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#1,(10),2020.

CTRI BULLETIN №1 (10) 2020

Journal Information: Read
Chief Editor: Ergeshov A.E.
Year of foundation: 2017
ISSN (Print): Browse
Publisher site: http://critub.ru
http://tb-bulletin.ru

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CONTENT

1)

The impact of mdr associated proteins of lung cells on reducing effectiveness of tb drugs

Erokhina M.V., Lepekha L.N.

5 READ MORE
2)

The results of financial monitoring of TB control activities and main funds of TB organizations in the Russian Federation in 2018

Sterlikov S.A., Rusakova L.I.

21 READ MORE
3)

Herpesvirus infections in TB patients

Shibanov A.M., Stakhanov V.A., Karazhas N.V., Sobkin A.L., Boshyan R.E.

30 READ MORE
4)

Clinical features and treatment efficacy in isoniazid-resistant pulmonary TB patients with additional MTB resistance to other drugs

Zakharov A.V.

38 READ MORE
5)

Radiological semiotics of pulmonary TB in patients with end-stage kidney disease

Gordeeva O.M., Karpina N.L., Amansakhedov R.B., Mikhailov S.G.

46 READ MORE
6)

The impact of antiretroviral therapy on the effectiveness of HIV/TB co-infection treatment based on the lipid spectrum rates

Makarov P.V.

57 READ MORE
7)

The hemostasis system state and morphological changes in the pulmonary microcirculation in TB patients with concomitant diabetes mellitus depending on the scope of lung surgery

Serebryanaya B.A., Lepekha L.N., Abdullaev R.Yu., Chitorelidze G.V., Berezovsky Yu.S., Nikitin S.S., Bagirov M.A.

63 READ MORE
8)

А case of generalized tuberculosis in a patient with HIV infection

Bayke E.E., Rogova O.O., Arkhipova M.V.

74 READ MORE
9)

The principles for preparation of diagnostic samples for microbiological detection of mycobacteria

Sevastyanova E.V., Larionova E.E., Andrievskaya I.Yu., Smirnova T.G.

79 READ MORE
10)

About the conference, dedicated to the 100th anniversary of Children and Adolescetns’ Clinic, CTRI

Ovsyankina E.S., Gubkina M.Ph., Panova L.V., Yukhhimenko N.V.

86  
11)

To the 75th anniversary of Evgeny Ivanovich Shmelev

89  

THE IMPACT OF MDR ASSOCIATED PROTEINS OF LUNG CELLS ON REDUCING EFFECTIVENESS OF TB DRUGS

Article 1.Page 5.
ARTICLE TITLE:

THE IMPACT OF MDR ASSOCIATED PROTEINS OF LUNG CELLS ON REDUCING EFFECTIVENESS OF TB DRUGS

DOI: 10.7868/S258766782001001X

AUTORS:

Erokhina M.V.1,2, Lepekha L.N.1

1 Central TB Research Institute, Moscow, Russia

2 M.V. Lomonosov Moscow State University, Moscow, Russia

DESCRIPTION OF ARTICLE:

Submitted as of 26.11.2019

The article reviews issues related to the development of multidrug resistance (MDR) of somatic cells in macroorganisms, which results in reducing effectiveness of TB drugs, including rifampicin. We highlight the history of resistance development and ways to overcome it in cancer patients. We survey the main transporter proteins responsible for delivery of drugs or other substrates across cell membranes. The most universal transporter is P-glycoprotein (Pgp) with the widest range of substrates; it provides the highest levels of MDR somatic cells and predicts a negative outcome of cancer. The article gives the examples of the first foreign and Russian publications related to increasing gene expression of MDR associated somatic cell proteins in the experiment, in clinical pulmonary TB, and under TB treatment. TB drugs are considered as modulators of endocytosis and activity of MDR associated proteins. We hypothesize that there could be synergism between M. tuberculosis ATP-binding transporters and a host’s MDR somatic cells.

The article was prepared under basic research topic no. 0515-2019-0015 “The development of drug resistance of mycobacteria and somatic cells to TB drugs”.

