Effect of Sulodexide on Circulating Blood Cells in Patients with Mild COVID-19.

Background. Despite the fact that COVID-19 usually manifests with severe pneumonia, there is a growing body of evidence that life-threatening multiorgan damage is caused by vascular and hemostatic abnormalities. Since there is no established therapy, assessing antithrombotics is indeed important. Sulodexide, a compound derived from porcine intestinal mucosa is a mixture of fast-moving heparin fraction (80%) and dermatan sulfate (20%), is approved in Europe and currently in trials for COVID-19 indication. Methods. This single-center, prospective, observational study included 28 patients with mild COVID-19 hospitalized in the Central Clinical Hospital of the Presidential Administration of the Russian Federation. Patients in the control group (n = 14) were treated using routine therapy according to current guidelines, while patients in the experimental group (n = 14) had the routine treatment supplemented with daily intravenous injections of sulodexide in 600-unit doses. Scanning electron microscopy was utilized to examine the blood specimens derived from the cubital vein at admission and at 10 days after hospitalization, which was approximately the average duration of patients' treatment in the hospital (11.6 ± 0.4 days). Results. Sulodexide significantly (by 40%) diminished the score of circulating endothelial cells, potentially indicating its antiviral endothelium-protective properties. It also prevented the extra activation of the platelets and the formation of erythrocytic sludges. Among patients in the control group, the share of activated platelets rose from 37 ± 5% to 45 ± 6% (p = 0.04) over the course of the study period, whereas among patients in the experimental group, the share of activated platelets remained practically unchanged (43 ± 6% vs. 38 ± 4%, p = 0.22). The score of erythrocytic sludges in the control group remained practically the same (4.8 ± 1.1 at admission vs. 3.9 ± 0.9 after 10 days, p = 0.67), whereas in the experimental group, it significantly decreased (from 5.7 ± 1.7 to 2.4 ± 0.9, p = 0.03). Conclusions. Sulodexide is able to defend endothelium, normalize blood, and, seemingly, prevent thrombosis. Therefore, it may be considered as a promising and effective agent for the treatment of patients with mild COVID-19. Broader randomized trials are needed to assess whether the observed findings will transform into sustained long-term clinical benefit.

CRP Is Transported by Monocytes and Monocyte-Derived Exosomes in the Blood of Patients with Coronary Artery Disease.

The objective of this work was to study the ability of blood cells and their microparticles to transport monomeric and pentameric forms of C-reactive protein (mCRP and pCRP) in the blood of patients with coronary artery disease (CAD). Blood was obtained from 14 patients with CAD 46 ± 13 years old and 8 healthy volunteers 49 ± 13.6 years old. Blood cells and microparticles with mCRP and pCRP on their surface were detected by flow cytometry. Messenger RNA (mRNA) of CRP was extracted from peripheral blood monocytes stimulated with lipopolysaccharide (LPS) and granulocyte-macrophage colony-stimulating factor (GM-CSF). mRNA of CRP in monocytes was detected with PCR. Monocytes were predominantly pCRP-positive (92.9 ± 6.8%). mCRP was present on 22.0 ± 9.6% of monocyte-derived exosomes. mCRP-positive leukocyte-derived microparticle counts were significantly higher (8764 ± 2876/µL) in the blood of patients with CAD than in healthy volunteers (1472 ± 307/µL). LPS and GM-CSF stimulated monocytes expressed CRP mRNA transcripts levels (0.79 ± 0.73-fold), slightly lower relative to unstimulated hepatocytes of the HepG2 cell line (1.0 ± 0.6-fold), but still detectable. The ability of monocytes to transport pCRP in blood flow, and monocyte-derived exosomes to transmit mCRP, may contribute to the maintenance of chronic inflammation in CAD.

Hypotensive effect of Oxacom® containing a dinitrosyl iron complex with glutathione: animal studies and clinical trials on healthy volunteers.

A comparative study of hypotensive effects of binuclear forms of dinitrosyl iron complexes (DNICs) with glutathione, S-nitrosoglutathione (GS-NO) and sodium nitrite (NaNO(2)) on rats has been carried out. The latter appeared to be the least efficient, viz., mean arterial pressure (MAP) decreased by 10 and 30 mmHg at 25 and 100 µmoles/kg of NaNO(2). In contrast, DNIC and GS-NO produced an appreciable hypotensive effect when used at much lower concentrations. GS-NO reduced MAP to the same extent, viz., to 90 mmHg, on a hundredfold dose scale (from 0.4 up to 50 µmoles/kg) with subsequent restoration of MAP within the next 6-15 min. A similar effect was observed for DNIC except that the amplitude of the MAP drop was lower and the duration of hypotension was essentially greater. DNIC with glutathione were selected as a basic material for pilot-scale production of a hypotensive drug (commercial name Oxacom®). Preliminary pharmacological testing of Oxacom did not establish any adverse or deleterious side effects. Clinical trials of Oxacom® were performed on 14 healthy male volunteers in whom single intravenous infusion of the drug (5mg/kg or 0.2 µmoles/kg of DNIC, respectively) evoked a characteristic response manifested as a 3-4 min drop by 24-27 mmHg of both diastolic and systolic AP with its subsequent slow restoration within the next 8-10h. The heart rate was quickly normalized after an initial increase. Cardiac output was unchanged despite reduced cardiac filling. A comprehensive analysis of clinical and biochemical data failed to establish any significant pathological changes in these parameters. The data obtained suggest that Oxacom® can be recommended for the second phase of clinical trials.