Get Adobe Flash player


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.



Authors: Romanjuk A. M., Moskalenko R. A., Rieznik A, V., Gapchenko A. V.

Pages: 417-426



Resume. In thyroid gland calcifications are found in benign as well as in malignant pathology, which are diagnosed by ultrasound investigation of the organ. The resulting diagnostic information about calcified objects in the thyroid gland are missed often by physicians or they have minimal clinical significance (Khoo M.L. et al, 2002).

The aim of the work is to analyze the scientific literature data for establishing the spread, mechanisms of origin and diagnostic value of pathological biomineralization in the thyroid gland.

The patient's age, sex, size and histological tumor affiliation, the presence of metastatic affection outside the thyroid gland, lymph node status are the significant markers for prognosis in patients with thyroid cancer (TC) (Bai Y. et al, 2008). Calcification is detected the most often by papillary thyroid carcinoma (PTC) among all thyroid diseases. However, the clinical value of calcification, including the clinical manifestations’ correlation, the impact on patient’s survival and molecular mechanisms, which are responsible for tumor tissue calcification, are unidentified. Thyroid calcifications were divided psammoma bodies (PBs), stromal calcification and bone tissue formation (ossification), in the works of Bai Y., et al, (2009), based on clinical pathological features of biomineralization. Most of authors consider the PBs presence as diagnostic feature of PTC. PBs are characterized as spherical calcified foci, that are constructed by concentric plates (LiVolsi V. et al., 2004, Johanessen J.V. et al., 1980). There are different views about the origin of PBs. Johanessen J.V. et al., (1980) consider PBs as a result of dystrophic tumor thrombuses’ calcification in the lymphatic and blood vessels’ lumen. According to the views of other authors PBs are formed by the intracellular calcifications in viable cells as the nidus. Cell degeneration and necrosis, which lead to the disappearance of tumor cells, are found only around the PBs, but not around predecessors. Based on these facts, the authors present the PBs as an active biological process, that leads to the death of tumor cells and prevents their growth and spread (Das D.K, 2009). There is also an original hypothesis of the PBs origin in the tumors of thyroid gland and ovaries, in which the participation of gram-negative nanobacterium (Chlamidia) in the biomineralization process are proved, these bacteriums are capable for calcium precipitation (Hudelist G. et al., 2004). Ossification or bone formation were found in the cases, in which bone matrix and osteocytes were identified (Bai Y. et al, 2008). All calcifications, that didn’t approach to the definitions of PBs and ossification, were considered as stromal calcification, including also psammosa like calcifications - round without a layered structure but with uneven borders. Stromal calcification is caused by calcium phosphate deposition in fibrous stroma. Bone formation proteins (bone morphogenetic protein - BMP) 1, 2, 4, 9 and 11, osteopontin, ALK1, TGF-β1 take part in pathological processes of thyroid gland biomineralization at the molecular level.

Thus, signs of pathological biomineralization (calcification) may be an important differential diagnostic criteria of thyroid gland tumors as during ultrasound, and pathohistological study. This touchs on especially patients with solitary calcified node, calcification of neck lymph nodes, microcalcifications in older patients (over 45 years) and coarse node calcification. Pathologists should pay particular attention to the PBs in the thyroid gland, which are not associated with tumor pathology, because it may be a sign of hidden PTC (microcarcinoma) or metastasis from the opposite gland lobe.

Key words: thyroid gland, calcification, psammoma bodies, ossification, diagnostic

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

The full text

In progress


1. Diseases of the thyroid/ Edited by Lewis E. Braverman. Humana Press, New Jersey. 2000; 432 pp.
2. Khoo M.L., Asa S.L., Witterick I.J., Freeman J.L. Thyroid calcification and its assotiation with thyroid carcinoma. Head Neck. 2002; 24:651-655.
3. Mazzaferri E.L. Management of a solitary thyroid nodule. N Engl J Med. 1993; 328:553–559.
4. Lee J., Lee S.Y., Cha S.H., Cho B.S., Kang M.H., Lee O.J. Fine needle aspiration of thy-roid nodules with macrocalcification. Thy-roid. 2013. 
5. Lyons R., Waters P.S., Sugrue C., Kerin M.J. An unusual presentation of calcified thyroid gland. BMJ Case Rep. 2012. Pii: bcr 2012007844. Doi:10.1136/bcr-2012-007844.
6. Wu C.W., Dionigi G., Lee K.W., Hsiao P.J., Paul Shin M.C., Tsai K.V., Chiang F.Y. Cal-cifications in thyroid nodule identified o pre-operative computed tomography: patterns and clinical significance. Surgery. 2012. Vol. 151, 151(3): 464-70. Doi 10.2016/j.surg.2011.07.032.
7. Bai Y., Zhou G., Nakamura M., Ozaki T., Mori I., Taniguchi E., Miyauchi A., Ito Y., Kakudo K. Survival impact of psammoma bodies, stromal calcifications, and bone for-mation in papillary thyroid carcinoma. Mod-ern pathology. 2009. 22, 887-894.
8. Yoo E.Y., Shin J.H., Ko E.Y., Han B.K. Contribution of the BRAF mutation analysis in calcified thyroid nodules. Am J Roentgenol. 2012; 198(4):891-5. doi: 10.2214/AJR.11.6866.
9. Shi C., Li S., Shi T., Liu B., Ding C., Qin H. Correlation between thyroid nodule calcifica-tion morphology on ultrasound and thyroid carcinoma. J Int Med Res. 2012; 40 (1):350-7.
10. Gungor B., Polat A.C., Polat C., Seren D., Erzurumlu K. Do the calcifications in the thyroid gland predict malignancy? Bratisl Lek Listy. 2012; 113 (9):552-5.
11. Kim B.K., Choi Y.S., Kwon H.J., Lee J.S., Heo J.J., Han Y.J., Park Y,H., Kim J.H. Relationship between patterns of calcification in thyroid nodules and histopathologic findings. Endocr J. 2013. 28;60 (2):155-60.
12. Chen G., Zhu X.Q., Zou X., Yao J., Liang J.X., Huang H.B., Li L.T., Lin L.X. Retro-spective analysis of thyroid nodules by clini-cal and pathological characteristics, and ultra-sonographically detected calcification corre-lated to thyroid carcinoma in South China. Eur Surg Res. 2009; 42 (3):137-42. doi:10.1159/000196506.
13. Liu H.F., Tang W.S., Yang Z.Y. [Thyroid nodules with calcification and thyroid carci-noma]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2003; 25(5):626-9 [Article in Chinese]. 
14. Kouvaraki M. A., et al. Role of preoperative ultrasonography in the surgical management of patients with thyroid cancer. Surgery, 2003, 134.6: 946-954.
15. Bai Y., Kakudo K., Li Y. et al. Subclassifica-tion of non-solid-type papillary thyroid carci-noma identification of high-risk group in common type. Cancer Sci. 2008; 99:1908-1915.
16. Consorti F., Anello A., Benvenuti C et al. Clinical value of calcifications in thyroid car-cinoma and multinodular goiter. Anticancer Res. 2003; 23:3089-3092.
17. Seiberling K.A., Dutra J.C., Grant T, et al. Role of intrathyroidal calcifications detected on ultrasound as a marker of malignancy. Laryngoscope. 2004; 114:1753-1757.
18. Triggiani V., Guastamacchia E., Licchelli B, et al. Microcalcifications and psammoma bodies in thyroid tumors. Thyroid. 2008; 18:1017-1018.
19. LiVolsi V.A., Mazzaferri E.L., Schneider A.B., Albores-Savedra J., Hay I. Papillary carcinoma. In: Delellis R.A., Lloyd R.V., Heitz P.U., Eng C. editors. World Health Or-ganization Classification of tumors, pathology and genetics of tumors of endocrine organs. Lyon, France: International Agency for Research on Cancer. 2004. p. 57-66.
20. Johannessen J.V., Sobrinho-Simoes M. The origin and significance of thyroid psammoma bodies. Lab. Invest. 1980:43:287-96.
21. Park S.H., Suh E.H., Chi J.G. A histopatho-logic study on 1095 surgically resected thy-roid specimens. Jpn J Clin Oncol. 1988;18:297-302.
22. Hunt J.L., Barnes E.L. Non-tumor-assotiated psammoma bodies in the thyroid. Am J Clin Pathol. 2003; 119:90-94.
23. Das D.K. Psammoma body: a product of dys-trophic calcification or of a biologically active process that aims at limiting the growth and spread of tumor? Diagn Cytopathol. 2009. 37 (7)534-41. doi: 10.1002/dc.21081.
24. Schneider N.I., Bauernhofer T., Schollnast H., Ott A., Langner C. Pancreatic adenocarcinoma with multiple eosinophilic extracellular deposits consistent with noncalcified psammoma bodies. Virchows Arch. 2011; 459:623-625.
25. Hudelist G., Singer C.F., Kubista E., Manavi M., Mueller R., Pischinger K. et al. Presence of nanobacteria in psammoma bodies of ovar-ian cancer. Evidence for pathogenetic role in intratumoral biomineralization. Histopatholo-gy. 2004. 45: 633-7.
26. Li S., Boudousquie A.C., Baloch Z.W., Min-da J.M., Gupta P.K. Aluminum silicate –containing psammoma bodies in a cervi-covaginal smear (Pap): cytological, ultrastructural, and radiographic microprobe studies. Diagn. Cytopathol. 1999. 21: 122-4.
27. Merlin Olivera P.S., del C. Leyva Bohorquez P., Martinez-Cruz R., Canseco S.P., Hernandez P et al. A study on inorganic ele-ments in psammomas from ovarian & thyroid cancer. Indian J Med Res. 2012; 135:217-220.
28. Hopkins D.R., Keles S., Greespan D.S. The bone morphogenetic protein 1 / Tolloid-like metalloproteinases. Matrix Biol. 2007; 26:508-523.
29. Hatakeyama S., Gao Y.N., Ohara-Nemoto Y, et al. Expression of bone morphogenetic pro-teins of human neoplastic epithelial cells. Bi-ochem Mol Biol Intern. 1997; 42:497-505.
30. Ge G., Greenspan D.S. BMP1 controls TGF-beta1 activation via cleavage of latent TGF-beta-binding protein. J Cell Biol. 2006; 175:111-120.
31. Sung J-Y., Na K.Y., Lee S.K., Jung W.W., Kim Y.W., Park Y.K. ALK-1 and BMP-9 overexpression as a cause of ossifying papil-lary thyroid carcinoma. Virchovs Arch. 2012; 461 (Suppl. 1): S 104.
32. Scatena M., Liaw L., Giachelli C.M. Osteo-pontin: A multifunctional molecule regulating chronic inflammation and vascular disease. Arterioscler Thromb Vasc Biol. 2007; 27:2302–2309.
33. Franzen A., Heinegard D. Isolation and char-acterization of two sialoproteins present only in bone calcified matrix. Biochemical J. 1985; 232: 715-24.
34. Giachelli C.M., Steitz S. Osteopontin: a ver-satile regulator of inflammation and bio-mineralization. Matrix. Biol.2000;19: 615-622.
35. Nemir M., De Vouge M.W., Mukherjee B.B. Normal rat kidney cells secrete both phos-phorylated and nonphosphorylated forms of osteopontin showing different physiological properties. J Biol Chem. 1989; 25:264(30):18202-8.
36. Gong T., Wang J. [The analysis of the calcification in differentiating malignant thyroid neoplasm and the molecular mechanisms for the formation of the calcification]. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2012;26(16):763-6. [Article in Chinese].



Authors: Mikheytseva I. N.

Pages: 427-437



Purpose: tostudy the possibility oftheformationof symptoms of primary glaucoma - elevated intraocular pressure and morphological changes of the optical apparatus of the eye - in agedanimals with introduction of the stress- hormone adrenaline.
Material and methods.

The study is conducted on 40 rabbits age 2-3 years, and 25 rats age 12-15 months. Glaucoma is modeled byinravenousinjections of 0.18% solution of adrenaline hydrotartrate in rabbits and intraperitoneal injections in rats, developed by us for the scheme, every 1st, 3rd the 5th day of the week. Unified single dose of the drug was calculated depending on weight from 12.5 to 25 mcg/kg in rabbits and from 10 to 15 mcg/100g in rats.
Control of intraocular pressure (IOP) is carried out before the introduction of adrenaline application with Maklakov' tonometer (the plunger weighing 7.5 g in rabbits and 2 g in rats) under local anesthesia. Histo - morphological studies of tissues of the animal enucleated eyes held on preparations stained with hematoxylin - eosin. For statistical evaluation of the experimental data we use ANOVA for repeated measurements.


