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#2,(7),2019.

CTRI BULLETIN №2 (7) 2019

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Chief Editor: Ergeshov A.E.
Year of foundation: 2017
ISSN (Print): Browse
Publisher site: http://critub.ru
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CONTENTS

1)

Сontributions of a guinea pig model to understanding the pathogenesis of tuberculosis

David N. McMurray

7 READ MORE
2)

Increasing expression of multi-drug resistance genes Mdr1a/b in the lung cells of mice infected with M. tuberculosis

Erokhina M.V., Lepekha L.N., Rybalkina E.Yu., Nikonenko B.V., Bocharova I.V., Ergeshov A.E.

16 READ MORE
3)

Pulmonary TB with concomitant mycobacteriosis in patients with late-stage HIV-infection

Mishin V.Yu., Mishina A.V., Ergeshov A.E., Romanov V.V., Sobkin A.L.

26 READ MORE
4)

The dynamics of tobacco consumption prevalence under the national tobacco control policy in the Russian Federation

Antonov N.S., Sakharova G.M., Peredelskaya M.Yu., Rusakova L.I.

35 READ MORE
5)

The destructive effect of first-line TB drugs on the membrane

Ryasensky D.S., Aseev A.V., Elgali A.I.

45 READ MORE
6)

Efficacy of systemic enzymotherapy in the complex treatment of destructive infiltrative pulmonary TB

Kampos E.D., Shovkun L.A.

50 READ MORE
7)

Adverse reactions to TB treatment in reproductive-age women

Kayukova S.I., Donnikov A.E., Romanov V.V., Lulueva Zh.S., Bagdasaryan T.R., Ergeshov A.E.

59 READ MORE
8)

Endobronchial valve blockage in management of destructive pulmonary TB: pulmonary ventilation in focus

Chushkin M.I., Popova L.A., Shergina E.A., Shabalina I.Yu., Karpina N.L.

65 READ MORE
9)

Clinical and laboratory indicators of different types of hypersensitivity pneumonitis

Makaryants N.N., Lepekha L.N., Amansakhedov R.B., Erokhina M.V., Evgushchenko G.V., Sivokozov I.V., Shmelev E.I.

73 READ MORE
10)

Microscopic detection of mycobacteria by Ziehl-Neelsen staining technique. Part 2. Sputum Smear microscopy

Sevastyanova E.V., Larionova E.E., Andrievskaya I.Yu.

81 READ MORE

Contributions of a guinea pig model to understanding the pathogenesis of tuberculosis

Article 1.Page 7.
ARTICLE TITLE:

Contributions of a guinea pig model to understanding the pathogenesis of tuberculosis

DOI: 10.7868/S2587667819020018

AUTORS:

David N. McMurray

College of Medicine Texas A&M University Health Science Center, College Station, Texas, USA

DESCRIPTION OF ARTICLE:

Submitted as of 25.02.2019

Experimental animal models of tuberculosis (TB) have played a major role in advancing our understanding of the host-pathogen relationship and have provided essential pre-clinical data on the efficacy of new TB drugs and vaccines. For more than 50 years, the guinea pig infected with very small numbers of virulent mycobacteria by the respiratory route has been recognized as a highly biologically relevant model of human pulmonary TB. In this review, the development and application of a guinea pig model to studies of TB pathogenesis and vaccine-induced resistance in the author’s laboratory is discussed. The characteristics of a “rational” TB model and the features of a respiratory exposure system that implants a few tubercle bacilli as droplet nuclei directly into the alveolar spaces are reviewed. The development of immunological tools, including recombinant guinea pig cytokines and antibodies to those cytokines, has facilitated the evaluation of the role of those host proteins in ex vivo cultures of infected macrophages from various anatomical sources. Laser capture microdissection has revealed the cytokine profiles of primary and secondary granulomas in the lungs of naïve and vaccinated guinea pigs exposed to virulent mycobacteria. Chronic, moderate protein deficiency exerted a deleterious effect on host resistance and blunted the protective effect of BCG vaccine, a finding that has relevance for vaccination of malnourished populations.  Tumor necrosis factor-alpha (TNF-α) was found to have both positive and negative effects on the host-pathogen interaction. Guinea pig neutrophils were observed to promote the control of virulent mycobacteria by macrophages that ingested apoptotic, infected neutrophils. Taken together, more than 5 decades of research with this model have revealed several novel features of tuberculosis pathogenesis. Most importantly, the availability of the sequenced and partially-annotated guinea pig genome and the development of additional reagents and methodologies have positioned the guinea pig model to continue to make critical contributions to the understanding of TB pathogenesis in the future.

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KEYWORDS:

tuberculosis, animal models, guinea pig, respiratory exposure, vaccination, cytokines.

FOR CORRESPONDENCE:

College of Medicine, Texas A&M University Health Science Center

College Station, TX 77843-1114, USA

David N. McMurray, PhD, Regents Professor Emeritus, Department of Microbial Pathogenesis & Immunology

Tel.: + 979-436-0837

E-mail: mcmurray@medicine.tamhsc.edu

Increasing expression of multi-drug resistance genes Mdr1a/b in the lung cells of mice infected with m. Tuberculosis*

Article 2.Page 16.
ARTICLE TITLE:

Increasing expression of multi-drug resistance genes Mdr1a/b in the lung cells of mice infected with m. Tuberculosis*

DOI: 10.7868/S258766781902002X

AUTORS:

Erokhina M.V.1,2, Lepekha L.N.1, Rybalkina E.Yu.1,3, Nikonenko B.V.1, Bocharova I.V.1, Ergeshov A.E.1

1Central TB Research Institute, Moscow, Russia 

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

3N.N. Blokhin National Medical Research Center of Oncology, Moscow, Russia

DESCRIPTION OF ARTICLE:

