[Influence of the Donor of Hydrogen Sulfide GYY4137 on the Activation of Human Neutrophils by E. coli Lipopolysaccharides].

Lipopolysaccharides (LPS), components of the cell wall of gram-negative bacteria, activate neutrophils that trigger pathological processes, including gram-negative sepsis. LPS inhibit spontaneous apoptosis of neutrophils that leads to inflammation. In this work we tested the action of H2S donor (GYY4137) on the activation of human neutrophils by E. coli LPS. We estimated the changes in redox status (ROS level, intracellularglutathione, NO), apoptosis and mitochondrial potential of neutrophils under the LPS action in the presence and absence of GYY4137. GYY4137 reduces the ROS level, slightly reduces GSH, does not influence the NO level and has no apoptogenic effect. LPS induce the increasing of ROS level and inhibit spontaneous apoptosis of neutrophils. We found that GYY4137 prevents the growth of ROS caused by LPS and leads to a reduction of LPS-induced inhibition of neutrophil apoptosis. Thus the mechanism of GYY4137 protection against inflammation, triggered by bacterial infection, is concerned with the neutralization of LPS effect on neutrophils.

Encapsulated Hsp70 decreases endotoxin-induced production of ROS and TNFα in human phagocytes.

Human heat shock protein Hsp70 was experimentally inserted into polyelectrolyte microcapsules. Encapsulated recombinant Hsp70 was studied in terms of its effects on neutrophil apoptosis, the production of reactive oxygen species, and the secretion of tumor necrosis factor alpha by promonocytic THP-1 cells. It was found that encapsulated Hsp70 effectively inhibits neutrophil apoptosis, unlike free exogenous protein used in solution. In THP-1 cells, encapsulated and free Hsp70 reduced LPS-induced tumor necrosis factor alpha production with a similar efficiency. Encapsulated Hsp70 reduces LPS-induced reactive oxygen species production by neutrophils in the course of its release from the microcapsules but not as much as free Hsp70. Thus, the polyelectrolyte microcapsules can be used as containers for the effective delivery of Hsp70 to neutrophils and monocytes to significantly improve the functioning of the innate immune system.

[NMR study of human biological fluids for detection of pathologies].

The paper deals with the NMR spectra obtained using preparations of five different human biological body fluids. Characteristic metabolite signals of blood, urine, tears, saliva, and sweat spectra have been determined and classified. The biological body fluid samples were used for search and identification of biomarkers of cardiovascular disease. Absolute functional biomarkers for diseases such as coronary heart disease (CHD) have not been recognized even in the case acute myocardial infarction. A hypothesis explaining reasons of lack of such markers has been formulated. The results of comparative analysis of blood and urine samples from humans and some laboratory animals are given. Identify and analyze signals of metabolites of pathogenic microflora and their dynamics in the urine from patients with urogenital diseases have been determined and analyzed and characteristic biomarkers have been recognized.

Influence of encapsulated heat shock protein HSP70 on the basic functional properties of blood phagocytes.

Microencapsulated heat shock proteins HSP 70 were studied in terms of their effects on neutrophil apoptosis, production of reactive oxygen species, and secretion of TNF-α by human neurtrophils and monocytes. Encapsulated HSP70 inhibited neutrophil apoptosis by 65% as compared to the effect of nonencapsulated HSP70; TNF-α production by the promonocytic THP-1 cells was similarly inhibited by the non-encapsulated and encapsulated HSP70. Thus, the polyelectrolyte micromolecules can be used as containers for effective delivery of HSP70 up to neutrophils and monocytes to correct the innate immunity functions.

[Arginase, nitrates, and nitrites in the blood plasma and erythrocytes in hypertension and after therapy with lisinopril and simvastatin].

Arginase activity in erythrocytes is higher in patients with arterial hypertension and atherosclerosis as compared with healthy people. Therapy with either lisinopril alone or in combination with simvastatin for 3-6 months causes a decrease in the arginase activity to the control level. Both the monotherapy and the combination therapy increased the concentrations of NO2(-), NO3(-), and total NOO2(-) + NO3(-)in the plasma of hypertensive patients. The NO2(-) + NO3(-) concentration in erythrocytes decreases in hypertensive patients but is completely restored after therapy with lisinopril alone or in combination with simvastatin. Thus, lisinopril and lisinopril plus simvastatin display a pronounced and equal normalizing effect on arginase activity in human erythrocytes, which is elevated in hypertension, as well as on the endothelial nitric oxide synthase activity, which is decreased in hypertension.

[Antioxidant enzymes in erythrocytes from hypertension patients receiving lisinopril monotherapy or combined lisinopril plus simvastatin therapy].

Statins and angiotensin-converting enzyme (ACE) inhibitors have beneficial impact on the serum cholesterol and blood pressure. It is supposed that statins and ACE inhibitors may modify the antioxidative status of erythrocytes. The study objective was to compare the effects of two treatments, lisinopril alone vs lisinopril plus simvastatin, on erythrocyte antioxidant enzyme activities. The study involved 32 patients with arterial hypertension, the initial serum total cholesterol, LDL-cholesterol and triglycerides within the normal range. Patients of two groups, each of 16 subjects, were treated with lisinopril (10 mg/day) or with lisinopril (10 mg/day) plus simvastatin (20 mg/day). Before and after 3 and 6 months of follow-up therapy, activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GLR) in purified erythrocytes were determined. In all patients, significantly higher catalase activity (by 79.3-106.5%, p < 0.0001) and significantly lower GPx activity (by 20.7-30.6%, p < 0.001) were observed after therapy as compared to the baselines. Just the same results were obtained in both groups (lisinopril and lisinopril + simvastatin), after both periods (3 and 6 month) of treatments. SOD activity was increased only in the lisinopril group and only after 6 months (p = 0.0345). No changes of GLR reductase activity were seen under all conditions indicated. Thus, the lisinopril monotherapy and combined lisinopril plus simvastatin therapy exhibit specific, pronounced and equipotent effects on antioxidant enzymes in human erythrocytes. Administration of lisinopril or lisinopril plus simvastatin may protect erythrocytes and other tissues from oxidative damage.