfariN, Buchwald D, Goldberg JGenetic pleiotropy between asthma and obesity in a community-based sample of twins. J Allergy Clin Immunol. 2005;116(6):1235–41.
  10. Akerman MJH, Calacanis CM, Madsen MK. Relationship between asthma severity and obesity. J Asthma. 2004;41(5):521–526.
  11. Mosen DM, Schatz M, Magid DJ, CamargoCA Jr. The relationship between obesity and asthma severity and control in adults. J Allergy Clin Immunol. 2008;122(3):50711.e6.
  12. Tantisira K, Weiss S. The pharmacogenetics of asthma treatment. Curr Allergy Asthma Rep. 2009;9(1):10–17.
  13. van Rossum EF, Koper JW, vandenBeldAW, Uitterlinden AG, Arp P, Ester W, Janssen JA, et al.Identification of the BclI polymorphism in the glucocorticoid receptor gene: association with sensitivity to glucocorticoids in vivo and body mass index. Clin Endocrinol (Oxf). 2003;59(5):585–92.
  14. Pietras T, Panek M, Tworek D,Oszajca K, Wujcik R, Grski P, Kuna P, SzemrajThe BclI single nucleotide polymorphism of the human glucocorticoid receptor gene h-GR/NR3C1 promoter in patients with bronchial asthma: pilot study. Mol Biol Rep. 2011;38(6):3953–3958.




Authors: Potapov O.O., Kmyta O.P.

Pages: s52-s57


Secondary changes in the brain that occur during the early posttraumatic period remain a major cause of death in patients with severe traumatic brain injury. The purpose of our study was to analyze brain changes over time in patients with severe traumatic brain injury studying the association between the results of computed tomography examinations and the -675 4G/5G polymorphism in the PAI-1 gene.

We examined 119 patients with severe traumatic brain injury. Computed tomography changes of brain tissues in patients with severe traumatic brain injury were investigated. Determination of the -675 4G/5G polymorphism in the PAI-1 genewas performed. Statistical processing of the results was done with programsSPSS-17.

We found an association between posttraumatic computed tomography changes of brain tissues in patients with severe traumatic brain injury and the genotypes for the -675 4G/5G polymorphism in the PAI-1 gene: namely, more evident and accelerated involution of lesions in patients with 5G/5G genotype; more rapid recovery in patients with 4G/4G genotype; confirmed predisposition to developing secondary complications, pathological lesions evolution in the brain, and secondary ischemic complications in patients with 4G/5G genotype for the investigated polymorphism.

The obtained results proved the availability of connection between genotypes -675 4G/5G polymorphism in the PAI-1 gene, secondary complications, pathological lesions evolution in the brain, and secondary ischemic complications in patients with severe traumatic brain injury.

Key words: traumatic brain injury, computed tomography examination of the brain, the -675 4G/5G polymorphism in the PAI-1 gene.

This email address is being protected from spambots. You need JavaScript enabled to view it.

The full text

To view the full text


  1. Bruns J Jr, Hauser WA. The epidemiology of traumatic brain injury: a review. Epilepsia. 2003;44(Suppl 10):2–10.
  2. Huk АP. [TBI epidemiology in Ukraine]. Epidemiologia cherepno-mozkovoi travmy v Ukraini [Proceedings of the V Congress of Ukrainian Neurosurgeons]. Uzhorod, 2013, p.38. (In Ukrainian).
  3. Lekhan VМ, Huk АP. [Specifics of traumatic brain injury epidemiology in Ukraine]. Ukrayina. Zdorovia natsii. 2010;2:7–14.
  4. Maas AI, Hukkelhoven CW, Marshall LF, Steyerberg EW.Prediction of outcome in traumatic brain injury with computed tomographic characteristics: a comparison between the computed tomographic classification and computed tomographic predictors. 2005;57(6):1173–82.
  5. Huq MA, Takeyama N, Harada M, Miki Y, Takeuchi A, Inoue S, Nakagawa T, Kanou H, et al.4G/5G Polymorphism of the plasminogen activator inhibitor-1 gene is associated with multiple organ dysfunction in critically ill patients. Acta Haematol. 2012;127(2):72–80.
  6. Genet GF, Johansson PI, Meyer MA, SlbeckS, Srensen AM, Larsen CF, WellingKL, et al. Trauma-induced coagulopathy: standard coagulation tests, biomarkers of coagulopathy, and endothelial damage in patients with traumatic brain injury. J Neurotrauma. 2013;30(4):301–306.
  7. Tsantes AE, Nikolopoulos GK, Bagos PG, Bonovas S, Kopterides P, Vaiopoulos G.The effect of the plasminogen activator inhibitor-1 4G/5G polymorphism on the thrombotic risk. Thromb Res. 2008;122(6):736–742.
  8. Asselbergs FW, Williams SM, Hebert PR, Coffey CS, Hillege HL, Navis G, et al.The gender-specific role of polymorphisms from the fibrinolytic, renin-angiotensin, and bradykinin systems in determining plasma t-PA and PAI-1 levels. Thromb Haemost. 2006;96:471–477.
  9. Dellas C, Loskutoff DJ. Historical analysis of PAI-1 from its discovery to its potential role in cell motility and disease. Thromb Haemost. 2005;93(4):631–640.
  10. Wiklund PG, Nilsson L, Ardnor SN, ErikssonP, Johansson L, Stegmayr B, Hamsten A, et alPlasminogen activator inhibitor-1 4G/5G polymorphism and risk of stroke: replicated findings in two nested case-control studies based on independent cohorts. Stroke. 2005;36(8):1661–1665.
  11. Sirko АH. [Clinical and CT features of severe TBI]. Patolohia. 2011;8(3):85–89.
  12. Trufanov HЕ, Ramishvili ТЕ. Luchevaia diagnostika travm golovy i pozvonochnika: rukovodstvo dlia vrachei [X-ray diagnostics of head and spinal cord injuries: manual for physicians]. SPb.: ELBI-SPb Publ., 2007. 196p.



Authors: Prystupa L.N., Psarova O.V.

Pages: s58-s65


Our aim was to investigate the level of blood lipids and inflammatory markers in patients with coronary artery disease (CAD) depending on carrier ɛ4-allele ɛ2/ɛ3/ɛ4-apolipoprotein E gene polymorphism.