Submitted as of: 4.02.2019

The investigation of the lung somatic cell resistance to antibiotics, TB drugs in particular, is in the initial stage, opening a new scientific field for TB researchers. The mechanisms of multi-drug resistance of the macroorganism’s somatic cells are realized via special transporter proteins, which transport chemicals (drugs) away from the cell. P-glycoprotein (Pgp) is the most universal of all these proteins, encoded by MDR1 gene in human cells and Mdr1a or Mdr1b gene in murine cells. The objective of our study was to evaluate the influence of progressive TB inflammation on expression of Mdr1a/b genes in the lung cells of mice infected with M. tuberculosis (MTB). Histological description of TB inflammation performed 21, 45 and 90 days after infecting the Balb/c-line mice with MTB showed TB progression. The comparison of the median values demonstrated that during development of TB inflammation expression of Mdr1a genes increased 2.8 times on the 21st day, and 3.5 times – on the 90th day of the experiment. The expression of Mdr1b genes almost twice increased by the 45th day of the experiment as compared to the control group and remained on the same level during the further progression of TB. Thus, we established that the expression of Mdr1a and Mdr1b genes in the lung cells reliably increased during TB progression in the untreated mice. The obtained data witnessed that the factors of TB inflammation development played the role of the gene expression inducer. It is necessary to continue researches in this new scientific field. We suggest that the induction of MDR1 gene expression and the increase of Pgp activity in the lung cells under continuous administration of some TB drugs might be one of the causes of low chemotherapy effectiveness in patients with progressive destructive TB.

*The research was performed under research topic no. 0515-2019-0015 “The development of mycobacteria and somatic cells drug resistance to TB drugs” and supported by the Russian Science Foundation grant no. 14-50-00029.

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KEYWORDS:

mice, infected with M. tuberculosis, drug resistance of the macroorganism’s somatic cells, Pgp, Mdr1a and Mdr1b genes.

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, Candidate of Biological Sciences, Docent, Cell Biology and Histology Department, Biology Faculty, M.V. Lomonosov Moscow State University; Senior Researcher, Department of Pathomorphology, Cell Biology and Biochemistry, Central TB Research Institute

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

E-mail: masha.erokhina@gmail.com​

Pulmonary tb with concomitant mycobacteriosis in patients with late-stage hiv infection*

Article 3.Page 26.
ARTICLE TITLE:

Pulmonary tb with concomitant mycobacteriosis in patients with late-stage hiv infection*

DOI: 10.7868/S2587667819020031

AUTORS:

Mishin V.Yu.1, 2, 3, Mishina A.V.1, Ergeshov A.E.2, Romanov V.V.2, Sobkin A.L.3

1 A.I. Evdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia

2Central TB Research Institute, Moscow, Russia

3Professor G.A. Zakharyin TB Clinical Hospital no. 3, Moscow, Russia

DESCRIPTION OF ARTICLE:

Submitted as of: 21.02.2019

We studied social status, clinical and radiological manifestations, microbiological and immunological peculiarities in 26 late-stage HIV infection patients with pulmonary TB and concomitant pulmonary mycobacteriosis. They all had CD4+ lymphocyte counts less than 30 cells/μL of blood, did not receive antiretroviral therapy (ART), and excreted both M. tuberculosis and nontuberculous mycobacteria (NTM). We found M. avium complex in 84.6%, M. kansasii – in 7.7%, M.  fortuitum – in 3.8% and M. xenopi – in 3.8% of the patients. The disease manifested 6-9 years after diagnosing HIV infection; it had pronounced intoxication syndrome, bronchopulmonary and extrapulmonary presentations and was accompanied by other opportunistic infections. Radiological studies revealed dissemination with predominant localization in the middle and lower lung departments, small infiltrates with cavities, and injury of interlobar and visceral pleura. We proposed a diagnostic algorithm to detect disseminated pulmonary TB, pulmonary mycobacterioses, and other opportunistic infections in immunosuppressed patients with late-stage HIV infection.

*The research was conducted under scientific theme 0515-2019-0015 “Modern approaches to diagnosis, epidemiology and treatment of drug resistant pulmonary TB, including TB associated with HIV infection or diabetes mellitus”.