REFERENCES:
  1. Vasilyeva I.A., Samoilova A.G., Lovacheva O.V., Chernousova L.N., Bagdasaryan T.R. Effect of different TB drugs and antimicrobials on effectiveness of treatment of multidrug-resistant TB patients. Tuberculosis and Lung Diseases, 2017, no. 10, pp. 9–15. (In Russ.)
  2. Erokhin V.V., Lepekha L.N., Erokhina M.V., Lovacheva O.V. The surfactant system in pulmonary tuberculosis. Moscow, New-Terra, 2014, 265 p. (In Russ.)
  3. Erokhina M.V. The somatic cell trapsporters and their influence on the effectiveness of TB treatment. Tuberculosis and Lung Diseases, 2004, no. 8, pp. 11–15. (In Russ.)
  4. Erokhina M.V., Lepekha L.N., Ergeshov A.E., Rybalkina E.Yu., Sadovnikova S.S., Sychevskaya K.A. Multidrug resistance associated proteins in human lung somatic cells and their expression in fibrocavernous TB. Tuberculosis and Lung Diseases, 2016, no. 9, pp. 53–58. – № 9. – С. 53–58. (In Russ.)
  5. Erokhina M.V., Lepekha L.N., Rybalkina E.Yu., Pavlova E.N., Onishchenko G.E. The effect of rifampicin and its encapsulated form on the functional activity of multidrug resistance associated protein Pgp in human myeloid cells. CTRI Bulletin, 2018, no. 2, pp. 309–325. (In Russ.) 6. Petrova L.V., Sevastyanova E.V.,
  6. Vasilyeva A.M., Kuklina E.A., Soloviev Yu.A., Chernousova L.N. The impact of real time PCR in the diagnostic algorithm on the effectiveness of multidrug resistant TB treatment. Tuberculosis and Lung Diseases, 2019, no. 9, pp. 40–44. (In Russ.)
  7. Stavrovskaya A.A. The neoplastic cell in defence. Sorosovsky obrazovatelny jurnal, 2011, vol. 7, no. 7, pp. 17–23. (In Russ.)
  8. Stavrovskaya A.A., Rybalkina E.Yu. New about molecular mechanisms of multidrug resistance upregulation in neoplastic cells. Biokhimiya, 2018, no. 7, pp. 963–971. (In Russ.)
  9. Fedoseeva V.V., Khalansky A.S., Mkhitarov V.A., Tsvetkov I.S., Malinovskaya Yu.A., Maksimenko O.O., Gelperina S.E., Balabanyan V.Yu., Razzhivina V.A., Gorelikov P.L., Mikhailova L.P., Makarova O.V. The antineoplastic activity of doxorubicin in poly- (lactic-co-glycolipid) nanoparticles in experimental glioblastoma. Klinicheskaya i eksperimentalnaya morfologia, 2017, vol. 22, no. 2, pp. 65–71. (In Russ.)
  10. Yakusheva E.N., Shchulkin A.V., Popova N.M., Chernykh I.V., Titov D.S. The structure and functions of P-glycoprotein, its role in rational pharmacotherapy. Obzory po klin. farmakol. i lek. terapii, 2014, vol. 12, no. 2, pp. 2–11. (In Russ.)
  11. Akamine Y., Yasui-Furukori N., Ieiri I., and Uno T. Psychotropic drug-drug interactions involving P-glycoprotein. CNS Drugs, 2012, vol. 26, no. 11, pp. 959–973.
  12. Al-Ghafli H., Kohl T.A., Merker M., Varghese B., Halees A., Niemann S., Al-Hajoj S. Drug-resistance profiling and transmission dynamics of multidrugresistant Mycobacterium tuberculosis in Saudi Arabia revealed by whole genome sequencing. Infect. Drug Resist., 2018, no. 11, pp. 2219–2229.
  13. Alberts B., Johnson A., Lewis J., Morgan D., Raff M., Roberts K., Walter P. Molecular biology of the cell, Sixth Edition. New York, Garland Science, 2014, 984 p.
  14. Alvarez A.I., Perez M., Prieto J.G., Molina A.J., Real R., Merino J. Fluoroquinolone efflux mediated by ABC transporters. Journal of Pharmaceutical Sciences, 2008, vol. 97, no. 9, pp. 3483–3493.
  15. Anisimova Y.V, Gelperina S.I., Peloquin C.A., Heifets L.B. Nanoparticles as antituberculosis drugs carriers: Effect on activity against Mycobacterium tuberculosis in human monocyte-derived macrophages.Yao Hsueh Hsueh Pao Acta Pharmaceutica Sinica, 2000, vol. 2, no. 2, pp. 165–171.
  16. Becquemont L., Camus M., Eschwege V., Barbu V., Rey E., Funck-Brentano C., Jaillon P. Lymphocyte P-glycoprotein expression and activity before and after rifampicin in man. Fundamental and Clinical Pharmacology, 2000, vol. 14, no. 5, pp. 519–525.
  17. Borst P., Evers R., Kool M., Wijnholds J. A Family of drug transporters: The multidrug resistance-associated proteins. JNCI Journal of the National Cancer Institute, 2000, vol. 92, no. 16, pp. 1295–1302.
  18. Borst P., Elferink R.O. Mammalian ABC transporters in health and disease. Annual Review of Biochemistry, 2002, no. 71, pp. 537–592.
  19. Te Brake L.H.M., de Knegt G.J., de Steenwinkel J.E. et al. The role of efflux pumps in tuberculosis treatment and their promise as a target in drug development: unraveling the black box. Annual Review of Pharmacology and Toxicology, 2018, no. 58, pp. 271–291.
  20. Bréchot J.M., Hurbain I., Fajac A., Daty N., Bernaudin J.F. Different pattern of MRP localization in ciliated and basal cells from human bronchial epithelium. J. Histochem. Cytochem., 1998, vol. 46, no. 4, pp. 513–517.
  21. Campbell L., Abulrob A.N., Kandalaft L.E., Plummer S., Hollins A.J., Gibbs A., Gumbleton M. Constitutive expression of P-glycoprotein in normal lung alveolar epithelium and functionality in primary alveolar epithelial cultures. The Journal of Pharmacology and Experimental Therapeutics, 2003, vol. 304, no. 1, pp. 441–452.
  22. Chen C.K., Law W.C., Aalinkeel R., Yu Y., Nair B., Wu J., Mahajan S., Reynolds J.L., Li Y., Lai C.K., Tzanakakis E.S., Schwartz S.A., Prasad P.N., Cheng C. Biodegradable cationic polymeric nanocapsules for overcoming multidrug resistance and enabling druggene co-delivery to cancer cells. Nanoscale, 2014b, vol. 6, no. 3, pp. 1567–1572.
  23. Chen Z., Shi T., Zhang L., Zhu P., Deng M., Huang C., Hu T., Jiang L., Li J. Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett., 2016, vol. 370, no. 1, pp. 153–164.
  24. Chen D., Wang J., Wang Y., Zhang F., Dong X., Jiang L., Tang Y., Zhang H., Li W. Promoting inter-/intra- cellular process of nanomedicine through its physicochemical properties optimization. Curr. Drug Metab. 2018, vol. 19, no. 1, pp. 75–82.
  25. Chigutsa E., Visser M.E., Swart E.C., Denti P., Pushpakom S., Egan D., Holford N.H., McIlleron H., Smith P.J., Maartens G., Owen A. The SLCO1B1 Rs4149032. polymorphism is highly prevalent in South Africans and is associated with reduced tifampin concentrations: dosing implications. Antimicrob. Agents Chemother., 2011, vol. 55, no. 9, pp. 4122–4127.
  26. Choudhuri Baisakhee Saha, Susmita Sen, and Parul Chakrabarti. Isoniazid accumulation in Mycobacterium smegmatis is modulated by proton motive forcedriven and ATP-dependent extrusion systems. Biochem. Biophys. Res. Commun., 1999, vol. 256, no. 3, pp. 682–684.
  27. Cole S.P., Bhardwaj G., Gerlach J.H., Mackie J.E., Grant C.E., Almquist K.C., Stewart A.J., Kurz E.U., Duncan A.M., Deeley R.G. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science (New York, N.Y.), 1992, vol. 258, issue 5088, pp. 1650–1654.
  28. Cordon-Cardo C., O’Brien J.P., Boccia J., Casals D., Bertino J.R., Melamed M.R. Expression of the multidrug resistance gene product (P-glycoprotein) in human normal and tumor tissues. J. Histochem. Cytochem., 1990, vol. 38, no. 9, pp. 1277–1287.
  29. Cui Y.J., Cheng X., Weaver Y.M., Klaassen С.D. Tissue distribution, gender-divergent expression, ontogeny, and chemical induction of multidrug resistance transporter genes (Mdria, Mdrib, Mdr2) in mice. Drug Metabolism and Disposition, 2009, vol. 37, no. 1, pp. 203–210.
  30. Doyle L.A., Yang W., Abruzzo L.V., Krogmann T., Gao Y., Rishi A.K., Ross D.D. A multidrug resistance transporter from human MCF‑7 breast cancer cells. Proceedings of the National Academy of Sciences of the United States of America, 1998, vol. 95, no. 26, pp. 15665–15670.
  31. Ehrhardt C., Bäckman P., Couet W., Edwards Ch., Forbes B., Fridén M., Gumbleton M., Hosoya K., Kato Y., Nakanishi T, Yumoto Takano R., Terasaki T. Current progress toward a better understanding of drug disposition within the lungs: Summary Proceedings of the 1st Workshop on Drug Transporters in the Lungs. Journal of Pharmaceutical Sciences, 2017, vol. 106, no. 9, pp. 2234–2244.
  32. Endter S., Becker U., Daum N., Huwer H., Lehr C.M., Gumbleton M., Ehrhardt C. P-glycoprotein (MDR1) functional activity in human alveolar epithelial cell monolayers. Cell and Tissue Research, 2007, vol., 328, no. 1, pp. 77–84.
  33. Fardel O., Lecureur V., Loyer P., Guillouzo A. Rifampicin enhances anti-cancer drug accumulation and activity in multidrug-resistant cells. Biochemical Pharmacology, 1995, vol. 49, no. 9, pp. 1255–1260.
  34. FDA guidance for industry. Drug interaction studies – study design, data analysis, implications for dosing, and labeling recommendations. Guidance Document, 2017, pp. 1–79.
  35. Fetsch P.A., Abati A., Litman T., Morisaki K., Honjo Y., Mittal K., Bates S.E. Localization of the ABCG2 mitoxantrone resistance-associated protein in normal tissues. Cancer Letters, 2006, vol. 235, no. 1, pp. 84–92.
  36. Flens M.J., Zaman G.J., van der Valk P., Izquierdo M.A., Schroeijers A.B., Scheffer G.L., van der Groep P., de Haas M., Meijer C.J., Scheper R.J. Tissue distribution of the multidrug resistance protein. The American Journal of Pathology, 1996, vol. 148, no. 4, pp. 1237– 1247.
  37. García-Carrasco M., Mendoza-Pinto C., Macías-Díaz S., Etchegaray-Morales I., Jiménez-Herrera E.A., Méndez-Martínez S., Soto-Santillán P., Pérez-Romano B., Ruiz-Argüelles A., Guzmán-Ruiz O. Clinical relevance of P-glycoprotein activity on peripheral blood mononuclear cells and polymorphonuclear neutrophils to methotrexate in systemic lupus erythematosus patients. Clin. Rheumatol., 2017, vol. 36, no. 10, pp. 2267–2272.
