[COVID-19 in haemodialysis patients: result analysis of the first year of the pandemic].

BACKGROUND: Present concepts of the novel coronavirus infection prognosis in haemodialysis (HD) patients are rather controversial. There is little information on therapy efficiency and safety in such patients. We studied COVID-19 course specifics, prognostic factors associated with fatal outcomes, therapy efficiency and its transformation at different stages of the pandemic first year. MATERIALS AND METHODS: Single-centre retrospective uncontrolled study included 653 COVID-19 HD-patients treated at Moscow City Nephrology Centre from April 1 to December 31, 2020. RESULTS: This period mortality rate was 21.0%. Independent predictors of COVID-19 unfavourable outcome in HD patients were pulmonary lesion extension (CT grades 34), high comorbidity index, and mechanical ventilation. Approaches to COVID-19 treatment modified significantly at different periods. Immunomodulatory drugs (monoclonal antibodies to IL-6, corticosteroids) were used largely at later stages. With tocilizumab administration, mortality was 15.1%, tocilizumab together with dexamethasone 13.3%; without them 37.8% (р0,001). Tocilizumab administration in the first 3 days after hospitalization of patients with CT grades 12 was associated with more favourable outcomes: 1 out of 29 died vs 6 out of 20 (tocilizumab administered at later periods); p0.04. There was no significant difference in death frequency in patients with CT grades 34 depending on tocilizumab administration time. CONCLUSION: COVID-19 in HD patients can manifest in a severe course with unfavourable outcome. It is urgent to identify reliable disease outcome predictors and develop efficient treatment in this population.

[The use of synthetic glycoconjugates as components of the immunochromatographic test for rapid serological diagnosis of leprosy.]

The glycoconjugates with BSA (bovine serum albumin) were synthesized using a next saccharide: disaccharide derivative M.leprae PGL-1 (phenolic glycolipid-1); a complex of the disaccharide fragment and the branched hexasaccharide fragment LAM (lipoarabinomannan); diarabinofuranose fragment LAM. These glycoconjugates were used as antigenic components for leprosy rapid serotest construction in immunochromatographic format (leprosy LF serotest). The data obtained with sera of leprosy patients, patients who have been in contact with leprosy, and healthy donors indicate that the most promising antigenic component is a BSA conjugate with two synthetic epitopes - a disaccharide derivative of PGL-1 and a branched hexasaccharide fragment of LAM. The leprosy LF serotest with such glycoconjugate demonstrated the greatest diagnostic sensitivity for main forms of leprosy - paucibacillary (PB) and multibacillary (MB).

N-Terminal Fragment of Brain-Type Natriuretic Peptide (NT-proBNP) as a Prognostic Marker in Patients with Newly Diagnosed Multiple Myeloma Complicated by Dialysis-Dependent Renal Failure.

Prognostic value of N-terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP) was analyzed in patients with multiple myeloma complicated by dialysisdependent renal failure. The prospective study included 20 patients with newly diagnosed multiple myeloma. The concentrations of NT-proBNP were measured before antimyeloma chemotherapy. The median age of the patients was 67 (63-76) years. The median glomerular filtration rate was 4 (4, 5) ml/min/1.73 m2. For overall survival, the area under ROC curve was 0.75 and the cut-off point was 7000 pg/ml. At median follow-up of 17.3 months, the overall survival was 76.6±14.8 and 27.3±13.4% (p=0.02) for cases with NT-proBNP levels below and above the cut-off point, respectively. There were no cases of death due to cardiovascular causes. We concluded that the increase in serum concentration of NT-proBNP>7400 pg/ml is associated with the severity of kidney damage and the risk of non-cardiac mortality.

Microphase separation in polymer solutions containing surfactants.

A microphase separation in solutions containing a polymer and a mixture of two solvents, one of which consists of amphiphilic molecules (surfactant), is considered theoretically in the weak-segregation regime. A surfactant molecule is described as a dimer consisting of hydrophobic and polar parts. The energy gain due to the orientation of surfactant molecules can lead to the appearance of non-homogeneities in the solution, where density fluctuations cause the orientational ordering of surfactant molecules. The difference in the interaction energies of hydrophobic and polar groups of a surfactant with solvent is considered as a main reason for orienting surfactant molecules. The free energy is calculated for various morphologies (lamellar, cylindrical hexagonal, spherical particles arranged at different cubic lattices). The phase diagrams are presented. With worsening the solvent quality, the transitions from disordered to a macro-separated state at low polymer and surfactant concentrations or to a body-centered-cubic, then hexagonal, and then lamellar structure at high polymer and surfactant concentrations are predicted. The amphiphilicity degree of surfactant molecules should exceed a certain critical value to make a microstructure formation possible. The period of the lamellar microstructure decreases with increasing the surfactant and polymer concentrations.