REFERENCES:
  1. HIV infection and AIDS. Ed. by V.V. Pokrovsky. The 4th edition, revised and amended. Moscow, GEOTAR-Media, 2019, 156 p. (In Russ.)
  2. Zyuzya Yu.R., Parkhomenko Yu.G., Zimina V.N., Alvarez Figueroa M.V. Morphological verification of HIV-associated mycobacteriosis caused by nontuberculous mycobacteria – аvium complex. Klinicheskaya i eksperimentalnaya morfologia, 2015, vol. 3, no. 15, pp. 11-21. (In Russ.)
  3. Mikhailovsky A.M., Churkin S.A., Pashkova N.A., Lepekha L.N. Occurrence and morphological traits of nontuberculous mycobacteriosis in patients with late-stage HIV infection (according to the data from Orenburgskaya oblast). Tuberculosis and Lung Diseases, 2016, vol. 94, no. 12, pp. 57-61. (In Russ.)
  4. Mishin V.Yu. TB and other mycobacterial infections. In: Pulmonology. National Guidelines. The 3rd edition, revised and amended. Ed. by A.G. Chuchalin. Moscow, GEOTAR-Media, 2018, Ch. 9, pp. 226-235. (In Russ.)
  5. Mishin V.Yu., Mishina A.V., Ergeshov A.E., Romanov V.V., Sobkin A.L. Dispensary follow-up and medical rehabilitation of TB patients with HIV co-infection. VICh infektsia i immunosuppressia, 2018, vol. 10, no. 3, pp. 81-90. (In Russ.)
  6. Mishin V.Yu., Ergeshov A.E., Mishina A.V. Diagnosis and differential diagnosis of disseminated pulmonary diseases in HIV patients (Review). CONSILIUM medicum, 2018, vol. 20, no. 3, pp. 8-13. (In Russ.)
  7. Panteleev A.M., Dracheva M.S., Nikulina O.V., Sokolova O.S., Zonova A.V. Clinical and laboratory manifestations of mycobacterioses in HIV patients. Jurnal infektologii, 2016, vol. 8, no. 3, pp. 40-45. (In Russ.)
  8. Panteleev A.M., Nikulina O.V., Khristusev A.S., Dracheva M.S., Sokolova O.S., Zonova A.V. Differential diagnosis of TB and mycobacteriosis in HIV-infected patients. Tuberculosis and Lung Diseases, 2017, vol. 95, no. 10, pp. 48-52. (In Russ.)
  9. TB/HIV in the Russian Federation. Epidemiology, clinical features and treatment outcomes. Moscow, RIO CNIIOIZ, 2018, 67 p. (In Russ.)
  10. Federal clinical recommendations on diagnosis and treatment of TB in HIV patients. Moscow-Tver, Triada, 2014, 56 p. (In Russ.)
  11. Shulgina M.V., Narvskaya O.V., Mokrousov I.V., Vasilyeva I.A. Pathogenic and opportunistic mycobacteria. Moscow, NEW TERRA, 2018, 104 p. (In Russ.)
  12. Ergeshov A.E., Shmelev E.I., Kovalevskaya M.N., Karpina N.L., Larionova E.E., Chernousova L.N. Mycobacterioses in pulmonology and phthisiology practice. Tuberculosis and Lung Diseases, 2016, vol. 94, no. 9, pp. 39-43. (In Russ.)
  13. British Thoracic Society (BTS) guidelines for the management of non-tuberculous micobacterial pulmonary disease (NTM-PD). Thorax. 2017. doi:10.1136/thoraxjni-2017-210927.
  14. Bartlett G., Gallant J., Pham P. Medical management of HIV infection (translated from English). Moscow, R. Valenta, 2012, 528 p. (In Russ.)
  15. Daley C.L., Griffith D.E. 36 nontuberculous mycobacterial infections. In Murray and Nadel’s. Textbook of Respiratory Medicine, The 6th Elsevier Inc., 2016, pp. 629-645.
  16. EACS European AIDS Clinical Society. Version 9.0, October 2017 (http://guidelines@eacsociety.org).
  17. Global tuberculosis report 2017 (http://www.who.int/tb/publications/global_report/en/), WHO, 2017, 147 p.
  18. Griffith D.E., Aksamit T., Brown-Elliott B.A., Catanzaro A., Daley C., Gordin F., Holland S.M., Horsburgh R., Huitt G., Iademarco M.F., Iseman M., Olivier K., Ruoss S., von Reyn C.F., Wallace RJ. Jr., Winthrop K. ATS Mycobacterial Diseases Subcommittee, American Thoracic Society, Infectious Disease Society of America. 2007. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. J. Respir. Crit. Care Med., no. 175, pp. 367-416. doi:10.1164/rccm.200604-571ST.
  19. Hedjazi A., Hosseini M., Hoseinzadeh A. Lymph node co-infection of mycobacterium avium complex and cytomegalovirus in an acquired immunodeficiency syndrome patient. Dis. Rep., 2013, vol. 22, no. 5(1):e2. doi: 10.4081/idr.2013.e2. eCollection 2013.
  20. Henkle E., Winthrop K.L. Nontuberculous mycobacteria infections in immunosuppressed hosts. Chest. Med., 2015, vol.36, no. 1, pp. 91-99.
  21. Tortoli E. Microbiological features and clinical relevance of new species of the Genus Mycobacterium. Clin. Microbiology Reviews, 2014, vol.27, no. 4, pp.727-752.
KEYWORDS:

TB, mycobacteriosis, HIV infection, opportunistic infection, immunodiagnosis, microbiological diagnosis, radiological diagnosis, diagnostic efficiency.

FOR CORRESPONDENCE:

A.I. Evdokimov Moscow State University of Medicine and Dentistry

20/1, Delegatskaya St., 127473, Moscow, Russia

Central TB Research Institute

2, Yauzskaya alley, 107564, Moscow; Russia

Vladimir Yu. Mishin, Doctor of Medical Sciences, Professor, Head of Phthisiology and Pulmonology Department, Principal Researcher of the Central TB Research Institute

Tel.: +7 (910) 436-56-88

E-mail: mishin.vy@mail.ru

The dynamics of tobacco consumption prevalence under the national tobacco control policy in the russian federation*

Article 4.Page 35.
ARTICLE TITLE:

The dynamics of tobacco consumption prevalence under the national tobacco control policy in the russian federation*

DOI: 10.7868/S2587667819020043

AUTORS:

Antonov N.S.1,2, Sakharova G.M.1,2, Peredelskaya M.Yu.3, Rusakova L.I.1

1Central TB Research Institute, Moscow, Russia

2Central Research Institute of Organization and Informatization of Health, Moscow, Russia  

3City Clinical Hospital no. 52, Moscow, Russia

DESCRIPTION OF ARTICLE:

Submitted as of 12.02.2019

Objective: To study effects of the national tobacco control policy on the prevalence of tobacco consumption and passive smoking among different groups of the population in the Russian Federation in 2004-2016.