Repeated systemic injections of adrenalin in rabbits and rats cause them to have a significant increase in IOP. In the period of drug administration, this increase is in rabbits 25%, rats - 52%. After termination of model induction with adrenaline IOP continues to grow. In rabbits, this index exceeds the original value by 38% after 6 months, after 12 months it increases by 57%. In rats, 10 weeks after injection of adrenaline, IOP increases by 72% and remains at this level after 20 weeks of observation. ANOVA for repeated measurements using a linear mixed model type shows that in the experiment with the simulation of glaucoma, extended in time, for the formation of high IOP does not matter the time factor, but adrenaline is essential factor for inducing pathologic process.
Histo-morphological studies reveal degenerative changes in the blood vessels of the eyes of experimental animals, it is accompanied by degeneration of the ganglion layer of the retina and tissues of the optic nerve with a deep excavation of the disc.
Chronic adrenal stress, induced by repeated application of adrenaline, is a triggering mechanism of primary glaucoma. On the basis of hyperadrenalinemiya by prolonged systemic injections of adrenaline in agedexperimental animals - rabbits and rats- we reproduce the main features of glaucoma - resistant ocular hypertension and specific structural changes of the nervous apparatus of the eye–retina and optical nerve structure.

Key words: glaucoma, model, adrenaline, stress, intraocular pressure, retina.

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

The full text

In progress


  1. Афендулова И.С., Захарова И.А. Влияние психо-эмоционального стресса на развитие первичной глаукомы.Глаукома 2008; 4:35-36.[Afendulova I.S., Zaharova I.A.Vliyaniepsiho-emotsionalnogo stressa na razvitie pervichnoy glaukomy. Glaucoma 2008;4:35-36.(In Russ)].
  2. Kaluza G. Maurer H.Stress and intraocular pressure in open angle glaucoma.Psychology and Health.1997; 5:667-675.
  3. Schwarts B.  Differences of adrenal stress control mechanisms in subjects with glaucoma and normal subjects.Arch. Ophthalmol.1981; 10:1770 – 1777.
  4. Луценко Н. С. Гормонально-метаболічні порушення при первинній відрито кутовій глаукомі та патогенетичне обґрунтування їх корекції в комплексному лікуванні: автореф…докт.мед.наук. Одеса: 2008; 32. [Lutsenko N.S. Gormonalno-metabolichni porushennya pri pervinniy vidritokutoviy glaukomi ta patogenetychne obgruntuvannya yih korektsiyi v kompleksnomu likuvanni: avtoref… Odesa: 2008; 32 (In Ukr)].
  5. Kwon Y.H., Caprioli J. Primary open angle glaucoma. Duane’s clinical ophthalmology.  – Philadelphia: Lippincott Williams and Wilkins: 1999:1-30.
  6. Jay J.L.  Murdoch  J.R. The rate of visual field loss in untreated primary open angle glaucoma.  Br.J.Ophthalmol.1993; 77(3):176-178.
  7. Leske M.C., Heijl A., Hyman L. [ et al.]  Predictors of long-term progression in the early manifest glaucoma trial.Ophthalmology2007; 114 (11):1965–1972.
  8. Кассиль Г.Н. Наука о боли. – М.: Наука:1975. 400.[Kassil G.N. Nauka o boli. – Moskow: 1975. 400 (In Rus.)].
  9. Шевалев В.Е.  Гиперболическая линейка для измерения тонограмм. Офтальмологический журнал1947;  3:140-144.[Shevalev V.E. Giperbolicheskayalineykadlyaizmereniyatonogramm.Oftalmologicheskiyzhurnal 1947; 3:140-144.(InRus.)].
  10. Ланг Т.А., Сесик М. Как описывать статистику в медицине.  Москва: 2011. 478[Lang T.A., Sesik M. Kak opisyvat statistiku v meditsine.Moskow: 2011. 478 (InRus)].
  11. Липовецкая Е.М., Степанок Е.Г. Гистоморфологические исследования при экспериментальной глаукоме. Офтальмологический  журнал 1967;1:52-56.[Lipovetskaya E.M., Stepanok E.G.Gistomorfologicheskie issledovaniya pri eksperimentalnoy glaukome. Oftalmologicheskiy zhurnal 1967;1:52-56.(InRus)].
  12. Самусенко И.А., АлексеевВ.Н.,АбузайедВ.Н. Морфологические проявления лечебного патофорфоза глаукомной оптической нейропатии при экспериментальной глаукоме.Глаукома 2003;4:3-9.[Samusenko I.A.Alekseev V.N., Abuzayed V.N. Morfologicheskie proyavleniya lechebnogo patoforfoza glaukomnoy opticheskoy neyropatii pri eksperimentalnoy glaukome. Glaukoma2003;4:3-9. (In Rus)].
  13. Quigley H. Histological and clinical features of the optic nerve head in early glaucomatous diagnosis. Ocular blood flow in glaucoma. Kugler Pub.:1988. 83.
  14. Егоров Е.А., Курмангалиева М.М., Федотовских Г.В. Морфологическое исследование сітчатки глаз больных глаукомой. Русский медицинский журнал 2004; 2: 54-56.[Egorov E.A., Kurmangalieva M.M., Fedotovskih G.V. Morfologicheskoe issledovanie setchatki glaz bolnyih glaukomoy. Russkiy meditsinskiy zhurnal 2004; 2: 54-56.(InRus)].



Authors: Hassan Ali Al-Saadi

Pages: 438-441



Colorectal cancer (CRC) is the third most common cancer diagnosed, and is associated with high rates of propagation and mortality for both men and women. Aimed to to analyze impact of presence of T-bet, Foxp3 and CD8 on colorectal cancer. During the period 1/October/2013 to 1/March/2014, fifty patients with colon cancer (14 female and 36 male) (7-75) years were taken from (Al-Hussain Hospital City/Kerbala, Digestive and Liver Disease /Education Hospital Medical City Baghdad and Teaching Oncology Hospital /Baghdad Medical City/ Baghdad /Iraq).Immunochemical studying of T-bet, Foxp3 and CD8 of colorectal biopsies by using DAKO Company/Denmark. There was a significant increase (p≤0.001) in the concentration of T-bet, Foxp3 and CD8 respectively in patients male compared with female, also there was a significant variance (p≤0.001) in the three age groups from (7-20), (21-40) and (41-75) in the levels of T-bet and CD8, whereas a significant difference (p≤0.05) in the concentration of Foxp3 in the three age groups. This study proved functional role of T-bet, Foxp3 and CD8 in cell-mediated immunity.

Key words: T-bet, Foxp3, CD8, Colorectal cancer.

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

The full text

In progress


  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J and Thun MJ. Cancer statistics, 2009. CA: a cancer journal for clinicians 2009; 59(4), 225-249.
  2. Zeestraten EC, Van Hoesel AQ, Speetjens FM, Menon AG, Putter H, van de Velde CJ, and Kuppen PJ. FoxP3-and CD8-positive infiltrating immune cells together determine clinical outcome in colorectal cancer. Cancer Microenvironment 2013; 6(1), 31-39.
  3. Goc J, Germain C, Vo-Bourgais TKD, Lupo A, Klein C, Knockaert S et al. Dendritic cells in tumor-associated tertiary lymphoid structures signal a Th1 cytotoxic immune contexture and license the positive prognostic value of infiltrating CD8+ T cells. Cancer research 2014; 74(3), 705-715.
  4. Yagi H, Nomura T, Nakamura K, Yamazaki S, Kitawaki T, Hori S, et al. Crucial role of FOXP3 in the development and function of human CD25+ CD4+ regulatory T cells. International immunology 2004; 16(11), 1643-1656.
  5. Hori S and Sakaguchi S. Foxp3: a critical regulator of the development and function of regulatory T cells. Microbes and Infection 2004; 6(8), 745-751.
  6. Gordon SM, Chaix J, Rupp LJ, Wu J, Madera S, Sun JC et al. The transcription factors T-bet and Eomes control key checkpoints of natural killer cell maturation.Immunity 2012; 36(1), 55-67.



Authors: Savchenko І. М.

Pages: 442-449



Introduction. Pathogenesis of the leiomyoma includes a thorough update of the tumor microenvironment. This process also involves the destruction of intertissue barriers and tumor neoangiogenesis, provided by the Zn-containing enzyme of the matrix (metaloproteіnaza–1 MMP-1). The polymorphism of MMP-1 gene might be closely connected with the contraction and further progression of this pathology.

Purpose. Detect the genotypes frequency by 1G/2G–1607 polymorphism of the MMP-1 gene in women, who suffer leiomyoma and have additional disorders.

Materials and Methods. We have used the venous blood of 108 women diagnosed with leiomyoma (average age was 47,82 ± 6,6 years) and the venous blood of 84 women, without this disease (average age was 69,75 ± 8,4 years). The detection of 1G/2G–1607 polymorphism of the MMP-1 gene was conducted with the help of polymerase chain reaction method with further restriction fragments length analysis while allocating them by electrophoresis in agarose gel. The AluI restriction enzyme was used for the restriction analysis. Statistical data processing was carried out with the help of SPSS-17 software package. In addition, the differences were determined by χ² criterion. Values with Р<0,05 were accepted as accurate.

Results. In women, who have chronic obstructive pulmonary disease and 2G/2G genotype, leiomyoma develops more often than in the 1G allele carriers (Р=0,035). Between patients with the chronic pyelonephritis, leiomyoma is more common for carriers of the 2G / 2G genotype (Р=0,034). In patients who have hypertension and 2G/2G genotype, risk of leiomyoma is higher than in carriers of the 1G / 1G genotype (Р=0,042). During the comparison of the 1G / 2G genotypes frequency in women, who had any disorders with cerebral or coronary blood circulation, the significant difference has been detected only in patients with leiomyoma, who didn’t have any interference with the blood flow (Р=0,030).

Conclusion. The connection between 1G/2G polymorphism and leiomyoma progression is particularly noticed in women, diagnosed with the chronic obstructive pulmonary disease, hypertension and patients, who do not have cerebral or coronary blood circulation failure.

Key words: matrix metaloproteіnaza–1, single nucleotide polymorphism, leiomyoma, pyelonephritis, hypertension.

