New untreated infiltrate pulmonary tuberculosis patients commonly demonstrated the same referent level of MMP-8, MMP-3 and multiple increase of MMP-9 level on the background of diverse changes of inhibiting potential (retaining the reference level of TIMP-1 and reduced α2 -МG). Destructive process is related to unbalanced increase of рro-ММР-1 and ММР-9. At the same time the level of рro-ММР-1 correlates to changes in ROF, activity of proteinases of other classes (serine proteinases) and depends on the dissemination of the disease, while the changes in MMP-9 level are influenced by the massiveness of bacillary excretion.

A series of 29,39-didehydro-29,39-dideoxyribonucleosides (ddeNs) [i.e., 29,39-dideoxythymidinene (ddeThd), 29,39-dideoxyuridinene (ddeUrd), 29,39-dideoxycytidinene (ddeCyd), and 29,39-dideoxyadenosinene (ddeAdo)] has been synthesized and the individual members compared in terms of their in vitro antiviral, antimetabolic, and cytostatic properties to their 29,39-saturated counterparts (ddNs) (i.e., ddThd, ddUrd, ddCyd and ddAdo). All ddeNs except ddeUrd are potent and/or selective inhibitors of human immunodeficiency virus (HIV) in vitro, ddeCyd being the most potent (MIC50, 0.30 microM). The inhibitory effect of ddeCyd on ATH8 cell proliferation and HIV-induced cytopathogenicity is comparable to that of ddCyd. ddeThd is a more potent anti-HIV agent than ddThd (MIC50, 3.4 microM and 84 microM, respectively), but also more cytostatic (ID50, 172 microM and greater than 2000 microM, respectively). However, its in vitro chemotherapeutic index is higher than that of 39-azido-29,39-dideoxythymidine, a drug which has recently proven effective in the treatment of acquired immunodeficiency syndrome. ddeAdo has a weaker anti-HIV and a stronger cytostatic effect than ddAdo. Neither ddeUrd nor ddUrd shows significant anti-retroviral activity at 500 microM. In contrast to their anti-retroviral activity, both ddNs and ddeNs lack any appreciable inhibitory activity against a series of nononcogenic RNA and DNA viruses, pointing to their selectivity as anti-retroviral agents. All ddeNs show a progressive loss of anti-retroviral effect upon prolonged incubation with virus-infected cells. This phenomenon is most likely due to the chemical instability of these compounds, and not to a preferential enzymatic phosphorolytic cleavage of the ddeNs. Evidence is presented that ddeCyd and ddCyd, and ddeThd and ddThd are phosphorylated by cellular dCyd kinase and dThd kinase, respectively. However, the Ki values as alternate substrate inhibitors for their respective kinases are high (greater than 500 microM), indicating poor substrate activity and, thus, poor anabolism in ATH8 cells.

Host-pathogen relations were analyzed on basis of the results of examinations of 42 patients with newly diagnosed, previously untreated infiltrative pulmonary tuberculosis (IPT) with regard for the biological characteristics of Mycobacterium tuberculosis (MBT) and the biomarkers of the inflammatory reaction — the acute phase proteins (APPs). The genotypes of MBT (Beijing and the others) and the efficacy of threeonth antituberculosis therapy were used as the grouping factors. Genotype Beijing MBT patients were significantly often characterised by multiple drug resistant, had widespread pulmonary damage and association of MBT cytoxicity with the effect of therapy. The patients with the best postreatment effect had initial (pretreatment) APPs levels in the range of the referent ones. These conclusions were confirmed by analysis of the correlation pleads of the characteristics of the “host-pathogen” system and their discriminant analysis with regard for MBT genotypes and results of antituberculosis three-month therapy. It was shown that the constellation of four host’s APP characteristics (haptoglobin, ceruloplasmin, elastase and adenoaminase activities) has above 90% prognostic efficacy of treatment in spite of MBT genotype. It is suggested that in IPT patients the first component of the “host-pathogen” system reflecting the reaction of the patient’s organism to the MBT induced inflammatory process is more prognostically important.

Design: Biochemical characteristics of the 42 newly diagnosed patients with PT. Blood levels of acute phases reactants-ARP: ceruloplasmin-CP, haptoglobin-Hg, C-reactive protein-CRP, orosomucoid-AGP, albumin-A, neopterin-Np, elastase-El, alpha1-protease inhibitor- alpha1-IP, adenosine deaminase activities-ADA; were tested before the start of treatment. Test results were analyzed considering clinical, radiologic and bacteriologic examination data after three months of adequate anti-TB therapy. Sputum negativation and closing of cavities were classified as an outcome significant improvement (SI) while sputum negativation - as improvement (I). Mycobacterium tuberculosis (MBT) isolate (the Pathogen) from sputum collected before the to treatment start had been studied as: MBT genotype (by spoligotyping), drug resistance patterns (DR), cytotoxicity (CT; MBT ability to stimulate THP-1 cells death). The data were analyzed according to MBT genotype Beijing (Bj) or another families and the therapy effect. Results. Both SI and I outcomes were observed regardless MBT genotypes. Nevertheless Bj-genotype (MBT-B) was associated with I (41% and 70%; p=0,05) and high levels of ARPs, CT and DR. Low levels of ARPs were associated with SI while their high levels with I. Discriminative analysis revealed the constellation of four ARPs (CP, Hg, El, ADA) as the complex with the highest predictive value of the 3 month chemotherapy outcome with a prognostic accuracy in 95,2% for MBT-B patients and in 100% for those with MBT of other genotypes families. Conclusion: In H-PS tuberculosis development is mainly determined by the host properties expressed as ARP levels. Complex of CP, Hg, El, ADA blood levels proved to be of the most prognostic value.

