The aim of this study was to examine the relationship between serum levels of parameters of the system metalloproteinase (MMP)/inhibitors with severity of infiltrative pulmonary tuberculosis (ITL), changes in examined parameters during the intensive phase treatment (IPT), as well as possibility of their use for prediction of IPT effectiveness, along with acute-phase proteins (AFP). The study included ITL patients which were subdivided into two groups (I and II) with different rates of reparative changes. It was shown that: 1) ITL is characterized by impairements in the system MMP/inhibitors: the levels of MMP-1, -9 increased, MMP-3, -8, TIMP-1 remained at the reference values and a 2-macroglobulin was low. 2) Changes of the parameters of the system MMP/inhibitors were associated with markers of severity and activity of the process: MMP-1, with the presence of destruction and sensitivity of the pathogen (Mycobacterium tuberculosis; MBT) to anti-TB drugs, MMP-9, with the volume of destruction, MMP-8 - with activity of tuberculosis. 3) TIMP-1 and MMP-9 concentrations decreased during treatment in groups with different rates of reparative process, whereas proMMP-1, MMP-3,-8 remained unchanged. 4) Before and after IPT, the level of TIMP-1 was higher in the group of patients with slower rate of reparative processes. 5) After IPT the imbalance in the system MMP/inhibitor preserved thus suggesting continuation of the reparative process. 6) Use of combination of MMP and AFR is more informative in predicting efficacy of IPT.
The imbalance in matrix metalloproteinase (MMP)/inhibitors system leads to degradation of extracellular matrix of connective tissue and pathological remodeling forming the morphological basis for respiratory dysfunction.The objective: to study the relationship between parameters of MMP/inhibitors system in blood and parameters of ventilation and gas exchange disorders in patients with chronic pulmonary tuberculosis (PTB).Subjects and Methods. Patients with the verified diagnosis of tuberculoma (n = 45) and fibrous-cavernous pulmonary tuberculosis (n = 85) were examined. All patients underwent computed tomography of the chest and assessment of respiratory function. Serum concentrations of MMP-1, -3, -8, -9 and their inhibitors TIMP-1 and α2-macroglobulin (MG) were tested by ELISA (R&D Systems, Minneapolis, MN, USA). Statistica 7.0 and an ANCOVA model were used for statistical analysis which considered the diagnosis and smoking status as factors, and the respiratory function parameters were considered as covariates.Results. In pulmonary tuberculosis patients, the concentrations of MMP-9 and MMP-8 in the blood correlated with extension of lung parenchyma lesions when compared to tuberculomas and fibro-cavernous tuberculosis, MMP-9 and TIMP-1 with changes in lung volumes (R2 = 0.60 and 0.80; p = 0.001), and MMP-8 correlated with functional disorders of gas exchange (R2 = 0.60 and 0.80; p = 0.001). Changes in MMP-1, MMP-3, and α2-MG (R2 = 0.60 and 0.80; p = 0.45) did not correlate with extension of lung parenchymal lesions and decreased lung function.
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