Materials and methods. The research was based on the data from the national representative studies: the Global Youth Tobacco Survey (GYTS) involving young people aged 13-15 conducted in 2004 and 2015, and the Global Adult Tobacco Survey (GATS) conducted in 2009 and 2016. The both studies used the international validated questionnaires, which included questions about the main measures of the WHO Framework Convention on Tobacco Control (WHO FCTC), implemented through Federal Law no. 15-FZ on Protecting the Health of Citizens from the Effects of Second-hand Tobacco Smoke and the Consequences of Tobacco Consumption, as well as other legislative acts under the national tobacco control policy.

Results. Due to the national tobacco control policy, the prevalence of tobacco consumption decreased among adults from 39.4% in 2009 to 30.9% in 2016, and among young people aged 13-15 – from 27.3% in 2004 to 15.1% in 2015. The similar dynamics was observed for passive smoking, which decreased among teenagers from 77.9% in 2004 to 35.0% in 2015. As for adults, essential decrease of passive smoking was observed in all public indoor areas. For instance, in workplaces the relative decline was 33.4%, in dwelling houses – 37.3%.

Conclusion. The implementation of the national tobacco control policy, after Russia joined the WHO FCTC in 2008, has resulted in essential decrease in the prevalence of tobacco consumption and passive smoking among the whole population of the Russian Federation.

*The research was conducted under scientific theme no. 0515-2019-0020 “Modern approaches to diagnosis, epidemiology and management of drug resistant pulmonary TB, including HIV-associated or diabetes mellitus associated TB”.

REFERENCES:
  1. The Global Action Plan for the Prevention and Control of Noncommunicable Diseases 2013-2020. WHO, 2013, 107 p. (www.who.int/ncd)
  2. The Bulletin of the World Health Organization 2017. The world’s top 10 causes of deaths. WHO, 2017. http://www.who.int/mediacentre/factsheets/fs310/ru/ (In Russ.)
  3. The concept of the national tobacco control policy implementation in 2010-2015. The Russian Federation Government order no. 1563-r of 23.09.2010. (In Russ.) https://rg.ru/2011/02/08/antitabak-site-dok.html
  4. The WHO Framework Convention on Tobacco Control. WHO, Geneva, 2003 (updated in 2004 and 2005). www.who.int/publications
  5. Sakharova G.M., Antonov N.S., Salagai O.O. Tobacco control: a complex approach at country level in the Russia Federation. WHO, 2017, p. 48. http://www.euro.who.int/__data/assets/pdf_file/0010/346699/WHO_Tobacco-control_a-comprehensive-approach-at-country-level-in-the-Russian-Federation_RUS.pdf?ua=1
  6. Sakharova G.M., Antonov N.S., Donitova V.V. The global tobacco survey among young people aged 13-15. Medicina, 2016, no. 4, pp. 1-12. (In Russ.)
  7. Sakharova G.M., Antonov N.S., Salagai O.O., Donitova V.V. The global tobacco survey among young people aged 13-15 in the Russian Federation: the comparison of trends 2004 and 2015. Pulmonologia, 2017, vol. 27, no. 2, pp. 179–186. (In Russ.)
  8. Sakharova G.M., Antonov N.S., Salagai O.O. The monitoring of tobacco consumption prevalence in the Russian Federation: The Global Adult Tobacco Survey 2009 and 2016. Medicina, 2017, no. 2, pp. 64-72. (In Russ.)
  9. Sakharova G.M., Antonov N.S., Salagai O.O. The Global Adult Tobacco Survey in the Russian Federation: GATS 2009 and GATS 2016. Narkologia, 2017, vol. 16, no. 7, pp. 8-12. (In Russ.)
  10. Federal Law no. 15-FZ of 23.02.2013 On Protecting the Health of Citizens from the Effects of Second-hand Tobacco Smoke and the Consequences of Tobacco Consumption. (In Russ.) http://www.consultant.ru/document/cons_doc_LAW_142515/
  11. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet, 2016, vol. 388, no. 10053, pp. 1659-1724.
KEYWORDS:

Keywords: tobacco, prevalence of tobacco consumption, tobacco control policy, youth   tobacco survey, adult tobacco survey.

FOR CORRESPONDENCE:

Central TB Research Institute

2, Yauzskaya alley, 107564, Moscow, Russia

Central Research Institute of Organization and Informatization of Health

11, Dobrolyubova St., 127254, Moscow, Russia

Nikolai S. Antonov, Doctor of Medical Sciences, Professor, Leading Researcher, Central TB Research Institute; Principal Researcher, Central Research Institute of Organization and Informatization of Health

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

Е-mail: pulmomail@gmail.com

 

The destructive effect of first-line tb drugs on the membrane

Article 5.Page 45.
ARTICLE TITLE:

The destructive effect of first-line tb drugs on the membrane

DOI: 10.7868/S2587667819020055

AUTORS:

Ryasensky D.S., Aseev A.V., Elgali A.I.

 Tver State Medical University, Tver, Russia

DESCRIPTION OF ARTICLE:

Submitted as of 24.12.2018

First-line TB drugs have a pronounced toxic effect. The changes in the structural and functional state of the peripheral blood mononuclears’ membranes at the end of the intensive phase of etiotropic treatment may serve as an important marker of the changes in immunological reactions of TB patients. We studied 184 patients with focal or infiltrative pulmonary TB on inpatient treatment at Tver Clinical TB Dispensary. Before and after the intensive phase of TB treatment we determined the following phospholipid fractions in the patients’ blood: total lysophospholipids, sphingomyelin, phosphatidylinositol, phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine. We established that first-line TB drugs contributed to disorganization of lipid membranes of immunocompetent cells, accumulation of membrane-destructive lysophospholipids in mononuclear leukocytes, and simultaneously reduced levels of phosphatidylcholine.