  38. Geick A., Eichelbaum M., Burk O. Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin. Journal of Biological Chemistry, 2001, vol. 276, no. 18, pp. 14581–14587.
  39. Gottesman M.M., Pastan I. Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu. Rev. Biochem., 1993, vol. 62, no. 1, pp. 385–427.
  40. Gottesman M.M., Hrycyna C.A., Schoenlein P.V., Germann U.A., Pastan I. Genetic analysis of the multidrug transporter. Annu. Rev. Genet., 1995, no. 29, pp. 607–649.
  41. Greiner B., Eichelbaum M., Fritz P., Kreichgauer H.P., von Richter O., Zundler J., Kroemer H.K. The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin. Journal of Clinical Investigation, 1999, vol. 104, no. 2, pp. 147–153.
  42. Gumbleton M., Al-Jayyoussi G., Crandon-Lewis A., Francombe D., Kreitmeyr K., Morris C.J. Spatial expression and functionality of drug transporters in the intact lung: Objectives for further research. Adv. Drug Deliv. Rev., 2011, vol. 63, no. 1–2, pp. 110–118.
  43. Hartkoorn R.C., Chandler B., Owen A., Ward S.A., Bertel Squire S., Back D.J., Khoo S.H. Differential drug susceptibility of intracellular and extracellular tuberculosis, and the impact of P-glycoprotein. Tuberculosis, 2007, vol. 87, no. 3, pp. 248–255.
  44. Hirota K., Hasegawa T., Nakajima T., Inagawa H., Kohchi C., Soma G., Makino K., Terada H. Delivery of rifampicin-PLGA microspheres into alveolar macrophages is promising for treatment of tuberculosis. Journal of Controlled Release, 2010, vol. 142, no. 3, pp. 339–346.
  45. Hodges L.M., Markova S.M., Chinn L.W., Gow J.M., Kroetz D.L., Klein T.E., Altman R.B. Very important pharmacogene summary: ABCB1 (MDR1, P-Glycoprotein). Pharmacogenetics and Genomics, 2011, vol. 21, no. 3, pp. 152–161.
  46. Izquierdo M.A., Scheffer G.L., Flens M.J., Schroeijers A.B., van der Valk P., Scheper R.J. Major vault protein LRP-related multidrug resistance. Eur. J. Cancer, 1996, vol. 32A, no. 6, pp. 979–984.
  47. Kedersha N.L., Rome L.H. Preparative agarose gel electrophoresis for the purification of small organelles and particles. Analytical Biochemistry, 1986, vol. 156, no. 1, pp. 161–170.
  48. Khamisipour G., Jadidi-Niaragh F., Jahromi A.S., Zandi K., Hojjat-Farsangi M. Mechanisms of tumor cell resistance to the current targeted-therapy agents. Tumor Biology, 2016, vol. 37, no. 8, pp. 10021–10039.
  49. Kim H., Barroso M., Samanta R., Greenberger L., Sztul E. Experimentally induced changes in the endocytic traffic of P-glycoprotein alter drug resistance of cancer cells. Am. J. Physiol., 1997, no. 273, pp. 687–702.
  50. Kim R.B. Drugs as P-glycoprotein substrates, inhibitors, and inducers. Drug Metabolism Reviews, 2002, vol. 34, no. 1–2, pp. 47–54.
  51. Kim M.S., Haney M.J., Zhao Y., Mahajan V., Deygen I., Klyachko N.L., Inskoe E., Piroyan A., Sokolsky M., Okolie O., Hingtgen S.D., Kabanov A.V., Batrakova E.V. Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells. Nanomedicine: Nanotechnology, Biology and Medicine, 2016, vol. 12, no. 3, pp. 655–664.
  52. Lechapt-Zalcman E., Hurbain I., Lacave R., Commo F., Urban T., Antoine M., Milleron B., Bernaudin J.F. MDR1-Pgp 170 expression in human bronchus. European Respiratory Journal, 1997, vol. 10, no. 8, pp. 1837–1843.
  53. Leslie E.M., Deeley R.G., Cole S.P.C. Multidrug resistance proteins: Role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense. Toxicology and Applied Pharmacology, 2005, vol. 204, no. 3, pp. 216–237.
  54. Li W., Zhang H., Assaraf Y.G., Zhao K., Xu X., Xie J., Chen Z., Yang D. Overcoming ABC rransporter-mediated multidrug resistance: Molecular mechanisms and novel therapeutic drug strategies. Drug Resist. Updat., 2016, no. 27, pp. 14–29.
  55. Magnarin M., Morelli M., Rosati A., Bartoli F., Candussio L., Giraldi T., Decorti G. Induction of proteins involved in multidrug resistance (P-glycoprotein, MRP1, MRP2, LRP) and of CYP 3A4 by rifampicin in LLC-PK1cells. Eur. Journal of Pharmacology, 2004, vol. 483, no. 1, pp. 19–28.
  56. Manceau S., Giraud C., Declèves X., Batteux F., Chouzenoux S., Tang R., Dauchy S., Scherrmann J.M., Weill B., Morini J.P., Perrot J.Y., Tréluyer J.M. Lack of P-glycoprotein induction by rifampicin and phenobarbital in human lymphocytes. International Journal of Pharmaceutics, 2010, vol. 395, no. 1–2, pp. 98–103.
  57. Marzolini C., Paus E., Buclin T., Kim R.B. Polymorphisms in human MDR1 (P-glycoprotein): Recent advances and clinical relevance. Clin. Pharmacol. Ther., 2004, vol. 75, no. 1, pp. 13–33.
  58. Nasiri M.J., Haeili M., Goudarzi H., Ghazi M., Pormohammad A., Fooladi A.A.I., Mehdi F.M. New insights in to the intrinsic and acquired drug resistance mechanisms in mycobacteria. Frontiers in Microbiology, 2017, no. 8, p. 681.
  59. Niemi M., Backman J.T., Fromm M.F., Neuvonen P.J., Kivistö K.T. Pharmacokinetic interactions with rifampicin: clinical relevance. Clinical Pharmacokinetics, 2003, vol. 42, no. 9, pp. 819–850.
  60. Owen A., Goldring C., Morgan P., Park B.K., Pirmohamed M. Induction of P-glycoprotein in lymphocytes by carbamazepine and rifampicin: The role of nuclear hormone response elements. British Journal of Clinical Pharmacology, 2006, vol. 62, no. 2, pp. 237–242.
  61. Poongavanam V., Haider N., Gerhard F.E. Fingerprintbased in silico models for the prediction of P-glycoprotein substrates and inhibitors. Bioorganic and Medicinal Chemistry, 2012, vol. 20, no. 18, pp. 5388–5395.
  62. Price D.F., Luscombe C.N., Eddershaw P.J., Edwards C.D., Gumbleton M. The differential absorption of a series of P-glycoprotein substrates in isolated perfused lungs from Mdr1a/1b genetic knockout mice can be attributed to distinct physico-chemical properties: An insight into predicting transporter-mediated, ulmonary speci. Pharm Res., 2017, no. 34, pp. 2498–2516.
  63. Riordan J.R., Ling V. Purification of P-glycoprotein from plasma membrane vesicles of Chinese hamster ovary cell mutants with reduced colchicine permeability. Journal of Biological Chemistry, 1979, vol. 254, no. 24, pp. 12701–12705.
  64. Rosenberg M.F., Velarde G., Ford R.C., Martin C., Berridge G., Kerr I.D., Callaghan R., Schmidlin A., Wooding C., Linton K.J., Higgins C.F. Repacking of the transmembrane domains of P-glycoprotein during the transport ATPase cycle. EMBO Journal, 2001, no. 20, pp. 5615–5625.
  65. Sakamoto A., Matsumaru T., Yamamura N., Uchida Y., Tachikawa M., Ohtsuki S., Terasaki T. Quantitative expression of human drug transporter proteins in lung tissues: Analysis of regional, gender, and interindividual differences by liquid chromatography-tandem mass spectrometry. J. Pharm. Sci., 2013, vol. 102, no. 9, pp. 3395–3406.
  66. Scheffer G.L., Wijngaard P.L., Flens M.J., Izquierdo M.A., Slovak M.L., Pinedo H.M., Meijer C.J., Clevers H.C., Scheper R.J. The drug resistance-related protein LRP is the human major vault protein. Nature Medicine, 1995, vol. 1, no. 6, pp. 578–582.
  67. Scheffer G.L., Pijnenborg A.C., Smit E.F., Müller M., Postma D.S., Timens W., van der Valk P., de Vries E.G.E., Scheper R.J. Multidrug resistance related molecules in human and murine lung. Journal of Clinical Pathology, 2002, vol. 55, no. 5, pp. 332–339.
  68. Schinkel A.H., Jonker J.W. Mаmmalian drug efflux transporters of the ATP binding cassette (ABC) family: An overview. Advanced Drug Delivery Reviews, 2003, vol. 55, no. 1, pp. 3–29.
  69. Schuetz E.G., Schinkel A.H., Relling M.V., Schuetz J.D. P-glycoprotein: A major determinant of rifampicininducible expression of cytochrome P4503A in mice and humans. Proc. Natl. Acad. Sci. USA, 1996, vol. 93, no. 9, pp. 4001–4005.
  70. Sinz M., Kim S., Zhu Z., Chen T., Anthony M., Dickinson K., Rodrigues A.D. Evaluation of 170 xenobiotics as transactivators of human pregnane X receptor (hPXR) and correlation to known CYP3A4 drug interactions. Current Drug Metabolism, 2006, vol. 7, no. 4, pp. 375–388.
  71. Stavrovskaya A.A., Shushanov S.S., Rybalkina E.Y. Problems of glioblastoma multiforme drug resistance. Biochemistry (Mosc), 2016, vol. 81, no. 2, pp. 91–100.
  72. Tanaka H., Tsukihara T. Structural studies of large nucleoprotein particles, vaults. Proceedings of the Japan Academy. Series B, Physical And Biological Sciences, 2012, vol. 88, no. 8, pp. 416–433.
  73. Theodoulou F.L., Kerr I.D. ABC transporter research: going strong 40 years on. Biochemical Society Transactions, 2015, vol. 43, no. 5, pp. 1033–1040.
  74. Van der Valk P., van Kalken C.K., Ketelaars H., Broxterman H.J., Scheffer G., Kuiper C.M., Tsuruo T., Lankelma J., Meijer C.J., Pinedo H.M. Distribution of multi-drug resistance-associated P-glycoprotein in mormal and neoplastic human tissues. Analysis with 3 monoclonal antibodies recognizing different epitopes of the P-glycoprotein molecule. Annals of oncology: official journal of the European Society for Medical Oncology, ESMO, 1990, vol. 1, no. 1, pp. 56–64.
  75. Van de Ven R., Oerlemans R., van der Heijden J.W., Scheffer G.L., de Gruijl T.D., Jansen G., Scheper R.J. ABC drug transporters and immunity: novel therapeutic targets in autoimmunity and cancer. Journal of Leukocyte Biology, 2009, vol. 86, no. 5, pp. 1075–1087.
  76. Vasir J.K., Labhasetwar V. Biodegradable nanoparticles for cytosolic delivery of therapeutics. Adv. Drug Deliv. Rev., 2007, vol. 59, no. 8, pp. 718–728.
  77. Wessler J.D., Grip L.T., Mendell J., Giugliano R.P. The P-glycoprotein transport system and cardiovascular drugs. Journal of the American College of Cardiology, 2013, vol. 61, no. 25, pp. 2495–2502.
  78. Global tuberculosis report, 2018. Switzerland, WHO.
KEYWORDS:

