[POSSIBILITIES FOR THE USE OF THE ANTI-LEUKOTRIENE DRUG MONTELUKAST IN COMBINED THERAPY OF PATIENTS WITH BRONCHIAL ASTHMA AND COLD-INDUCED BRONCHIAL HYPERACTIVITY].

AIM: To study effectiveness of the use of the anti-leukotriene drug montelukast in combination with inhalation glucocorticoid and long-acting beta-agonist in patients with bronchial asthma (BA) and cold-induced bronchial hyperactivity (CBHA) with a view to optimizing control of the disease. MATERIALS AND METHODS: We carried out an open comparative prospective study of patients with persistent BA in a cold season under conditions of real clinical practice. The patients were divided into 2 groups. Group 1 included patients with CBHA, group 2 consisted of subjects with constant bronchial reactivity in response to cold in the standard provocative test. The patients were followed up for 24 weeks. During the first 12 weeks of the treatment, the patients of group I were given sodium montelukast with budesonide/formoterol. In the next 12 weeks they received only budesonide/formoterol at the same dose. Patients of group 2 were treated with budesonide/formoterol during the entire study period. Efficacy of therapy was assessed by asthma control test (ACT). RESULTS: Control of BA in group 1 (20-25 scores in A CT) was achieved in 83% of the patients within the first 12 week period The result was comparable (87%) with that in group 2. Impairment of control (to 52%) was documented in group I during the last 12 weeks although it was preserved (20-25 scores) in group 2 (81%). CONCLUSION: The use of sodium montelukast in combination with budesonide/formoterol for the treatment of BA with CBHA in winter season ensured control of the disease in most patients during 12 weeks. Withdrawal of montelukast in the subsequent period leads to the loss of control and a rise in the frequency of exacerbation.

[The antioxidizing activity of malonic acid derivatives]. / Antiokislitel'naia aktivnost' proizvodnykh malonovoi kisloty.

Nine newly synthesized malonic acid derivatives were shown to have antioxidizing activity which makes up from 30 to 60% of the antioxidizing activity of ionol and vitamin E in vitro and does not yield to the activity of the latter substances in vivo. It is suggested that malonic acid derivatives may influence the antioxidizing enzymes--catalase, glucose-6-phosphate dehydrogenase and superoxide dismutase.

[Structural-functional properties of erythrocyte membranes in patients with infectious-allergic bronchial asthma]. / Strukturno-funktsional'nye svoistva membran éritrotsitov u bol'nykh infektsionno-allergicheskoi bronkhial'noi astmoi.

A decrease in activity of Ca2(+)-ATPase and activation of Na+, K(+)-ATPase, correlating with elevation in content of phosphatidyl inositol and phosphatidyl serine, were detected in erythrocyte membranes of patients with the infectional-allergic form of bronchial asthma. Microviscosity of the erythrocyte membranes, estimated by fluorescence spectra of pyrene, was not altered, while negative charge as shown by ANS- fluorescence, was slightly increased on the membrane surface. Euphylline, intal, levamizole and glucocorticosteroid were found to regulate the ATPases activity in vivo and in vitro.

[Phospholipid restoration of microsome membranes damaged by Fe2+--ascorbate-dependent lipid peroxidation]. / Vosstanovlenie fosfolipidami membran mikrosom, povrezhdennykh Fe2+--askorbat-zavisimym perekisnym okisleniem lipidov.

The incubation of microsomes damaged by Fe2+--ascorbate-dependent lipid peroxidation with phosphatidylcholine liposomes and micelles is accompanied by the rate decrease of the reduced cytochrome P450 inactivation in microsome membranes. It indicates the elimination of lipid bilayer injuries. The results of study of the saturation degree, surface charge and size of liposomes and micelles influence on the ability to reconstruct the damaged lipid bilayer are presented.

[Cytochrome P450 inactivation in microsomal membranes damaged by Fe2+-ascorbate-dependent lipid peroxidation]. / Inaktivatsiia tsitokhroma P450 v membranakh mikrosom, povrezhdennykh Fe2+-askorbat-zavisimym perekisnym okisleniem lipidov.

It has been established that Fe2+-ascorbate-dependent lipid peroxidation in rat liver microsome membranes is followed by the decrease of microsome cytochrome P450 content and the increase of the reduced haemoprotein inactivation rate. These changes are proportional to the amount of lipid peroxidation products (malonic dialdehyde) accumulating in the membranes.

[Extraction of cholesterol from biological membranes with positively charged micelles of phosphatidylcholine]. / Ekstraktsiia kholesterina iz biologicheskikh membran polozhitel'no zariazhennymi mitsellami fosfatidilkholina.

The content of cholesterol in red cell and platelet membranes was lowered in rabbits with experimental atherosclerosis after intravenous injection of positively charged micelles of soybean phosphatidylcholine. That lowering was accompanied by a reduction in membrane microviscosity, rise of the activity of Na,K- and Ca-ATPases of red cells, and a decrease in the rate of the ADP- and collagen-induced platelet aggregation. Injection of phosphatidylcholine gave rise to an increase in the blood serum content of phospholipids and cholesterol in high density lipoprotein fractions, to a reduction in the content of triglycerides and the atherogenicity index, as well as to the lowering of the microviscosity of high density lipoproteins. The aortal area affected by atherosclerotic lesions was 2 times less in the group of animals given phosphatidylcholine.