Material and Methods. The study involved 150 patients with CAD. Gene polymorphism of apolipoprotein E studied by Hixson et. al. (1990). DNA was extracted from whole blood using the sets DIAtom DNA Prep 100 («Isogene», Russia). rs7412 and rs429358 polymorphisms exon 4 was determined by polymerase chain reaction followed by restriction fragment length analysis. We performed enzymatic colorimetric method using a set of reagents "Olveks diagnosticum" (Russia) in accordance with the manufacturer's methods to study total cholesterol, HDL and TG. We identified CRP, IL-6 and TNF-α to assess the presence of systemic inflammatory response of the body. Their quantitative assessment was performed using the kits JSC "VECTOR-BEST" (Russia) and by enzyme immunoassay technique according to the manufacturer. Processing of the results was performed using the statistical analysis package SPSS 17.0

Results. Analysis of the genetic polymorphism of apoE showed that among 150 patients with CAD carriers ɛ4-allele were 37 (24.7%) patients, whereas no carriers – 113 (75.3%). We established that carriers ɛ4-allele were mostly men 28 (75.7%), while women – 9 (24.3%); statistically significant differences in Pearson χ2 criterion were found (p = 0.566). We found that in patients who are not carriers of allele frequency ɛ4-hypertension, SBP and DBP levels were significantly higher compared with native ɛ4-allele (p = 0.007, 0.058, 0.03, respectively). The analysis of HDL levels in patients with CAD depending on carrier ɛ4-allele showed that patients who are carriers of ɛ4-allele HDL was significantly lower compared with non-carriers ɛ4-allele (p = 0.013). Atherogenic index (AI) was significantly higher in patients who are carriers ɛ4-allele compared with non-carriers ɛ4-allele (p = 0.006). Patients who are carriers ɛ4-allele had higher levels of CRP and IL-6, but statistically significant differences in the Pearson χ2 criterion were found (p = 0.295, 0.492, respectively).

Conclusion. ɛ4-allele carriers have higher levels of blood lipids and inflammatory markers, indicating the progression of atherosclerosis.

Key words: coronary heart disease, apoE gene polymorphism, lipid profile, inflammatory markers.

The full text

To view the full text


  1. Derzhavna sluzhba statystyky Ukrainy [State Statistics Service of Ukraine]. Retrieved from:
  2. Kovalenko VM, Kornatskyi VM, editors. Dynamika stanu zdorovia narody Ukrainy ta rehionalni osoblyvosti. Analitychno-statystychnyi posibnyk [Dynamics of health status of Ukrainian population and regional features. Statistic and analytic manual]. Кyiv, 2012. 211 p.
  3. Boiko ER, Kanaeva AM. [Apolipoprotein E and its value in clinical physiology]. Uspekhi Phisiol Nauk. 2009;40(1):3–15. 
  4. Pavlenko MA, Bairamukova AA, Alibaeva NT, Dronov DA, Mirakhimov EM. [The role of apolipoprotein E gene polymorphism in the development of atherosclerosis (review)]. Vestnik 2007;7(9):32–35.
  5. Bennet AM, Di Angelantonio E, Ye Z, Wensley F, Dahlin A, Ahlbom A, Keavney B, et al. Association of apolipoprotein E genotypes with lipid levels and coronary risk. 2007;298(11):1300–1311.
  6. Hagberg JM, Kennet KR, Ferrell RE. APO E gene and gene-enviromental effects on plasma lipoprotein-lipid levels. Physiol Genomics. 2004;4(2):1011–08.
  7. Gerdes LU, Gerdes C, Kervinen K, Savolainen M, Klausen IC, Hansen PS, Kesaniemi YA, Faergeman O. The apolipoprotein epsilon4 allele determines prognosis and the effect on prognosis of simvastatin in survivors of myocardial infarction: a substudy of the Scandinavian simvastatin survival study. Circulation. 2000;101(12):1366–1371.
  8. Chiodini BD, Franzosi MG, Barlera S, Signorini S, Lewis CM, D'Orazio A, Mocarelli P, et al.Apolipoprotein E polymorphisms influence effect of pravastatin on survival after myocardial infarction in a Mediterranean population: the GISSI-Prevenzione study. Eur Heart J. 2007;28(16):1977–1983.
  9. Song Y, Stampfer VJ, Liu S. Meta-analysis: apolipoprotein E genotypes and risk for coronary heart disease. Ann Intern Med. 2004;141(2):137–47.
  10. Eiriksdottir G, Aspelund T, Bjarnadottir K, Olafsdottir E, Gudnason V, Launer LJ, Harris TB.Apolipoprotein E genotype and statins affect CRP levels through independent and different mechanisms: AGES-Reykjavik Study. 2006;186(1):222–4.
  11. Khashimov ShU, Bekmetova FM, Akhmedova ShS, Shek AB,Kurbanov RD. [The specific features of lipid profile and inflammation markers in patients with unstable angina depending on apolipoprotein E gene polymorphism]. Profilac Medicine2011; 14(1):16–18.



Authors: Davidova T. V., Volianskiy A. Yu.

Pages: 391-404



Liposomal technology vaccine delivery is currently experiencing a new renaissance. Liposomes (phospholipid vesicles with bilayer) is a versatile and reliable systems of antigens delivery to induce antibodies and T lymphocytes. Over the past 15 years, improved technology liposomal vaccines and today several vaccines containing liposomes with adjuvants approved or have reached the last stage of clinical evaluation. With this in mind, we have provided a systematic review of physical and chemical factors that should be considered designing liposomal vaccines. The overall analysis of the literature clearly shows that these factors (size, charge, composition, method of attachment of the antigen) have significant implications for the potential immunogenicity of the drug and should be carefully chosen. Despite the tendencies of associative connection biophysical parameters vesicles of immunogenicity, the interconnectedness of various biophysical factors determines need to optimize some specific compositions for vaccination programs for each. Although a large number of literary references describes the importance of biophysical parameters of liposomal formulations for the exercise of their specific immunogenicity, many important questions remain unanswered. At the cellular level is not clear how lipid substances affect the processing of the antigen and its presentation? Little is known about the cellular distribution of lipid modified peptides.
Further research is needed to determine mechanistic basis adjuvant action of cationic lipids and liposomal formulations in general. Given the versatility of liposomal carriers and their ability to simultaneous operation of several molecules adjuvants, liposomes seemingly ideal system model to study the phenomenon of synergism in great detail in vitro and in vivo.

Keywords: vaccines, liposomes, immunogenicity.

This email address is being protected from spambots. You need JavaScript enabled to view it.

The full text

In progress


1.  Zanetti A.R. The global impact of vaccination against hepatitis B: a historical overview Zanetti A.R., Van Damme P., Shouval D. // Vaccine. -  2008.- Nov 18.- 26(49)6266–73.