MDR somatic cell proteins, TB drugs, pulmonary TB.

FOR CORRESPONDENCE:

Central TB Research Institute

2, Yauzskaya alley, 107564, Moscow, Russia

M.V. Lomonosov Moscow State University

1, Building 12, Leninskie Gory, 119991, Moscow, Russia

Maria V. Erokhina, Doctor of Biological Sciences, Senior Researcher, Department of Pathomorphology,

Cell Biology and Biochemistry, Central TB Research Institute; Docent, Cell Biology and Histology

Department, Biology Faculty, M.V. Lomonosov Moscow State University

Tel.: +7 (499) 939-45-67

E-mail: masha.erokhina@gmail.com

Central TB Research Institute

2, Yauzskaya alley, 107564, Moscow, Russia

Larisa N. Lepekha, Doctor of Biological Sciences, Acting Principal Researcher, Professor, Head

of Department of Pathomorphology, Cell Biology and Biochemistry

Tel.: +7 (499) 785-91-79

E-mail: lep3@yandex.ru

THE RESULTS OF FINANCIAL MONITORING OF TB CONTROL ACTIVITIES AND MAIN FUNDS OF TB ORGANIZATIONS IN THE RUSSIAN FEDERATION IN 2018

Article 2.Page 21.
ARTICLE TITLE:

THE RESULTS OF FINANCIAL MONITORING OF TB CONTROL ACTIVITIES AND MAIN FUNDS OF TB ORGANIZATIONS IN THE RUSSIAN FEDERATION IN 2018

DOI: 10.7868/S2587667820010021

AUTORS:

Sterlikov S.A.1,2, Rusakova L.I.2

1 Central Research Institute of Organization and Informatization of Health, Moscow, Russia

2 Central TB Research Institute, Moscow, Russia

DESCRIPTION OF ARTICLE:

Submitted as of 02.12.2019

Aim: To revise the methods of calculation of per capita funding rates related to TB control activities, and monitor the rates related to funding of TB control activities and the state of main funds of TB institutions. Based on a single statistical observation form, we analyzed the rates of dynamic funding of TB control activities from different sources, the state and the update of the main funds of TB institutions. The total amount of funding was compared to the data from different countries provided by the WHO global database. The amount of funding for TB control activities in the Russian Federation was 94.5–93.1 billion roubles, or 1450.7 billion USD, which was more than in any other country. This allowed rapid reduction of TB incidence. The inclusion of antiretroviral drugs in the calculation of per capita funding rates in some Russian regions accounted for a 3–5% error. The methods currently used for per capita funding calculation did not consider discrepancies in medical care costs in different regions, which made an illusion of favourable funding of the Far East regions. In 2018 we observed unprecedented growth of salaries and other payments to health personnel, especially physicians. At the same time, updating of the main funds decreased resulting in the wear of equipment and vehicles. The share of TB control activities funding by the Russian Federation Subjects increased, since they were responsible for payments to health personnel. In order to harmonize the Russian and international definitions of the rate: “funding of TB control activities”, it was recommended to introduce a system of financial monitoring of TB control activities without consideration of antiretroviral drugs, since it had resulted in overestimating TB control activities funding in the Russian Federation by 1.8%. The calculation of per capita funding rates by the Russian Federation Subjects should use the differentiation coefficient. Underfunding of updating the main funds of TB institutions resulted in high wear of equipment and vehicles, which could negatively influence TB control in general.

REFERENCES:
  1. Nechaeva O.B., Sterlikov S.A., Obukhova O.V. Funding of TB control and the state of the main funds of TB institutions. In: Sectoral and economical rates of TB control in 2016–2017. An analytical review of main rates and statistical data. Moscow, RIO CNIIOIZ, 2018, pp. 26–28. (In Russ.)
  2. Omarova K.A. The problems of investing into material resource base of the social sphere. Problemy sovremennoi ekonomiki, 2009, no. 3, pp. 388–391. (In Russ.)
  3. Sectoral and economical rates of TB control in 2017–2018. An analytical review of main rates and statistical data. Moscow, RIO CNIIOIZ, 2019, 59 p. (In Russ.)
  4. Starodubov V.I., Pachin M.V. The report on “Resource base of health institutions in Russia”. Moscow, 2003 p. (In Russ.)
  5. The strategy of health development in the Russian Federation for a long-term period of 2015–2030. (In Russ.) [Electronic resource]. Mode of access: https://kraszdrav.ru/ (dateof referral: 20.08.19).
  6. Tokun L.V. Investments as a factor of sustainable Russian health care. MIR, 2016, vol. 2, no. 7, pp. 132–138. (In Russ.) doi: 10.18184/2079-4665.2016.7.2.132.138
  7. Global tuberculosis report 2017. Geneva, WHO, 2018, 249 p.
  8. Global tuberculosis report 2018. Geneva, WHO, 2018, 265 p.
  9. WHO’s global tuberculosis database [Electronic resource]. Mode of access: https://www.who.int/tb/country/data/download/en/ (date of referral:28.10.19)
KEYWORDS:

funding of TB control activities, financial burden due to TB, funding sources for TB control, state of TB institutions, main funds, depreciation of main funds of TB institutions.

FOR CORRESPONDENCE:

Central Research Institute of Organization and Informatization of Health

Dobrolyubova St., 127254, Moscow, Russia

Sergey A. Sterlikov, Deputy Head, TB Monitoring Center for Program Monitoring, Doctor of Medical

Sciences

Тел.: +7 (925) 507-82-21

E-mail: sterlikov@list.ru

Central TB Research Institute

Yauzskaya alley, 107564, Moscow, Russia

Larisa I. Rusakova, Principal Researcher, Head, Research Administration Department, Doctor of Medical

Sciences

Tel.: +7 (499) 785-91-87

E-mail: larisa.rusakova@mail.ru

HERPESVIRUS INFECTIONS IN TB PATIENTS

Article 3.Page 30.
ARTICLE TITLE:

HERPESVIRUS INFECTIONS IN TB PATIENTS

DOI: 10.7868/S2587667820010033

AUTORS:

Shibanov A.M.1, Stakhanov V.A.2, Karazhas N.V.3, Sobkin A.L.1, Boshyan R.E.3,4

1 TB Clinical Hospital No. 3 named after Prof. G.A. Zakharyin, Moscow, Russia

2 Russian National Research Medical University named after N.I. Pirogov, Moscow, Russia

3 N.F. Gamaleya Research Institute of Epidemiology and Microbiology, Moscow. Russia

4 First Moscow State Medical University named after I.M. Sechenov, Moscow, Russia

DESCRIPTION OF ARTICLE:

Submitted as of 05.12.2019

Aim: To study the peculiarities of TB process in herpesvirus infection (HVI) patients with a negative or positive HIV status. Materials and methods. We carried out a pilot case-control study of 350 TB patients. To establish a possible cause of acute TB progression, we studied patients’ blood sera and cells for opportunistic infection markers to detect antibodies to herpesviruses and their antigens. Results. The high level of infection (up to 97%) was established in both HIV-positive and HIV-negative TB patients. We discovered the association between drug resistance of M. tuberculosis and HVI activity markers. Conclusion. Patients with advanced pulmonary TB and detected markers of HVI activity should undergo additional examinations, and patients with confirmed HVI should be considered for administration of antiviral drugs.