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

The full text

In progress


  1. Wichlaewa EM. Rukovodstvo po endokrinnoi gynekologii [Guide endocrine gynecology]. Medicinskoe informacionnoe agenstvo Publ., 2006.463 р.
  2. Sidorova IS. Mioma matki (sovremennie aspekty etiologii, patogenesa, klassifikacii i profilaktiki) [Mioma matki]. M. Medicinskoe informacionnoe agenstvo Publ., 2003.256 р.
  3. Tichomirov AL, Lubnin DM. Mioma matki [Mi-oma matki]. M. Medicinskoe informacionnoe agenstvo Publ., 2006.176 р.
  4. Dolzhikow АА, Churnosow МI, Pachomow SP. [Molecular genetic prognostic factors smooth muscle tumors of the uterus: the role of matrix metalloproteinases]. NIU BеlGU Chеlоvеk I ego zdorowie. 2012;2:138-146.
  5. Liotta LA, Tryggvason K, Garbisa S. et al. Meta-static potential correlates with enzymatic degra-dation of basement membrane collagen. Nature. 1980;284:67-68.
  6. Birkedal-Hansen H1, Moore WG, Bodden MK, Windsor LJ, Birkedal-Hansen B, DeCarlo A, Engler JA. Matrix metalloproteinases: a review. Crit Rev Oral Biol Med. 1993;4(2):197-250.
  7. Matsumura S, Oue N, Kitadai Y, Chayama K, Yoshida K, et al. A single nucleotide polymor-phism in the MMP-1 promoter is correlated with histological differentiation of gastric cancer. J Cancer Res Clin Oncol. 2004;130(5):259-265.
  8. Baroneza J, Santos A, Massa B, Munhoz F, Fernand es T, Santos M. MMP-1 promoter gen-otype and haplotype association with posterior tibial tendinopathy. Gene 2014;547(2):334-7.
  9. Zitka O, Kukacka J, Krizkova S, Huska D, Adam V, Masarik M, Prusa R and Kizek R. Matrix Metalloproteinases. Current Medicinal Chemis-try. 2010;17:3751-3768.
  10. Snarskaya ES, Molochkov VA, Frank GA, Zavalishina LE. Matrix metalloproteinases and their tissue inhibitors in basal cell and metatypi-cal cancer of the skin. Ark. Pathol. 2005;67(3):14-16.
  11. Xiao X, Wang X, Zang D. MMP1-1607 1G/2G polymorphism and lung cancer risk: a meta-analysis. Tumour Biol 2012;33(6):2385-92.
  12. Zhu Y1, Spitz MR, Lei L, Mills GB, Wu X. A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter enhances lung cancer susceptibility. Cancer Res. 2001;61(21):7825-9.
  13. Hirata H, Naito K, Yoshihiro S, Matsuyama H, Suehiro Y, Hinoda Y. A single nucleotide pol-ymorphism in the  matrix metalloproteinase-1 promoter is associated with conventional renal cell carcinoma. Int J Cancer 2003;106(3):372-374
  14. Shiozawa J1, Ito M, Nakayama T, Nakashima M, Kohno S Expression of matrix metallopro-teinase-1 in human colorectal carcinoma. Mod Pathol. 2000;13(9):925-33.
  15. Przybylowska K, Zielinska J, Zadrozny M, Krawczyk T, Kulig A, Wozniak P, Rykala J, Kolacinska A, Morawiec Z, Drzewoski J and Blasiak J. An association between the matrix metalloproteinase 1 promoter gene polymor-phism and lymphnode metastasis in breast can-cer. J Exp Clin Cancer Res. 2004;23:121-125.
  16. Kanamori Y, Matsushima M, Minaguchi T, Kobayashi K, Sagae S, et al. Correlation be-tween expression of the Matrix metalloprotein-ase-1 gene in ovarian cancers and an inser-tion/deletion polymorphism in its promoter re-gion. Cancer Res. 1999;59(17):4225-7.
  17. Ghilardi G, Biondi ML, Mangoni J, Leviti S, DeMonti M, Guagnellini E, Scorza R. Matrix metalloproteinase-1 promoter polymorphism 1G/2G is correlated with colorectal cancer inva-siveness. Clin Cancer Res. 2001;7(8):2344-6.
  18. Jiang Hu, Jun Pan, Zhi-Guo Luo. MMP1 rs1799750 single nucleotide polymorphism and lung cancer risk: a meta-analysis. Asian Pac J Cancer Prev. 2012;13(12):5981-4.
  19. Wenham RM, Calingaert B, Ali S, McClean K, Whitaker R, Bentley R, Lancaster JM, Schildkraut J, Marks J, Berchuck A. Matrix metalloproteinase-1 gene promoter polymor-phism and risk of ovarian cancer. J Soc Gynecol Investi. 2003;10(6):381-7.
  20. Sugimoto M, Kennedy S, Deguchi M, Ohara N, Maruo T. Matrix metalloproteinase-1 and -9 promoter polymorphisms and endometrial car-cinoma risk in a Japanese population. Journal of the Society for Gynecologic Investigation 11/2006;13(7):523-9.



Authors: Lukavenko I. M., Andriushchenko V. V., Yazykov O. V.

Pages: 450-457



With the development of modern technologies committed step in the study of the pathogenesis of breast tumors. However, despite the advances of science, diagnosis of benign mammary dysplasia remains difficult. A promising direction is to develop methods by which a forecast of possible pretumor pathology. Important in the progression of cell proliferation in the mammary gland is the receptor cell state as a violation of the expression of steroid hormone receptors is associated with risk of breast cancer. To date, there are no clear criteria for the expression of estrogen receptor interactions with the degree of proliferation in the mammary gland during its dysplasia. Meeting this challenge will not only help to explain the pathogenesis of breast dysplasia, but also help to build the circuit of individual treatment, justify the appropriateness of hormone therapy. The level of expression depends on many factors including the structure of the gene that encodes it. Nowadays many published papers about the association of single nucleotide polimorfima PvuII gene EsRα with breast pathology. However, the information collected mainly in the study of breast cancer. The question of influence on the development of PvuII  mammary dysplasia remains relevant.

Purpose - to analyze the association PvuII polymorphism of the gene EsRα with the degree of proliferation and expression of EsRα in breast tissue with its benign dysplasia.

To achieve the goal of an analysis of surgical treatment of 84 patients with benign mammary dysplasia. Separately studied 134 morphological sample of breast tissue in operated patients. Used molecular genetic, immunohistochemical methods. Statistical analysis was performed using the program SPSS-17. Thus the significance of differences was determined by the χ2-test. The value of P <0,05 was considered significant. It is shown that there is a connection between the PvuII polymorphism EsRα with different levels of expression EsRα(χ2 =51,041; P < 0,0001) and the degree proliferation(χ2 =43,142; P < 0,0001) in breast tissue with its benign dysplasia. This information may be useful to clinicians considering the fact that the proliferative changes in the breast are considered as background for the development of cancer, and (С/С) homozygous for the PvuII polymorphism of the gene EsRα - a reliable indicator of increased proliferation with a penchant for atypia in breast tissue when it dysplasia.

Keywords: estrogen receptor alpha, benign mammary dysplasia, genetic polymorphism, genetic medicine.

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

The full text

In progress


  1. Neyshtadt E. L. Patologiya molochnoy zhelezyi / E. L. Neyshtadt, O. A. Vorobeva. – SPb. : Fo-liant, 2003. – 208 р.
  2. Pinder S. E. The diagnosis and management of pre-invasiv breast disease: ductal carcinoma in situ (DCIS) and atypical ductal hyperplasia (ADH)-curent definition and classification / S. E. Pinder, I. O. Ellis // Breast Cancer Res. – 2003. – № 5. – Р. 254–257.
  3. McCormack V. A. Breast density and paren-chymal patterns as markers of breast cancer risk: a meta-analysis / V. A. McCormack, Sil-va I. dos Santos // Cancer Epidemiol. Bi-omarkers Prev. – 2006. – № 15. – Р. 1159–1169.
  4. Smolanka I. I. Disgormonalnyie giperplazii mo-lochnoy zhelezyi: etiologiya, klinicheskie formyi, printsipyi terapii / I. I. Smolanka, I. V. Dosenko // Meditsinskie aspektyi zdorovya zhenschinyi. – 2007. – № 3 (6). – Р. 42–43.
  5. Lutsenko N. S. Mastopatiya: problemyi i resh-eniya / N. S. Lutsenko // Reproduktivnoe zdo-rove zhenschinyi. – 2006. – № 1 (25). – Р. 55–57.
  6. Vliyanie preparatov gestagennogo ryada na morfofunktsionalnoe sostoyanie molochnyih zhelez / E. F. Kira, S. V. Beskrovnyiy, A. B. Ilin i dr. // Zhurnal akusherstva i zhenskih bolezney. – 2000. – T. 49, № 2. – Р. 75–84.
  7. Genetic polymorphisms of ESR1 and ESR2 that may influence estrogen activity and the risk of hypospadias / S. Ban, F. Sata, N. Kurahashi et al. // Hum. Reprod. – 2008. – № 23. – Р. 1466–1471.
  8. Association of estrogen receptor beta gene pol-ymorphisms with left ventricular mass and wall thickness in women / I. Peter, A. M. Shearman, R. S. Vasan et al. // Am. J. Hypertens. – 2005. – № 18. – Р. 1388–1395.
  9. Analysis of the ERalpha germline PvuII marker in breast cancer risk / R. Gonza´lez-Mancha, J. J. Gala´n, C. Crespo et al. // Med. Sci. Monit. – 2008. – № 14 (3). – CR136–CR143.
  10. Estrogen receptor alpha polymorphisms and postmenopausal breast cancer risk / A. M. Gonza´lez-Zuloeta Ladd, A. A. Va´squez, F. Rivadeneira et al. // Breast Cancer Res. Treat. – 2008, Feb. – № 107 (3). – Р. 415–419. – еРub. 2007. – Apr. 24.
  11. Estrogen receptor alpha gene polymorphism and endometrial cancer risk-a case-control study / S. Wedre´n, L. Lovmar, K. Humphreys et al. // BMC Cancer. – 2008. – № 8. – Р. 322.
  12. Prognostic and predictive factors in breast can-cer by immunohistochemical analysis / D. C. Allred, J. M. Harvey, M. Berardo, G. M. Clark // Modern Pathology. – 1998. – Vol. 11, № 2. – P. 155–168.
  13. Estrogen receptor-alpha, bcl-2 and c-myc gene expression in fibroadenomas and adjacent nor-mal breast: association with nodule size, hor-monal and reproductive features / R. Cericatto, A. Pozzobon, D. M. Morsch et al. // Steroids. – 2005. – Vol. 70, № 3. – P. 153–160.
  14. Progesterone receptors A and B and estrogen receptor alpha expression in normal breast tis-sue and fibroadenomas / G. Branchini, L. Schneider, R. Cericatto et al. // Endocrine. – 2009. – Vоl. 35, № 3. – P. 459–466.
  15. Estrogen receptor alpha (ESR1) gene amplifica-tion is frequent in breast cancer / F. Holst, P. R. Stahl, C. Ruiz et al. – Department of Pa-thology, University Medical Center Hamburg Eppendorf, D-20246. – Hamburg, Germany, 2007, May. – № 39 (5). – Р. 655–660. – еРub. 2007. – Apr. 8.
  16. Patent JP2012034633A1. Method for determin-ing estrogen-related disease / Inventors: Mizu-kami, Yoichi; Applicant: Yamaguchi univ; Pri-ority Number: EP20070121810 ; Publication date: February 23, 2012.
  17. Polymorphisms in estrogen-metabolizing and estrogen receptor genes and the risk of devel-oping breast cancer among a cohort of women with benign breast disease / L. Gallicchio, S. L. Berndt, М. А. McSorley et al. // BMC Cancer. – 2006. – Vol. 29, № 6. – P. 173–184.



Authors: Grek A. V., Savenko I. I., Sasiuk O. S.

Pages: 458-465



Introduction. Cardiovascular system diseases take one of the first places in the structure of mortality and disability in the world and Ukrainian population and are the most spread diseases. In the pathogenesis of ischemic heart disease theendothelial dysfunction plays an important role, and the increased level of homocysteine is one of its etiological factor. Increase of the blood homocysteine level may be caused by genetic predisposition, in particular, C677T polymorphism of methylenetetrahydrofolate reductase gene (MTHFR). Therefore, the purpose of this research was to compare the frequency of C677T polymorphism of MTHFR gene in the practically healthy and among patients with IHD with ACS manifestation.

Materials and methods of investigation. 161 patients with IHD and ACS manifestation, who were treated in Municipal Company of Sumy Regional Council “Sumy Regional Cardiology Clinic” from January till July 2012, were examined. Control group consist of 87 almost healthy humans. ACS had been diagnosed according to Decree №436 MPH Ukraine.

The determination of the allelic polymorphism 4th exon of MTHFR C677T gene (rs1801133) was performed by the method of chain polymerase reaction with following analysis of the restriction fragments lengths.

Visualization of DNA after electrophoresis was made using transiluminator (“Biokom” Russia), in the scientific laboratory of molecular genetic studies at the Sumy State University. Statistic analysis was performed using the programme SPSS – 17. The reliability of differences determined by χ2 – Pirson criterion. The value P – <0,05 was considered possible.

Discussion. The frequencyof C/C, C/T and T/T genotype by C677T polymorphism of MTHFR gene among almost healthy humans was: 47,1 %, 42,5 %, 10,4 %, and in patients with ACS 52,7 %, 35,3 %, 12 % respectively. Absence of the statistic differences in the distribution of genotype depending on sex was proved. Investigation of the distribution of genotypes by C677T polymorphism of MTHF gene depending on age surveyed, showed, that in groups of patients of young, middle and elderly ages the statistically reliable difference is absent (P=0,554,P=0,876, P=0,320 respectively).

Availability of statistically reliable difference was found in control group and senile age patients with ACS (P=0,041). The association of T/T gene by investigated polymorphism with severe course ACS was detected.Thereby, distribution of genotypes polymorphism of MTHFR gene statistically did not differ in control group and in patients with ACS but was associated with the severity of its course.

Keywords: coronary artery disease, acute coronary syndrome gene polymorphism, methylentetrahydrofolate reductase.

