System matrix metalloproteinase/inhibitors in pathogenesis of infiltrative pulmonary tuberculosis, depending on the resistance of Mycobacterium tuberculosis strains for anti tuberculosis therapy

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Abstract

Introduction. The search for molecular markers of adverse treatment outcomes in individuals with pulmonary tuberculosis (PT) is relevant due to the worldwide increase in drug resistance of Mycobacterium tuberculosis (MBT) strains to anti-tuberculosis drugs (PTP). Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) they are markers of destruction and remodeling.

The aim of the study. To study the features of the levels of the MMP in patients with infiltrative PT (IPT), depending on the MBT to PTP. To determine their significance as molecular markers of the effectiveness of therapy.

Methods. The concentrations MMP-1,-3,-8,-9 and TIMP-1 were measured using the ELISA method, kit «R&D Systems» (Minneapolis, MN, USA), the activity of α2-macroglobulin, neutrophils elastase (EL) – enzyme assays in the blood serum of 115 patients with ITL (58 drug – sensitive and 57 DR MBT). The effectiveness of the intensive phase of treatment was evaluated retrospectively. We used Statistica 10.0 (StatSoft, Inc.) and R.

Results. Regardless of the DR of MBT strains, patients with ITL have an imbalance in the MMP/inhibitors system towards proteinases. Regardless of the DR, the changes in circulating levels of MMP, TIMP-1 and EL were unidirectional with the otal volume of focuses and decay, as well as the number of neutrophils. Combinations from proteinase with results of chest X-rays methods of research at baseline levels in patients with ITL can be molecular prognostic markers of treatment outcomes.

Conclusion. The methods of multidimensional statistics showed that changes in the baseline levels of the MMPs and inhibitors in patients with ITL are not associated with the characterization of the resistance of MBT strains to the PTP, but are an objective criterion for the activity and prevalence of a specific process, and combinations from the MMP reflect the direction of its changes.

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About the authors

Dilyara S. Esmedlyaeva

St. Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation; St. Petersburg University

Email: diljara-e@yandex.ru
ORCID iD: 0000-0002-9841-0061

candidate of Biological Sciences, senior researcher, St. Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation

Russian Federation, Ligovsky Prospekt, 2–4, St. Petersburg, 191036; Universitetskaya emb., 7/9, St. Petersburg, 199034

Nina P. Alekseeva

St. Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation; St. Petersburg University

Email: ninaalexeyeva@mail.ru

candidate of Physical and Mathematical Sciences, senior researcher of Scientific Technical Information Departme

Russian Federation, Ligovsky Prospekt, 2–4, St. Petersburg, 191036; Universitetskaya emb., 7/9, St. Petersburg, 199034

Marina E. Dyakova

St. Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation; St. Petersburg University

Author for correspondence.
Email: marinadyakova@yandex.ru
ORCID iD: 0000-0002-7810-880X

doctor of Biological Sciences, senior researcher, St. Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation

Russian Federation, Ligovsky Prospekt, 2–4, St. Petersburg, 191036; Universitetskaya emb., 7/9, St. Petersburg, 199034

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2. Two-dimensional diagram of discriminant functions (DF) of the prognosis of the effectiveness of therapy: in terms of the results of the results of biochemical and clinical-radiological research methods (DF1), only according to clinical and radiological methods (DF2). Groups: with a significant improvement (1), with improvement (2)

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