Management of Chronic Obstructive Pulmonary Disease.

The relevance of the study of chronic obstructive pulmonary disease (COPD) can be explained by the persistence of unfavorable dynamics of the disease, even despite the achieved success in the pharmacotherapy of this pathology. In 2016, World Health Organization (WHO) ranked COPD as the third leading cause of death worldwide, far exceeding the experts' predictions, who believed that such an increase in the death rate would occur by 2030. This study aimed to determine the level of senior medical students' knowledge in the management of patients with COPD, based on the method of anonymous questioning. This research work describes the results of the second stage of the ASCO project (Assessment of Senior Medical Students in the Field of COPD) conducted in 2017-2019 among 338 senior medical students from six large cities of Russia and Ukraine. The survey revealed the average level of knowledge among senior medical students, based on the average level of correct answers (56.6%) obtained in the study. The best results were obtained for the questions about COPD risk factors, influenza vaccine prevention, and pneumococcal vaccine prevention in COPD patients. The worst results were recorded on the questions about the severity of COPD clinical symptoms, the choice of initial therapy for COPD with advanced symptoms, a high risk of exacerbations, and the moderate exacerbation of COPD. The obtained results indicated an insufficient level of students' basic knowledge in questions regarding etiopathogenesis, diagnosis, treatment, and prevention of COPD.

[Correction of endothelial dysfunction by L-arginine under experimental pre-eclampsia conditions].

The ADMA-like pre-eclampsia in pregnant rats was modeled by daily introduction of L-NAME in a dose of 25 mg/kg for 7 days. L-arginine (200 mg/kg) prevented the development of arterial hypertension and a decrease in placentary microcirculation and microalbuminuria. The possibility of using L-arginine for the prevention of competitive eNOS inhibition by ADMA is discussed.

[Integrated assessment of endothelio- and cardioprotective activity of macrolide antibiotics in nitric oxide deficiency model].

Experiments on laboratory animals with nitric oxide deficiency modeled by the introduction of L-NAME (NO-synthase inhibitor) revealed the endothelio- and cardioprotective effects of clarithromycin, josamycin, roxithromycin, midecamycin and azythromycin. The administration of these macrolides leads to a decrease in the resulting area of the diagram of functional indices of the state of vessels and myocardium, which is approaching the corresponding area for intact animals.

[Experimental study of cardioprotective and endothelioprotective action of macrolides and azalides].

The cardioprotective and endothelioprotective effects of the macrolide antibiotics roxithromycin, azythromycin, and midecamycin have been studied on laboratory animals with models of the coronaro-occlusional myocardial infarction and endothelial dysfunction. The drugs led to a dose-dependent decrease in lethality, reduced the zone of necrosis of the left ventricle after coronary occlusion, and produced a positive effect on the functioning of endothelium.

[Pharmacological correction of experimental chronic limb ischemia].

In tests on a group of 250 rats, we studied (i) the level of microcirculation in the muscles of a healthy limb in the norm and (ii) the dynamics of microcirculation for 6 h after treatment with pentoxifylline in a dose of 60 mg/kg dose and L-arginine in a dose of 30 and 200 mg/kg. The chronic ischemia was modeled by excision of basic femoral artery. There was no significant difference in pentoxyfilline-treated animals in comparison to the control. In the group treated with L-arginine in a dose of 30 mg/kg, a significant increase in microcirculation was observed on the 28-th day of experiment. In the group treated with L-arginine in a dose of 200 mg/kg, there was an increase of microcirculation in all terms of the experiment in comparison to the control. The results of laser doppler flow measurements are correlated with the results of morphological investigation.

[Endothelioprotective properties of L-arginine in a nitric oxide deficiency model].

In laboratory animals with endothelial dysfunction (nitric oxide deficiency) modeled by the introduction of NO-synthase inhibitor L-NAME, the activation of endothelioprotective effects of enalapril, lozartan, amlodipine, indapamide and nebivolol is revealed for their introduction in combination with L-arginine. This result was confirmed by the behavior of a generalizing parameter, the coefficient of endothelial dysfunction (CED) calculated using the results of tests on endothelium-dependent and -independent vasodilation.