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

The full text

In progress


  1. Global status report on noncommunicable di-saeses 2010. Geneva, World Health Organiza-tion, 2011. Retrieved from:
  2. Gorbas IM, Barna OM, Sakalosh VY, Ba-kumenko MA. [Estimated prevalence and control of risk factors for cardiovascular disease in the population and physicians]. Liky Ukrainy. 2010;(1):24–26.
  3. Gaydaev YO, Kornatchkyi VM. [Health prob-lems and directions of its improvement in modern conditions]. Ukr. Kardiol. J. 2007;(5):7.
  4. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med, 2006;3(11):442.
  5. Austin RC, Lentz SR, Werstuck GH. Role of hyperhomocysteinemia in endothelial dys-function and atherothrombotic disease. Cell Death Differ. 2004;11(1):56–64.
  6. Klimenko MO, Ataman YO. [Atherosclerosis as inflammation]. Eksper. i klin. medycyna. 2007;(4):3−11.
  7. McCully KS. Chemical pathology of homo-cysteine. IV. Excitotoxicity, oxidative stress, endothelial dysfunction, and inflammation. Ann Clin Lab Sci. 2009;39(3):219–232.
  8. Dwivedi MK, Tripathi AK, Shukla S, Khan S, Chauhan UK Homocysteine and cardiovascu-lar disease. Biotechnology and Molecular Bi-ology Review. 2011;5(5):101–107.
  9. Fetisova IN, Lipin MA, Polyakov AV. [Poly-morphisms in genes of folate metabolism and human diseases]. Vestnik novyh medicinskih tehnologiy. 2007;10(1):7–12.
  10. Trifonova EA, Spiridonova MG, Stepanov VA. [Genetic diversity and linkage disequilib-rium at the locus of the methylenetetrahydro-folate]. Genetika. 2008;44(10):1410–1419.
  11. Bailey LB, Gregory JF. Polymorphisms of methylenetetrahydrofolate reductase and other enzymes: metabolic significance, risks and impact on folate requirement. J Nutr. 1999;129(5):919–22.
  12. Pepe G, Vanegas OC, Giusti B. Heterogeneity in world distribution of the thermolabile C677T mutation in 5,10–methylenetetrahydrofolate reductase. Am J Hum Genet. 1998;63(3):917–920.
  13. Sadewa AH, Sunarti, Retno S. The C677T Mutation in the Methylenetetrahydrofolate Reductase Gene among the Indonesian Javanese Population. Kobe J. Med. Sci. 2002;48(4):137–144.
  14. Weisberg I, Tran P, Christensen B. A second genetic polymorphism in methylenetetrahy-drofolate reductase (MTHFR) associated with decreased enzyme activity. Mol. Genet. Metab. 1998;(64):169–172.
  15. Klerk M, Verhoef P, Clarke R. MTHFR Stud-ies Collaboration Group. MTHFR 677C–>T polymorphism and risk of coronary heart dis-ease: a meta–analysis. JAMA. 2002;288(16):2023–2031.
  16. Grechanina YuB. Vyvchennya vplyvu po-limorfizmiv mtDNK ta polimorfnyh variantiv geniv C677T MTHFR, A66G MTRR na klin-ichni proyavy mitohondrialnyh dysfunkciy [Study the effect of mtDNA polymorphisms and polymorphic variants of genes C677T MTHFR, A66G MTRR clinical manifestations of mitochondrial dysfunction]. Odesa: 2012. 48p.
  17. Garbuzova VYu, Sukhareva VA, Ataman AV. [The frequency of methylenetetrahydrofola-tereductase gene C677T single nucleotide pol-ymorphism in individuals of different sex]. Journal of Clinical and experimental medical research. 2013;1(4):385–389.
  18. González–Pérez E, Via M, López–Alomar A. Lack of association between methylenetetra-hydrofolate reductase (MTHFR) C677T and ischaemic heart disease (IHD): family–based association study in a Spanish population. Clin Genet. 2002;62(3):235–239.
  19. Morita H, Taguchi J, Kurihara H. Genetic pol-ymorphism of 5,10–methylenetetrahydrofolate reductase (MTHFR) as a risk factor for coronary artery disease. Circulation. 1997;95:2032–2036.
  20. Keijzer MB, den Heijer M, Blom HJ, Bos GM, Willems HP, Gerrits WB, Rosendaal FR. Interaction between hyperhomocysteinemia, mutated methylenetetrahydrofolatereductase (MTHFR) and inherited thrombophilic factors in recurrent venous thrombosis. Thromb Hae-most. 2002;88(5):723–728.
  21. Fekih–Mrissa N., Berredjeb–Benslama D., Haggui A., Haouala Н., Gritlia N. Combina-tion of factor V Leiden and MTHFR muta-tions in myocardial infarction. Ann Saudi Med. 2013; 33(2):192–193.



Authors: Orlovskyi V. F., Kuchma N. G., Orlovskyi O. V.

Pages: 466-472



Plasma homocysteine levels in patients with nonalcoholic fatty liver disease. The purpose of this investigation was to determine the level of homocysteine blood plasma in patients with nonalcoholic fatty liver disease. In investigations took part 63 patients with nonalcoholic fatty liver disease. Patients were divided into two groups. The first group( I group) included 30 nonalcoholic liver steatosis and second group (II group) included 33 patients with nonalcoholic steatohepatitis. The control group consisted of 20 almost healthy humans, which consist the control group. The presence of hepatic steatosis was confirmed ultrasound, and testified in favor of the nonalcoholic steatohepatitis, in addition to the ultrasound changes, increased activity of serum transaminases – alanine aminotransferase, aspartate aminotransferase.

In the process of investigation detected significantly increase the level of homocysteine blood plasma in patients from both groups, compared to the control group. I group – 13,5±3,59 mmol /l, II group – 15,5±3,33 mmol/. In patients with nonalcoholic steatohepatitis average values hyperhomocysteinemia were higher than in patients with non-alcoholic steatosis. Total cholesterol and atherogenic index were increased in both groups of patients. Triacylglycerol level was increased only in patients with nonalcoholic steatohepatitis ( II group). The level of high-density lipoprotein in patients with nonalcoholic fatty liver disease both groups was significantly lower than in the control group, but the differences between the level of this index in the two groups have been found. Also had been detected positively correlation dependence of homocysteine levels with body mass index and dependence of homocysteinemias level of cholesterol in patients with steatohepatitis comparing to patients with steatosis. The levels of alkaline phosphatase and gamma-glutamine transferase compared with the control group did not change, but increases in patients with nonalcoholic steatohepatitis. Revealed the positive correlation between transaminase liver and plasma homocysteine in patients with nonalcoholic steatohepatitis.

In the study, we conclude that nonalcoholic fatty liver disease is accompanied by the development of hyperhomocysteinemia, which progresses with the development of nonalcoholic steatohepatitis. This allows us to treat hyperhomocysteinemia as a factor in progression disease of liver.

Key words: non-alcoholic fatty liver disease, hepatic steatosis, steatohepatitis, homocysteine.

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

The full text

In progress


  1. Bellentani S, Scaglioli F, Marino M, Bedogni G. Epidemiology of non–alcoholic fatty liver disease. Dig Dis. 2010;28:155–161. Retrieved from:
  2. Babak AIa, Kolesnikova EV. Cirroz i ego oslozhneniia [Cirrhosis and its complications]. Kiev: Zdorove Ukrainy, 2011. 576 p.
  3. Tkach SM. [Prevalence, diagnosis and treatment strategies for non-alcoholic fatty liver disease]. Zdorovia Ukrainy. 2009;(1-2):63-65
  4. Glushchenko SV. [Pathogenetic mehanіzmі development of NAFLD]. News of medicine and pharmacy. Gastroenterology. 2012;(414). Retrieved from:
  5. Skvortsov YuI, Korolkova AS. [Homocysteine as a risk factor of ischemic heart disease development (review)]. Saratov Journal of Medical Scientific Research. 2011;7(3):619-624
  6. Moschen A. Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology. 2010;52(5):1836–1846 Retrieved from:
  7. Polyzos S, Kountouras J, Zavos Ch. Nonalcoholic fatty liver disease: the pathogenetic roles of insulin resistance and adipocytokines. Curr Mol Med. 2009; 9(3):299–314 Retrieved from:
  8. Adinolfi L, Hepatits C and fatty liver. Hot topics in viral hepatitis. Hepatitis C and metabolism. 2006;2:21-29 Retrieved from:
  9. Silva AdeS, Mota MP. Effects of physical activity and training programs on plasma homocysteine levels: a systematic review. Amino Acids. 2014;46(8):1795-1804.
  10. Fetisova IN [Polymorphisms of folate cycle genes and human disease]. Herald Ivan. Med. Acad. 2006;11(1-2):77-82
  11. Zhilyaeva TV [Desordered folate metabolism in the light of dysontogenetic theory of schizophrenia]. Social and Clinical Psychiatry. 2012;22(1):88-94
  12. Carvalho, Maria Muniz, Maria Siqueira. Plasmatic higher levels of homocysteine in Non-alcoholic fatty liver disease. Nutrion Journal. 2013;12 Retrieved from:
  13. F Brochado, Domenici FA, C Martinelli,Zucoloto S. Methylen-etetrahydrofolate Reductase Gene Polymorphism and Serum Homocysteine Levels in Nonalcoholic Fatty Liver Disease. Nutrition and Metabolism. 2013;63(3):193-199
  14. Polyzos SA, Kountouras J, Patsiaoura K, Katsiki E, Zafeiriadou E et al. Serum homocysteine levels in patients with nonalcoholic fatty liver disease. Ann Hepatology. 2012;11(1):68-76.
  15. Alan L, Miller ND, Gregory S, Kelly ND. Homocysteine Metabolism: Nutritional Modulation and Impact on Health and Disease. Alternative Medicine. 1997;2(4): 234–254.
  16. Dahlhoff C, Worsch S, Sailer M, Hummel BA, Fiamoncini J et al. Methyl-donor supplementation in obese mice prevents the progression of NAFLD, activates AMPK and decreases acyl-carnitine levels. Molecular Metabolism. 2014;5(3):565-580.
  17. Li H, Lewis A, Brodsky S et al. Homocysteine induces 3–hydroxy–3–methylglutaryl coenzyme A reductase in vascular endothelial cells. Circulation. 2002;105(9):1037–1043 Retrieved from:2014;3(5):565–580



Authors: Baiduja O. М.

Pages: 473-481



Purpose: to determine the visco-elastic properties of blood vessels and endothelial function and their relationship in patients with essential hypertension (EH) of ІІ stage.

Materials and methods. The study enrolled 150 patients with average age 51,6 ± 10,9 years. The main group consisted of patients with EH of ІІ stage. The control group consisted of 30 healthy individuals of comparable age.

Discussion. It was determined that in patients with ІІ stage of EH there were significant changes in the visco-elastic properties of arterial vessels of musculo-elastic and muscular type. This was manifested in increased tone of large, medium and small arteries and reduced slow fast blood flow and in them. These changes prevailed in the shoulder and the internal carotid artery basin with advantage in the last one.

The direct dependence of these changes in the vessels from blood pressure level with advantage in the grade 3 of hypertension was revealed. Similar changes were observed in parameters of pulse wave velocity.

Using compressive brachial artery hyperaemia we determined that significant changes of endothelial function took place already in patients with the grade 1 of arterial hypertension. Such changes were depended from the degree of blood pressure elevation and have its maximum significant changes in subjects with grade 3 of arterial hypertension. Correlation between parameters of visco-elastic properties of arterial vessels and endothelial dysfunction confirms important pathogenic role of the last one in the development and progression of remodelling process and process of blood flow disturbances in vessels at the II stage of hypertension.

Keywords: visco-elastic properties of blood vessels, endothelial dysfunction, essential hypertension, arterial hypertension.

