[Features of metabolic activity of vascular endothelium in patients with pulmonary tuberculosis].

81 patients with active pulmonary tuberculosis were investigated. The morpho-functional status of vascular endothelium was evaluated by plasma levels of stable metabolites of nitric oxide, endothelin-1 and von Willebrand factor antigen. Typical increase of endothelin-1 in positive correlation with systemic inflammatory response syndrome (SIRS) expression was established. Nitric oxide level decreased in patients with chronic and severe course of disease. Decrease of nitric oxide level was not associated with SIRS but was consequence of specific intoxication. von Willebrand factor antigen decreased in patients with recent and limited spread of tissue damage but increased progressively with intensity of SIRS. This complex of changes (contrast shifts of nitric oxide and endothelin-1 and von Willebrand factor antigen increase) manifested in endothelium metabolic dysfunction syndrome and developed pre-conditions for microcirculation disturbances.

[The specific features of iron intake in patients treated for pulmonary tuberculosis].

Two hundred and forty-three patients with different forms of active pulmonary tuberculosis were examined. The iron intake was estimated by the serum iron (SI) concentrations, total iron-binding capacity (TIBC), unsaturated iron-binding capacity, transferring iron saturation factor (SF), and ferritin (FT) levels. The findings were compared with the values of red blood cells and the systemic inflammatory response assessed from the levels of acute phase reactants (APR). The obtained results were assessed, comparing with the normal range of values separately in male and female patients. Reductions in SI concentrations and TIBC were found to be typical of patients with active tuberculosis. These changes are the components of a systemic inflammatory response and associated with the development of hypochromic anemia. FT, as an ARR, shows heterodirectional changes. The reduction in this index in female patients with pulmonary tuberculosis frequently indicates their susceptibility to the development of true SI deficiency. In males, FT mainly behaves as an APR, which hinders the clarification of the nature of hypochromic anemia. The levels of SI and SF become normal during effective treatment while ineffective treatment deteriorates hypoferremia.

[Serum nitric oxide level in the assessment of systemic inflammation in patients with drug-resistant pulmonary tuberculosis].

Two hundred and forty-three patients with active pulmonary tuberculosis were examined. Their sera were tested for the level of stable nitric oxide (NO) metabolites, by using the Griess reagent after previous reduction of nitrates to nitrites by a copper-impregnated cadmium reducer. The frank active pulmonary tuberculosis was ascertained to follow the lower serum levels of NO metabolites. The serum NO level did not correlate with inflammatory markers, but reduced when the process was recurrent or chronic. By taking into account the role of NO in the performance of the body's different systems, its serum reduction in patients with pulmonary tuberculosis should be probably referred to as the manifestations of metabolic decompensation as the suppressed endothelial NOS activity that determines the level of NO in circulation.

[Evaluation of hepatic function in new cases of pulmonary tuberculosis due to the use of standard chemotherapy regimens I and IIB].

The frequency and magnitude of hepatotoxic reactions were compared in 147 new cases of pulmonary tuberculosis within the first three months of chemotherapy (CT) by standard regimen 1 [H, R, Z, S (E)] (Group 1) and regimen 2B [the same drugs + kanamycin (amikacin) and fluoroquinolones] (Group 2). Their efficiency was evaluated from 6 serum indices--the level of bilirubin, the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), and gamma-glutamyl transpeptidase (GGTP), and thymol test results. Tests were monthly carried out. The results were separately analyzed in patients with and without baseline abnormalities in the indices being tested. Within the first two months of CT, the patients without baseline abnormalities showed the slightly higher frequency and magnitude of hepatotoxic reactions on receiving regimen 2B. Following 3 months of CT combined with hepatoprotectors, the patients treated by standard regimen 1 had solitary laboratory signs of hepatic damage, but there was a regular elevation of GGTP in the regimen 2B group. After a month of regimen 1 CT in combination with hepatoprotectors, the patients with baseline abnormalities has positive changes in all the studied indices. In the patients treated by regimen 2B in combination with hepatoprotectors, the changes were the same, except for GGTP that remained to be at the increased baseline levels. Following 2 months of CT, in Group 1 positive changes continued in the studied markers and, with regimen 2B treatment, abnormal changes began increasing again. After 3 months abnormal changes were single in the markers of hepatic damage with regimen 1 treatment and there was a repeated significant rise in the values of AP and GGTP with regimen 2B. It is concluded that in addition to ALT and AST, GGTP is of great informative value in controlling the hepatotoxic effects of CT.