REFERENCES:
  1. Berezkina V.G. The quantitative analysis using chromatography methods. Ed. by V.G. Berezkina. Moscow, 1990, 238 p. (In Russ.)
  2. Eliseeva I.I., Kurysheva S.V., Egorova I.I. Moscow, Prospekt, 2015, 448 p. (In Russ.)
  3. Kargapolov A.V. The analysis of lipid composition of mitochondrial and endoplasmic membranes based on horizontal flow chromatography. Biokhimia, 1981, no. 4, pp. 691-698. (In Russ.)
  4. Knoring B.E. Clinical immunology. In: Guidelines on pulmonary and extrapulmonary TB management. Ed. by Yu.N. Levashev, Yu.M. Repin, St. Petersburg, 2006, pp. 115-136. (In Russ.)
  5. Knoring B.E., Freidlin I.S., Simbirtsev A.S. The character of specific immune response and cytokine production by blood mononuclears in patients with different forms of pulmonary TB. Medicinskaya immunologia, 2001, vol. 3, no. 1, pp. 61-68. (In Russ.)
  6. Mordyk A.V., Plekhanova M.A., Patsula Yu.I., Zhokiptseva S.I., Soldanota I.A., Glinskikh O.S., Tsygankov E.A. The evaluation of specific cell-mediated immunity in children and adolescents with TB. Vestnik sovremennoi klinicheskoi mediciny, 2010, no. 4, pp. 60-64. (In Russ.)
  7. Pinegin B.V., Stakhanov V.A., Arshinova S.S. The role of immunomodulators in treatment of pulmonary TB. Lechashchy vrach, 2001, no. 8, pp. 21-26. (In Russ.)
  8. Ryasensky D.S., Makarov V.K. The application of computer programmes for densitometry of lipid composition of blood. Farmacia, 2008, no. 1, pp. 5-7. (In Russ.)
  9. Khasanova R.R., Voronkova O.V., Urazova O.I. The role of cytokines in the modulation of subpopulational composition of blood lymphocytes in pulmonary TB patients. Problems of Tuberculosis and Lung Diseases, 2008, no. 3, pp. 31-35. (In Russ.)
KEYWORDS:

mononuclears, cell membranes, phospholipid spectrum, first-line TB drugs, lysophospholipids.

FOR CORRESPONDENCE:

Tver State Medical University

4, Sovetskaya St., 170100, Tver, Russia

Dmitry S. Ryasensky, Candidate of Medical Sciences, Docent, Phthisiology Department

Tel: +7 (920) 692-73-64

E-mail: meddim3@mail.ru

 

Efficacy of systemic enzymotherapy in the complex treatment of destructive infiltrative pulmonary tb

Article 6.Page 50.
ARTICLE TITLE:

Efficacy of systemic enzymotherapy in the complex treatment of destructive infiltrative pulmonary tb

DOI: 10.7868/S2587667819020067

AUTORS:

Kampos E.D., Shovkun L.A.

Rostov State Medical University, Rostov-on-Don, Russia

DESCRIPTION OF ARTICLE:

Submitted as of 23.01.2019

The purpose of this study was to evaluate clinical efficacy of wobenzym in the complex treatment of destructive infiltrative pulmonary TB and occurrence of wobenzym-induced toxic reactions.

Materials and methods: We studied 60 patients with destructive infiltrative pulmonary TB sensitive to TB drugs. They were divided in two groups. The main group received wobenzym (one tablet twice a day) plus TB drugs. The control group received standard TB treatment. All the patients underwent clinical and laboratory examinations, as well as studies of immune and cytokine statuses: the immunoregulatory index, levels of circulating immune complexes (CICs), the phagocytosis stimulation coefficient, levels of interleukin-2 (IL-2), IL-4, IL-6, interferon gamma (IFNγ), tumor necrosis factor-α (TNF-α), free radical oxidation. Control studies were performed after 4 months.

Results. The comparative analysis of treatment efficacy revealed that positive dynamics of clinical symptoms (general weakness, fever, cough, expectoration, chest pain, hemoptysis), reduced intensity of infiltration, cavity closure, sputum negativation were more pronounced in the main group versus the control. Administration of wobenzym in the complex treatment resulted in more significant improvement of immune and cytokine statuses and free radical oxidation, as well as decreased occurrence of hepatotoxic reactions to TB drugs, which allowed uninterrupted treatment.

Conclusion. Administration of systemic enzymotherapy as a pathogenetic therapy in the complex treatment of destructive infiltrative pulmonary TB demonstrated essential positive dynamics of clinical and laboratory signs, better resolution of infiltrates, cavity closure, sputum negativation, decreased occurrence and lower severity of toxic reactions, which allowed uninterrupted treatment.