[Molecular and cellular mechanisms of compensation for respiratory failure in nonspecific lung diseases]. / Molekuliarno-kletochnye mekhanizmy kompensatsii dykhatel'noi nedostatochnosti pri nespetsificheskikh zabolevaniiakh legkikh.

Some molecular and cellular mechanisms of compensation for respiratory failure (RF) were examined in 90 patients with nonspecific pulmonary diseases. In acute RF, the content of 2,3-DPH in red blood cells was increased. As RF progressed, the compensatory-adaptation reaction became less marked. In chronic RF, the 2,3-DPH content in red blood cells did not differ from the control values. The disease was characterized by cholesterol a and sphingomyelin accumulation, a reduction in red blood cell ATPase activity, and an increase in microviscosity of red blood cell membranes. Decelerated utilization of ATPases in red blood cells is of a role in the genesis of a rise of the 2,3-DPH content in acute RF.

[Extraction of cholesterol from erythrocyte ghosts by phospholipids]. / Izvlechenie kholesterina iz tenei éritrotsitov fosfolipidami.

Removal of cholesterol from erythrocyte ghosts by liposomes and micellas of different phospholipids was investigated. It was shown that the positively charged micelles of polyunsaturated phospholipids are the most efficient for cholesterol removal from biological membranes.

The influence of cholesterol incorporation and removal on lipid-bilayer viscosity and electron transfer in rat-liver microsomes.

The incorporation and removal of cholesterol from rat liver microsomes was used as a methodical approach to investigate the molecular organization of microsomal redox-chains. It was shown that the incorporation of cholesterol in microsomes increases and removal of cholesterol decreases lipid bilayer viscosity as indicated from the rate of fluorescent probe-pyrene eximerisation in cholesterol-enriched and cholesterol-depleted microsomes. The increase of membrane viscosity slows down the initial rates and decreases the rate constants of cytochrome b5 reduction by NAD(P)H, whereas the decrease of membrane viscosity enhances the initial rates and increases the rate constants of these reactions. The rates of cytochrome P450 reduction by reduced pyridine nucleotides do not depend on the viscosity of lipid bilayer. The incorporation and removal of cholesterol from microsomes was not followed by any essential changes in the rates of dimethylaniline N-demethylation, aniline p-hydroxylation, p-nitroanisole O-demethylation, oxygen consumption, oxidation of NADH and NADPH. Thus the reduction of cytochrome b5 by NADH and NADPH is the diffusion-dependent reaction in the redox-chains of microsomes only.

[Effect of incorporation and removal of cholesterol on the lipid bilayer viscosity and the rate of oxidative reactions in rat liver microsomal membranes]. / Vliianie vstraivaniia i vyvedeniia kholesterina na viazkost' lipidnogo bisloia i skorost' okislitel'nykh protsessov v membranakh mikrosom pecheni Krysy.

The interrelationship between the lipid bilayer viscosity and the rate of oxidative reactions in rat liver microsomal membranes were investigated. The viscosity of the lipid bilayer is increased upon incorporation of cholesterol into the microsomes and is decreased upon its removal. This results in a corresponding decrease and increase of the rate of cytochrome b5 reduction by NAD(P)H. The rates of cytochrome P-450 reduction and oxidation of dimethylaniline, aniline, p-nitroanisol and NAD(P)H, as well as those of oxygen uptake and lipid peroxidation do not depend on the bilayer viscosity. Hence only the reactions of cytochrome b5 reduction by NADH- and NADPH-specific flavoproteins are diffusion-dependent processes in the microsomal oxidation chain.

[Isolation of cholesterol from erythrocyte ghosts microsomes and blood plasma using specific sorbent and phospholipid liposomes]. / Izvlechenie kholesterina iz tenei éritrotsitov, mikrosom i plazmy krovi spetsifichnym sorbentom i fosfolipidnymi liposomami.

A sorbent specific for cholesterol enabled to isolate effectively the substance from blood plasma and membranes of erythrocyte shadows. Cholesterol was not isolated from microsomal membranes neither with the sorbent MGU-I nor by means of phospholipid liposomes. The phenomenon was apparently related to the localization of cholesterol on the inner surface of lipid bilayer of microsomal membranes.

[Cholesterol content in human and rabbit erythrocytes in atherosclerosis and experimental hypercholesteremia]. / Soderzhanie kholesterina v éritrotsitakh cheloveka i krolika pri ateroskleroze i éksperimental'noi giperkholesterinemii.

Direct correlation was observed between the content of cholesterol in erythrocytes and the level of alimentary hypercholesterolemia as well as the severity of heart ischemic disease in patients. Data on alterations in cholesterol content in erythrocytes may be used as a prognostic test for development of ischemic impairments of heart.