2.  Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine in women aged 24–45 years: a randomised, double-blind trial / Munoz N., Manalastas R. Jr., Pitisuttithum P., Tresukosol D., Monsonego J., Ault K., et al. // Lancet. 2009  Jun 6; 373(9679), 1949–57. 

3. O’Hagan D. Recent advances in the discovery and delivery of vaccine adjuvants / O’Hagan D., Valiante N. // Nature Reviews Drug Discovery. 2003; 2, 727–35.

4.  Vaccine adjuvant systems: Enhancing the efficacy of sub-unit protein antigens / Perrie Y., Mohammed A., Kirby D., McNeil S., Bramwell V. // Int J Pharm.- 2008. - 364.- 272.–80.

5. The antigenic value of toxoid precipitated by potassium-alum Glenny A., Pope C., Waddington H., Wallace V.J. // Pathol Bacteriol. 1926; 29 38–45.

6. Harper D.M. Currently approved prophylactic HPV vaccines. Harper D.M.: Expert Rev Vaccines. 2009  Dec; 8(12), 1663–79.

7.  Allison A.G. Liposomes as immunological adjuvants / Allison A.G., Gregoriadis G. // Nature. 1974.  Nov  15. 252(5480) 252.

8. Gregoriadis G. Entrapment of proteins in liposomes prevents allergic reactions in pre-immunised mice   Gregoriadis G., Allison A.C.// FEBS Lett. 1974. - Sep 1. 45(1) 71–4.

9. Liposomal vaccine delivery systems. Expert Opin Drug Deliv / Henriksen-Lacey M., Korsholm K.S., Andersen P., Perrie Y., Christensen D. // 2011.  Apr 8(4). 505–10.

10.  Liposomes as immunological adjuvants and vaccine carriers Gregoriadis G., Gursel I., Gursel M., McCormack B. // J Control Release. 1996. 41(1–2). 49–56.

11. Alving C. Lipid A and liposomes containing lipid A as antigens and adjuvants / Alving C., Rao M. //  Vaccine. 2008. 26(24) 3036–45.

12.  Eleven years of Inflexal V-a virosomal adjuvanted influenza vaccine / Herzog C., Hartmann K., Kunzi V., Kursteiner O., Mischler R., Lazar H., [et al.] // Vaccine.  2009.  Jul 16;27(33) 4381–7. 

13. Mischler R. Inflexal V a trivalent virosome subunit influenza vaccine: production / Mischler R., Metcalfe I.C. // Vaccine. 2002.  Dec 20. 20( Suppl 5) B17–23.

14. Bovier P.A. Epaxal: a virosomal vaccine to prevent hepatitis A infection / Bovier P.A. // Expert Rev Vaccines. 2008.  Oct.7(8) 1141–50.

15. Antibody titres after primary and booster vaccination of infants and young children with a virosomal hepatitis A vaccine (Epaxal) / Usonis V., Bakasenas V., Valentelis R., Katiliene G., Vidzeniene D., Herzog C. // Vaccine.  2003  Nov 7 21(31) 4588–92

16.  Randomized phase IIB trial of BLP25 liposome vaccine in stage IIIB and IV non-small-cell lung cancer  / Butts C., Murray N., Maksymiuk A., Goss G,. Marshall E., Soulieres D.[et al.] //J Clin Oncol. 2005.  Sep 20. 23(27) 6674–81. 

17. North S. Vaccination with BLP25 liposome vaccine to treat non-small cell lung and prostate cancers / North S., Butts C. // Expert Rev Vaccines. 2005.  Jun;4(3) 249–57.

18. Regules J.A. The RTS,S vaccine candidate for malaria Regules J.A., Cummings J.F., Ockenhouse C.F.// Expert Rev Vaccines. 2011.  May;10(5) 589–99.

19. Evaluation of the safety and immunogenicity of the RTS,S/AS01E malaria candidate vaccine when integrated in the expanded program of immunization / Agnandji S.T,. Asante K.P., Lyimo J., Vekemans J., Soulanoudjingar S.S., Owusu R.[et al.]// J Infect Dis.  2010.- Oct 1 —202(7) 1076–87.

20. Torchilin V.P. Recent advances with liposomes as pharmaceutical carriers / Torchilin V.P.: Nat Rev Drug Discov. 2005.  Feb;4(2) 145–60.

21. Tollemar J. Liposomal amphotericin B (AmBisome) for fungal infections in immunocompromised adults and children / Tollemar J., Klingspor L., Ringden O.// Clin Microbiol Infect.  2001. 7( Suppl 2) 68–79.

22.  Randomized comparative trial of pegylated liposomal doxorubicin versus bleomycin and vincristine in the treatment of AIDS-related Kaposi’s sarcoma / Stewart S., Jablonowski H., Goebel F.D., Arasteh K., Spittle M., Rios A.[et al.]// International Pegylated Liposomal Doxorubicin Study Group. : J of Clinical Oncology. 1998. 16(2). 683–91.

23. Liposomal malaria vaccine in humans: a safe and potent adjuvant strategy / Fries L.F.,. Gordon D.M., Richards R.L., Egan J.E., Hollingdale M.R., Gross M.[et al.] //  Proc Natl Acad Sci U S A.  1992 . Jan 1. 89(1) 358–62.

24.  First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children / Agnandji S.T., Lell B., Soulanoudjingar S.S., Fernandes J.F., Abossolo B.P., Conzelmann C.[et al.]// N Engl J Med.  2011.  Nov 17. 365(20). 1863–75.

25. Liposome-based cationic adjuvant formulations (CAF): past, present, and future / Christensen D., Agger E.M., Andreasen L.V., Kirby D., Andersen P., Perrie Y. // J Liposome Res. - -2009. 19(1). 2–11.

26. Cationic liposomes as vaccine adjuvants / Christensen D., Korsholm K.S., Rosenkrands I., Lindenstrom T., Andersen P., Agger E.M. // Expert Rev Vaccines. 2007.  Oct 6(5). 785–96.

27. Chen W.C. Non-viral vector as vaccine carrier /  Chen W.C., Huang L. // Adv Genet.  2005. 54. 315–37.

28. Vangasseri D.P. Lipid-protamine-DNA-mediated antigen delivery / Vangasseri D.P., Han S.J., Huang L.// Curr Drug Deliv.  2005.  Oct.2(4). 401–6.