Pentraxin 3 in primary percutaneous coronary intervention for ST elevation myocardial infarction is associated with early irreversible myocardial damage : Kinetic profile, relationship to interleukin 6 and infarct size.

BACKGROUND: The inflammatory marker long pentraxin 3 (PTX3) has been shown to be a strong predictor of 30-day and one-year mortality after acute myocardial infarction. The aim of this study was to evaluate the kinetic profile of PTX3 and its relationship with interleukin 6 (IL-6), high-sensitive C-reactive protein (hs-CRP) and infarct size. METHODS: PTX3, IL-6 and hs-CRP were measured at predefined time points, at baseline (before percutaneous coronary intervention (PCI)), at 12 and 72 hours after PCI in 161 patients with first-time ST elevation myocardial infarction (STEMI). RESULTS: PTX3 and IL-6 levels increased in the early phase, followed by a gradual decrease between 12 and 72 hours. There were statistically significant correlations between PTX3 and IL-6 in general, for all time points and for changes over time (0-72 hours). In a linear mixed model, PTX3 predicted IL-6 (p < 0.001). PTX3 is also correlated with hs-CRP in general, and at each time point post PCI, except at baseline. PTX3, IL-6 and hs-CRP were all significantly correlated with infarct size in general, and at the peak time point for maximum troponin I. In addition, there was a modest correlation between IL-6 levels at baseline and infarct size at 72 hours after PCI (ρ = 0.23, p = 0.006). CONCLUSIONS: PTX3 had a similar kinetic profile to IL-6, with an early increase and decline, and was statistically significantly correlated with markers of infarct size in STEMI patients post primary PCI. Baseline levels of IL-6 only predicted infarct size at 72 hours post PCI.

Triton X-100 as a specific inhibitor of the mammalian NADH-ubiquinone oxidoreductase (Complex I).

Triton X-100 inhibits the NADH oxidase and rotenone-sensitive NADH-Q1 reductase activities of bovine heart submitochondrial particles (SMP) with an apparent Ki of 1x10-5 M (pH 8.0, 25 degrees C). The NADH-hexammineruthenium reductase, succinate oxidase, and the respiratory control ratio with succinate as the substrate in tightly coupled SMP are not affected at the inhibitor concentrations below 0.15 mM. The succinate-supported aerobic reverse electron transfer is less sensitive to the inhibitor (Ki=5x10-5 M) than NADH oxidase. Similar to rotenone, limited concentrations of Triton X-100 increase the steady-state level of NAD+ reduction when the nucleotide is added to tightly coupled SMP oxidizing succinate aerobically. Also similar to rotenone, Triton X-100 partially protects Complex I against the thermally induced deactivation and partially activates the thermally deactivated enzyme. The rate of the NADH oxidase inhibition by rotenone is drastically decreased in the presence of Triton X-100 which indicates a competition between these two inhibitors for a common specific binding site. In contrast to rotenone, the inhibitory effect of Triton X-100 is instantly reversed upon dilution of the reaction mixture. The NADH-Q1 reductase activity of SMP is inhibited non-competitively by added Q1 whereas a simple competition between Q1 and the inhibitor is seen for isolated Complex I. The results obtained show that Triton X-100 is a specific inhibitor of the ubiquinone reduction by Complex I and are in accord with our previous findings which suggest that different reaction pathways operate in the forward and reverse electron transfer at this segment of the mammalian respiratory chain.

Unidirectional effect of lauryl sulfate on the reversible NADH:ubiquinone oxidoreductase (Complex I).

Lauryl sulfate inhibits the Deltamu;(H)(+)-dependent reverse electron transfer reactions catalyzed by NADH:ubiquinone oxidoreductase (Complex I) in coupled bovine heart submitochondrial particles and in vesicles derived from Paracoccus denitrificans. The inhibitor affects neither NADH oxidase (coupled or uncoupled) nor NADH:ferricyanide reductase and succinate oxidase activities at the concentrations that selectively prevent the succinate-supported, rotenone-sensitive NAD(+) or ferricyanide reduction. Possible uncoupling effects of the inhibitor are ruled out: in contrast to oligomycin and gramicidin, which increases and decreases the rate of the reverse electron transfer, respectively, in parallel with their coupling and uncoupling effects, lauryl sulfate does not affect the respiratory control ratio. A mechanistic model for the unidirectional effect of lauryl sulfate on the Complex I catalyzed oxidoreduction is proposed.

[Comparative efficacy, safety, cardio-hemodynamic effects of isosorbide dinitrate (ID) aerosol and sublingual tablets of nitroglycerin]. / Sravnitel'naia éffektivnost', bezopasnost', kardiogemodinamicheskie éffekty aérozolia izosorbida dinitrata i sublingval'nykh tabletok nitroglitserina.