REFERENCES:
  1. Human herpesvirus infections. Guidelines for physicians. Ed. V.A. Isakov. Second edition. St. Petersburg, SpetsLit, 2013, 670 p. (In Russ.) ISBN 978-5-299-00454-0
  2. Malashenkova I.K. et al. Clinical forms of chronic EpsteinBarr virus infection: diagnosis and treatment. Lechashchy vrach, 2003, no. 9, pp. 8–10. (In Russ.)
  3. The modern aspects of herpesvirus infection. Epidemiology, clinical presentations, diagnosis, treatment and prevention. Moscow Government Health Department. Compiled by Karazhas N.V. et al. Moscow, Spetskniga, 2012, 128 p. (In Russ.)
  4. Agut H. Acute human herpesvirus 6 (HHV‑6) infections: when and how to treat? Pathol. Biol. (Paris), 2011, vol. 59, no. 2, pp. 108–112.
  5. Boeckh M., Nichols W.G. Immunosuppressive effects of beta-herpesviruses. Herpes, 2003, vol. 10, pp. 12–16.
  6. Fishman J.A., Rubin R.H. Infection in organ-transplant recipients. N. Engl. J. Med., 1998, vol. 338, pp. 1741– 1751.
  7. Ljungman P. β-Herpesvirus challenges in the transplant recipient. J. Infect. Dis., 2002, vol. 186, Suppl. 1, pp. 99–109.
  8. Maciejewski J.P., Luppi M., Torelli G. Human cytomegalovirus, human herpesvirus 8, and other herpesviruses. Clinical hematology, St. Louis, Mosby, 2006, pp. 967–980.
  9. Miller R. HIV-associated respiratory diseases. Lancet, 1996, vol. 3, no. 348 (9023), pp. 307–312.
  10. Patience T. et al. Mycobacterium tuberculosis subverts negative regulatory pathways in human macrophages to drive immunopathology. PLOS, June 1, 2017, vol. 13, no. 6. https://doi.org/10.1371/journal.ppat.1006367
  11. Pebody R.G. et al. The seroepidemiology of herpes simplex virus type 1 and 2 in Europe. Sex Transm. Infect. 2004, vol. 80, pp.185–191.
  12. Rea T.D. et al. Prospective study of the natural history of infectious mononucleosis caused by EpsteinBarr virus. J. Am. Board Fam. Pract., 2001, vol. 14, pp. 234–242.
  13. Salgame P. Host innate and Th1 responses and the bacterial factors that control Mycobacterium tuberculosis infection. Curr. Opin. Immunol., 2005, vol. 17, pp. 374–380.
  14. Zerr D.M., Meier A.S., Selke S.S. et al. A populationbased study of primary human herpesvirus 6 infection. N. Engl. J. Med., 2005, vol. 352, pp. 768–776.
KEYWORDS:

TB, HIV-infection, herpesvirus infection, Epstein-Barr virus, cytomegalovirus, simple herpes virus, human herpes virus 6, drug resistance of M. tuberculosis.

FOR CORRESPONDENCE:

TB Clinical Hospital No. 3 named after Prof. G.A. Zakharyin

29, Kurkinskoye shosse, 125466, Moscow, Russia

Aleksey M. Shibanov, Phthisiatrician, Division for Phtisiology, Head

Tel.: +7 (495) 571-24-30

E-mail: shiblo@mail.ru

Alexander L. Sobkin, Candidate of Medical Sciences, Chief Physician

Tel.: +7 (495) 572-71-45

E-mail: Tkb_3@mail.ru

Russian National Research Medical University named after N.I. Pirogov

1, Ostravityanov St., 117997, Moscow, Russia

Vladimir A. Stakhanov, Doctor of Medical Sciences, Head of Phthisiology Department

Tel.: +7 (499) 120-82-95

E-mail: stakhanov03@rambler.ru

N.F. Gamaleya Research Institute of Epidemiology and Microbiology

18, Gamaleya St., 123098, Moscow, Russia

Natalia V. Karazhas, Doctor of Biological Sciences, Head of Laboratory of Opportunistic Infections Epidemiology

Tel.: +7 (499) 193-43-89

E-mail: karazhas@inbox.ru

First Moscow State Medical University named after I.M. Sechenov

8, Build. 2, Trubetskaya St., 119991, Moscow, Russia

Roman E. Boshyan, Candidate of Medical Sciences, Associate Professor, Department of Microbiology, Virology and Immunology

Tel.: +7 (903) 160-29-85

E-mail: rbrm@mail.ru

CLINICAL FEATURES AND TREATMENT EFFICACY IN ISONIAZID-RESISTANT PULMONARY TB PATIENTS WITH ADDITIONAL MTB RESISTANCE TO OTHER DRUGS

Article 4.Page 38.
ARTICLE TITLE:

CLINICAL FEATURES AND TREATMENT EFFICACY IN ISONIAZID-RESISTANT PULMONARY TB PATIENTS WITH ADDITIONAL MTB RESISTANCE TO OTHER DRUGS

DOI: 10.7868/S2587667820010045

AUTORS:

Zakharov A.V.

Yaroslavl Oblast Clinical TB Hospital, Yaroslavl, Russia

DESCRIPTION OF ARTICLE:

Submitted as of 16.12.2019

In the WHO consolidated guidelines on drug-resistant tuberculosis (TB) treatment [5] the study of optimization of treatment for isoniazid-resistant TB with confirmed sensitivity to rifampicin and additional resistance to other drugs is considered as one of the priority areas of research. To investigate the clinical course and the treatment efficacy in isoniazid-resistant TB patients we carried out a retrospective analysis of 650 case histories of HIV-negative patients with different spectra of drug

resistance. We established that in 58.9% of patients isoniazid-resistant TB was diagnosed during retreatment, and in 48.6% of patients this disease had infiltrative form. Different extent lung lesions were equally frequent in isoniazid-resistant patients, with some tendency to segmental or lobar localizations. We observed multiple cavities in 58.8% of patients; in 49.5% cavity size reached 2–4 cm. There were 15 variants of the isoniazid-resistance spectrum; HSE and HSEKm dominated. The case histories of 53.9% of MDR TB patients showed isoniazid-resistant spectra of M. tuberculosis. Sputum conversion by the end of the 8th month of treatment was observed in 49.7% of patients with resistance to isoniazid, cavity closure – in 38.3% of such patients. We established that M. tuberculosis resistance to isoniazid was associated with severe clinical and radiological presentations; treatment efficacy in such patients was lower than that in drug-susceptible patients by 20–25%.

REFERENCES:
  1. Burmistrova I.A., Samoilova A.G., Glebov K.A. et al. The drug resistance spectrum of M. tuberculosis with sensitivity to rifampicin and resistance to isoniazid in pulmonary TB patients. Tuberculosis and Lung Diseases, 2018, vol. 96, no. 12, pp. 63–64. (In Russ.) DOI: 10.21292/2075-1230-2018-96-12-63-64.
  2. Vasilyeva I.A., Samoilova A.G., Ergeshov A.E. TB chemotherapy: problems and prospects. Annals of the Russian academy of medical sciences, 2012, no. 11, pp. 9–14. (In Russ.)
  3. Nechaeva O.B., Gordina A.V., Sterlikov S.A., Kucheryavaya D.A., Son I.M., Zaichenko N.M., Ponomarev S.B. The resources and the activities of TB organizations in the Russian Federation in 2016–2017 (statistical data). Moscow, RIO CNIIOIZ, 2018, 95 p. (In Russ.)
  4. Salina T.Yu., Morozova T.I. The prevalence of mutations in M. tuberculosis genes encoding resistance to isoniazid and rifampicin in TB patients of different age groups. Tuberculosis and Lung Diseases, 2019, vol. 97, no. 4, pp. 12–18. (In Russ.) DOI: 10.21292/2075-1230-2019-97-4-12-18.
  5. The WHO consolidated guidelines on drug-resistant tuberculosis treatment. Geneva, WHO, 2019, 99 p.
  6. Federal clinical recommendations on diagnosis and treatment of pulmonary TB with multi- and extensive drug resistance. The third edition. Moscow–Tver, Triada, 2015, 68 p. (In Russ.)
  7. Federal clinical recommendations on diagnosis and treatment of pulmonary TB. Moscow, New Terra, 2016, 52 p. (In Russ.)
  8. Zhang Y., Yew W.W. Mechanisms of drug resistance in Mycobacterium tuberculosis. The International Journal of Tuberculosis and Lung Disease, 2009, vol. 13, no. 1, pp. 1320–1330.
KEYWORDS:

TB, drug resistance, treatment, isoniazid, M. tuberculosis.