29. Virosomes for antigen and DNA delivery Daemen T., de Mare A., Bungener L., de Jonge J., Huckriede A., Wilschut J. //  Adv Drug Deliv Rev. 2005.  Jan 10. 57(3). 451–63.

30.  The virosome concept for influenza vaccines / Huckriede A., Bungener L., Stegmann T., Daemen T., Medema J., Palache A.M.[et al.] // Vaccine. 2005.  Jul. 8. 23( Suppl 1). — 26-38.

31. Krishnan L. Archaeosome adjuvants: immunological capabilities and mechanism(s) of action Krishnan L. , Sprott G. D. // Vaccine. 2008.  Apr. 16. 26(17). 2043–55.

32. Azeem A. Niosomes in sustained and targeted drug delivery: some recent advances / Azeem A., Anwer M.K., Talegaonkar S. // J Drug Target. 2009 . -Nov.17(9). 671–89.

33. Vyas S.P. Vesicular carrier constructs for topical immunisation / Vyas S.P., Khatri K., Mishra V. // Expert Opin Drug Deliv. 2007.- Jul.4(4). 341–8.

34. Davis D. Liposomes as adjuvants with immunopurified tetanus toxoid: influence of liposomal characteristics / Davis D., Gregoriadis G. // Immunology. 1987. —Jun.61(2). 229–34.

35. Shahum E. Immunopotentiation of the humoral response by liposomes: encapsulation versus covalent linkage / Shahum E., Therien H.M. // Immunology. 1988.  Oct.65(2). 315–7.

36. Shahum E. Liposomal adjuvanticity: effect of encapsulation and surface-linkage on antibody production and proliferative response / Shahum E., Therien H.M. // Int J Immunopharmacol. 1995 -  Jan.17(1). 9–20.

37. Tan L. Comparison of the immune response against polio peptides covalently-surface-linked to and internally-entrapped in liposomes Tan L., Weissig V., Gregoriadis G. // Asian Pac J Allergy Immunol.  1991. Jun.9(1). 25–30.

38. Therien H.M. Liposomal vaccine: influence of antigen association on the kinetics of the humoral response / Therien H.M., Lair D., Shahum E. // Vaccine. 1990.  Dec.8(6). 558–62.

39. Shahum E. Correlation between in vitro and in vivo behaviour of liposomal antigens/ Shahum E., Therien H.M. // Vaccine. -1994.  Sep.12(12). 1125–31.

40. Vannier W.E. Antibody responses to liposome-associated antigen / Vannier W.E., Snyder S.L.// Immunol Lett. 1988.  Sep.19(1). 59–64

41. Antibody and cytotoxic T-lymphocyte responses to a single liposome-associated peptide antigen / White W.I., Cassatt D.R., Madsen J., Burke S.J., Woods R.M., Wassef N.M.[et al.] // Vaccine. 1995. 13(12). 1111–22.

42. Liposomal formulations of synthetic MUC1 peptides: effects of encapsulation versus surface display of peptides on immune responses/ Guan H.H., Budzynski W., Koganty R.R., Krantz M.J., Reddish M.A., Rogers J.A.[et al.]// Bioconjug Chem. 1998. —Jul-Aug.9(4). 451–8. 

43.  Influence of peptide acylation, liposome incorporation, and synthetic immunomodulators on the immunogenicity of a 1–23 peptide of glycoprotein D of herpes simplex virus: implications for subunit vaccines/ Brynestad K., Babbit B., Huang L., Rouse B.T. // J Virol. 1990.  - Feb.64(2). 680–5.

44. Parameters affecting the immunogenicity of a liposome-associated synthetic hexapeptide antigen / Frisch B., Muller S., Briand J., Van Regenmortel M., Schuber F. Eur J.// Immunol. 1991. 21(1). 185–93.

45.Chen W. Induction of cytotoxic T-lymphocytes and antitumor activity by a liposomal lipopeptide vaccine / Chen W., Huang L. // Mol Pharm. 2008. —May-Jun. 5(3) 464–71. 

46.Liposomal peptide vaccine inducing CD8+ T cells in HLA-A2.1 transgenic mice, which recognise human cells encoding hepatitis C virus (HCV) proteins/ Engler O., Schwendener R., Dai W., Wolk B., Pichler W., Moradpour D.[et al.]// Vaccine. 2004. 23(1). 58–68.

47. Antigen-specific, IgE-selective unresponsiveness induced by antigen-liposome conjugates  Comparison of four different conjugation methods for the coupling of antigen to liposome Nakano Y., Mori M., Nishinohara S., Takita Y., Naito S., Horino A.[et al.]// Int Arch Allergy Immunol. 1999.  Nov.120(3). 199–208

48.Garcon N.M. Universal vaccine carrier. Liposomes that provide T-dependent help to weak antigens / Garcon N.M., Six H.R. // J Immunol.- 1991.- Jun.1.- 146(11) 3697–702. 

49. Liposomes that provide T-dependent help to weak antigens (T-independent antigens)/ Pietrobon P.J., Garcon N., Lee C.H., Six H.R.// Immunomethods. 1994.- Jun .4(3). 236–43. 

50. Design of highly immunogenic liposomal constructs combining structurally independent B cell and T helper cell peptide epitopes/ Boeckler C., Dautel D., Schelte P., Frisch B., Wachsmann D., Klein J.P.[et al.]// Eur J Immunol.  1999.  Jul. 29(7). 2297–308.

51. Synthesis of thiol-reactive lipopeptide adjuvants. Incorporation into liposomes and study of their mitogenic effect on mouse splenocytes/ Roth A., Espuelas S., Thumann C., Frisch B., Schuber F. // Bioconjug Chem. 2004.  May-Jun. —15(3). 541–53.

52. Metallochelating liposomes with associated lipophilised norAbuMDP as biocompatible platform for construction of vaccines with recombinant His-tagged antigens: preparation, structural study and immune response towards rHsp90Masek J., Bartheldyova E., Turanek-Knotigova P., Skrabalova M., Korvasova Z., Plockova J.[etal.]// J Control Release. - 2011.  Apr. 30. —151(2). 193–201.

53. Antibody response in mice to polyhistidine-tagged peptide and protein antigens attached to liposomes via lipid-linked nitrilotriacetic acid / Watson D.S., Platt V.M., Cao L., Venditto V.J., Francis C., Szoka J// Clin Vaccine Immunol.  2011. —18(2). 289–97.

53. Liposomes based on dimethyldioctadecylammonium promote a depot effect and enhance immunogenicity of soluble antigen/  Henriksen-Lacey M., Bramwell V.W., Christensen D., Agger E.M., Andersen P., Perrie Y.// J Control Release.-2010.  Mar. 3.- 142(2). 180–6.