[Estimation of serum C-reactive protein values in patients with pulmonary tuberculosis].

Two hundred and forty-three patients with different forms of active pulmonary tuberculosis were examined. The level of C-reactive protein (CRP) was determined by immunoturbidimetry. Its normal values were taken to be 0-3 mg/l. The increased CRP levels revealed in 80.7% of the patients formed two peaks in the ranges of 4-5 (25.1%) and 21-100 (28.9%) mg/l. The higher values of CRP with the maximum of 239 mg/l were found in 11.1% of patients. The values of CRP clearly correlated with the degree of intoxication, the presence and rate of bacterial discharge, the extent of the process, the absence or presence of decay. By the end of an intensive phase of chemotherapy (3 months) in case of its efficiency, the level of CRP significantly decreased, tending to the upper subclinical range (12.1 +/- 1.9 mg/l) whereas in ineffective treatment it substantially unchanged.

[Use of fluoroquinolones in the intensive phase of treatment of new tuberculosis cases].

The efficiency of treatment using the routine (I) versus IIB regime was evaluated in 161 new HIV-negative cases of destructive tuberculosis within the first 3 months of chemotherapy. The IIB regimen used in the intensive phase of chemotherapy in new tuberculosis cases before obtaining data on the drug resistance of Mycobacterium tuberculosis significantly enhance the efficiency of treatment in eliminating bacterial excretion and destructive resolution in the lung. The IIB regimen used in new tuberculosis cases with primary multidrug resistance allowed bacterial excretion to be stopped in 80% by month 3 of therapy whereas this index in the similar patients treated by the I regimen was as high as 25%. Decay cavities could be also resolved significantly more frequently by month 6 of therapy in the group of patients treated by the IIB regimen in 59% versus 29% of the patients treated by the I regimen. The inclusion of fluoroquinolones into chemotherapy caused no increase in the incidence of undesirable adverse reactions.

[A systemic inflammatory response in teenagers with new-onset tuberculosis].

Fifty-eight adolescents aged 13-17 years who had new-onset pulmonary tuberculosis were examined. The serum levels of C-reactive protein (CRP), alpha-antitrypsin (alpha1-AT), haptoglobin (Hp), serum protein fractions, medium-weight molecules (MWM), and malonic dialdehyde (MDA) were assayed in the patients on admission, 2 weeks, and 1, 2, 3, and 6 months after treatment. The parameters of a systemic inflammatory response were ascertained to naturally vary in the adolescents with new-onset tuberculosis, by reflecting as both a defense reaction (increases in the levels of CRP, a,-AT, Hp) and as metabolic decompensation manifestations (increases in the concentrations of MWM and MDA and a reduction in the almubin/globulin (A/G) ratio. The magnitude of these changes makes it possible to judge the severity of a process to a certain extent and it is unassociated with the genesis of the disease. The levels of acute-phase reagents and MDA undergo positive changes just 2 weeks of effective specific chemotherapy whereas there are no changes after ineffective treatment. After correction of chemotherapy and achieving a clinical effect, there was a complete normalization in the levels of CRP, Hp, and A/G ratio, but a slight increase in alpha1-AT and MDA in all the children by month 6 of therapy. In all the adolescents, the baseline increased concentration of MWM increased at the early stage of chemotherapy and returned to the original value after 6-month therapy, by remaining significantly higher than the normal values.

[Efficiency of a new standard chemotherapy regimen in the treatment of patients with recurrent pulmonary tuberculosis].