FOR CORRESPONDENCE:

Yaroslavl Oblast Clinical TB Hospital

43, Sobinov St., 150000, Yaroslavl, Russia

Andrey V. Zakharov, Doctor of Medical Sciences, Head of Pulmonary TB Department

Tel.: +7 (4852) 43-91-03

E-mail: Yrzahan@mail.ru

RADIOLOGICAL SEMIOTICS OF PULMONARY TB IN PATIENTS WITH END-STAGE KIDNEY DISEASE

Article 5.Page 46.
ARTICLE TITLE:

RADIOLOGICAL SEMIOTICS OF PULMONARY TB IN PATIENTS WITH END-STAGE KIDNEY DISEASE

DOI: 10.7868/S2587667820010057

AUTORS:

Gordeeva O.M., Karpina N.L., Amansakhedov R.B., Mikhailov S.G.

Central TB Research Institute, Moscow, Russia

DESCRIPTION OF ARTICLE:

Submitted as of 10.12.2019

The TB incidence rate in patients with end-stage chronic kidney disease (ESKD) exceeds the similar rate in the general population ten times. The absence of typical radiological semiotics hinders TB diagnostics in such patients. We analyzed the radiological data from 80 ESKD patients with newly detected changes in the lungs and/or the intoxication syndrome of unclear genesis. The investigation revealed TB in 61.25% of the patients: 40% had active TB, and 21.25% had residual post-TB changes in the lungs. Chronic non-tuberculous pulmonary diseases were diagnosed in 38.75% of the patients. We established low informativity of plain chest radiography compared to computed tomography (CT) scanning of the chest in ESKD patients. These methods allowed diagnosing infiltrative (23.75% vs. 48.75%) and focal (71.25% vs. 17.5%) changes in the lungs, which indicated the necessity to perform CT scanning for all ESKD patients with presumed TB. The detection of infiltrative and focal changes in the lungs or their combination witnessed a pulmonary disease, which required immediate diagnostics, but such changes were not pathognomonic for TB. The analysis of CT data allowed determining a number of radiological signs typical for active pulmonary TB in ESKD patients. It was essential for TB diagnostics in this category of immunocompromised individuals.

REFERENCES:
  1. Banaga Amin S.I., Siddiq Nihad K., Alsayed Randa T., Babiker R., Elmusharaf K. Prevalence and presentation of tuberculosis among hemodialysis patients in Khartoum, Sudan. Saudi J. Kidney Dis. Transpl., 2016, vol. 27, no. 5, pp. 992–996.
  2. Kane Y., Faye M., Lemrabott A.T., Keita A.I., Seck S.M., Cisse M.M., Diallo K., Ka E.F., Niang A., Diouf B. Relevance of the GeneXpert test for the diagnosis of TB in chronic hemodialysis patients in Casamance, South of Senegal. J. Kidney, 2016, vol. 2, p. 133. DOI: 10.4172/2472-1220.1000133
  3. Kayabasi H. The prevalence and the characteristics of tuberculosis patients undergoing chronic dialysis treatment: experience of a dialysis center in southeast Turkey. Renal failure, 2008, vol. 30, no. 5, pp. 513–519.
  4. National Tuberculosis Advisory Committee: Position statement on interferon-gamma release immunoassays in the detection of latent tuberculosis infection [Electronic resource]. Australian Government, Department of Health and Ageing. Mode of access: Available at http://www.health.gov.au/internet/main/publishing.nsf/Content/cdna-ntac-interferon.htm
  5. Rao T.M. Tuberculosis in haemodialysis patients: A single centre experience. Indian Journal of Nephrology, 2013, vol. 23, no. 5, pp. 340–345.
  6. Reis-Santos B., Gomes T., Lessa H.B., Leonor N.M.E. Tuberculosis prevalence in renal transplant recipients: systematic review and meta-analysis. J. Bras. Nefrol., 2013, vol. 35, no. 3, pp. 206–213. DOI: 10.5935/0101-2800.20130033
  7. Unsal A., Ahbap E., Basturk T., Koc Y., Sakaci T., Arar A.S., Kayabasi H., Sevinc M. Tuberculosis in dialysis patients: a nine-year retrospective analysis. J. Infect. Dev. Ctries., 2013, vol. 7, no. 3, pp. 208–213.
  8. Vartian C.V. Tuberculosis in dialysis patients: An old association revisited. Infectious Diseases in Clinical Practice, 1997, vol. 6, no. 4, pp. 247–249.
KEYWORDS:

TB diagnostics, end-stage kidney disease, computed tomography of the chest, radiological semiotics of TB.

FOR CORRESPONDENCE:

Central TB Research Institute

2, Yauzskaya alley, 107564, Moscow

Olga M. Gordeeva, Junior Researcher, Phthisiatrician

Tel.: +7 (499) 785-90-26

E-mail: hobbetxe@mail.ru

Natalia L. Karpina, Doctor of Medical Sciences, Phthisiatrician, Head of Centre for Diagnosis and Rehabilitation of Pulmonary Diseases, Deputy Director

Tel.: +7 (499) 785-90-26

E-mail: natalya-karpina@rambler.ru

Resulguly B. Amansakhedov, Senior Researcher, Candidate of Medical Sciences, Radiologist

Tel.: +7 (499) 780-49-56

E-mail: rasul.amansahedov@mail.ru

Stanislav G. Mikhailov, Radiologist

Tel.: +7 (916) 234-66-04

E-mail: docses@mail.ru

THE IMPACT OF ANTIRETROVIRAL THERAPY ON THE EFFECTIVENESS OF HIV/TB CO-INFECTION TREATMENT BASED ON THE LIPID SPECTRUM RATES

Article 6.Page 57.
ARTICLE TITLE:

THE IMPACT OF ANTIRETROVIRAL THERAPY ON THE EFFECTIVENESS OF HIV/TB CO-INFECTION TREATMENT BASED ON THE LIPID SPECTRUM RATES

DOI: 10.7868/S2587667820010069

AUTORS:

Makarov P.V.

Tver State Medical University, Tver, Russia

DESCRIPTION OF ARTICLE:

Submitted as of 10.12.2019

TB is one of the most common secondary diseases during late stage HIV infection; TB causes severe damages in different anatomical sites and is responsible for many lethal outcomes. According to the accepted standards, administration of antiretroviral therapy (ART) is indicated for all patients with HIV/TB co-infection. However, different obstacles may affect this option. For example, the intoxication syndrome development after ART commencement at the 4th stage of HIV is a frequent indication for ART discontinuation. It is necessary to develop simple criteria for predicting ART effectiveness in HIV/TB co-infected patients.

Aim: To improve treatment effectiveness in HIV/TB co-infected patients based on lipid exchange rates.

Materials and methods. We studied the lipid spectrum of the blood serum from patients with HIV/TB coinfection. Patients were divided in three groups. We studied cholesterol levels, some phospholipid fractions in the blood serum from 50 healthy individuals (control group), 50 HIV/TB patients on TB treatment without ART (group 1), 50 HIV/TB patients with preserved drug sensitivity on TB treatment with ART (group 2), 50 HIV/TB patients with multidrug resistance (MDR) on TB treatment with ART (group 3).

Results. ART decreased the level of cholesterol, which was a nutrient for M. tuberculosis. The lowest level of cholesterol was reached in MDR TB patients. Based on the study outcomes, we have developed a method for predicting ART effectiveness in HIV/TB patients: the numeric value of cholesterol-to-triglyceride ratio less than 5.0 is a marker of ART effectiveness (Patent no. 2 666 233 of 06.09.2018).

REFERENCES:
  1. Dolgova E.A., Alvarez Figueroa M.V., Lobasheva G.P. et al. Determination of resistance to rifampicin in HIV-infected TB patients with secondary diseases. Tuberculosis and Lung Diseases, 2014, no. 4, pp. 129–130. (In Russ.)
  2. Kaminskaya G.O., Abdullaev R.Yu. Tuberculosis and lipid exchange. Tuberculosis and Lung Diseases, 2016, no. 6, pp. 53–63. (In Russ.)
  3. Makarov V.K. Phospholipid spectrum of blood serum in diagnostic of different stages of combined hepatic viral-alcoholic damage. Biomed. Khim., 2004, vol. 50, no. 5, pp. 498–501. (In Russ.)
  4. Nechaeva O.B. The situation of TB and HIV-infection in Russia. Tuberculosis and Lung Diseases, 2014, no. 6, pp. 9–15. (In Russ.)
  5. Panteleev A.M. Drug-resistant TB in HIV-infected patients. In: Relevant problems and prospects of TB service in the Russian Federation. Proceeding of the 1st Congress of the National Association of Phthisiatricians. St. Petersburg, 2012, pp. 281–283. (In Russ.)
  6. Frolova O.P., Shchukina I.V., Frolov E.G. The analysis of mortality due to TB associated with HIV infection. Tuberculosis and Lung Diseases, 2014, no. 7, pp. 32–36. (In Russ.)
  7. Crain R.C. Phospholipid transfer proteins as probes of membrane structure and function. Subcell. Biochem.,1990, no. 16, pp. 45–67.
  8. Folch J., Lees M., Stanley G.H.G. A simple method for the isolation and purification of total lipids from animal tissues. J. Biol. Chem., 1957, no. 226, pp. 497–509.
  9. Marsh J.B., Weinstein P.B. Simple charring methods for determination of Lipids. J. Lip., 1966, no. 7, pp. 574–576.
  10. Martens G.W., Arikan M.C., Lee J. et al. Hypercholesterolemia impairs immunity to tuberculosis. Infection and Immunity, 2008, vol. 76, no. 8, pp. 3464–3472. 11. Tarchovskaya T.I. et al. Cholesterol extracted from skin surface as a discriminant of atherosclerosis. Bull. Exp. Med. Biol., 1992, no. 5, pp. 481–483.
KEYWORDS:

TB, HIV infection, antiretroviral therapy, triglycerides, cholesterol, lipids.