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

The full text

In progress


  1. Vizir VA, Berezin AE. [The role of endothelial function in formation and progression of essential hypertension. Prognostic importance and prospects of treatment]. Ukr. Med. Chasopys. 2000;(5):23–33.
  2. Ivanova OV, Rohozova LN, Balakhonova TV. [Definition of shoulder artery sensitivity to tension shear on endothelia as method of detection of endotheliainduced vasodilatation with high definition ultrasound in patients with hypertension]. Cardiology. 1998;38(3):37–41.
  3. Kovalenko VN, Kornatsky VN. Rehional'ni medyko-sotsial'ni problemy khvorob systemy krovoobihu – statyst. posibnyk [Regional health and social problems of cardiovascular diseases - extras. guidances]. Kyiv, 2013. 239 p.
  4. Kovalenko VM, Sirenko YuM, Dorohoy AP. [The program of prevention and treatment of hypertension in Ukraine]. Ukr. Card. Journal. 2010;Suppl.1:3–13.
  5. Svishchenko YeP, Bahriy AYe, Yena LM. et al. Robocha hrupa z arterial'noyi hipertenziyi Ukrayins'koyi asotsiatsiyi kardiolohiv [Working Group on hypertension Ukrainian Heart Association]. Kyiv, 2008. 55 p.
  6. Sirenko YM. Arterial'na hipertenziya [Hypertension]. Kyiv: Morion Publ., 2001. 176 p.
  7. Profilaktika serdechno-sosudistyh zabolevanij: populjacionnaja strategija i individualizirovannaja programma (na osnove Evropejskih rekomendacij po profilaktike serdechno-sosuditstyh zabolevanij v klinicheskoj praktike 2012) [Profylaxis of cardiovascular diseases: population private strategy and programs (based on Europe prevention recommendations for cardio-vascular diseases in clinical practice 2012). Kiev, 2013. 89 p.
  8. Mancia G, Laurent S, Agabiti-Rosei E et al. Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document. J. Hypertens. 2009;27(11):2121-2158.
  9. Sehestedt T, Jeppesen J, Hansen TW et al. Which marker of subclinical organ damage to measure in individuals which high normal blood pressure? J. Hypertens. 2009;27(6):1165-1171.



Authors: Fushtey I., Gura E.

Pages: 482-490



Purpose: to determine the status of endothelial function and peculiarities of remodelling of the left ventricle (LV) in patients with essential hypertension (EH) in combination with diabetes mellitus type II (DM type II).

Materials and methods. The study involved 90 patients at a mean age 59,2 ± 8,6 years. In 60 patients we diagnosed EH in combination with diabetes mellitus type II.

Discussion. Using Doppler-cardiographs, biochemical and immune methods it was found that in patients with essential hypertension stage II in conjunction with type II diabetes mellitus there is significant endothelial dysfunction, manifested by an increase in the concentration of serum endothelin 1 on the background of lower metabolic products of nitric oxide and endothelium-dependent vasodilatation. Direct dependence of endothelial function from the type of left ventricular remodelling determined, and it is significantly more important in patients with eccentric hypertrophy and concentric remodelling. In patients with the combination of diabetes mellitus type II and EH stage II we determined systolic and diastolic LV dysfunction, which are determined by a decrease in ejection fraction, myocardial contraction of the circular on the background of high rates of myocardial mass and LV myocardial mass index with their prevalence of hypertrophic and restrictive type of diastolic dysfunction. These changes in intracardiac hemodynamics prevail with concentric remodelling of the left ventricle. Highly reliable pair correlations between the main parameters of intracardiac hemodynamics and endothelial dysfunction determine the value of the latter in myocardial remodelling in hypertensive patients and diabetes type II.

Key words: remodelling of the left ventricle myocardium, endothelial function, essential hypertension, diabetes mellitus type II.

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

The full text

In progress


  1. Ivanov VP,Denisjuk VI,Konovalova NV et al.[Structural and heometrical remodeling of left ventricle at arterial hypertension].2000;(3):17–19.
  2. Ivanova OV, Rohozova LN, Balakhonova TV. [Definition of shoulder artery sensitivity to tension shears on endothelia as method of detection of endotheliainduced vasodilatation with high definition ultrasound in patients with hypertension].Cardiology.1998;38(3):37–41.
  3. Kaminskij AV. [Diabetes mellitus: new views and old misbeliefs. Part 4 Modern views about pathogenesis and pathogenetic therapy of type 2 diabetes mellitus].Mizhnar. endokrynol. zhurn.2012;(6):50–53.
  4. Kovalenko VM, Sirenko YuM, Dorohoy AP. [The program of prevention and treatment of hypertension in Ukraine].Ukr. Card. Journal.2010;Suppl.1:3–13.
  5. Sirenko YM. Arterial'na hipertenziya [Hypertension]. Kyiv: Morion Publ., 2001. 176 p.
  6. Virtanen MP, Niemincu T, Kahomen MA et al. The influence of hemodynamic factors in left ventricular mass.Hum. Hypertens.2008;22(2):126–128.
  7. De Simone G, Verdecchia P, Pede S et al.Prognosis of inappropriate left ventricular mass in hypertension: the MAVI Study.2002;40(4);470–476.
  8. Sullivan JM, Vandez Zwaag RV, el-Zeky F. Left ventricular hypertrophy: effect on survival.J Am Coll Cardiol.1993;22(2):508–513.



Authors: Seman-Minko J. S., Buryak A. G.,Nechitailo D. Y.

Pages: 491-497



The aim of the study was to assess the development of children and formative stage of sleep in children who are breastfed, and explore features of health and functional status of nursing mothers.

To achieve this goal were examined dyad-pair «Mother feeding baby first year of life». Study design was descriptive construction of longitudinal observation over 4-6 months. Inclusion criteria were feeding breast milk at the time of the first survey. Examined – 87 pairs. Age of children at time of first examination ranged from 1 to 12 months. Age calculated in each child in weeks by subtracting the birth date from the date of inspection and the average was 24.0±1.76 weeks.

Established that the physical development of the surveyed children had a tendency to advance from age norms and accompanied by a significant increase in weight gain during the first month of life indicators rough motility within the 90% range on a scale Denver test. Formation of monophasic sleep in most children occurred in the first three months. In 13.8% of the surveyed children in the age group of 6 month sleeping was steel polyphasic, which can lead to inhibition of psychomotor development (correlation between nocturnal sleep duration and age at which the child is alone (r =-0.76; p<0.05), walking (r=-0.91; p<0.05), the formation of motor speech (r =-0.40; p<0.05) and modulated babble (r=-0.72, p<0.05).

Thus, in modern principles of breastfeeding physical and psychomotor development of children tends to advance the age norm. Irrational daily routine, unhealthy diet and bad habits of mother – smoking and alcohol consumption negatively affect the duration of breastfeeding and the individual performance of children.

Key words: breastfeeding, physical and psychomotor development, sleep, functional status of nursing mothers.

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

The full text

In progress


  1. Barriere H. Prenatal breastfeeding information: Survey in Pays de Loire, France / H. Barriere, M. Tanguy, L. Connan // Arch. Pediatr. – 2011. № 25. – P. 365-369.
  2. Battersby S.A. Topic in 10 questions: How to support breastfeeding mothers / Battersby S.A. //J. Fam. Health Care. – 2011. – Vol. 21, № 2. – P. 22-24.
  3. Семань-Мінько І.С. Оптимізація взаємодії пари «мати-дитина» при грудному вигодову-ванні дітей першого року життя / І.С. Семань-Мінько, О.Г. Буряк, В.В. Патрабой // «Хист» Всеукраїнський медичний журнал студентів і молодих вчених. – 2013. – № 15. – С. 264.
  4. Яворская О.В. Психогигиенический подход к поддержке грудного вскармливания основа новой организационной формы оптимизации питания детей грудного возраста / Яворская О.В. // Уральский медицинский журнал. – 2008. – № 8. – С. 56-65.
  5. Dierckx B. Spot the Red Herring: Breastfeeding, Fruitpuree, and Infant Autonomic Functioning, the Generation R Study / B. Dierckx, A. Tharner, J.H. Tulen // Pediatr. Res. – 2011. – № 23. –P. 192-197.
  6. Hart S.L., Jackson S.C., Boylan L. Compro-mised weight gain, milk intake, and breastfed newborns of depressive mothers / S.L. Hart, S.C. Jackson, L. Boylan // J. Pediatr. Psychol. – 2011. – № 36 (8). – Р. 942-950.
  7. Нечитайло Ю.М. Нутріціологія дитячого віку / Нечитайло Ю.М. – Чернівці: БДМУ, 2008. – 208 с.
  8. Семань-Мінько І.С. Особливості фізичного розвитку немовлят при грудному вигодовуванні у сучасних умовах / І.С. Семань-Мінько, О.Г. Буряк, Д.Ю. Нечитайло // Актуальні питання педіатрії, акушерства та гінекології. – 2013. – № 2 (12). – С. 40-42.



Authors: Pochinok T. V., Veselova T. V.

Pages: 498-507




In recent years, scientists from many countries pay special attention to the problem of increasing the frequency of cases of connective tissue dysplasia in children. Earlier studies suggest that adolescence children with connective tissue dysplasia had been observed decreasing of major bio-elements in plasma index that are involved in the metabolism of connective tissue. Moreover, the same category of patients has manifestations of autonomic dysfunction. The increase of pathological changes in the connective tissue and chronic deficiency leads to increasing bio-elements of clinical manifestations with age, including autonomic changes. Despite the increased interest of scientists to this problem, the development of methods for correction of electrolyte imbalance and autonomic disorders is relevant and unsolved.


To evaluate the effectiveness of the correction of electrolyte imbalance and autonomic disturbances in children with puberty manifestations of connective tissue dysplasia.

Materials and Methods.

We examined the effectiveness of the correction of electrolyte imbalance by determining the level of macro and microelements in blood plasma by atomic emission spectrometry with inductively coupled plasma, and autonomic disorders with Wayne’s tables, cardiointervalography, clinoorthostatic sample, and Roofie’s tests in 63 adolescence children (33 children with manifestations of connective tissue dysplasia and 30 children without dysplasia).


Children with connective tissue dysplasia used a 30-day rehabilitation complex, which included a rational mode of the day with a sufficient duration to age-appropriate night's sleep, morning gymnastics, daily rest, 2-hour dosage walking in the fresh air, the alternation of mental work with physical exercise, balanced by basic food ingredients with a daily consumption of foods with a high content of proteins, glycosaminoglycans, vitamin "C", «E», «A», the group «B», «PP», macro and microelements; body massage, as well as drugs: "Calcemin", and "Magne - B6". Also, the choice of drugs for the correction of electrolyte balance and autonomic dysfunction due to the presence of the bulk composition of macro and micronutrients are a part of enzymes metalloproteinase and provide structural integrity of connective tissue.

There were determined the level of basic bio-elements in plasma and performed functional tests for monitoring indicators vegetative maintenance before and after the rehabilitation course in children.

Also, we have observed significant changes of electrolyte balance indicators (decrease of magnesium, calcium, inorganic phosphorus, zinc, iron, copper, selenium) before the treatment of children with connective tissue dysplasia as compared with those of the children without dysplasia.

After the course in adolescence children with hereditary connective tissue dysplasia the level of frequency of asthenic complaints and vegetative character decreased, which leads to the restoration of autonomic dysfunction in this group of patients.

The tests showed normalization of electrolyte balance indicators  as the principal bio-elements failure which gives the structure and metabolism of connective tissue.

Keywords: children, connective tissue dysplasia, electrolyte balance.