The efficiency of conventional chemotherapy regimens was comparatively studied in 75 patients with recurrent pulmonary tuberculosis. In the patients with recurrent pulmonary tuberculosis, conventional chemotherapy regimen "2b" including isoniazid, rifampicin, pyrazinamide, ethambutol, fluoroquinolone (ofloxacin, ciprofloxacin, and levofloxacin), and canamycin (amikacin) versus conventional chemotherapy regimen "2a" including isoniazid, rifampicin, pyrazinamide, ethambutol, and streptomycin could cease bacterial isolation after 3-month therapy, as evidenced by sputum microscopy (86.1 and 62.5%, respectively; p < 0.05). Cavity closure was more frequently observed after 6-month chemotherapy using regimen "2b" (76.7 and 48.0%, respectively; p < 0.05). In patients with recurrent pulmonary tuberculosis who isolated Mycobacterium tuberculosis (MBT) resistant to isoniazid and other antituberculous drugs (exclusive of rifampicin), 3-month use of conventional regimen "2b" led to cessation of bacterial isolation (as evidenced by the inoculation test) in 66.7% of cases; but this did not occur with conventional regimen "2a" in any case. Similarly, 3-month use of regimens "2b" and "2a" in patients isolating MBT resistant to rifampicin and other agents (exclusive of isoniazid) resulted in the cessation of bacterial isolation in 80 and 0% of cases, respectively. In multidrug resistance, these parameters were 11.1 and 0%, respectively.

[Qualitative assessment of metabolic shifts accompanying the acutely progressive course of pulmonary tuberculosis].

Eighty-one patients with acutely progressive pulmonary tuberculosis (APPT) (a study group) and 63 patients with involutive pulmonary tuberculosis (a control group) were examined. The magnitude of a systemic inflammatory response was estimated by the values of acute phase reagents (APR) and the blood protein spectrum; the body's iron provision, the state of the hemostatic and fibrinolytic systems, the functional status of mononuclear leukocytes and neutrophils were determined by the basal level of oxygen-dependent and nitrite oxide metabolism and by the capacity of these systems to respond to specific stimulation. In APPT, along with increased APR levels reflecting the mobilization of various components of endogenous defense, the serum (plasma) was found to show the signs of metabolic decompensation as increased catabolic processes and hepatic protein-synthesizing dysfunction in the presence of intravascular inactivation of functionally significant proteins. Noteworthy is hypochromic anemia caused by the body's redistribution of iron (in the absence of its genuine deficiency) and by the reduced plasma concentration of transferring. The patients with APPT had a significant hypercoagulation syndrome with the signs of latent intravascular blood coagulation. Antimicrobial defensive processes involved mononuclear leukocytes and neutrophils wherein free radical oxidation and nitric oxide generation became intensive. In APPT, the permanent reirritation of these systems led to the exhaustion of functional reserves of cells and their response to specific stimulation diminished. In the neutrophils, rearrangement of their metabolism correlated with other manifestations of a systemic inflammatory response and in the mononuclear leukocytes, this correlated with the size of a bacterial population and with the presence of drug sensitivity/resistance of the causative agent.

[Changes in the levels of nitric oxide in the mononuclear cells and neutrophils of patients with tuberculosis with varying courses of pulmonary tuberculosis]. / Izmeneniia urovnei oksida azota v mononuklearakh i neitrofilakh krovi u bol'nykh s raznym techeniem tuberkuleza legkikh.

A hundred and forty four patients with different types of the course of pulmonary tuberculosis were examined. Before and 20 hours after incubation with BCG-killed cultures, mononuclear cells and neutrophils were used to estimate the level of generation of nitric oxide (NO) from the content of its stabile metabolites--nitrites determined by Griess reagent. Crucially active pulmonary tuberculosis was found to follow the increased leukocytic generation of NO. The most profound shifts occurred in the mononuclear cells. During a favorable involutional process, the mononuclear cells increased their baseline generation of NO and, moreover, preserved their potential for a responsive "nitric oxide burst" when they met a specific causative agent. In patients with acute pulmonary tuberculosis, the basal level of NO in the mononuclear cells was high, but their response to BCG proved to be decreased. In the neutrophils, the basal level of NO exhibited a significant scatter and their higher response to BCG was noted only during the involutional course of tuberculosis. Changes in the leukocytic levels of NO were related to the magnitude of a systemic inflammatory response, to the severity of respiratory failure, and to the rate of cellular lipid peroxidation. A clear relationship was observed between the nature of baseline changes in the values of NA and the efficiency of subsequent treatment.

[The phenotypes of haptoglobin and the level of acute-phasic proteins in the sera of children with local form of intrathoracic tuberculosis]. / Fenotipy gaptoglobina i uroven' ostrofaznykh belkov v syvorotke krovi u detei s lokal'nymi formami vnutrigrudnogo tuberkuleza.