AIM: To study efficacy, safety, cardiohemodynamic effects of ID aerosol--isoket--for relief of anginal attacks and their prevention in long-term treatment. MATERIALS AND METHODS: 15 patients with ischemic heart disease suffering from stable angina class II-III. Isoket was tried for efficacy, tolerance, hemodynamic parameters, morphofunctional status of the heart, exercise tolerance. RESULTS: Isoket aerosol in a dose 1.25 mg as a single oral spray arrested anginal attacks in all the patients. In long-term regimens good antianginal effect was achieved in 60% of cases. The ID aerosol produces a fast antianginal effect, improves morphofunctional cardiac parameters and exercise tolerance. CONCLUSION: Isoket spray is effective and safe antianginal drug.

[Functional activity of platelet guanylate cyclase and cardiac hemodynamics in patients with chronic heart failure and relevant changes after treatment with isosorbide-5-mononitrate]. / Funktsional'naia aktivnost' guanilattsiklazy trombotsitov i kardiodinamika u bol'nykh s khronicheskoì serdechnoì nedostatochnost'iu i ikh izmeneniia pod vliianiem lecheniia izosorbida-5-mononitratom.

AIM: To study effects of long-term administration of isosorbide-5-mononitrate (monochinquare retard-MR) on functional activity of soluble guanylate cyclase (GC), cardiohemodynamics and exercise tolerance in patients with coronary heart disease (CHD) complicated by chronic cardiac failure (CCF). MATERIALS AND METHODS: The trial included 20 males aged 58 to 77 years with CHD, effort angina (NYHA class II-III), CCF (NYHA class I-II). Endothelial function was assessed before the treatment and 12 weeks after it by indirect measurement of production of endothelial relaxing factor (NO)--by activation of platelet soluble GC in the presence of its activators: L-arginine, disulphide, sodium nitroprusside and protoporfirine IX. Hemodynamic parameters, morphofunctional condition of the heart, exercise tolerance test results were compared with changes in GC functional activity after 12 weeks of MR monotherapy. RESULTS: Two types of the changes were revealed. Type I (n = 14): high GC basal activity and low activity before the treatment with normalization of all the parameters after the treatment. Type II (n = 6): initially normal basal activity and GC activation with their lowering after the treatment. MR in a single daily dose 50 mg given for 12 weeks has improved morphofunctional cardiac parameters with a reduction of left ventricular volume, a 8.3% increase in the ejection fraction and a 117% increase in exercise tolerance. GC activity inhibition was recorded in some cases, in angina class III, in particular. In patients with normalization of GC activity the response was higher than in those who demonstrated inhibition of GC activity. CONCLUSION: MR therapeutic action may be due to enhancement of soluble GC activity which was observed in 70% of the cases.

[Free amino acids in the blood before and after short-term space flight]. / Svobodnye aminokisloty krovi do i posle kratkovremennykh kosmicheskikh poletov.

The amino acid composition of plasma and serum of the crewmembers who performed short-term space flights (of 3 to 14 days) onboard the Salyut-6 orbital station was investigated. Immediately postflight total amino acids remained unchanged while variations in isolated amino acids (tendency toward increased aspartic acid and decreased cysteine in plasma, and increased leucin in serum) were adaptive.

[Characteristics of bacterial discharge in patients with different forms of pulmonary tuberculosis]. / Kharakteristika bakteriovydeleniia u bol'nykh s razlichnymi formami tuberkuleza legkikh.

Clinical implications of L-form pulmonary tuberculosis have been investigated in 268 patients. Of them 223 had active respiratory tuberculosis, 45 demonstrated residual disease. New cases of L-form tuberculosis were characterized by poor clinical symptoms and favourable outcomes. Association of L-forms with bacterial discharge produced apparent symptoms and progressive trends. Detection of L-forms in inactive pulmonary process indicated latent activity of tuberculosis apt to recur.

[Clinical significance of drug resistance of tuberculosis mycobacteria and L-forms]. / Klinicheskoe znachenie lekarstvenno-ustoichivykh mikobakterii tuberkuleza i L-form.

The clinical features of a tuberculous process were studied in 101 patients with active pulmonary tuberculosis among whom 76% of the patients lost their social adaptation. The patients were divided into 2 groups: group 1 comprising 61 (60.4%) subjects who excreted tuberculosis mycobacteria and L-forms and group 2 consisting of 40 (39.6%) who excreted only tuberculosis mycobacteria. The frequency and degree of drug resistance were more manifest in 63.8% of the patients of group 1 and in 40% of those of group 2 (p less than 0.01). Drug resistance to relatively new antituberculosis drugs (ethambutol and rifampicin) was found in 30% of the patients. Mixed bacillary population was found 2 times more frequently in patients with serious progressive forms of tuberculosis, which gives evidence to consider it as a prognostically unfavourable indicator.