Functional Activity of Blood Neutrophils in Patients with Stable Course and Exacerbation of Chronic Obstructive Pulmonary Disease.

We performed a comparative study of the parameters of chemiluminescence of blood neutrophils in patients with different severity of chronic obstructive pulmonary disease in its different periods. The maximum values of induced and spontaneous chemiluminescence were recorded at moderate severity of the disease during exacerbation. Low levels of chemiluminescence indicators were found in severe chronic obstructive pulmonary disease in the stable phase. The values of the induction period of the chemiluminescent response in patients with moderate chronic obstructive pulmonary disease were higher than in the control group. Correlations between the values of induced chemiluminescence of neutrophils and the respiration function parameter FEV1 were established, which may indicate the influence of multidirectional changes in the functional activity of systemic neutrophils on the development and worsening of airway obstruction in chronic obstructive pulmonary disease patients.

Autoregulation and Autoinhibition of the Main NO Synthase Isoforms (Brief Review).

Nitric oxide (II) (NO) is the most important mediator of a wide range of physiological and pathophysiological processes. It is synthesized by NO synthases (NOSs), which have three main isoforms differing from each other in terms of activation and inhibition features, levels of NO production, subcellular localization, etc. At the same time, all isoforms are structurally very similar, and these differences are determined by NOS autoregulatory elements. The article presents an analysis of the autoregulatory and autoinhibitory mechanisms of the NOS reductase domain that determine differences in the productivity of isoforms, as well as their dependence on the concentration of Ca2+ ions. The main regulatory elements in NOS that modulate the electron transfer from flavin to heme include calmodulin (CaM), an autoinhibitory insert (AI), and the C-terminal tail (C-tail). Hydrophobic interactions of CaM with the surface of the NOS oxidase domain are assumed to facilitate electron transfer from flavin mononucleotide (FMN). CaM binding causes a change in the inter-domain distances, a shift of AI and the C-tail, and, as a result, a decrease in their inhibitory effect. CaM also shifts the conformational equilibrium of the reductase domain towards more open conformations, reduces the lifetime of conformations, their stereometric distribution, and accelerates the flow of electrons through the reductase domain. The AI element, apparently, induces a conformational change that hinders electron transfer within the reductase domain, similar to the hinge domain in cytochrome P450. Together with CaM, the C-tail regulates the electron flow between flavins, the distance and relative orientation of isoalloxane rings, and also modulates the electron flow from FMN to the terminal acceptor. Together with the C-tail, AI also predetermines the dependence of neuronal and endothelial forms of NOS on the concentration of Ca2+ ions, and the C-tail length affects differences in the productivity of NO synthesis. The inhibitory effect of the C-tail is likely to be reduced by CaM binding due to the C-tail shift due to the electrostatic repulsive forces of the negatively charged phosphate and aspartate residues. The autoregulatory elements of NOS require further study, since the mechanisms of their interaction are complex and multidirectional, and hence provide a wide range of characteristics of the observed isoforms.

Comparative Study of the Levels of IL-1ß, IL-4, IL-8, TNFα, and IFNγ in Stable Course and Exacerbation of Chronic Obstructive Pulmonary Disease of Varying Severity.

In patients with chronic obstructive pulmonary disease, the levels of cytokines IL-1ß, IL-4, IL-8, TNFα, and IFNγ depended on the degree of bronchial obstruction and severity and period of the disease. The maximum levels of IL-4, IL-8, and TNFα were observed in severe chronic obstructive pulmonary disease during exacerbation. The highest concentration of IL-1ß and IFNγ were recorded during activation of inflammation in patients with moderate bronchial obstruction. The revealed correlations between the tested cytokines and spirometry parameters make it possible to consider the levels of these proteins as quantitative markers of systemic inflammation progression.

[Oxidative stress in pathogenesis of bronchial asthma: a method of correction by inhalation of phospholipid nanoparticles].

The authors present the results of a prospective simple blind randomized placebo-controlled study for the evaluation of dynamics of biomarkers of oxidative stress (total concentration of nitrate- and nitrite-anions in condensed exhaled breath and plasma, pH of exhaled breath, total antioxidative activity of plasma in patients with bronchial asthma inhaling phospholipid nanoparticles. The results suggest significant positive effect of proposed therapy on dynamics of the main parameters of oxidative stress including reduced concentration of nitric oxide metabolites and increased total antioxidative activity of plasma. No clinically significant reactions were documented.

[Experience with the use of phospholipid preparations in the combined treatment of bronchial asthma].