REFERENCES:
  1. Mazurov V.I., Lila A.M., Stvolov S.B., Kimko N.N. Immunological aspects of systemic enzymotherapy in some visceral diseases. Cytokiny i vospalenie, 2002, vol. 2, no. 2, pp. 169-170. (In Russ.)
  2. Knorring G.Yu. The cytokine network as a target of systemic enzymotherapy. Cytokiny i vospalenie, 2005, no. 4, pp. 32-44. (In Russ.)
  3. Mazurov V.I. Systemic enzymotherapy. The modern approaches and perspectives. In: Mazurov V.I., Loza A.M., Aleshin Yu.N. et al. St. Petersburg, Piter, 1999, 224 p. (In Russ.)
  4. Annenkova G.A., Kleikov N.I., Martynova L.P., Puzanov V.A. About possible application of natural lipases and esterases for inhibition of Mycobacterium tuberculosis. Problems of Tuberculosis and Lung Diseases, 2004, no. 6, pp. 52-56. (In Russ.)
  5. Patent no. 2323739 of the Russian Federation. A method of treatment of pulmonary TB. Shovkun L.A., Romantseva N.E., Sarycheva A.V., Kampos E.D. – no. 2007103953/14, application of 01.02.2007, published on 10.05.2008, bulletin no. 13. (In Russ.)
  6. Patent no. 2491089 of the Russian Federation. A method of treatment of tuberculous exudative pleurisy. Shovkun L.A., Volodko N.A., Konstantinova A.V., Romantseva N.E., Kampos E.D. – no. 2012126218/15, application of 22.06.2012, published on 27.08.2013, bullerin no. 24. (In Russ.)
  7. Patent no. 2526121 of the Russian Federation. A method of treatment of pulmonary TB with concomitant non-specific bronchitis. Shovkun L.A., Romantseva N.E., Kharseeva G.G., Kampos E.D. – no. 2013133075/15, application of 16.07.2013, published on 20.08.2014, bulletin no. 23. (In Russ.)
  8. Patent no. 2611391 of the Russian Federation. A method of treatment of pulmonary TB. Shovkun L.A., Kampos E.D., Konstantinova A.V., Volodko N.A., Franchuk I.M. – no. 2015142956, application of 08.10.2015, published on 21.02.2017, bulletin no. 6. (In Russ.)
  9. Patent no. 2621875 of the Russian Federation. A method of treatment of pulmonary TB. Shovkun L.A., Aksenova V.A., Kampos E.D., Kharseeva G.G., Konstantinova A.V., Volodko N.A., Franchuk I.M. – no. 2016118450, application of 11.05.2016, published on 07.06.2017, bullerin no. 16. (In Russ.)
  10. Sizyakina L.P. Systemic enzymotherapy in treatment of allergic and immune-mediated diseases. St. Petersburg, Intermedika, 2006, 360 p. (In Russ.)
  11. Shovkun L.A., Aksenova V.A., Romantseva N.E. New trends in pathogenetic therapy of pulmonary TB. Rostov-on-Don, RostGMU, 2007, 114 p. (In Russ.)
  12. Shovkun L.A., Sizyakina L.P., Aksenova V.A., Romantseva N.E. Systemic enzymotherapy in TB treatment. Rostov-on-Don, RostGMU, 2009, 123 p. (In Russ.)
KEYWORDS:

infiltrative pulmonary TB, pathogenetic therapy, systemic enzymotherapy.

FOR CORRESPONDENCE:

Rostov State Medical University

29, Nakhichevansky per., 344022, Rostov-on-Don, Russia

Elena D. Kampos, Assistant, TB department

Tel.: +7 (906) 429-20-36

E-mail: campos84@mail.ru

Adverse reactions to tb treatment in reproductive-age women*

Article 7.Page 59.
ARTICLE TITLE:

Adverse reactions to tb treatment in reproductive-age women*

DOI: 10.7868/S2587667819020079

AUTORS:

Kayukova S.I.1, Donnikov A.E.2, Romanov V.V.1, Lulueva Zh.S.1, Bagdasaryan T.R.1, Ergeshov A.E.1

1Сentral TB Research Institute, Moscow, Russia

2V.I. Kulakov Research Centre for Obstetrics, Gynecology and Perinatology, Moscow, Russia

²ФГБУ «Научный центр акушерства, гинекологии и перинатологии им. В.И. Кулакова»

DESCRIPTION OF ARTICLE:

Submitted as of 02.02.2019

We studied 54 women with pulmonary TB at the stage of TB treatment selection and during subsequent 40-150 days of treatment. We collected their records: physical examinations; data on X-ray and CT studies, bronchological studies, external respiration function tests; clinical, hemostasiological, biochemical blood tests; ultrasound studies of the pelvic organs; cytological studies of vaginal smears; microbiological and molecular-genetic studies of sputum for MTB detection and MTB DNA extraction. A special study of the vaginal microbiota was conducted using the novel test system ”Femoflor” (manufactured by LLC “NPO DNA-Technology”, Russia) with real-time PCR detection and quantitative description of 28 opportunistic microorganisms. After 40-150 days of TB treatment we established a reliable decline of the major normocenosis indicator – Lactobacillus spp., from 66.2% to 15.2% or 9.3% (р ≤ 0.001). On the contrary, the share of opportunistic microflora reliably increased, from 33.8% to 84,8% or 90.7% (р ≤ 0.05). The most indicative were Gardnerella vaginalis and Candida spp. The analysis of the vaginal microbiota species demonstrated gradual transition from normocenosis to moderate aerobic and anaerobic dysbiosis as treatment continued.

*The research was conducted under scientific theme 0515-2019-0019 “A multidisciplinary approach to diagnosis, differential diagnosis of TB and other pulmonary diseases in the present conditions”.