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

The full text

In progress


1. [Discussion about new strategy of health improvement in Ukraine «Health – 2020: Ukrainian dimension»]. Sovremennaya pedyatryya 2012;1(41):11–12.
2. Pochinok TV, Veselova TV. [The electrolyte balance from children in adolescence with undifferentiated connective tissue dysplasia]. Vplyv naukovo-tekhnichnogho proghresu na rozvytok medychnoji nauky ta praktyky: realiji sjoghodennja: materialy naukovo-praktychnoi konferencii [Proceeding of scientific conference: The influence of scientific and technical progress on the development of medical science and practice: the realities of today]. Kiyv, 2013, pp.12–16. (In Ukrainian).
3. Pochinok TV, Vasyukova MM, Antoshkina AM. [Undifferentiated connective tissue dysplasia and particularly the exchange of magnesium in children]. Pediatrics, obstetrics and gynecology. 2010;2:7–9.
4. Gromova OA, Torshin IYu. [Dysplasia of connective tissue, cell biology and molecular mechanisms of action of magnesium]. Rus. Med. J. 2008;16(1):1–10.
5. Davidova SV, Bershova TV, Bakanov MI. [The role of matrix metalloproteinases in the pathogenesis of bronchopulmonary dysplasia in children]. Aktualnyie problemyi pediatrii: materialy naukovo-praktychnoi konferencii [Proceeding of scientific conference: Actual problems of paediatrics]. Moscow, 2008, pp.101. (In Russian).
6. Majdannyk VGh., Khajtovych MV, Ivanyshyn LJa. [The state of the vegetative homeostasis in children with arterial hypotension]. Pediatrics, obstetrics and gynecology. 2003;2:20–24.
7. Moscalyuk ON. [Electrolyte imbalance in children with undifferentiated connective tissue dysplasia, with mitral valve prolapse]. Pytannja eksperymentaljnoji ta klinichnoji medycyny. 2010;14(2):248–252.
8. Nikolaev KYu., Oteva EA, Nikolaeva AA. [Dysplasia of connective tissue and organ pathology in children of school age]. Pediatrics. 2006;2:89–91.
9. Pochinok TV, Veselova TV, Melnichuk VV. [Vegetative dysfunction syndrome in children with undifferentiated connective tissue dysplasia]. Pediatrics, obstetrics and gynecology. 2013;4:10–15.
10. Frolova TV, Ohapkina OV. [Features mikroelementov balance at displasticheskogo pathology of connective tissue in children]. Pediatricheskie aspektyi displazii soedinitelnoy tkani. Dostizheniya i perspektivyi: materialy naukovo-praktychnoi konferencii [Proceeding of scientific conference: Pediatric aspects of connective tissue dysplasia. Achievements and prospects]. Moscow-Tver-St. Petersburg, 2010, pp.86–91. (In Russian).
11. Tosiello L. Hypomagnesemia and diabetes mellitus. Arch Intern Med. 1996;156:1143–1148.
12. Torshin IYu, Gromova OA. Magnesium and pyridoxine: fundamental studies and clinical practice. Nova Science J. 2009, ISBN-10:1-60741-704-9:250.
13. Zavadenko NN, Nesterovsky YuE. [Clinical manifestations and treatment of vegetative dysfunction syndrome in children and adolescents]. Pediatrics. 2012;91(2):17–19.
14. Torshin IYu, Gromova OA, Gusev EI. [The mechanisms of anti-stress and antidepressant action of magnesium and pyridoxine]. Journal of neurology and psychiatry. 2009;109(11):107–111.
15. Gromova OA, Torshin IYu, Egorova EYu. [Molecular role of magnesium and pyridoxine in alcohol protect the body]. Doctor J. 2010;7:51–54.
16. Gromova OA. [Magnesium and pyridoxine: basic knowledge. New technologies of diagnostics and correction of magnesium deficiency]. Obuchayuschie programmyi YuNESKO [Trainings of UNESCO] – Moskva: RSTs Institut mikroelementov; Yunesko Publ., 2006. 176 p.
17. Gromova OA., Rebrov VG, Fedoseenko MG. Klinicheskaya elementologiya. [Clinical elementology]. Geotar Med Publ, 2010. 632p.
18. Ahvazi B, Boeshans KM, Rastinejad F. The emerging structural understanding of transglutaminase 3. J Struct Biol. 2004; 147(2).
19. Baranov AA, Shcheplyagina LA. Fiziologiya rosta i razvitiya detey i podrostkov (teoreticheskie i klinicheskie voprosyi) [Physiology of growth and development of children and adolescents (theoretical and clinical issues)]. Moscow: GEOTAR-Media Publ, 2006. 432 p.
20. Pochinok TV, Vasyukova MM, Gorobetc NI. [The use of vitamin D3 and glareosa calcium for the correction of immune disorders in children with undifferentiated connective tissue dysplasia]. XIII Kongres World Federation of Ukrainian Medical Societies: materialy naukovo-praktychnoi konferencii [XIII Congress of the World Federation of Ukrainian Medical Societies]. Kiyv, 2010, pp.16–19. (In Ukrainian).
21. Welch TR, Bergstrom WH, Tsang RC. Vitamin D-deficient rickets: the reemergence of a once-conquered disease. J Pediatr. 2000;137(2):143–145.
22. Evseeva GP. Mikroelementnyiy status i vzaimosvyaz ego disbalansa s razvitiem zabolevaniy u detey [Mikroelementy status and the relationship imbalance with the development of diseases in children]. Khabarovsk. 2009:42.
23. Nikonov AA, Samohvalov PI. [The probable role of copper, zinc and selenium with psychovegetative syndrome] Journal of neurology and psychiatry. 2006(4):54–66.
24. Gres NA, Tarasyuk IV. [The microelementoses person: prevalence] Medicine J. 2007;2:28–29.
25. Spirichev VB. [Vitamins and minerals complex in the prevention and treatment of osteoporosis] Nutrition. 2003(1):34–36.
26. Cimmerman M. Mikroelementyi v meditsine [Trace elements in medicine]. Moscow: Apnebia Publ., 2006. 232 p.
27. Skalniy AV, Rudakov IA. Bioelementyi v meditsine [Bioelements in medicine]. Moscow: ONIKS XXI Publ., 2004. 272 p.
28. Nasledstvennyie narusheniya soedinitelnoy tkani v kardiologii. Diagnostika i lechenie [Heritable disorders of connective tissue in cardiology. Diagnostics and treatment]. Rus.Card J., 2013;1(99):1.
29. Pochinok TV. Sposib prognozuvannya formuvannya displaziyi spoluchnoyi tkanini ta porushen imunitetu u ditey [A method for predicting the formation of connective tissue dysplasia and immunity disorders in children]. Ukrainian patent, no 15959, 2006.
30. Opredelenie soderzhaniya himicheskih elementov v diagnostiruemyih biosubstratah, polivitaminnyih preparatah s mikroelementami, v biologicheski aktivnyih dobavkah k pische i v syire dlya ih izgotovleniya metodom atomnoy emissionnoy spektrometrii s induktivno svyazannoy argonovoy plazmoy [The determination of the content of chemical elements in diagnosable biosubstrata, multivitamin preparations with microelements, biologically active additives to food and raw materials for their production by the method of atomic emission spectrometry with inductively coupled argon plasma]. Metodicheskie ukazaniya 4.1.1482-03. Moskow: Minzdrav Rossii Publ.2003.17 p.
31. Bitter I, Muir HA. Modified uronicacid carbosol reaction. Anial. Biochem. J. 1968;4.(4):240–244.
32. Perfilov VP, Perilova TN, Levenetc LC. [The use of benzoylacetonitrile (chloramine B) as an oxidant in opredeleniya hydroxyproline]. Rationalization proposals and inventions in medicine J., 1974:168.
33. Veyn AM. [State mechanisms vegetative regulation of arterial hypotension]. Journal of neurology and psychiatry.1998;4(98):20–24.
34. Baevsky RM. K probleme otsenki stepeni napryazheniya regulyatornyih sistem organizma. Adaptatsiya i problemyi obschey patologii [The problem of assessing the degree of tension of regulatory systems of the body. Adaptation and problems of general pathology]. Novosibirsk: SGU Publ.1974, pp. 44–48.
35. Oshevensky LV, Krilova EV, Ulanova EA. [The study of the human health by functional parameters of an organism]. Nizhniy Novgorod, 2007. 67.
36. Voropay LA, Pirozchkova NI, Voropay NG. [Metabolic correction in connective tissue dysplasia heart]. Meditsina i obrazovanie v Sibiri. 2012:3.



Authors: Popov S. V., Bokova S. I., Smiyan A. I., Bugaenko V. A.

Pages: 508-512



Introduction. Heart murmurs are diagnosed in pediatric patients often. The structural changes in the heart, which may be cause, in most cases fails to detect. Such murmurs are functional or innocent.The one of the factors which causes sound changes may be small anomalies of the heart. The aim was to study features heart structural and intracardiac hemodynamics.

Material and Methods. The 137 children with innocent heart murmurs in age from one year to 16 years were examined by echocardiography. Criteria for allocation in the groups were years old of children. Children aged from 1 to 3 years were included in the first group, from 4 to 7 years were included in the second group and from 7 to 14 years were included in the third group. We identified small malformations of the heart and made the analysis of indicators intracardiac hemodynamics.

Discussion. The innocent heart murmurs were detected in children of the first group - 23,36%, of the second group - 46,72% (p<0,05) and third group - 29,93% (p<0,05). The detection rate of small defects was high from 46% to 53%. Abnormally located chord and trabeculae were the most common. Changes in intracardiac hemodynamics in children up to 3 years were 71,88%, from 4 to 7 years - 82,81% and older than 7 years - 46,34%. The basic indicators of hemodynamics showed changes in systolic and diastolic function of myocardium.

Conclusion. Small heart malformations were detected in 50% of children. Abnormally located chord and trabeculae were the most common. The intracardiac hemodynamics changes were observed in most of the children. They showed an increase of left ventricular preload and right ventricle afterload.

Keywords: innocent murmurs, hemodynamics, small malformations of the heart.

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

The full text

In progress


  1. Basargina YeN. [Dysplasia of the heart connective tissue among children]. Current pediatrics. 2008;7(1):148.
  2. Beloserov YuM, Gnusaev SF. Normativi ehometrichescih pokazateley serdca u detey [The standarts of ultrasonography indications of heart in children] Moscow: Publ., 2006. 24 p.
  3. Pycov MI, Vatolin KV. Detscaya ultrazvucovaya diagnostica [Baby’s ultrasound diagnosis] Moscow: Vidar Publ., 2001. 680 p.
  4. Samsygina GA, Shcherbakova MYu. Cardiologiya I rheumatologiya detskogo vozrasta [Cardiology and rheumatology of children’s ages] Moscow:Publ., 2004. 736 p.
  5. Ter-Galstyan AA, Galstyan ArA, Potapenko TF. [The abnormally located chord and mitral valve prolapse in children and adolescents]. Russian Bulletin of perinatology and pediatrics. 2004; 49(3):32-37.
  6. Trisvetova YeL, Yudina OA. [The anatomical characteristics and classification of abnormally located chordae of the heart]. Medical Bulletin of the North Caucasus. 2008; 2:34-39.
  7. Schiller N, Osipov M. Klinicheskaya echocardiographiya [The clinical echocardiography]Moscow: Publ., 2005. 344 p.
  8. Barrett MJ, Lacey CS, Sekara AE, Linden EA, Gracely EJ. [Mastering cardiac murmurs: the power of repetition]. Chest. 2004; 2:470-475.
  9. Bhatikar SR, Degroff C, Mahajan RL: [A classifier based on the artificial network approach for cardiologic auscultation in pediatrics].Artif. Intell. Med. 2005; 33 (3):251-260.
  10. Biancaniello T. [Innocent murmurs].Circulation. 2005; 111 (3):20-22. doi: 10.1161/01.CIR.0000153388.41229
  11. Chavhan GB, Parra DA, Mann A, Navarro M. [Normal Doppler spectral wave forms of major pediatric vessels: specific patterns] Radiographics. 2008; 3: 691–706.
  12. Park MK. Pediatric Cardiology for Practitioners.5th ed. St Louis. Mosby, 2007. 680p.



Authors: Khyzhnjak M. V., Potapov A. A., Makeeva T. I. Bodnarchuk J. А.

Pages: 513-517



The incidence of traumatic spinal injuries increased with the development of science and technology, including the spinal column. Only 10-25% of spinal injuries are complicated by spinal cord or its neural structures. There are stable and unstable injuries of the spinal column. Instable lesions there is no possibility of secondary traumatic vascular-neural structures of the spinal canal, with unstable fractures it is possible and that leads to surgical operations aimed at stabilizing the damaged segment. At this time in Ukraine puncture introduction of bone cement is included to the relevant clinical protocols for acute traumatic fractures and post-traumatic osteonecrosis of the vertebral bodies.

The purpose of the study was to examine long-term results of treatment the traumatic fractures of vertebral by рunctive percutaneous  methods.

Long-term results of percutaneous vertebroplasty and kifoplasty in the surgical treatment of 65 patients aged 51 ± 1,6 with traumatic compression fractures of the vertebral bodies were analyzedand presented. We made 65 operations. All operations were carried out by transpedicular access under discrete intraoperative radiological control using electron-optical converter. The average duration of the operation on a single vertebra was 26 ± 0,4 minutes. The dynamics of the intensity of pain and restoration of life by Oswestry scale and assessment of posttraumatic deformity by measuring the Cobb angle were evaluated. The positive trend in a regression of pain, improved quality of life for patients.  Increase the value of post-traumatic deformities in the postoperative period were revealed.

Based on the findings of  long-term results of treatment  patients with compression fractures of the vertebral bodies by these methods of surgical intervention  we can  report about their high efficiency, which reduces the degree of disability and significantly reduce post-operative rehabilitation.

Keywords: trauma, fracture, vertebra, percutaneous vertebroplasty, kifoplasty, posttraumatic deformity.