The authors report the results of a single-blind randomized placebo-controlled study of the efficacy and safety of inhalation of phospholipid nanoparticles in patients with bronchial asthma. They give evidence of the statistically significant positive effect of the proposed therapeutic modality on the clinical status of the patients and lung functional tests. No clinically significant adverse events were documented during the study.

Peroxiredoxin VI in human respiratory system.

Peroxiredoxins (Prxs) constitute a novel family of antioxidant proteins, which specifically prevent enzymes from metal-catalyzed oxidation. The localization of a member of the mono-cystein subfamily of Prxs, Prx VI in human respiratory system and its antioxidant properties were investigated. By immunoblotting, the Prx VI was found to be present in human respiratory epithelium. Immunostaining with rabbit polyclonal antibody raised against the Prx VI revealed that the said protein was present in apical areas and mucus of all respiratory airways from trachea to bronchioles. Immunodepletion of the Prx VI profoundly decreased the antioxidant activity of the respiratory epithelium extract.

[N-Acetylcysteine: low and high doses in the treatment of chronic obstructive lung diseases in Chernobyl accident liquidators]. / N-Atsetiltsistein: malye i bol'shie dozy pri lechenii khronicheskikh obstruktivnykh boleznei legkikh u likvidatorov Chernobyl'skoi avarii.

AIM: To study clinical effectiveness and antioxidant activity of N-acetylcisteine (NAC) in daily doses 600, 1200, 1800 and 2400 mg in Chernobyl wreckers suffering from chronic obstructive pulmonary diseases (COPD). MATERIAL AND METHODS: Cough intensity and expectoration, malonic dialdehyde (MD), plasma calcium ions concentrations were studied in patients taking NAC. RESULTS: Cough intensity diminished insignificantly. Expectoration improved significantly only after intake of 1200 mg/day NAC. In higher doses expectoration difficulties appeared again. Five patients received a maintenance dose 200 mg/day as a result of which their expectoration improved. MDA in the above patients was 3.3 times higher than normal level, free calcium ion concentration was 1.7 times higher. Only 1200 mg/day dose of NAC brought MDA level to normal, higher doses made it subnormal. Calcium ions concentration decreased but insignificantly. Maintenance dose 200 mg/day returned MDA and calcium to initial level. CONCLUSION: For patients with radiation-induced affection of the respiratory tracts NAC dose 1200 mg/day is optimal both clinically and in terms of antioxidant activity.

[Formation of active forms of oxygen by rat peritoneal macrophages under the effect of cytotoxic dust]. / Obrazovanie aktivnykh form kisloroda peritoneal'nymi makrofagami krys pod vliianiem tsitotoksicheskikh pylei.

The velocity of superoxide radicals (O2) production by rat peritoneal macrophages, phagocyting the dust particles (quartz and crocidolite-asbestos was measured by using the method of cytochrome c reduction. Generation of hydroxyl radicals (HO) by cells and intensity of lipid peroxidation in the membranes of phagocytes were also investigated. It was found, that under the action of quartz the cells form mainly O2, and under the action of crocidolite--O2 and HO(.). The differences observed were caused by catalytic properties of the surface of asbestos fiber, where the reaction of HO. formation from O2 takes place. The quartz particles increased the concentration of malondialdehyde in macrophages by 53% as compared with control; and lipid peroxidation intensity in the presence of crocidolite-asbestos fibers increased fourfold. The role of hydroxyl radicals in initiating of lipid peroxidation, cytotoxicity and mutagenicity of asbestos is discussed.

Are quinones producers or scavengers of superoxide ion in cells?

The effects of quinones (benzoquinone, menadione, and doxorubicin) on the superoxide production in cell free systems (xanthine oxidase and rat liver microsomes) and of polycationic electrolyte- and latex-stimulated rat peritoneal macrophages have been studied. Contradictory results were obtained in cell free systems when two traditional assays for detection of superoxide ion, the cytochrome c reduction and the lucigenin-dependent chemiluminescence (CL), were used: all quinones inhibited the lucigenin-dependent CL at sufficiently large concentrations, but they did not inhibit at all the reduction of cytochrome c. It was proposed that the cytochrome c assay gave erroneous results due to the reversibility of the interaction of semiquinones with dioxygen. The effect of quinones on the superoxide production by peritoneal macrophages was biphasic: all quinones stimulated the O2-. formation at low concentrations and inhibited it at elevated concentrations. It was concluded that among the quinones studied, only menadione was capable of stimulating the superoxide production via a one-electron transfer mechanism in cell free systems, while the stimulatory effect of small concentrations of quinones on the O2-. production in macrophages was possibly due to their action on the activation of NADPH oxidase.