The systemic analysis of the inflammatory process in untreated patients with newly diagnosed infiltrative-destructive tuberculosis has been performed in the context of host mycobacterium interaction. Variability of acute phase proteins (APP) reflecting mobilization of nonspecific protective systems of the body did not depend on cytotoxicity of Mycobacterium tuberculosis (MBT). In 87.5% of patients the dependence between effectiveness of antituberculous chemotherapy (for three months) and combination of MBT characteristics and initial APP levels was found. Patients with effectiveness of therapy, which was inadequate to MBT cytotoxicity, were characterized by its dependence on the APP level and MBT sensitivity to antituberculous agents. Results of multifactorial analysis of parameters reflecting intensity of the inflammatory response, pathological process in the lungs, and characteristics of MBT suggest that the overall result of the host-pathogen interactions primarily depends on adequateness of protective systems of the host organism.

The comprehensive prospective examination of 66 patients with first established non-treated infiltrative tuberculosis of lungs was used to analyze the possibility of optimization of assessment of course of specific inflammatory process on the basis of levels of proteins-reactants of acute phase. The characteristics of dynamics of clinical roentgenologic data and terms of coming of abacillarization as a result of three months anti-tuberculosis therapy has been used as grouping factors. It is established that the constellation of 3 out of 12 basic (before treatment) analyzed level indicators are the most prognostic informative--haptoglobin, ceruloplasmin and blood albumin. Their combined application according the proposed decisive rule provides 90.6% of effectiveness of prognosis of the results of treatment in the discussed category of patients.

Functional activity of circulating phagocytes (macrophages and neutrophils — Ns) was studied in 30 patients with infiltrative and 30 patients with fibro-cavernous pulmonary tuberculosis (IPT and FCPT, respectively), characterized by similar biological properties of mycobacterium tuberculosis (MTB), dissemination of the process, and manifestations of intoxication. Differences of the functional activity of both types of cells depending on the PT form were found: a more significant increase in the oxygen-depending activity in FCPT while bactericide potential estimated with the zymosan induced NST-test was more pronounced in IPT patients. These data correlate with the blood levels of neopterin and elastase, the markers of the mononuclear and neutrophil activity, respectively. Involvement of adenosine deaminase (ADA) and neopterin in realization of intracellular oxygen-dependent processes was demonstrated. Results of the multivariate analysis of the whole set of the studied phagocyte parameters, reflecting their different roles in this pathological process demonstrated a prevailing role of mononuclears in newly diagnosed IPT and neutrophils in the chronic progressive process.

The comprehensive prospective examination of 66 patients with first established non-treated infiltrative tuberculosis of lungs was used to analyze the possibility of optimization of assessment of course of specific inflammatory process on the basis of levels of proteins-reactants of acute phase. The characteristics of dynamics of clinical roentgenologic data and terms of coming of abacillarization as a result of three months anti-tuberculosis therapy has been used as grouping factors. It is established that the constellation of 3 out of 12 basic (before treatment) analyzed level indicators are the most prognostic informative haptoglobin, ceruloplasmin and blood albumin. Their combined application according the proposed decisive rule provides 90.6% of effectiveness of prognosis of the results of treatment in the discussed category of patients.

The authors have compared the informative value of the tests determining the activity of adenosine deaminase (ADA) and the levels of interferon-gamma (INF-gamma) and neopterin in the diagnosis of pleural effusions of tuberculous (n = 67) and nontuberculous (n = 30) origin. The equally high diagnostic value has been found in the study of the activities of ADA (94.8%) and INF-gamma, which are markers of lymphocytic cellular immunity. There are great differences in the sensitivity of the neopterin test depending whether tuberculosis is isolated or complicates the course of tuberculosis of the lung or intrathoracic lymph nodes, which may be regarded as a reflection of the different status of macrophageal cellular immunity.

The paper analyzes the diagnostic value of methods for the laboratory diagnosis of postpericardiotomy syndrome (PPS) in patients who have undergone open heart surgery. The prospective study included 63 patients, of whom 53 had the clinical manifestations of PPS. Ultrasensitive assay of serum procalcitonin and the determination of relative albumin levels in pleural and pericardial fluids are noted to be of high diagnostic value.