54. Comparison of the depot effect and immunogenicity of liposomes based on dimethyldioctadecylammonium (DDA), 3beta-[N-(N′,N′-Dimethylaminoethane)carbomyl] cholesterol (DC-Chol), and 1,2-Dioleoyl-3-trimethylammonium propane (DOTAP): prolonged liposome retention mediates stronger Th1 responses/ Henriksen-Lacey M., Christensen D., Bramwell V.W., Lindenstrom T., Agger E.M., Andersen P.[et al]// Mol Pharm. 2011. Feb. 7.-8(1). 153–61.

55. Liposomal cationic charge and antigen adsorption are important properties for the efficient deposition of antigen at the injection site and ability of the vaccine to induce a CMI responseHenriksen-Lacey M., Christensen D., Bramwell V.W., Lindenstrom T., Agger E.M., Andersen P.[et al.]// J Control Release. 2010. Jul. 14. —145(2).102–8.

56. CAF01 potentiates immune responses and efficacy of an inactivated influenza vaccine in ferrets / Martel C.J., Agger E.M., Poulsen J.J., Hammer Jensen T., Andresen L., Christensen D. [et al.]// PLoS ONE —2011. —6(8). 22891.

57. Phillips W.T. Novel method of greatly enhanced delivery of liposomes to lymph nodes/ Phillips W.T., Klipper R., Goins B.// J Pharmacol Exp Ther.- 2000.  Oct. —295(1). 309–13

58. Lipophosphoglycan of Leishmania major that vaccinates against cutaneous leishmaniasis contains an alkylglycerophosphoinositol lipid anchor/ McConville M.J., Bacic A., Mitchell G.F., Handman E.//  Proc Natl Acad Sci U S A. 1987.  Dec. —84(24). 8941–5.

59. Shek P. Immune response mediated by liposome-associated protein antigens. III. Immunogenicity of bovine serum albumin covalently coupled to vesicle surface /Shek P., Heath T. // Immunology. —1983. —50(1). 101–6.

60. Positively charged liposome functions as an efficient immunoadjuvant in inducing cell-mediated immune response to soluble proteins/ Nakanishi T., Kunisawa J., Hayashi A., Tsutsumi Y., Kubo K., Nakagawa S.[et al]// J Control Release. 1999.  Aug. 27. —61(1–2). 233–40.

61. Yasuda T. Immunogenicity of liposomal model membranes in mice: dependence on phospholipid compositionYasuda T., Dancey G.F., Kinsky S.C. // Proc Natl Acad Sci U S A  1977.  Mar.74(3). 1234–6.

62. Vaccination against murine cutaneous leishmaniasis by using Leishmania major antigen/liposomes. Optimization and assessment of the requirement for intravenous immunizationKahl L.P., Scott C.A., Lelchuk R., Gregoriadis G., Liew F.Y. // J Immunol.  1989. Jun. 15. —142(12) 4441–9.

63. Enhancement of in vivo and in vitro T cell response against measles virus haemagglutinin after its incorporation into liposomes: effect of the phospholipid composition/ Garnier F., Forquet F., Bertolino P., Gerlier D.// Vaccine.  1991. —9. 340–5.

64. Mazumdar T. Influence of phospholipid composition on the adjuvanticity and protective efficacy of liposome-encapsulated Leishmania donovani antigens Mazumdar T., Anam K., Ali N. // J Parasitol. 2005. Apr. 91(2) 269–74.

65. Enhancement of immune response and protection in BALB/c mice immunized with liposomal recombinant major surface glycoprotein of Leishmania (rgp63): the role of bilayer composition/ Badiee A., Jaafari M.R., Khamesipour A., Samiei A., Soroush D., Kheiri M.T.[et al.]// Colloids Surf B Biointerfaces.  2009.  Nov. 1. —74(1) 37–44.

66. Ellens H.  Fusion of phosphatidylethanolamine-containing liposomes and mechanism of the L alpha-HII phase transition / Ellens H., Bentz J., Szoka F.C. // Biochemistry (Mosc).-1986. Jul. 15. —25(14). 4141–7.

67. Legendre J.Y. Jr Delivery of plasmid DNA into mammalian cell lines using pH-sensitive liposomes: comparison with cationic liposomes. Pharm Res/ Legendre J.Y. , Szoka F.C. // 1992. - Oct.9(10). 1235–42. 

68.  Li W. Jr Lipid-based nanoparticles for nucleic acid delivery/ Li W., Szoka F.C. //  Pharm Res.  2007.  Mar.24(3). 438–49

70. Role of fusogenic non-PC liposomes in elicitation of protective immune response against experimental murine salmonellosis/ Ahmad N., Deeba F., Faisal S.M., Khan A., Agrewala J.N., Dwivedi V.[et al.]// Biochimie. —2006.  Oct.88(10). 1391–400.

71. A novel vaccine delivery system using immunopotentiating fusogenic liposomes / Hayashi A., Nakanishi T., Kunisawa J., Kondoh M., Imazu S., Tsutsumi Y.[et al]// Biochem Biophys Res Commun. 1999.  Aug. 11. —261(3). 824–8.

72. Owais M. Liposome-mediated cytosolic delivery of macromolecules and its possible use in vaccine development/ Owais M., Gupta C.M. // Eur J Biochem.  2000. —267(13). 3946–56

73. Interactions of cationic lipid vesicles with negatively charged phospholipid vesicles and biological membranes/ Stamatatos L., Leventis R., Zuckermann M.J., Silvius J.R.// Biochemistry (Mosc). 1988. May. 31. —27(11). 3917–25.

74. Yan W. Reactive oxygen species play a central role in the activity of cationic liposome based cancer vaccine/ Yan W., Chen W., Huang L. //  J Control Release.  2008. —130(1). 22–8.

75. Vasievich E.A. Enantiospecific adjuvant activity of cationic lipid DOTAP in cancer vaccine/ Vasievich E.A., Chen W., Huang L. // Cancer Immunol Immunother — 2011.- 60(5). 629–38.

76. Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid / Mucida D., Park Y., Kim G., Turovskaya O., Scott I., Kronenberg M.[et al.]// Science. - 2007. -  317(5835)/ 256–60.