[Effect of nonelectrolytes on the polymerization of G-actin]. / Vliianie neélektolitov na polimerizatsiiu G-aktina.

The non-electrolytes--urea, thiourea, sucrose, glycerin, polyethylendioxid, glutaraldehyde--inhibit polymerization of G-actin in vitro. The results are discussed in association with the capability of some non-electrolytes preventing colloid reactions of alterated protoplasm and increasing the stability of cells to injuring agents.

[NADPase and NADase in the peritoneal macrophages of mice]. / NADFaza i NADaza peritoneal'nykh makrofagov myshei.

Murine peritoneal macrophages are able to hydrolyse NAD+ and NADP+. The NADPase activity exceeds that of NADase by 22-24%. The pH optima for both the enzymes are, respectively, 6.0 and 7.0. NAD hydrolysis is considerably activated by Mg2+, whereas NADP hydrolysis remains not affected. NAD+ does not change NADPase activity, while NADase activity is inhibited by NADP by 25-30%. A diazonium salt of sulfanilic acid, known to be an inhibitor of cell plasma membranes, does not affect NADP+ hydrolysis and causes a 20-30% retardation of NAD+ hydrolysis. The data obtained suggest that murine peritoneal macrophages contain two hydrolytic enzymes: NADase and NADPase.

[Synthesis and breakdown of pyridine nucleotide coenzymes in the cell nuclei of guinea pig kidneys in diphtheria intoxication]. / Sintez i raspad piridinnukleotidnykh kofermentov v iadrakh kletok pochek morskoi svinki pri difteriinoi intoksikatsii.

The effect of diphteria toxin on the synthesis and degradation of NAD+ and the hydrolysis of NADP+ in the nuclei of guinea pig kidney were studied. Treatment of animals with diphteria toxin (DT) results in considerable reduction of NADpyrophosphorylase activity, which starts 12 hours after incubation and is minimal (50% of that of the control animals) 18 hours after it. During this time interval DT does not affect the activity of NADase and decreases that of NADPase in the nuclei. Thus under diphterial intoxication a decrease of NADPase activity, the synthesis of NAD+ being reduced, probably provides for kidney cells more favourable conditions for maintenance of their synthetic reactions and for restoration of their normal metabolism. It was found that the non-ionic detergent Triton X-100 promotes the NADpyrophosphorylase activity in cell nuclei of intact animals by 40% (on the average) and does not affect the NAD+ synthesis in DT injected animals. Therefore DT not only reduces the nuclear NADpyrophosphorylase activity but also affects the nuclear envelope. The alteration of nuclei under DT treatment is suggested by the decrease of their histone content (30% on the average as compared with the control). The decrease of NADpyrophosphorylase activity under DT intoxication can be considered as an adaptive reaction limiting the availability of NAD+ as the substrate of the EF2 mono (ADP-ribosilation) which results in its unability to promote translation.

[NAD+ synthesis in the isolated kidney cell nuclei of dogs after the intravenous administration of amphotericin B]. / Sintez NAD+ v izolirovannykh iadrakh kletok pochek sobak posle vnutrivennogo vvedeniia amfoteritsina B.

A study was made of the synthesis of nicotinamide adenine dinucleotide (NAD+) in the nuclei of kidney cells of dogs under normal conditions and upon the effect of the polyenic antibiotic amphotericin B. An active NAD-pyrophosphorylase has been found in the nuclei of kidney cells. It has been established that a intervenous introduction of amphotericin B stimulates NAD+ production. Amphotericin B also causes a decrease in the amount of histones in the nucleus. In the case of the nuclear membrane damage by a non-ionic detergent Triton X-100, no increase in the synthesis of NAD+ has been observed in the nuclei of kidney cells of animals treated with antibiotics, as opposed to the control ones. Under discussion is a question of a possible mechanism of the effect of polyenic antibiotics on the synthesis and metabolic activity of NAD+.