The paper analyzes whether it is possible to predict a risk for postoperative empyema, by studying a totality of characteristics of a patient, a pathological process, and the properties of MBT in 46 patients with progressive fibrocavernous tuberculosis. It also shows it actual to accomplish this task with a prediction accuracy of 89.5-100%, by simultaneously taking into account both the bacteriological properties of MBT (the magnitude of Mycobacterium tuberculosis excretion and viability) and different combinations of serum biological parameters that reflect the activity of an inflammatory process.

Functional activity of the bronchoalveolar lavage fluid (BALF) phagocytes was studied in 33 and 16 patients with fibro-cavernous and infiltrative pulmonary tuberculosis (FCPT and IPT, respectively). Complex examination of BALF, alveolar macrophages and neutrophils sedimented from BALF has shown interrelationship between functional activity of the cells and the form of pulmonary tuberculosis. Higher neopterin content and activity of elastase mainly secreted into BALF by activated alveolar macrophages and neutrophils, respectively, reflect higher secretory activity of both types of cells in FCPT. In FCPT this is combined with higher bactericidal activity of neutrophils, which significantly correlates with their adenosine deaminase (ADA) activity. Comparison of changes of the biochemical parameters studied in BALF (neopterin, elastase, ADA and its isoenzymes, 2-deoxy-ADA) and bactericidal activity of the sedimented cells obviously reflects different sides of BALF phagocytes functioning. Taking into consideration modern concepts on the mechanisms of regulation of phagocyte cells one may suggest the existence of differences in intercellular interactions in various forms of pulmonary tuberculosis.

The paper compares the characteristics of the informative value of tests determining the activity of adenosine deaminase (ADA) activity and the level of gamma-interferon (gamma-IFN) for the differential diagnosis of tuberculous pleurisy (n = 35) and non-tuberculous pleural effusion (n = 53). Both tests were ascertained to have the similar differentially diagnostic capacities with their threshold values of 35 U/l and 180 pg/ ml, respectively. At the same time, the sensitivity and specificity of the ADA test were 98.4% and these of the gamma-IFN test were 94.3 and 96.2%, respectively, with the positive and negative predictive value being 91.3 and 98.3% and 94.3 and 96.2%, respectively, and with the diagnostic value of 94.5% for the ADA test and 96.4% for the gamma-IFN test. There was a high unidirectionality of changes in both values: it was higher than the cut-off points in 94.1% of the patients with tuberculous pleurisy and below them in 88.7% of those with other pleural effusions.

The paper summarizes the results of studies of the activity of adenosine deaminase (ADA) in biological fluids (including that during tuberculin tests) as a tool for the differential diagnosis of different forms of extrapulmonary tuberculosis, such as pleuritis, synovitis, meningitis, tuberculosis of female genitals and peripheral lymph nodes, and uveitis. The threshold for the activity of ADA or the magnitude of its increase in antigenic stimulation, which provides the optimum ratio of the sensitivity to specificity of the tests and their maximum diagnostic efficiency, are given. The optimization of diagnosis of tuberculous synovitis is shown to facilitate the study of ADA activity concomitantly with the determination of the level of antituberculosis antibodies. The tests under discussion are economically sound and yield results in several hours and, in case of a provocative test, in 3 days.

The results of examination of 56 patients with destructive pulmonary tuberculosis, which involved the study of biochemical parameters characterizing different stages of an inflammatory process, as well as clinical and X-ray findings were analyzed, by applying various multivariate statistical methods. This approach was shown to be promising for estimating the severity of the process and for specifying the stage of development of an inflammatory process in some patients.

A hundred and three patients with destructive pulmonary tuberculosis were examined. These patients had heterodirectional changes in the serum levels of alpha2-macroglobulin (MG) and its forms. The lowering of the level of the F-form of the inhibitor outstripped the decrease in the activity of total alpha2-MG and it was detectable in the lobar processes with moderate symptoms of intoxication and with the inoculation of adjacent segments. The preservation of the low total activity of the inhibitor and its forms during antituberculous therapy characterize a diminished process. The high content of the S form of alpha2-MG is a feature in patients showing positive changes before and 2 months after treatment whereas the changes in total alpha2-MG and its F form may vary. Whether it is expedient to study the fractional composition of alpha2-MG is determined by the heterodirectionality of changes in its S and F forms depending on the pattern of a process.

Sixty-three patients with fibrocavernous pulmonary tuberculosis were examined before and 1 month after preoperative therapy with antituberculosis agents. The time course of changes in the clinical and X-ray characteristics of the severity of the disease were compared with the alterations of different biochemical indices, including acute-phase proteins, proteolysis inhibitors, intoxication severity. It was demonstrated that improvement of clinical and X-ray characteristics of the severity of a process after preoperative preparation could be predicted with an accuracy of 83% from the baseline serum concentrations of albumin and ceruloplasmin. The accuracy of prediction does not increase when the levels of protease inhibitors, C-reactive protein, adenosine deaminase, medium-weight molecules are simultaneously studied. The likelihood of the clinical and X-ray characteristics becoming better is higher with enhanced ceruloplasmin activity and decreased albumin levels.