REFERENCES:
  1. Voroshilina E.S., Zornikov D.L., Plotko Ye.E. The normal state of vaginal microbiocenosis: subjective, expert and laboratory assessment. Bulletin of the Russian State Medical University, 2017, no. 2, pp. 42-46. (In Russ.)
  2. Lipova E.V., Boldyreva M.N., Trofimov D.Yu., Vetvitskaya Yu. G., Chekhrienko I.Yu., Mirzoyani M.A. Urogenital infections caused by opportunistic biota in reproductive-age women (clinical and laboratory diagnosis). Educational manual. Moscow, 2009, 36 p. (In Russ.)
  3. Vaginal microbiocenosis from the point of view of real-time PCR. Possibilities of correction of dysbiotic disturbances in the vagina. Educational manual. Ekaterinburg, 2018, 71 p. (In Russ.)
  4. Brotman R.M., Klebanoff M.A., Nansel T.R. Bacterial vaginosis assessed by gram stain and diminished colonization resistance to incident gonococcal, chlamydial, and trichomonal genital infection. Infect. Dis., 2010, no. 202, pp. 1907-1915.
  5. Cherpes T.L., Hilier S.L., Meyn L.A. A delicate balance: risk factors for acquisition of bacterial vaginosis include sexual activity, absence of hydrogen peroxide-producing lactobacilli, black race, and positive herpes simplex virus type 2 serology. Sex Trancm. Dis., 2008, no. 35, pp. 78-83.
  6. Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature, 2012, no. 486 (7402), pp. 207-214.
  7. Donnarumma G., Molinaro A., Cimini D. Lactobacillus crispatus L1: high cell density cultivation and exopolysaccharide structure characterization to highlight potentially beneficial effects against vaginal pathogens. BMC Microbiol., 2014, vol. 30, no. 14, p. 137.
  8. Grice E.A., Segre J.A. The human microbiome: our second genome. Annu Rev Genomics Hum Genet., 2012, no. 13, pp. 151-170.
  9. Jespers V., Menten J., Smet H. Quantification of bacterial species of the vaginal microbiome in different groups of women, using nucleic acid amplification tests. BMC Microbiol., 2012, no. 12, p. 83.
  10. Ling Z., Kong J., Liu F. Molecular analysis of the diversity of vaginal microbiota associated with bacterial vaginosis. BMC Genomics., 2010, no. 11, p. 488.
KEYWORDS:

TB, TB treatment, vaginal dysbiosis, reproductive-age women.

FOR CORRESPONDENCE:

Central TB Research Institute

2, Yauzskaya alley, 107564, Moscow, Russia

Svetlana I. Kayukova, Candidate of Medical Sciences, Senior Researcher

Tel.: +7 (915) 396-85-34

E-mail: kajukovalnp@gmail.com

 

Endobronchial valve blockage in management of destructive pulmonary tb: pulmonary ventilation in focus*

Article 8.Page 65.
ARTICLE TITLE:

Endobronchial valve blockage in management of destructive pulmonary tb: pulmonary ventilation in focus*

DOI: 10.7868/S2587667819020080

AUTORS:

Chushkin M.I.1,2, Popova L.A.2, Shergina E.A.2, Shabalina I.Yu.2, Karpina N.L.2

1Institute of Postgraduate Education of Federal Medical-Biological Agency of Russia, Moscow, Russia  

2Central TB Research Institute, Moscow, Russia

DESCRIPTION OF ARTICLE:

Submitted as of 1.02.2019

Aim: To study consequences of endobronchial valve blockage for the pulmonary ventilation function and detect factors influencing changes in the functional indicators in destructive pulmonary TB patients. Materials and methods. The research involved 88 patients with destructive pulmonary TB. We studied the functional state of the lung in dynamics while performing local artificial collapse after the endobronchial valve placement. We evaluated changes in the spirometric functional indicators. Results. Endobronchial valve blockage led to significant worsening of the pulmonary ventilation function in only 36% of patients. It was due to reduced lung vital capacity or deteriorated bronchial permeability. The frequency and expressiveness of pulmonary ventilation reduction were inversely proportional to the baseline forced vital capacity (FVC) and forced expiratory volume in one second (FEV1); they did not depend on patients’ age, TB dissemination process, an anatomical site of the endobronchial valve placement or volume of “turned off” lung tissue. Conclusion. Endobronchial valve blockage led to significant reduction of the pulmonary function in only one third of patients, and baseline functional disturbances did not increase the risk of such reduction.

*The research was conducted under scientific theme 0515-2019-0015 “Modern approaches to the diagnosis, epidemiology and treatment of drug-resistant respiratory tuberculosis associated with HIV-infection and diabetes mellitus”.

REFERENCES:
  1. Kanaev V.V. General issues of research methods and criteria for evaluation of respiratory indicators. Ed. by L.L. Shika, N.N. Kanaeva, Leningrad, 1980, pp. 21-36. (In Russ.)
  2. Levin A.V., Tseimakh E.A., Nikolaeva O.B., Zimonin P.E., Askalonova O.Yu., Levin L.A. Collapse therapy methods in treatment of infiltrative pulmonary TB patients with cavities and drug resistance. Tuberculosis and Lung Diseases, 2013, vol. 90, no. 12, pp. 65-70. (In Russ.)
  3. Myshkova E.P., Sklyuev S.V. Preliminary results of endobronchial valve blockage influence on external respiratory function in pulmonary TB patients with concomitant chronic non-specific pulmonary diseases. RMZh, 2017, vol. 25, no. 18, pp. 1296-1299. (In Russ.)
  4. Popova L.A., Shergina E.A., Lovacheva O.V., Bagdasaryan T.R., Chernykh N.A., Nefedov V.B. Functional response to an endobronchial valve placement in destructive pulmonary TB patients. Tuberculosis and Lung Diseases, 2016, no. 9, pp. 30-37. (In Russ.)
  5. On endorsement of methodical recommendations on improvement of pulmonary TB diagnosis and treatment. Chapter IX. Chemotherapy regimens. Edict no. 951 by RF MoH as of 29.12.2014. (In Russ.)
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KEYWORDS:

TB, cavity, endobronchial valve blockage, pulmonary ventilation function.