77. Retinoic acid imprints gut-homing specificity on T cells/ Iwata M., Hirakiyama A., Eshima Y., Kagechika H., Kato C., Song S.Y.// Immunity. 2004. —21. 527–38

78. Erridge C. Saturated fatty acids do not directly stimulate Toll-like receptor signaling/ Erridge C., Samani N.J. // Arterioscler Thromb Vasc Biol.  2009.  —29(11). 1944–9.

79. Pegylated liposomes have potential as vehicles for intratumoral and subcutaneous drug delivery/ Harrington K.J., Rowlinson-Busza G., Syrigos K.N., Uster P.S., Vile R.G., Stewart J.S.// Clin Cancer Res.  2000. —6(6). 2528–37.

80. Efficient presentation of multivalent antigens targeted to various cell surface molecules of dendritic cells and surface Ig of antigen-specific B cells/ Serre K., Machy P., Grivel J.C., Jolly G., Brun N., Barbet J.[et al.]// J Immunol.  1998.  —161(11). 6059–67.

81. Batista F.D. The who, how and where of antigen presentation to B cells/ Batista F.D., Harwood N.E. // Nat Rev Immunol. - 2009. —9(1). 15–27.

82. Schwendener R.A. The effects of charge and size on the interaction of unilamellar liposomes with macrophages/ Schwendener R.A., Lagocki P.A., Rahman Y.E.// Biochim Biophys Acta.   1984.  —772(1). 93–101.

83. Liposome-cell interactions in vitro: effect of liposome surface charge on the binding and endocytosis of conventional and sterically stabilized liposomes/ Miller C.R., Bondurant B., McLean S.D., McGovern K.A., O’Brien D.F. // Biochemistry (Mosc). 1998.—37(37). 12875–83.

84. Lee K.D. Recognition of liposomes by cells: in vitro binding and endocytosis mediated by specific lipid headgroups and surface charge density/ Lee K.D., Hong K., Papahadjopoulos D.// Biochim Biophys Acta. —1992. 1103(2). 185–97.

85.  Siegel D.P. The mechanism of lamellar-to-inverted hexagonal phase transitions in phosphatidylethanolamine: implications for membrane fusion mechanisms/ Siegel D.P., Epand R.M. // Biophys J. 1997. —73(6). 3089–111.

86. Zhou F. Liposome-mediated cytoplasmic delivery of proteins: an effective means of accessing the MHC class I-restricted antigen presentation pathway/ Zhou F., Huang L. // Immunomethods. - 1994.—4(3). 229–35

87. Zhou F. Characterization and kinetics of MHC class I-restricted presentation of a soluble antigen delivered by liposomes/ Zhou F., Watkins S.C., Huang L. // Immunobiology. - 1994. 190(1–2). 35–52.

88. Endocytosis of an HIV-derived lipopeptide into human dendritic cells followed by class I-restricted CD8(+) T lymphocyte activation./  Andrieu M., Loing E., Desoutter J.F., Connan F., Choppin J., Gras-Masse H.[et al.]// Eur J Immunol. 2000.  —30(11). 3256–65.

89. Two human immunodeficiency virus vaccinal lipopeptides follow different cross-presentation pathways in human dendritic cells/  Andrieu M., Desoutter J.F., Loing E., Gaston J., Hanau D., Guillet J.G.[et al.]// J Virol — 2003. —77(2). 1564–70.

90. In vitro processing and presentation of a lipidated cytotoxic T-cell epitope derived from measles virus fusion protein/ Stittelaar K.J., Hoogerhout P., Ovaa W., van Binnendijk R.R., Poelen M.C., Roholl P.[et al.]// Vaccine. - 2002. —20(1–2). 249–61.



Authors: Bereznyakov I. G., Levadna Y. V., Doroshenko, O. V., Sidorov D. Y , Pozhar V. I.

Pages: 405-416



The article deals with the socio-economic status (SES) and the prevalence of risk factors (RF) in patients with diabetes mellitus (DM) type 2 and essential hypertension (EH). Determined the prevalence of risk factors, depending on the occupational status, smoking, alcohol consumption, low physical activity influence on mortality according to age. Paying special role metabolic syndrome, its dependence on SES. Attention is given to the link between SES, presence of DM type 2, the presence of hypertension and the prevalence of risk factors for cardiovascular disease. Comorbid diseases becomes actualer when combined diseases have great medical and social importance. These diseases include such common diseases accompanied by high morbidity, disability and mortality, treatment and which prevention causes high economic costs. Diabetes mellitus (DM) type 2 and hypertension can be included for these deasease confidently. Distribution and danger of these diseases give necessity to study the pathogenesis, treatment and prevention.

Diabetes, especially type 2, is a very common disease, and epidemiological studies in recent years suggest the "epidemic of diabetes." primary goal of treatment of patients with hypertension is "to achieve maximum reduction in the long-term total risk of cardiovascular morbidity and mortality. It requires the treatment of all modified risk factors, including smoking, dyslipidemia, abdominal obesity or diabetes, adequate therapy associated with hypertension clinical conditions and reduce high blood pressure. Personal risk factors for cardiovascular disease (smoking, alcohol abuse, sedentary lifestyle, poor diet, obesity) are more common in individuals with low SES. Obesity and smoking are often seen as indicators of social stress. Most studies have reported on the relationship between the parameters of SES and cardiovascular disease. An inverse relationship between SES and metabolic syndrome is established, which is largely mediated by lifestyle.

Кеу words: diabetes mellitus, essential hypertension, socio-economic status, risk factors.

This email address is being protected from spambots. You need JavaScript enabled to view it.

The full text

In progress


  1. Zimmet P. Global and societal implications of the diabetes epidemic. Nature. 2001; 414: 782–787.

2. Engberg S, Vistisen D, LauC. [et al.]Progression to impaired glucose regulation and diabetes in the population-based Inter 99 study. Diabetes Care. 2009;32( 4): 606–611.

3. Cowie C.C., Rust K.F., Ford E.S.[et al.] Full accounting of diabetes and pre-diabetes in the U.S. population in 1988-1994 and 2005-2006.Diabetes Care. 2009;32:287–294.

4. American Diabetes Association. Economic costs of diabetes in the U.S. in 2007. Diabetes Care.2008;31:596–615.

5. Ripsin C.M. Management of blood glucose in type 2 diabetes mellitus. Am. Fam. Physician. 2009;79(1): 29–36.

6. Centers for Disease Control and Prevention. National Diabetes Fact Sheet: General Information and National Estimates on Diabetes in the United States, 2007. Atlanta, GA, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2008.