Seventy-seven children aged 4-12 years who had local forms of primary intrathoracic tuberculosis were examined. On admission to and discharge from hospital, haptoglobin (Hp) was phenotyped and the content of Hp was measured, and the activity of alpha1-antitrypsin (alpha1-AT) was determined. In all ill children, the distribution of Hp phenotypes did not differ from the normal level, but all patients with tuberculous pleurisy were found to be carriers of Hp1 gene (among them the phenotype Hp 2-2 was absent and the minor variant of Hp 1-1 was detectable in half the cases). In patients of this group, alpha1-AT acted as a typical acute phase reagent and remained moderately increased by the termination of treatment in the vast majority of the examinees. On the contrary, on admission the content of Hp was to be decreased. Its increase was natural only in patients with tuberculous pleurisy. The level of Hp was associated with its phenotype. Carriers of Hp1-1 had elevated levels of Hp in the overwhelming majority of cases whereas those of Hp 2-2 had its decreased levels. It is concluded that in children with primary tuberculosis, the serum level of Hp may not be used as an indicator of the activity of the process. Possible causes and the values of decreased levels of circulating Hp in children with primary tuberculosis are discussed in the paper.

[Diagnosis of latent primary intrathoracic tuberculosis of respiratory system in the phase of calcification in children]. / Diagnostika skrytoi aktivnosti pervichnogo vnutrigrudnogo tuberkuleza organov dykhaniia v faze kal'tsinatsii u detei.

The paper shows the latent activity of newly diagnosed intrathoracic tuberculosis in the phase of calcification in children: clinical and X-ray changes, tuberculin sensitivity (Manteaux test), the presence of Mycobacterium tuberculosis (MBT) in the sputum and blood (cultivation, bacterioscopy, polymerase chain reaction PCR), the blood levels of acute-phase reagents: haptoglobin and alpha 1-protease inhibitor (alpha 1-PI), immunological parameters, tuberculosis antibodies (TAb), and MBT antigen. Ninety children were examined before treatment. Twenty-five children (Group 1) were found to have single minor calcified masses in one group of intrathoracic lymph nodes or in the lung. Thirty-five children (Group 2) had multiple lymph nodes or foci in the lung in the phase of consolidation and calcification. Thirty children (Group 3, controls) were diagnosed as having intrathoracic tuberculosis in the phase of infiltration. The signs of the latent activity of tuberculosis were detected in all the children of all three groups, being more pronounced in Group 3. Thus, MBT and TAb were revealed in 90% of the children in Group 3 and in 52.9 and 76.0% in Groups 1 and 2, respectively. There were higher levels of alpha 1-PI in 96.6 and 75.0% in Groups 3 and 1, respectively. There were signs of intoxication in 80 and 88% and a hyperergic Mantoux reaction in 44.0 and 43.3%, respectively. The frequency of the signs of activity did not greatly differ. Thus, children with newly diagnosed respiratory tuberculosis in the phase of calcification should be regarded as having the signs of tuberculosis activity, followed up as Group I patients, and prescribed chemotherapy for 3-6 months or more, depending on the extent of the process.

[Biochemical characteristics of fluid and cells of bronchoalveolar washings in patients with extrinsic allergic alveolitis]. / Biokhimicheskie kharakteristiki zhidkosti i kletok bronkhoal'veoliarnykh smyvov u bol'nykh ékzogennym allergicheskim al'veolitom.

In 43 patients with exogenous allergic alveolitis (EAA), including 30 and 13 in its acute and chronic disease, bronchoalveolar lavage was performed, bronchoalveolar washing fluid (BAWF), isolated alveolar macrophages (AM) and unfractionated cellular sediment (NFCS) were separately studied. The BAWF showed high rates of lipid peroxidation (LPO), decreased antiproteolytic defense, and activated local synthesis of haptoglobin (Hp), fibronectin (FN), platelet activation factor (PAF), and enzymes of antioxidative defense (AOD). There was a rise in FN and PAF concentrations in the acute phase of the disease and higher PLO rates and elevated Hp levels in chronic EAA. The rate of oxidative metabolism in AMs was much higher in acute EAA than that in chronic EAA and accompanied by imbalance in the PLO-AOD system. AM levels of PAF was high in patients in both groups. The rate of LPO was higher in NFCS than in AM and was also followed by simultaneous AOD mobilization with preserved imbalance. A particularly significant AOD insufficiency in the NFCS was noted in chronic EAA, which was accompanied by decreased PAF. Thus, local pathochemical processes are of significance in developing the pattern of the process in EAA.