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

The full text

In progress


  1. Pedachenko EG, Kushchaev SV. Punkciina vertebroplastika [Punctive vertebroplasty]. Кiev: А.L. D. Publ., 2005. 520 p.
  2. Nikiforov AS, Konovalov AN, Gusev EI. Klinicheskaja nevrologia [Clinical neurology]. Мoscow: Medicina Publ., 2004. 448 p.
  3. Polishchuk NE, Korgh NA, Korgh VJ. Povrezhdenija pozvonochnika i spinnogo mozga [Spine and spinal cord injurious]. Кiev: Kniga-plus Pabl., 2001.368 p.
  4. Denis F. The three column spine and its significance in the classification of acute thoracolumbar spinal injures. Journ. Spine; 1983. (8):817.
  5. Holdswokth FW, CHIR M. Fractures, dislocations and fracture-dislocations of the spine. J. Bone Jt. Surg; 1970. 52 (A):1534.
  6. Bekov ММ. Hirurgicheskoe lechenie travmy grydnogo i smeghnyh otdelov pozvonochnika I spinnogo mozga [Surgical treatment of thoracical injuries and related spine and spinal cord]. St. Petersburg: St. Ptb. Institute of neurosurgery Polenov by name, 2010. 25 p.
  7. Orlov SV. Nestabilnost pozvonochnika pri pozvonochno-spinnomozgovoi travme [Instability of the spine for spinal injury]. St. Petersburg: St. Ptb. Institute of neurosurgery Polenov by name, 2011. 32 p.
  8. Sagdeev RR. Klinika i hirurgicheskoe lechenie syndroma nestabilnosti pozvonochnika. [Clinic and surgical treatment of the syndrome of spinal instability]. Kazan: Kazan national medical academy, 2009. 17 p.
  9. Deinichenko JK, Sereda DA, Ivahnenko DS. [Vertebroplasty in the treatment of pain syndrome in osteoporosis spine]. Ukr. Neurosurg. J. 2009; (3):14.
  10. Popov АІ. Eksperimentalno-klinichne obgryntyvannja punkciinoi vertebroplastiki y hvoryh z kompresiinumu perelomamu grydnuh ta poperekovuh til hrebciv pri osteoporozi [Experimental and clinical reasoning of puncture vertebroplasty in patients with compression fractures of the thoracic and lumbar vertebral bodies in osteoporosis]. Kharkiv: Inst. of the spine and joints pathology Sitenko by name, 2005. 20 p.
  11. Barr JD, Barr MS, Lemley TI. Percutaneus vertebroplasty for pain relief and spinal stabilization. Spine. 2000; (15):923-928.
  12. Thillainadesan J, Schlaphoff G, Gibson KA. Long-term outcomes of vertebroplasty for osteoporotic compression fractures. Journ. Med. Imaging Radiat. Oncol. 2010; 54(4): 307-314.
  13. Klazen CA, Lohle PN, Vries J. Vertebroplasty versus conservative treatment in acute osteoporotic vertebral compression fractures (Vertos II): an open-label randomised trial. Lancet; 2010. 376(9746): 1085-1092.
  14. Babkin AV, Chumak NA. [Percutaneous vertebroplasty in the spinal pathology]. News of medicine. 2008; (10):21–25.
  15. Durov OV, Shevelev IN, Tissen TP. [Percutaneous vertebroplasty in the treatment of spinal disorders]. Journ. Questions of neurosurgery Burdenko by name. 2004; (2):21-25.
  16. Valiev АК, Musaev ER, Borzov KA. [Percutaneous vertebroplasty in the treatment of osteoporotic vertebral compression fractures]. Journ. Manual therapy. 2009; (4):74-83.
  17. Movshovich IA, Ric IA. Rentgendiagnostika i princupu lechenia skolioza [X-rays diagnosis and principles of scoliosis treatment]. Мoscow. Medicina Publ.. 1969. 248 p.
  18. Francis A, Burgener O, Kormano M. Bone and joint disorders, Conventional Radiologic Differential Diagnosis. Journ. Thieme New York. 1997; (4):218 – 221.



Authors: Fedorov S.V.

Pages: 518-524



Introduction. Heart failure (HF) is the end stage of most diseases of the cardiovascular system and is a major cause of morbidity and mortality. About 26 million adults worldwide are living with HF, leading some to describe it as a global pandemic. This syndrome caused of 5% of acute hospital admissions, 10% of hospital bed occupancy, and accounts for approximately 2% of national expenditure on health, mostly due to the cost of hospital admissions. Across the globe, 17-45% of patients hospitalized with HF die within 1 year of admission and the majority die within 5 years of admission.

An inflammatory activation in CHF patients has long been recognized. Indeed, immune mechanisms modulate interstitial fibrosis, cardiomyocyte apoptosis, and hypertrophy, all of which are central processes leading to maladaptive remodeling in response to a variety of stimuli (ischemia, glucose intolerance, obesity, pressure overload etc.). Especially for heart failure evolving from large myocardial infarction there is substantial evidence for a causal contribution of immunity early in the course of the disease.
Pharmacological therapy of HF including administration of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor II blocker (ARB), beta-blocker (BB), and aldosterone receptor antagonist (AA) can reduce morbidity and mortality in patients with HF. Ivabradine is a new therapeutic agent designed to reduce heart rate at rest and during exercise by selective inhibition of a novel receptor (If channel) located on the pacemaker-cell membrane within the sinoatrial node. As such, ivabradine joins a list of rate-limiting medications already available to prescribers for the control of heart rate in coronary artery disease (CAD) and HF with systolic dysfunction. The ω-3 polyunsaturated fatty acids (ω-3 PUFA), such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are known as anti-inflammatory factors, and are using for HF treatment.

The aim of study was to investigate the possible influence of ivabradine and ω-3 polyunsaturated fatty acids for immunity values in patients with ischemic heart failure.

Material and Methods. 357 patients with ischemic HF and sinus rhythm were observed. In accordance to treatment all patients were divided into four groups: I group – basic treatment (89 patients); II group - basic treatment and Ivabradine (Coraxan, Les Laboratoires Servier Іndustrie, France) – 5 or 7,5 mg twice a day (depends of heart rate); III group - basic treatment and PUFA (Omacor, Abbott Laboratories GmbH, USA-Germany) – 1000 mg per day; IV group – basic treatment with Ivabradibe and PUFA in similar doses. All patients were examined before and after 6 months of treatment. Control group – 30 practically healthy persons. The study was performed in accordance with the Helsinki Declaration and Good Clinical Practice Guideline. The study was approved by the local ethics committee and written informed consent was obtained from all patients.

We investigated of lymphocyte’s populations count by indirect immunofluorescence method and immunoglobulin’s level by ELISA. All analyses were undertaken using the Statistica 12.0 (StatSoft, Tulsa, OK, USA). Statistical significance was assumed at p<0.05.

Results and Discussion. The average age of observed patients with HF was (67,98±12,06) years. Among all patients 278 persons (77.82 %) were males. HF FC ІІ (NYHA) was verified in 63 patients (17.65 %); ІІІ – in 238 (66.67 %); IV – in 56 (15.68 %). The averageduration of HF was (10.0 [5.0; 15.0]) years.

No influences for CD3+, CD4+, CD8+, CD16+ cells count were observed in all groups. Usage of ω-3 PUFA caused of stronger decline of CD19+, CD25+ and CD95+ lymphocytes levels for 9.5%, 16.5% and 50.9% respectively (p<0,05).

Conclusion. Thus, omega-3 polyunsaturated fatty acids have immunomodulative effect for normalization of of CD19+, CD25+ and CD95+ lymphocytes.

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. Lozano R., Naghavi M., Foreman K. et al.Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2095-2128.
  2. Go A.S., Mozaffarian D., Reger V.L. et al.Heart diseases and stroke statistics – 2013 update: a report from the American Heart AssociationCirculation. 2013; 127: e6-e245.
  3. Ambrosy A.P., Fonarov G.C., Butler al.The global health and economic burden of hospitalizations for heart failure: lessons learned from HHF registries Am. Coll. Cardiol. 2014;63:1123-1133.
  4. Maggioni A.P., Dahlstrom U., FillipatosG. et al.EURObservational research programme: regional difference and 1-year follow-up results of the Heart Failure Pilot Survey.. 2013;15:808-817.
  5. Ionita M.G., Arslan F., de Kleijn D.P. et al.Endogenous inflammatory molecules engage Toll-like receptors in cardiovascular disease. Journal of Innate Immunity. 2010; 2:307–315.
  6. Chung E.S., Packer M., Lo K.H. et al.Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial.Circulation. 2003;107:3133–3140.
  7. Torre-Amione G., Anker S.D., Bourge al.Results of a non-specific immunomodulation therapy in chronic heart failure (ACCLAIM trial): a placebo-controlled randomised trial. Lancet. 2008;371:228–236.
  8. Orea-Tejeda A., Arrieta-Rodriguez O., Castillo-Martinez L. et al.Effects of thalidomide treatment in heart failure patients. Cardiology. 2007;108:237–242.
  9. Roos B., Mavrommatis Y., Brouwer I.Effects of LC n-3 PUFA on inammation and CHD/B. Roos.British Journal of Pharmacology. 2009; 158: 413–428.
  10. den Ruijter H.M., Berecki G., Verkerk A.O. et al. Acute administration of sh oil inhibits triggered activity in isolated myocytes from rabbits and patients with heart failure. Circulation. 2009; 117: 536–544.
  11. Daviglus M.L., Stamler J., Orencia A.J. et al.Fish consumption and the 30-year risk of fatal myocardial infarction. N. Engl. J. Med. 1997; 336:1046–1053.
  12. Hall C. Effects of two-lowering therapies on immune responses in hyperlipidemic subjects. ACC14: Innovation and Intervention. JACC, 2014, pp.1259.
  13. Weiss L., Assoumou L., Chevalier M.C. et al. A pilot study of the impact of rosuvastatin administration on residual chronic immune activation under antiretroviral therapy: the CESAR-IMEA trial. 20thInternational AIDS Conference. Melbourne, 2014, p.p.095.



Authors: Skiba T.A.

Pages: 525-529



Introduction. The possibility of using pentoxifylline and L-arginine additionally to basic treatment of exacerbation of chronic obstructive pulmonary disease, concomitant with osteoarthrosis was considered in the article. Purpose. The aim of this investigation was to study the effectiveness of combination pentoxifylline and L-arginine on general pathogenetic mechanisms of chronic obstructive pulmonary disease concomitant with osteoarthritis, particularly on systemic inflammation, estimated on the level of leukotriene B4 (LTВ4) at the patient’s serum.

Matherials and methods. Was observed 33 patients in age (54,4±3,1) years old. All patients were smokers. As a marker of chronic systemic inflammation was used a level of leukotriene (LT)B4 at the serum. Results. Initial level of LTВ4 of observed patients was 14,6-fold more from normal (P<0,001) and achieved (8748,4±462,37) pg/ml. All patients were divided on two representative subgroups A and B. Subgroup A used only basic treatment according to protocol. To patients of subgroup B were added pentoxifylline and L-arginine. As a result, among the patients of subgroup B was achieved more significant positive clinical results and decreasing of serum LTВ4 concentration. Strong negative correlation between the FEV1 and the level of LTВ4 at all patients before the treatment was changed on moderate negative at the patients subgroup A and on wick negative at the patients of subgroup B.

Key words: chronic obstructive pulmonary disease, octeoarthrosis, treatment.