7.Johannesson A., Larsson G.-U., RamstrandN. [et al.]Incidence of lower-limb amputation in the diabetic and nondiabetic general population. A 10-year population-based cohort study of initial unilateral and contralateral amputations and reamputations. Diabetes Care. 2009; 32(2):275–280.

8. MankovskyiB.N.  [2013 indiabetologykeyeventsrelevantresearchandnewclinicalguidelines]. Health Ukraine.- 201406 (331):24-26.

9. Chobanian AV., Bakris GL., Black HR[et al.] for the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, National Heart, Lung, and Blood Institute, National High Blood Pressure Education Program Coordinating Committee Seventh report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. Hypertension. 2003;42:1206–1252.

10. CovalenkoVNTalaevaTV, Bratus VV. [The significance of hypertension as a factor for cardiovascular disease, the mechanisms of its pro-atherogenic actions]. Ukrain. cardіol. J.  2010;1:28-41.

11. Sirenko YuM.Arterialna gipertenziya [Hypertension]. КievMorion, 2001. 176 p.

12. ErmacovichIISiroshtanGMGerasimenkoZhD, Pashchenko LS.[CardiaccareintheKharkivregionandopportunitiestoimprove].Ukrain. Cardіol. J. 2009; 6: 56–61.

13. KovalenkoVMKornatsky VM. [ImplementationofgovernmentprogramsagainsthypertensioninUkraine].Ukrain. cardіol. J. 2010;6:7–12.

14. KornatskyVMRevenkoLI. [MedicalandsocialaspectsofcerebrovasculardiseaseinUkraine].Ukrain. cardіol. J.  2011;1:86–92.

15. Lloyd-JonesDAdamsRCarnethonM[et al.] for the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2009 Update. A Report From the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation.2009;119:e21–e181.

16. Vilensky BS. Stroke - state of the art . Nevrologich J. 2008;2:4–10.

17. Kovalenko VN, Kornatsky VM, Manoylenko T. et al. Demografіya i zdorovya populacii Ukraini. [Demographics and health of the people of Ukraine]. Kyiv: 2010.  142p.

18. Mishchenko TS. [Analysis of the epidemiology of cerebrovascular disease in Ukraine] Vascular diseases of the brain.  2010; 3:2-9.

19. Khobzey NK, Mishchenko TS, Golik VA Ipatov AVю Epidemiology of stroke, clinical aspects and expertise in Ukraine.Vascular diseases of the brain. 2010; 4: 2-5.

20. Dolzenko MN How to prevent organ damage in hypertension? Correction of metabolic disorders. Health of Ukraine. 2014; 06 (331):18-19

21. A guideline on hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC) 2013.Hypertension2013;4:61-130

22. Ose D, Wensing, Szecsenyi MJ. [et al.] Impact of primary care-based disease management on the health-related quality of life in patients with type 2 diabetes and comorbidity. Diabetes Care. 2009;32(9): 1594–1596.

23. Mancia G, de Backer G, Dominiczak A.[et al.]. 2007 Guidelines for the Management of Arterial Hypertension. The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) J. Hypertens. 2007; 25:1105–1187.

24. Izzo R, Simone GDe, ChinaliM. [et al.]. Insufficient control of blood pressure and incident diabetes. Diabetes Care. 2009; 32(50):845–850.

25. Monami M, Vivarelli M, DesideriCM [et al.].  Pulse pressure and prediction of incident foot ulcers in type 2 diabetes. Diabetes Care. 2009; 32 (5):897–899.

26. Obrezan AG, Bicadze RM. Structure of cardiovascular disease in patients with Type 2 diabetes, diabetic cardiomyopathy as a special state of the myocardium. InternEndocrinologyJ. 2010; 4:18-22.

27. Adler AI, Stratton IM, Neil HA[et al.]. Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): Prospective observational study. BMJ. 2000; 321:412–419.

28. Karlamanglaa AS , Singerb BH, William DR [et al.]. Impact of socioeconomic status on longitudinal accumulation of cardiovascular risk in young adults: the CARDIA Study (USA). Soc. Sci. Med. 2005;60: 999–1015.

29. Mieczkowska J. Mosiewicz J.  Socioeconomic status and cardiovascular disease risk. Heart. 2008; 94(8):1075.

30. Rosero-Bixby L. Dow WH. Surprising gradients in mortality, health, and biomarkers in a Latin American population of adults. J. Gerontol. Series B. 2009; 63 (1): 105–117.

31. Lantz PM, Golberstein E, House JS, Morenoff J. Socioeconomic and behavioral risk factors for mortality in a national 19-year prospective study of U.S. adults. Soc. Sci. Med.  2010; 70:1558–1566.

32. Khang YH, Lynch JW, Yang S. [et al.]. The contribution of material, psychosocial, and behavioral factors in explaining educational and occupational mortality inequalities in a nationally representative sample of South Koreans: relative and absolute perspectives. Soc. Sci. Med.  2009; 68(5): 858–866.

33. Meara ER Richards S, Cutler DM. The gap gets bigger: changes in mortality and life expectancy, by education, 1981-2000. Health Affairs. 2008; 27(2}:350–360.

34. Dray-Spira R, Gary-Webb TL, Brancati FL. Educational disparities in mortality among adults with diabetes in the U.S. Diabetes Care. 2010;33(6).1200–1205.

35. Feinglass J, Lin S, Thompson J. [et al.]. Baseline health, socioeconomic status and 10-year mortality among older middle-aged Americans: findings from the health and retirement study, 1992–2002. J. Gerontol. 2007; 62B(4): S209–S217.

36. Kokkinos P, Myers J, Nylen E.[et al.] Exercise capacity and all-cause mortality in African American and Caucasian men with type 2 diabetes. Diabetes Care. 2009;32(4):623–628.

37. Sui X, LaMonte MJ, Laditka JN [et al.]. Cardiorespiratory fitness and adiposity as mortality predictors in older adults. J. Am. Med. Ass. 2007; 298 (21): 2507–2516.

38. Preiss D, Zetterstrand S,. McMurrayJJV [et al.]. Predictors of development of diabetes in patients with chronic heart failure in the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) program. Diabetes Care. 2009;32(5):915–920.

39. Orpana HM, Berthelot JM, Kaplan MS [et al.] BMI and mortality: results from a national longitudinal study of Canadian adults. Obesity. 2010;18(1 ): 214-218.

40. Reis JP, Araneta MR, Wingard DL [et al.]. Overall obesity and abdominal adiposity as predictors of mortality in U.S. white and black adults. Annals Epidemiol. 2009;19: 134–142.

