[Impact of surgical sanation of patients with destructive tuberculosis on the prevalence of tuberculosis and mortality of these patients]. / Vliyanie khirurgicheskoi sanatsii kontingentov bol'nykh destruktivnym tuberkulezom na osnovnye pokazateli rasprostranennosti i smertnosti ot tuberkuleza.

OBJECTIVE: To analyze the impact of surgical sanation of patients with destructive tuberculosis on the prevalence of tuberculosis and mortality of these patients. MATERIAL AND METHODS: Treatment strategy for destructive pulmonary tuberculosis de novo was developed in the Sechenov First Moscow State Medical University. This strategy was applied at the Surgical Department of the Regional Tambov Tuberculosis Dispensary in 2013-2017. We formed a register of patients with pulmonary destruction and bacterial excretion and developed a personal treatment plan. All patients were divided into 3 groups (group A - surgical treatment, group B - no surgery due to refusal or discontinuation of treatment, group C - patients with contraindications or no indications for surgical treatment). RESULTS: Treatment efficacy considering closure of destruction cavities and abacillation was maximal in group A - 97.2%, 41.4% in group B and 39.8% in group C. The number of patients with pulmonary destruction and bacterial excretion has decreased by 3.3 times (from 516 to 158) or 69.8% for 4 years of extensive application of surgical treatment protocol. A significant reduction of 'bacillary core' interrupted infection chain and affected the main epidemiological characteristics. Short-term reduction of the incidence of tuberculosis may be expected. However, even more significant impact of this factor should be expected in the long-term period. CONCLUSION: Surgical treatment of destructive pulmonary tuberculosis improves efficacy of the management of these patients and reduces mortality rate.

[Influence of surgical sanation of patients with destructive tuberculosis on the prevalence of tuberculosis and mortality]. / Vliianie khirurgicheskoi sanatsii kontingentov bol'nykh destruktivnym tuberkulezom na osnovnye pokazateli rasprostranennosti i smertnosti ot tuberkuleza.

OBJECTIVE: To analyze the influence of surgical sanation of patients with destructive tuberculosis on the prevalence of tuberculosis and mortality. MATERIAL AND METHODS: The strategy of treatment for new cases of destructive pulmonary tuberculosis was developed in the Perelman Department of Phthisiopulmonology and Thoracic Surgery of the Sechenov First Moscow State Medical University. This strategy was applied in the tuberculosis surgical department of the Tambov Regional Dispensary in 2013-2017. A register of patients with pulmonary destruction and bacterial excretion was developed and personal treatment plans were applied. Patients were divided into 3 groups depending on the treatment mode. The main group A consisted of patients who underwent surgical treatment. Surgery was not performed due to failure or discontinuation of treatment in the comparison group B. Group C included patients without indications or with contraindications for surgical treatment. RESULTS: Treatment efficacy considering destruction cavities closure and abacillation was 97.2% in group A, 41.4% in group B and 39.8% in group C. Surgical approach for patients with destructive tuberculosis reduced the number of patients in the register by 3.3 times (from 516 to 158) within 4 years. A significant reduction of the bacillary core allows breaking the infection chain, that affects the main epidemiological indicators. Reduced incidence of tuberculosis is observed in short-term period, but even greater impact of this factor should be expected in long-term follow-up. CONCLUSION: Surgical approach in complex treatment of destructive pulmonary tuberculosis is valuable to improve efficacy of management of these patients and reduce mortality rate.

Kinetics of merthiolate-induced aggregation of human platelets.

Incubation of human platelet-rich plasma (PRP) or washed platelets with merthiolate (MT; sodium ethylmercurithiosalicylate; an inhibitor of lysophosphatide: arachidonoyl transferase) leads to irreversible platelet aggregation which is parallelled by an increase in thromboxane A2 synthesis. MT-induced aggregation is preceded by a pronounced lag-period (0.5-10 min). Duration of the latter is inversely related to the concentration of MT ([MT]). Platelet responses to MT are similar to those triggered by arachidonate (AA) in that the relationships of the aggregation rates both to [MT] and [AA] are threshold and exhibit characteristic super-high values of the apparent Hill coefficients (h > 30). A typical MT-induced response can be subdivided in two sequential phases: i) cyclooxygenase-independent slow aggregation, and ii) indomethacin-abrogated rapid aggregation. MT-induced responses are blocked by PGE1 or ajoene (which inhibits binding of fibrinogen to its cell surface receptor, GPIIb/IIIa). The obtained data are interpreted both quantitatively and qualitatively in terms of a model assuming the existence of: i) a relationship between the rate of MT-inhibitable AA incorporation into phospholipids and the concentration of intracellular free AA, [AA]i; ii) a certain threshold value of [AA]i essential for triggering the second phase of the aggregation.

Cell response kinetics: the phenomenon of supercooperativity in aggregation of human platelets.

Concentration-response relationships of human platelet aggregation rates were analyzed for a variety of agonists and inhibitors. Their approximation by the Hill equation showed that the values of the Hill coefficient (h) were agonist-dependent and increased as follows: hADP = hL-EPINEPHRINE = hPAF = hPGH2 = hU46619 less than hPMA less than hA23187 less than hMERTHIOLATE = hARACHIDONATE. The results were interpreted in terms of a model assuming varying degrees of cooperativity for each step of signal transduction involved in platelet aggregation. Super-high values of h (greater than 30) obtained with arachidonate and merthiolate, as well as in the case of inhibition of an arachidonate-induced response by indomethacin and PTA2, suggested that at least one region of signal transduction pathway leading to aggregation exhibited supercooperative properties.