FOR CORRESPONDENCE:

Institute of Postgraduate Education of Federal Medical-Biological Agency of Russia

16, Moskvorechie St., 115409, Moscow, Russia

Central TB Research Institute

2, Yauzskaya alley, 107564, Moscow, Russia

Mikhail I. Chushkin, Doctor of Medical Sciences, Assistant of Clinical Physiology and Functional Diagnosis Department; Leading Researcher of Clinical Diagnostic Department, Central TB Research Institute

Tel.: +7 (499) 785-90-48

Е-mail: mchushkin@yandex.ru

Clinical and laboratory indicators of different types of hypersensitivity pneumonitis*

Article 9.Page 73.
ARTICLE TITLE:

Clinical and laboratory indicators of different types of hypersensitivity pneumonitis*

DOI: 10.7868/S2587667819020092

AUTORS:

Makaryants N.N., Lepekha L.N., Amansakhedov R.B., Erokhina M.V., Evgushchenko G.V., Sivokozov I.V., Shmelev E.I.

Central TB Research Institute, Moscow, Russia

DESCRIPTION OF ARTICLE:

Submitted as of 16.01.2019

 

The aim of the study: To optimize diagnosis of different types of hypersensitivity pneumonitis (HP) by establishing the most significant clinical and laboratory indicators of blood and bronchoalveolar washings (BAW).

Materials and methods. The study enrolled 107 patients with diagnosed HP. We analyzed clinical, X-ray, functional and laboratory indicators of venous blood and BAW, determined the subpopulational composition of lymphocytes using flow cytofluorometry.

Results. Clinical and X-ray changes in the lungs in acute and subacute types of HP correlate with high lymphocytic content in BAW, but there is a double difference in the CD4/CD8 ratios. In chronic HP we observe the lowest rates as compared to the norm. The lymphocytic subpopulational composition in the venous blood from HP patients corresponds to the disease type and can be used as an independent laboratory indicator: the CD4/CD8 ratio is elevated in acute HP, decreased – in chronic HP, and normal – in subacute HP.

*The research was conducted under scientific theme 0515-2019-0019 “Multidisciplinary approach to diagnosis, differential diagnosis of tuberculosis and other respiratory diseases in modern conditions”

REFERENCES:
  1. Antipova A.V., Evgushchenko G.V., Sivokozov I.V. A comparative analysis of bronchoalveolar washing cell compositions in exogenous alveolitis of different genesis. Aktualnye voprosy voennoi ftiziatrii, Pushkino, 2017, pp. 40-46. (In Russ.)
  2. Bolevich S.B., Kogan E.A., Kornev B.M., Lebedeva M.V., Moiseev S.V., Popova E.N., Fomin V.V. Differential diagnosis of interstitial lung diseases. In: Interstitial lung diseases. Practical guidelines. Ed. by N.A. Mukhina, Moscow, Literatura, 2007, pp. 308-325. (In Russ.)
  3. Vasilyeva O.S. Hypersensitivity pneumonitis. Respiratory medicine. Ed. by A.G. Chuchalin, vol. 2, Moscow, 2007, pp. 351-366, 374-382. (In Russ.)
  4. Ilkovich M.M., Novikova L.N. Exogenous allergic alveolitis. Interstitial lung diseases. by M.M. Ilkovich, A.N. Kokosova, St. Petersburg, 2005, pp. 183-211. (In Russ.)
  5. Lepekha L.N., Aleksandrova E.A., Evgushchenko E.V., Makaryants N.N., Lovacheva O.V. Cytological indicators of bronchoalveolar lavage in evaluation of exogenous allergic alveolitis course. RAMS Bulletin, 2012, no. 11, pp. 34-39. (In Russ.)
  6. Lepekha L.N., Burtseva S.A., Kalugina S.M. Morphological features of exogenous alveolitis of different genesis. Aktualnye voprosy voennoi ftiziatrii, Pushkino, 2017, pp. 153-160. (In Russ.)
  7. Makaryants N.N., Lepekha L.N., Shmelev E.I., Evgushchenko G.V., Amansakhedov R.B. Differential diagnosis and treatment of different types of exogenous allergic alveolitis. Vrach, 2013, no. 2, pp. 7-12. (In Russ.)
  8. Barrios R. Hypersensitivity pneumonitis. Dail and Hammar Pulmonary Pathology, 2008, vol. 1, pр. 650-668.
  9. Cormier Y., Belanger J., Laviolette M. Prognostic significance of bronchoalveolar lymphocytosis in farmer’s lung. Am. Rev. Respir. Dis., 1987, no. 135, pp. 692-695.
KEYWORDS:

hypersensitivity pneumonitis, endopulmonary cytogram, cytofluorometry.

FOR CORRESPONDENCE:

Central TB Research Institute

2, Yauzskaya alley, 107564, Moscow, Russia

Natalia N. Makaryants, Doctor of Medical Sciences, Leading Researcher, Department of Differential Diagnosis of TB and Extracorporal Treatments, Head of Therapeutic Unit no. 2

Tel.: +7 (499) 785-91-56

E-mail: roman4000@yandex.ru

Microscopic detection of mycobacteria by ziehl-neelsen staining technique

Part 2. Sputum smear microscopy

Article 10.Page 81.
ARTICLE TITLE:

Microscopic detection of mycobacteria by ziehl-neelsen staining technique

Part 2. Sputum smear microscopy

DOI: 10.7868/S2587667819020109

AUTORS:

Sevastyanova E.V., Larionova E.E., Andrievskaya I.Yu.

Central TB Research Institute, Moscow, Russia

DESCRIPTION OF ARTICLE:

Submitted as of 11.03.2019

We have described the microscopic detection of mycobacteria using Ziehl-Neelsen staining of smears. We described the techniques and the algorithm of a microscopic study, as well as morphological traits of mycobacteria detected in native diagnostic samples or grown cultures. We also represented M. tuberculosis cultures grown on liquid or solid media as they might be viewed under the microscope. We analyzed possible errors, which could occur during a smear microscopy procedure.

KEYWORDS:

mycobacteria, Ziehl-Neelsen microscopy.

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