41. Mitchenko AI,  Logvynenko AA, Romanov V. [Optimization of treatment of dyslipidemia and disorders of carbohydrate metabolism in patients with hypertension with metabolic syndrome and thyroid dysfunction]. Ukr. cardiology. J. 2010;1:73–80.

42. Nieto F.J. Understanding the pathophysiology of poverty. Int. J. Epidemiol. 2009; 38: 787–790.

43. Kivimaki M, Lawlor DA, Davey Smith G [et al.]. Socioeconomic position, co-occurrence of behavior-related risk factors, and coronary heart disease: the Finnish Public Sector study. Am. J. Public Health. 2007; 97: 874–879.

44. Roberts BA, Der G, Deary IJ, Batty GD. Reaction time and established risk factors for total and cardiovascular disease mortality: comparison of effect estimates in the follow-up of a large, UK-wide, general-population based survey. Intelligence.  2009;37:561–566.

45. Vasilieva NYu, Zharinov OI, Kuts VA, Epanchintseva OA.[ Diagnosis of cognitive impairment in patients with hypertension]. UkrkardіolJ.  2009;5:91-100.

 46. Gale CR, Deary IJ, Batty GD. Intelligence and carotid atherosclerosis in older people: Cross-sectional study. J. Am. Geriatr. Soc.  2008;56:769−771.

47. Steptoe A, Shamaei-Tousi A, Gylfe A. [et al.]. Socioeconomic status, pathogen burden and cardiovascular disease risk. Heart.  2007;93(12):1567–1570.

48. Mankovsky BN.[Type 2 diabetes and metabolic syndrome: what you need to know about satellites practitioner diabetes].Health Ukraine. 2014;10:29.

49. Hrebtіy GI. [Structural and geometric remodeling of the left ventricle of the heart, hemodynamic and vascular endothelial function in patients with hypertension depending on body weight]. Ukr. cardiology. J. 2009;4: 49-52.

50. TodurovBMKundinVYNobisOE.[Modernpossibilitiesofmyocardialscintigraphyinthediagnosisoflesionsoftheleftventriclemyocardiumoftheheart].UkrkardіolJ.  2010;5: - P. 100-108.

51. KimBJKimBS, SungKC [etal.]. Association of smoking status, weight change, and incident metabolic syndrome in men: a 3-year follow-up study. Diabetes Care. 2009;32(7): 1314–1316.

52. Wada T, Urashima M, Fukumoto T. Risk of metabolic syndrome persists twenty years after the cessation of smoking. Intern Med. 2007; 46:1079–1082.

53. Sánchez-Chaparro MA, Calvo-Bonacho E, González-Quintela A [et al.] on behalf of the Ibermutuamur CArdiovascular RIsk Assessment (ICARIA) study group.Occupation-related differences in the prevalence of metabolic syndrome. Diabetes Care. 2008;31(9): 1884–1885.

54. Chen Y, Sigal RJ, Lin M. Impacts of diabetes and hypertension on the risk of hospitalization among less educated people. J. Human Hypertens. 2007;21: 225–230.

55. Gregg EW, Gu Q, Cheng YJ [et al.]. Mortality trends in men and women with diabetes, 1971-2000. Ann. Intern Med. – 2007;147:149–155.

56. Ferrara A, Mangione CM, Kim C. [et al.] for the Translating Research Into Action for Diabetes (TRIAD) study group Sex disparities in control and treatment of modifiable cardiovascular disease risk factors among patients with diabetes. Translating Research Into Action for Diabetes (TRIAD) study. Diabetes Care.  2008;31(1): 69–74.

57. The TRIAD study group. Health systems, patients factors, and quality of care for diabetes. A synthesis of findings from the TRIAD Study. Diabetes Care. 2010;33(4): 940–947.

58. Heraclides A., Chandola T, Witte DR, Brunner EJ. Psychosocial stress at work doubles the risk of type 2 diabetes in middle-aged Women. Evidence from the Whitehall II study. Diabetes Care. 2009;32(12): 2230–2235.

59. Carlsson AC, Wändell PE, U. de Faire, Hellénius ML. Risk factors associated with newly diagnosed high blood pressure in men and women. Am. J. Hypertens. 2008;21(7): 771–777.

60. Davydova IV. [Features of the course and tactics of hypertensive patients aged 60 years and older according to current guidelines]. Health Ukraine. 2014;06 (331):22-23

61. Marotta T, Viola S, Ferrara F, Ferrara LA. Improvement of cardiovascular risk profile in an elderly population of low social level: the ICON (Improving Cardiovascular risk profile in Older Neapolitans) study. J. Human Hypertens. 2007; 21: 76–85.

62. Halldin M, Rosell M, de Faire U, Hellenius ML. The metabolic syndrome: prevalence and association to leisure-time and work-related physical activity in 60-year-old men and women.Nutr. Metab. Cardiovasc. Dis– 2007. – Vol. 17. – Р. 349–357.

63. Gu D, Wildman RP, Wu X [et al.]. Incidence and predictors of hypertension over 8 years among Chinese men and women. J. Hypertens.  2007; 25: 517–523.

64. Haslam D. W. Obesity. Lancet2005; 366:1197–1209.

65. Radchenko AD, Martsovenko IM, Syrenko N. [Do doctors in Ukraine risk stratification of patients with hypertension?] Radchenko AD. Ukr. kardіol. J.  2009;5:7-16.

66. Sirenko Y.M. [The program of prevention and treatment of hypertension in Ukraine]. Hypertension. 2008;2:S.83-88.

67. Kupchynskaya OG. The evolution of left ventricular hypertrophy in hypertensive patients provided occasional intake of antihypertensive drugs. Ukr. Cardiology. J. 2011; 3:  50-54.

68. Piette JD, Kerr EA. The impact of comorbid chronic conditions on diabetes care. Diabetes Care. 2006; 29(3):725–731.

69. Hofer TP, Zemencuk JK, Hayward RA. When there is too much to do: how practicing physicians prioritize among recommended interventions. J. Gen. Intern. Med.2004;19:646–653.

70. Egan BM, Lackland DT, Cutler NE. Awareness, knowledge, and attitudes of older americans about high blood pressure: implications for health care policy, education, and research. Arch Intern. Med2003;163:681–687.

71. Moser M. No surprises in blood pressure awareness study findings: we can do a better job. Arch Intern. Med. 2003;163:654–656.

72. Kovalenko VM. [Prevention and treatment of myocardial infarction in Ukraine]. Ukr. cardiology. J.  2009; 4: 7-12.