FOR CORRESPONDENCE:

Tver State Medical University

4, Sovetskaya St., 170100, Tver, Russia

Pavel V. Makarov, Assistant, Department of Infectious Diseases and Epidemiology

Tel.: +7 (904) 023-13-25

Е-mail: global-create@yandex.ru

THE HEMOSTASIS SYSTEM STATE AND MORPHOLOGICAL CHANGES IN THE PULMONARY MICROCIRCULATION IN TB PATIENTS WITH CONCOMITANT DIABETES MELLITUS DEPENDING ON THE SCOPE OF LUNG SURGERY

Article 7.Page 63.
ARTICLE TITLE:

THE HEMOSTASIS SYSTEM STATE AND MORPHOLOGICAL CHANGES IN THE PULMONARY MICROCIRCULATION IN TB PATIENTS WITH CONCOMITANT DIABETES MELLITUS DEPENDING ON THE SCOPE OF LUNG SURGERY

 DOI: 10.7868/S2587667820010070

AUTORS:

Serebryanaya B.A., Lepekha L.N., Abdullaev R.Yu., Chitorelidze G.V., Berezovsky Yu.S., Nikitin S.S., Bagirov M.A.

Central TB Research Institute, Moscow, Russia

DESCRIPTION OF ARTICLE:

Submitted as of 12.12.2019

The research is relevant due to the necessity to characterize the hypercoagulation syndrome with intravascular coagulation and assess morphological changes in the microcircular bed in the lungs of TB patients with concomitant diabetes mellitus (DM) after surgical intervention. Aim: To determine the variability of the hemostasis system indicators, the morphological peculiarities of the pulmonary microcirculation of TB/DM patients depending on the scope of lung surgery. Materials and methods. We analyzed the clinical and laboratory data of 89 TB/DM patients after different scope lung surgery. The patients were divided in 3 groups depending on the scope of lung surgery and compared by intraoperative blood loss. The patients of group 1 underwent lung segmental resection, group 2 – pneumonectomy, group 3 – lobectomy. The hypercoagulation syndrome course was determined by the coagulogram indicators, and the pulmonary microcirculatory bed was studied morphologically. Results. We demonstrated the general tendency in all studied groups – the markers of hypercoagulation started to increase 3–5 days after surgery. By day 20–22, we observed a decrease in the hypercoagulation syndrome markers; however, they still exceeded the baseline values. The most expressive changes in the hemostasis indicators typical for the hypercoagulation syndrome were observed in TB/DM patients after lobectomy. Conclusion. The obtained results can be used to develop anticoagulation therapy regimens.

The article was prepared under scientific research topic no. 0515-2019-0017 “The modern methods of surgical treatment of pulmonary TB with concomitant diabetes mellitus.”

REFERENCES:
  1. Barkagan Z.S., Momot A.P. The principles of diagnosis of haemostatic disorders. Moscow, 1999. (In Russ.)
  2. Barkagan Z.S., Momot A.P. Diagnosis and directly observed therapy of haemostatic disorders. Moscow, 2001. (In Russ.)
  3. Gilmanov A.Zh., Fazylyev M.M. Disseminated intravascular blood coagulation. Klin. Lab. Diagnostika, 2004, no. 4, pp. 25–32. (In Russ.)
  4. Elipashev A.A., Nikolsky V.O., Shprykov A.S. The predictive value of morphological signs of TB inflammation process in patients with restricted forms of drug resistant pulmonary TB. Arkhiv patologii, 2010, no. 4, pp. 40–43. (In Russ.) DOI:10.17116/patol201779413-17
  5. Erokhin V.V. The morphofunctional state of lung cells in TB inflammation. In: Cell biology of the lungs in health and pathology. Ed. by V.V. Erokhin, L.K. Romanova. Moscow, Medicine, 2000, pp. 422–448. (In Russ.) ISBN 5-225-02675-3
  6. Erokhin V.V., Gedymin L.E., Zemskova Z.S., Lepekha L.N., Parkhomenko Yu.G., Zyuzya Yu.R., Burtseva S.A., Dyukanova M. Ya., Fligil D.M. Pathoanatomical diagnosis of the main forms of TB (according to resection studies). Problems of Tuberculosis and Lung Diseases, 2008, vol. 85, no. 7–8, pp. 45–64. (In Russ.)
  7. Erokhin V.V., Zemskova Z.S. The modern concepts of TB inflammation. Problems of Tuberculosis, 2003, no. 3, pp. 11–21. (In Russ.)
  8. Erokhin V.V. The functional morphology of the lungs. Moscow, Medicine, 1987, 296 p. (In Russ.)
  9. Zhilin Yu.A., Kaminskaya G.O., Serebryanaya B.A., Shipileva N.M., Dmitrenko L.V. The assessment of hemocoagulation disorders in the post-operative period in pulmonary TB patients. The collected works of the Institute, 1997, vol. 21, pp. 110–111. (In Russ.)
  10. Zyuzya Yu.R., Lepekha L.N., Gedymin L.N. et al. Tissue and cell reactions in the lungs in drug resistant TB. Tuberculosis and Lung Diseases, 2004, no. 8, pp. 53–56. (In Russ.)
  11. Zyuzya Yu.R., Lepekha L.N., Gedymin L.N., Burtseva S.A., Erokhin V.V. On the question of morphological diagnosis of drug resistant pulmonary TB. Tuberculosis and Lung Diseases, 2006, no. 10, pp. 56–60. (In Russ.)
  12. Kaminskaya G.O., Serebryanaya B.A., Dmitrenko L.V., Zhilin Yu.N., Shipileva N.M. On pathogenesis of hemocoagulation complications in thoracic surgery. Problems of Tuberculosis, 1976, no. 6, pp. 48–53. (In Russ.)
  13. Kaminskaya G.O., Serebryanaya B.A., Komissarova O.G., Martynova E.V., Mishin V.Yu. Intravascular coagulation as a typical concomitant of acute pulmonary tuberculosis. Problems of Tuberculosis, 1997, no. 3, pp. 42–46. (In Russ.)
  14. Kaminskaya G.O., Martynova E.V., Serebryanaya B.A., Komissarova O.G. The fibrinolytic system in the hypercoagulation syndrome in patients with pulmonary tuberculosis. Problems of Tuberculosis and Lung Diseases, 2004, no. 3, pp. 51–54. (In Russ.)
  15. The clinical laboratory analytics. Ed. by V.V. Menshikov, vol. 3. Moscow, 2000. (In Russ.)
  16. Loshchilov V.G., Serebryanaya B.A., Kazakova L.V. Evaluation of the hemostasis system and detection of intravascular coagulation in phthisiosurgery patients in the modern conditions. Abstracts of the 11th Congress of phthisiatricians, 1992, p. 267. (In Russ.)
  17. Momot A.P., Sidor N.V. Possible involvement of factor XIII in forming a trend towards thrombosis in patients with various types of thrombophilia. Klin. Lab. Diagnostika, 2007, no. 2, pp. 45–47. (In Russ.)
  18. Kokturk N., Varol A., Kilic H., Ekim N. Quantitative D-Dimer levels in pulmonary thromboembolism and community acquired pneumonia. Eur. Respir. J., 2007, no. 30.
  19. Seyhan T.C., Cetinkaya E., Altin S. et al. Evaluation of d-dimer levels in in patients with active pulmonary tuberculosis and latent tuberculosis infection. Eur. Respir. J. 2006, no. 28, suppl. 50, p. 164s.
KEYWORDS:

pulmonary TB, diabetes mellitus, surgical intervention, hypercoagulation syndrome, microcircular bed.