[Some metabolic characteristics of circulating phagocytes in patients with different types of pulmonary tuberculosis]. / Nekotorye metabolicheskie kharakteristiki tsirkuliruiushchikh fagotsitov u bol'nykh s raznymi variantami techeniia tuberkuleza legkikh.

Before and 2 and 3 months after chemotherapy, spontaneous and BCG-stimulated nitroblue tetrazolium (NBT) tests, superoxide dismutase (SOD) and catalase activities, the levels of malonic dialdehyde (MDA) and platelet activation factor (PAF) in isolated mononuclear cells and neutrophils were estimated in 169 patients with different forms of pulmonary tuberculosis. Before treatment, in the patients the monocytic bactericidal potential assessed by NBT test parameters was found to increase, but the neutrophilic one reduced due to their basal overirritation. All other test parameters were higher in both types of cells. The magnitude and balance of changes were interrelated to the onset and nature of the process. Following 3 months of treatment, the bactericidal potential increased much more in the monocytes and returned to normal values if the changes in the processes were favourable. In both types of the cells, SOD activity became normal to normal values, MDA levels were maintained in the normal range due to the a preserved enhancement in catalase activity. PAF remained in the upper normal range. Both types of the cells showed drastically increased levels of MDA and drastically decreased PAF levels with progression due to therapy.

[Red blood cell metabolic changes in patients with acutely progressive pulmonary tuberculosis]. / Izmeneniia metabolizma éritrotsitov u bol'nykh ostroprogressiruiushchim tuberkiulezom legkikh.

In 52 patients with acutely progressive pulmonary tuberculosis (APPT), their red blood cells were used to determine the values of their energy metabolism by lactate dehydrogenase (LDG) and glucose-6-phosphate dehydrogenase (G-6-PDG), the antioxidative defense from the activity of superoxide dismutase (SOD) and catalase and from the levels of malonic dialdehyde (MDA), as well as the intraerythrocytic level of platelet activation factor (PAF) and 2,3-diphosphoglycerinic acid (2,3-DPGA). The concentration of plasma hemoglobin (Hb) was measured as an indicator of spontaneous hemolysis. In the red blood cells from patients with APPT, the activity of LDG and SOD was found to be drastically suppressed, the content of MDA was increased, the intracellular level of PAF was lowered and the concentration of 2,3-DPGA was very moderately elevated. The plasma concentration of free Hb is thrice as high as the normal value. Following 3 months of chemotherapy with 4-5 drugs, the activity of LDG became higher, yet remaining less than the normal values and that of G-6-PDG significantly dropped. The activity of SOD and catalase increased, but the level of MDA remained high. There was a drastic fall in the intracellular levels of PAF. The plasma concentration of free Hb dropped, but remaining significantly higher than the normal values. Possible ways of correcting the changes found are discussed in the paper.

[Iron metabolism in patients with different variants of pulmonary tuberculosis]. / Osobennosti metabolizma zheleza u bol'nykh s raznymi variantami techeniia tuberkuleza legkikh.

Prior to treatment, 48 patients with different forms of pulmonary tuberculosis were examined. Serum iron concentrations, total iron-binding capacity of the serum (STIBC), its unsaturated iron-binding capacity (SUSIB), serum transferrin iron saturation coefficient (SC), total protein in the serum, red blood cells, hemoglobin, colour index were determined. All the parameters under study were in the normal range in patients with a favourable involutional course of pulmonary tuberculosis. In patients with acutely progressive pulmonary tuberculosis, serum iron levels, STIBC, SC were drastically decreased, while SUSIB was in the normal range. All this was attended by phenomena of hypochromic anemia. The pattern of the found changes leads to the conclusion that patients with acutely progressive tuberculosis develop iron-redistributing anemia caused by the changes in the amount and quality of transferrin, iron binding during free radical processes and mobilization of the antioxidant defense system rather than true iron deficiency.