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

The full text

In progress


  1. Feschenko Ju.I. Mesto khronicheskogo vospalenija v patogeneze khronicheskoj obstructivnoj bolezni legkih [text] / Ju. I. Feschenko, L.A. Jashina // Zdorovja Ukrainy. – 2008. – № 3 (1). – S. 20-21.
  2. Ostrovskij M.M. Do pytannya polymorbidnosty ta komorbidnosty u khvorih na COPD [Text] / М.М. Ostrovskij, P.R. Gerich // Ukr. pulmonol. zhurn. – 2011. – № 4. – S. 19-24.
  3. Nasonova V.A. Osteoarthroz – problema polymorbidnosti [Text] / V.A. Nasonova // Consilium Medicum. – 2009. – Т. 11, № 2. – S. 43-48.
  4. Trofimenko I.N. Predictory tyazheloj odishki u bolnich khronicheskoj obstruktivnoj bolezn’ju legkih srednej stepeni tyazhesty [Text] / I.N. Trofimenko, B.A. Chernyak // Pulmonologija – 2014. – № 2. – S. 55-59.
  5. Zabolotnov V.A. Functsionalnaja aktivnost’ neutrophilov i soderzhanie leukotriena В4 v dinamike beremennosty na fone khronicheskih obstruktivnih boleznej legkih [Текст] / V.A. Zabolotnov // Ukr. pulmonol. zhurn. – 2000. – № 2. – S. 48-49.
  6. Nomenclatura, klasyficatsija, kriterii diagnostiki ta programy likuvannya revmatichnikh khvorob [Text] pid red. N. М. Shubi. – К., 2004. –156 s.
  7. Kevra, М.К. Ischerpani li potentsialnije vozmozhnosti klinicheskogo primenenija pentoxyphyllina? [Text] /М.К. Кevra // Belorusskij medicinskij zhurnal. – 2002. – № 1. – S. 21-25.
  8. Stepanov, Ju.М. Arginin v medicinskoj practike [Text] / Ju.М. Stepanov, I.N. Кononov // Zhurn. АМN Ukraine. – 2004. - № 10(1). – S. 340–352.
  9. Pentoxifylline in vivo down-regulates the release of IL-1 beta, IL-6, IL-8 and tumour necrosis factor-alpha by human peripheral blood mononuclear cells [Теxt] / P. Neuner, G. Klosner, E. Schauer et al. // Immunology. – 2004. – № 83. – Р. 262-267.
  10. The Role of Arginine in Infection and Sepsis [Теxt] / Y. C. Luiking, M. Poeze, G. Ramsay, N. E. P. Deutz // J. Parenter. Enteral. Nutr. – 2005. – Vol. 29. – P. S70 – S74.



Authors: Potapov O. O., Kmyta O. P.

Pages: 530-535



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 by means of studying the association between the results of computed tomography examinations and the -675 4G/5G polymorphism in the PAI-1 gene with the prediction of the secondary thrombohemorrhagic complications.

119 patients with severe traumatic brain injury have been examined. Computed tomography changes of brain tissues in patients with severe traumatic brain injury have been investigated. Determination of the -675 4G/5G polymorphism in the PAI-1 gene performed. Statistically results processing have been done with using of programs SPSS-17.

We have 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 pronounced 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.

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 patient with severe traumatic brain injury.

Key words: severe traumatic brain injury, computed tomography of the brain, prediction of the secondary thrombohemorrhagic complications, 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

In progress


  1. Bruns J. The epidemiology of traumatic brain injury: a review. Epilepsia. 2003;44 (1): 2–10.
  2. Huk АP. [TBI epidemiology in Ukraine]. Epidemiologia cherepno-mozkovoi travmy v Ukraini [Materials of the V Congress of Ukrainian Neurosurgeons]. Uzhorod, 2013, p. 38. (In Ukrainian).
  3. Lekhan VМ, Huk А
  4. Maas AI, Hukkelhoven CW, Marshall LF. Prediction of outcome in traumatic brain injury with computed tomographic characteristics: a comparison between the computed tomographic classification and computed tomographic predictors. Neurosurgery. 2005;57:1173–1182.
  5. Huq MA, Takeyama N, Harada M. 4G/5G Poymorphism 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. Genét GF, Johansson PI, Meyer MA. 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. 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. 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. Plasminogen activator inhibitor-1 4G/5G polymorphism and risk of stroke: replicated findings in two nested case-control studies based on indepen-dent cohorts. Stroke. 2005;36(8):1661–1665.
  11. Sirko А
  12. Trufanov HЕ, Ramishvili ТЕLuchevaia diahnostika travm holovy i pozvonochnika: rukovodstvo dlia vrachei [X-ray diagnostics of head and spinal cord injuries: manual for physicians]. SPb.: ELBI-SPb Publ., 2007. 196 p.



Authors: Pruystupa L. N., Bondarkova A. M., Guyva T. O.


Pages: 536-541



According to the data of international authors it was proven, that there existed direct connection between severity level of bronchial asthma (BA) and polymorphism Gln27Glu gene β2-adrenoceptor (ADRB2), but in Ukrainian population this connection wasn’t investigated. Therefore, the purpose of our investigation was to study severity level of BA in dependence of Gln27Glu polymorphism ADRB2 gene in Ukrainian population.

Materials and methods. 186 patients with easy, average and severity persistent BA in ages from 18 toll 70 had been investigated. The diagnosis had been determined on the base of GINA (2011) recommendations and Decree of Ukrainian Ministry of Public Health №128 19.03.2007. The control group involved 87 almost healthy humans without allergopatology and unencumbered with allergic history. Determination of the allelic polymorphism of 1st exon ADRB2 Gln27Glu (rs1042714) had been performed by polymerase chain reaction method with following analyze of the lengths of restrictions fragments. The statistic processing of results had been done with help of SPSS-17.

Results of  investigation. Depends on severity level of BA patients which had been divided into3 groups. 1st group involved 103 patients with easy course, 2 group – 52 with average severity course, and 3 group – 31 with severe course. After conducting investigation in first group results were such frequency of genotypes ADRB2: Gln27Gln – 80,6%; Gln27Glu – 15,6%; Glu27Glu – 3,8% respectively, in second group: 7,7%; 90,4%; 1,9% respectively, and in third group – 27,9%; 4,4%; 67,7% respectively.

Obtained results showed that genotype Gln27Gln likely more often met in patients with easy course of BA, genotype Gln27Glu – in patients with average severity course, and genotype Glu27Glu more likely detected in patients with severe course (p=0,02; p<0,05 by χ2 – Pirson’s criteria). Using genotype Gln27Gln as reference had been determined that existence of homozygotes by minor allele Glu27Glu genotype in patients regardless of the sex increased the risk of BA occurrence with severe course twice.

Thereby, there is a connection between polymorphism Gln27Glu ADRB2 gene and the severity of bronchial asthma course.

Key words: β2-adrenoceptor, Gln27Glu allelic polymorphism, bronchial asthma, asthma severity

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

The full text

In progress


  1. The genetic basis of the etiopathogenesis of bronchial asthma. [Text] /Asanov AY, Namazova LS, Zhurkova NV. [The genetic basis of the etiopathogenesis of bronchial asthma]. Sib. Med. J. 2010;3(3):82-85.
  2. Belevsky AS. [Global strategy for the treatment and prevention of asthma]. Moscow: Russian Respiratory Society, 2012. 108 p.
  3. Santillan AA, Camargo CA, Ramires-Rivera AA. Association between b2-adrenoreceptor polymorphism and asthma diagnosis among Mexican adultsJ. of All. and  Clin. Immunol. 2003;112(112):1095-1100
  4. Haitova NM. Genetically caused forms of chronic nonspecific pulmonary diseases [On the study of the prognostic value of biological markers of hereditary predisposition in patients with bronchial asthma]. Kiev, 2006, pp. 57-61
  5. Trofimov VI. [Molecular genetic and pharmacogenetic aspects of steroid resistance in asthma]. Rus. Med. Acad. J. 2006;6(1):150-162.
  6. Mironov JA,Trofimov VI,DubinPharmacogenetic aspects steroidorezistentnosti in patients with severe asthma [Proceedings XVI National Congress on Respiratory Disease]. 2006, p. 23.
  7. Trofimov VI, Mironov JA, Yanchina ED. Pharmacogenetic aspects of severe asthma. Pulmonology, 2008. pp. 111-116.
  8. Martinez FD, Graves PE, Baldini MO. Association between genetic polymorphisms of the beta2-adrenoceptor and response to albuterol in children with and without a history of wheezing. J. Clin. Invest. 1997;100,(12):3184—3188.
  9. D'Amato MI, Vitiani LR, Petrelli GA. Association of persistent bronchial hyper responsiveness with b2-adrenoceptor haplotypes. J. Respir. Crit. Med.1998;158:1968-1073.
  10. HizawaN.Beta-2adrenergicreceptorgeneticpolymorphismsandasthma.
  11. Magita O, Noguchi E., Jian Z.  ADRB2 polymorphisms and asthma susceptibility: transmission disequilibrium test and meta-analysis. Int. Arch. Allergy Immunol. 2004;134:150-157.
  12. Hellstron JM, Lin YG, Qiu CC. Association of polymorphism of human beta 2-adrenergic receptor gene and bronchial asthma. J. Clin. Invest. 1999; 6:626-631.
  13. Mak JC, Nishikawa MT, Barnes PJ. Glucocorticosteroid sincrease beta 2-adrenergic receptor transcription in human lung. JPhysiol.1995;268:141-1
  14. Limsuwan T, Thakkinstian A, Verasertniyom O. Possible protective effects of the Glu27 allele of beta2-adrenergic receptor polymorphism in thai asthmatic patients. J. Aller. Immunol. 2010; 28(2-3):107-114.
  15. Mandate of the Ministry of Health №128 from 19.03.20070 of Ukraine; IBC Code 10: J 45.Protocols of care for patients with asthma.



Authors: Khyzhnjak M. V., Potapov A. A., Tanasiichuk A. F., Novakovic E. S., Priymak E. V.

Pages: 542-546



Every year in the United States carried out more than 200 thousand primary microdiscectomy, the frequency of repeated interventions of up to 22% [1,2], and the relapses of hernias of intervertebral discs(ID) are between 3-15% [2]. However, despite the good results microdiscectomy, the problem of recurrence of pain syndromes are still relevant. Recurrences of pain syndromes can be caused by the formation of a hernia operated or adjacent vertebral-motor segment, segmental instability, various forms of degenerative spinal canal stenosis, epidural fibrosis [3, 4, 5]. Medical and social problems relapses of hernias of intervertebral discs caused by a decrease in the quality of life of the working population, significant economic losses and disability of patients. In Ukraine, the proportion of patients with spinal osteochondrosis of the working population in the structure of diseases of the musculoskeletal system reaches 40%.

The purpose of the study was to examine nearest, intermediate and long-term results of surgical re-treatment in patients with discogenic syndrome of lumbar spine, on the basis of differentiated application of surgical techniques.

A dynamic observation of 364 patients who were re-operated on in the department of minimally invasive spinal neurosurgery and laser State Institute of Neurosurgery. Acad. AP Romodanov Kyiv in the period from 2003 to 2012 for recurrent discogenic pain syndromes. Patients were divided into five main groups. 1) I ─ 196 patients who were operated on for ipsilateral (true relapse) hernia ID. 2) IІ ─ 22 patients who underwent microdiscectomy ID, followed by the installation of systems transpedicular fixation. 3) IIІ─ 11 patients who underwent removal of recurrent hernia ID, and the installation of a dynamic system such as fixing DIAM or COFLEX. 4) IV ─ 46 patients who underwent microsurgical removal of contralateral hernia previously operated ID. 5) V ─ 89 patients who underwent microdiscectomy on an adjacent level ID. Estimation of efficiency of surgical treatment of re-operated patients with herniated discs of the lumbar spine was performed in early (1months), intermediate (6 months) and long-term (12 months) the period of observation.

Results of surgical treatment were also evaluated on the basis of the relationship structures in the operated using PDS roentgenometer. Postoperative studies conducted during the second and third groups of observations indicated restore biomechanical relationships PDS, which was a proof of the correctness of the operation. The results of radiometric studies in patients of group III were carried out at different times after surgery.

Key words: osteochondrosis, discogenic pain syndrome, re microdiscectomy , Oswestry index , the index of the Roland -Morris.

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

The full text

In progress


  1. Dreval O N. Nejrohirurgija: rukovodstvo dlja vrachej [Neurosurgery: guide for physicians]. M.: Litterra Pabl., 2013. 864 p.
  2. Kremer J U, Shirokova V A. Zabolevanija mezhpozvonkovyh diskov [Diseases of the intervertebral disc]. M.: MEDpress-inform Pabl., 2013. 472 p.
  3. Shсhedrenok V V, Jakovenko I V, Anikeev N V. Maloinvazivnaja hirurgija degenerativnyh zabolevanij pozvonochnika [Minimally invasive surgery of degenerative diseases of the spine]. Spb.: Izd–vo FGU «RNHI im. prof. A. L. Polenova» Minzdravsocrazvitija Rossii, Pabl., 2011. 435 p.
  4. Prodan A I, Radchenko V A, Korzh N A. Degenerativnye zabolevanija pozvonochnika. Konservativnoe lechenie [Degenerative diseases of the spine. Nonoperative treatment]. Harkov Pabl., 2009. 261 p.
  5. Cherepanov E A. [Russian version of the questionnaire Oswestry: cultural adaptation and disability]. Hirurgija pozvonochnika. 2009; (3): 93–98.