[Kinetics of merthiolate-induced aggregation of human platelets]. / Kinetika mertioliat-indutsirovannoi agregatsii trombotsitov cheloveka.

Incubation of human platelets (in the form of platelet rich plasma or washed platelet suspension) with sodium merthiolate (ethyl mercuric salicylate inhibiting the arachidonic acid incorporation into phospholipids) induces their irreversible aggregation, which is accompanied by TxB2 synthesis. The merthiolate-induced aggregation has a lag-period of 0.5-10 min, whose magnitude is inversely correlated with the merthiolate concentration. The concentration dependencies of the rate of the merthiolate-induced and arachidonate-induced aggregation are threshold ones; the Hill coefficients are more than 30. The merthiolate-induced aggregation occurs in two phases: a slow phase which is independent of the arachidonic acid cyclooxygenase metabolism and a fast phase which is fully blocked by indomethacin. This aggregation is inhibited by PGE1 and ajoene (an inhibitor of the fibrinogen interaction with the fibrinogen receptor, GPIIb/IIIa). Quantitative and qualitative analyses of the experimental data were performed, using a model which took account of: (a) increase in the concentration of free endogenous arachidonic acid resulting from the inhibition by merthiolate of the arachidonic acid re-incorporation into phospholipids, and (b) existence of a threshold intracellular arachidonic acid concentration needed for the irreversible aggregation of platelets.

[The ajoene blockade of integrin-dependent processes in an HIV-infected cell system]. / Blokada adzhoenom integrinzavisimykh protsessov v sisteme kletok, infitsirovannykh VICh.

Ajoene, (E,Z)-4,5,9-trithiadodeca-1,6,11-triene-9-oxide, isolated from extracts of garlic (Allium sativum) has been previously shown to inhibit platelet aggregation by inactivating allosterically the platelet integrin, GP IIb/IIIa. The structural and functional similarity of integrins led the authors to suggest that ajoene may also inhibit adhesive interactions and fusion of leukocytes. Synthetic stereoisomers of ajoene synthesized by the authors exhibited equal antiaggregatory activities (IC100 approximately 50 microM for platelets; IC100 approximately 10 microM for fMLP-stimulated neutrophils). Racemic ajoene inhibited the fusion of H9 cells with HIV-infected H9:RF cells (IC50 approximately 45 microM; 16 h of incubation) and also exhibited a degree of antiviral activity (IC50 approximately 5 microM as assessed by inhibition of HIV-1/CEM/Lav 1 Bru replication in CEM13 cells; m. o. i. 0.1; 72 h). A considerable increase in the latter became evident when the compound was administered in aliquots of 50 microM per 12 h of incubation (inhibition by 30%; total concentration 0.25 microM; 72 h).(ABSTRACT TRUNCATED AT 250 WORDS)

The role of adhesive interactions and extracellular matrix fibronectin from human polymorphonuclear leukocytes in the respiratory burst.

The Arg-Gly-Asp (RGD) tripeptide and ajoene were used for studying the role of adhesive receptors in the respiratory burst. Activation of the respiratory burst was examined by using luminol-dependent and lucigenin-dependent chemiluminescence. Recently, it was shown that ajoene, (E, Z)-4,5,9-trithiadodeca-1,6,11-trien-9-oxide, a substance isolated from garlic extract, inhibits the binding of fibrinogen to activated platelets by direct interaction with fibrinogen receptor (Apitz-Castro, R., Lederma, E., Escalante, J. and Jain, M.K. (1986) Biochem. Biophys. Res. Commun. 141, 145-150). Taking into consideration the structural and functional similarity of integrins, it would be reasonable to assume that ajoene as well as RGD can inhibit adhesive interactions of human neutrophils. We have shown that the effect of various activators on the respiratory burst was abolished by ajoene or RGD treatment. The inhibitory effect of RGD and ajoene was dose-dependent. The treatment of neutrophils with antiserum against human plasma fibronectin inhibited the respiratory burst in response to formyl-methionyl-leucylphenylalanine (fMLP) and phorbol 12-myristate 13-acetate (PMA). This effect is dose-dependent and reversible with the addition of fibronectin. These data indicate that the respiratory burst in human neutrophils is mediated by the integrin family of receptors and that interactions between the extracellular matrix fibronectin and cells are necessary for the respiratory burst.

[Preparation and properties of prostaglandin D2 labelled with tritium with high molar radioactivity]. / Poluchenie i svoistva mechennogo tritiem prostaglandina D2 s vysokoi moliarnoi radioaktivnost'iu.

Kinetic parameters of enzymatic and non-enzymatic transformations of [3H]prostaglandin H2 (PGH2) were determined; the maximum yield of [3H]PGD2 being obtained at the keobs/koobs ratio equal to 10. The two-stage enzymatic synthesis of [3H]PGD2 with high molar radioactivity (3.15 TBq/mmol) from [3H]arachidonic acid carried out. Its identity in properties to the natural PGD2 was shown in experiments on the inhibition of ADP-induced aggregation of thrombocytes and on enzymatic oxidation with 15-hydroxyprostaglandin dehydrogenase.