[Use of soluble ozone in combined treatment of pulmonary tuberculosis: lipid peroxidation and blood antioxidative defense systems]. / Sostoianie sistemy perekisnogo okisleniia lipidov i antioksidantnoi zashchity krovi pri ispol'zovanii rastvorennogo ozona v kompleksnom lechenii tuberkuleza legkikh.

Changes in lipid peroxidation and blood antioxidative defense systems and red blood cell function were studied in 16 patients with prolonged progressive pulmonary tuberculosis in response to intravenous soluble ozone (SO) administration. There was a drastic rise in the activity of intraerythrocytic superoxide dismutase (SOD) and a reduction in intracellular malonic dialdehyde (MDA) levels. In the remaining patients, there was a decrease in the activity of SOD and an increase in intraerythrocytic MDA concentrations. Plasma catalase activity increased in all patients and MDA levels lowered. It is proposed that initial SO doses for patients with chronic pulmonary tuberculosis should be chosen on an individual basis by taking into account intraerythrocytic SOD-MDA changes due to SO initiation.

[Oxidative metabolic changes, antioxidantion, and platelet activation rat phagocytes during development of experimental specific tuberculous changes]. / Izmeneniia okislitel'nogo metabolizma, sostoianie antioksidatnoi sistemy i uroven' factora aktivatsii trombotsitov v fagotsitakh krys pri razvitii éksperimental'nykh spetsificheskikh tuberkuleznykh izmenenii.

An experiment was made on 100 noninbred albino rats, of which 80 rats were intraperitoneally inoculated by Mycobacterium tuberculosis (MT) in a dose of 7.5 mg. Examinations were conducted 1 day, 1, 2, and 8 weeks after inoculation. Alveolar macrophages, nonfractionated cellular sediment of bronchoalveolar lavage, and leukocytes were the object of the studies. Spontaneous and BCG-stimulated HCT test, the activities of superoxide dismutase (SOD) and catalase, the content of malonic dialdehyde (MDA), and platelet activation factor (PAF) were determined in all cell populations. The course of the process was histologically controlled. Following a fortnight, specific foci developed in the organs, they began spontaneously resolving 6 weeks later. In all types of cells, an infectious process resulted in an increase in the rate of oxidative metabolism, which did not lead to their functional exhaustion. In early infection, the activity of SOD dropped, the level of MDA and the activity of catalase increased. During involution of specific changes, their normalization of MDA and catalase variables corresponded to the high values of SPD in the cells. The level of PAF moderately elevated during the formation of specific changes in the organs and fell below the control values in the involutional phase of the process.

[Features of oxidative metabolism and level of platelet activating factor in pulmonary and circulating phagocytes of tuberculosis-resistant animals at stages of experimental infection]. / Osobennosti okislitel'nogo metabolizma i uroven' faktora aktivatsii trombotsitov v legochnykh i tsirkuliruiushchikh fagotsitakh rezistentnykh k tuberkulezu zhivotnykh na étapakh éksperimental'noi infektsii.

An experiment was conducted on noninbred albino rats intraperitoneally inoculated with Mycobacteria tuberculosis (MBT) in a dose of 0.025 mg. Alveolar macrophages (AM), non fractionated cell sediments (NFCS) and circulating leukocytes were studied 1 day, 1, 2, and 6 weeks after inoculation. Spontaneous and killed BCG culture-stimulated killed HCT-test, the activity of superoxide dismutase (SOD) and catalase, the level of malonic dialdehyde (MDA) and platelet activation factor (PAF) were determined. Morphological changes were histologically controlled. The rats administered the MBT dose sufficient to initiate generalized tuberculosis in guinea pigs were found to develop nonspecific changes which became reversible by the end of the experiment. Throughout the process, there was no splash of basal oxidative metabolism in all phagocytic types and their functional decompensation did not develop. Following 1.5 months, all the types of phagocytes showed an increased oxygen burst during specific stimulation. The level of MDA did not exceed the control values in all periods. The activity of anti-oxidative enzymes changed heterodirectionally. At the final stage, the activity of catalase repeatedly increased with normal or reduced SOD values. In early infection, the concentration of PAF rose in the pulmonary phagocytes. When resistance was formed, in all cell types it fell below the control values.