FOR CORRESPONDENCE:

Central ТВ Research Institute

2, Yauzskaya alley, 107564, Moscow, Russia

Bella A. Serebryanaya, Candidate of Biological Sciences, Leading Researcher, Department of Pathomorphology, Cell Biology and Biochemistry

Tel.: +7 (917) 582-72-66

E-mail: bellaabramovna@yandex.ru

Larisa N. Lepekha, Doctor of Biological Sciences, Professor, Acting Principal Researcher, Head of Department of Pathomorphology, Cell Biology and Biochemistry

Tel.: +7 (495) 785-91-79

E-mail: lep3@yandex.ru

Rizvan Yu. Abdullaev, Doctor of Medical Sciences, Professor, Head of Biochemistry Laboratory, Department of Pathomorphology, Cell Biology and Biochemistry

Tel.: +7 (495) 748-30-23

E-mail: rizvan0403@yandex.ru

Georgy V. Chitorelidze, Postgraduate, Surgery Department

Tel.: +7 (964) 622-84-44

А CASE OF GENERALIZED TUBERCULOSIS IN A PATIENT WITH HIV INFECTION

Article 8.Page 74.
ARTICLE TITLE:

А CASE OF GENERALIZED TUBERCULOSIS IN A PATIENT WITH HIV INFECTION

DOI: 10.7868/S2587667820010082

AUTORS:

Bayke E.E., Rogova O.O., Arkhipova M.V.

Chita State Medical Academy, Chita, Russia

DESCRIPTION OF ARTICLE:

Submitted as of 06.12.2019

Clinical observation of a HIV-positive patient with developing generalized TB is represented. The patient did not receive antiretroviral therapy (ART). Despite advanced injury of the organs and the systems, adequate treatment resulted in a favourable outcome.

REFERENCES:
  1. Vasilyeva I.A., Belilovsky E.M., Borisov S.E., Sterlikov S.A., Sinitsyn M.V. Tuberculosis with concurrent HIV infection in the Russian Federation and the world. Tuberculosis and Lung Diseases, 2017, vol. 95, no. 9, pp. 8–18. (In Russ.)
  2. Nechaeva O.B. The epidemic situation of TB among people living with HIV in the Russian Federation. Tuberculosis and Lung Diseases, 2017, vol. 95, no. 3, pp. 13–19. (In Russ.)
  3. Panteleev A.M. Clinical understanding of the pathogenesis of TB generalization in HIV-infected patients. Tuberculosis and Lung Diseases, 2015, no. 2, pp. 26–31. (In Russ.)
  4. Shimao T. Speculation on reasons why co-infection of tuberculosis and HIV is rather rare in Japan. Kekkaku, 2014, vol. 89, nо. 2, pp. 57–60.
KEYWORDS:

tuberculosis, Mycobacterium tuberculosis, HIV infection, antiretroviral therapy.

FOR CORRESPONDENCE:

Chita State Medical Academy

39A, Gorky St., 672000, Chita, Russia

Evgeny E. Bayke, Candidate of Medical Sciences, Associate Professor, Head of Tuberculosis Department

Tel.: +7 (914) 485-11-71

E-mail: eugenij.bee@yandex.ru

Olga O. Rogova, a sixth-year student, Medical Faculty

Tel: +7 (914) 139-90-82

E-mail: rogova.olga.97@mail.ru

Maria V. Arkhipova, a sixth-year student, Medical Faculty

Tel: +7 (914) 495-50-62

THE PRINCIPLES FOR PREPARATION OF DIAGNOSTIC SAMPLES FOR MICROBIOLOGICAL DETECTION OF MYCOBACTERIA

Article 9.Page 79.
ARTICLE TITLE:

THE PRINCIPLES FOR PREPARATION OF DIAGNOSTIC SAMPLES FOR MICROBIOLOGICAL DETECTION OF MYCOBACTERIA

DOI: 10.7868/S2587667820010094

AUTORS:

Sevastyanova E.V., Larionova E.E., Andrievskaya I.Yu., Smirnova T.G.

Central TB Research Institute, Moscow, Russia

DESCRIPTION OF ARTICLE:

Submitted as of 18.12.2019

We have outlined the guiding principles, which underpin the preparation of diagnostic samples for microbiological detection of mycobacteria. We presented the basic provisions related to quality  ontrol during collection, storage or transportation of diagnostic samples, reception and registration by a laboratory.

REFERENCES:
  1. Golyshevskaya V.I., Shulgina M.B., Sevastyanova E.V., Akimkin B.G., Vanina G.M., Vakhrusheva D.V., Vishnevsky B.I., Vladimirsky M.A., Irtuganova O.A., Kravchenko M.A., Otten T.F., Popov S.A., Safonova S.G., Fedorova L.S. Cultural methods of TB diagnosis: an educational manual for the basic training course for bacteriologists of TB institutions. Ed. by V.V. Erokhin, Moscow-Tver, Triada, 2008, 208 p. (In Russ.)
  2. GOST R ISO 15189-2015 Medical laboratories. The detailed requirements for quality and competence. The national standard of the Russian Federation. (In Russ.)
  3. On improvement of TB control measures in the Russian Federation. Edict no. 109 by RF MoH as of 21.03.2003. Annex no. 11. The instruction for the unified methods of microbiological studies for detection, diagnosis and treatment of TB. (In Russ.)
  4. Chernousova L.N., Sevastyanova E.V., Larionova E.E., Smirnova T.G., Andreevskaya S.N., Popov S.A., Zhuravlev V.Yu., Puzanov V.A., Maryandyshev A.O., Vakhrusheva D.V., Kravchenko M.A., Safonova S.G., Vasilyeva I.A., Ergeshov A.E. The federal clinical recommendations on organization and implementation of microbiological and molecular genetic diagnosis of TB. ROF, Moscow, 2015, 35 p. (In Russ.)
  5. European Centre for Disease Prevention and Control. Handbook on tuberculosis laboratory diagnostic methods in the European Union. ECDC, Stockholm, 2016, 111 p. ISBN 978-92-9193-739-4 DOI: 10.2900/216384
  6. Guidance. Tuberculosis (TB) screening and early detection methods, for professionals working with atrisk populations in the UK, 2018, https://www.gov.uk/guidance/tuberculosis-screening
  7. Hadad D.J., David A.P., Brum D.L., Nogueira L.R., Sales C.M.M., Fregona G. Metodologia para coleta de escarro espontâneo para confirmação microbiológica do diagnóstico de tuberculose pulmonar, doença pulmonar por micobactérias não tuberculosis ou para controle de tratamento desses agravos em ambientes ambulatorial e hospitalar. J. Infect. Control, 2014, vol. 3, no. 1, pp. 1–30.
  8. Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância. Manual Nacional de vigilância laboratorial da Tuberculose e outras micobactérias, Brasília, Ministério da Saúde, 2008, 459 p.
  9. Oblitas F.Y.M., Loncharich N., Salazar M.E., David H.M.L., Silva I., Velásquez D. Nursing’s role in tuberculosis control a discussion from the perspective of equity. Rev. Latino-Am. Enfermagem, 2010, vol. 18, no. 1, pp. 130–138.
  10. Pinto L.M., Udwadia Z.F. Xpert MTB/RIF and pulmonary tuberculosis time to delve deeper? Thorax, 2013, no. 68, pp. 987–988.
  11. WHO European Region. Algorithm for laboratory diagnosis and treatment-monitoring of pulmonary tuberculosis and drug-resistant tuberculosis using stateof- the-art rapid molecular diagnostic technologies. World Health Organization, 2017, 29 p. http://www.euro.who.int/__data/assets/pdf_file/0006/333960/ELIAlgorithm.pdf
KEYWORDS:

mycobacteria, diagnostic samples.

FOR CORRESPONDENCE:

Central TB Research Institute

2, Yauzskaya alley, 107564, Moscow, Russia

Elina V. Sevastyanova, Doctor of Biological Sciences, Leading Researcher, Microbiology Department

Tel.: +7 (499) 785-90-91

Е-mail: elinasev@yandex.ru

Elena E. Larionova, Candidate of Biological Sciences, Senior Researcher, Microbiology Department

Tel.: +7 (499) 785-90-91

E-mail: larionova_lena@mail.ru

Irina Yu. Andrievskaya, Researcher, Microbiology Department

Tel.: +7 (499) 785-90-91

Е-mail: andrievskaya.iri@mail.ru

Tatiana G. Smirnova, Candidate of Medical Sciences, Senior Researcher, Microbiology Department

Tel.: +7 (499) 785-90-91

Е-mail: s_tatka@mail.ru