Xenon Antiaggregant Effects.

In in vitro model of short-term therapeutic inhalation of Xe/O2 mixture, xenon in millimolar concentrations led to a pronounced decrease in induced platelet aggregation in the platelet-enriched blood plasma. The maximum and statistically significant decrease occurred in response to induction by collagen (by ≈30%, p≤0.01) and ADP (by ≈25%, p≤0.01). A slightly weaker but statistically significant reduction in aggregation appeared in response to ristocetin (by ≈12%, p≤0.01) and epinephrine (by ≈9%, p≤0.01). It should be noted that the spontaneous aggregation exceeded the reference values in the control group. Nevertheless, even at minimal absolute values, spontaneous platelet aggregation decreased by 2 times in response to xenon (p≤0.01). The reasons for the decrease of spontaneous and induced aggregation are xenon accumulation in the lipid bilayer of the membrane with subsequent nonspecific (mechanical) disassociation of membrane platelet structures and specific block of its distinct from neuronal NMDA receptor.

Effect of Xe/O2 Inhalation on Hemostasis in Experimental Thromboplastin Pneumonitis.

We studied the effectiveness of Xe/O2 mixture inhalation (30% Xe and 70% O2, 20 min for 5 days) in a model of experimental thromboplastin pneumonitis. Inhalation of the studied mixture decreased the intensity of the inflammatory process in the lung tissue assessed by the temperature response of animals, changed lung weight and lung weight coefficient. At acute stage of pneumonitis, an increase in xenon consumption was recorded due to its retention in the gas exchange zone and a natural decrease in oxygen consumption due to partial alveolar/capillary block. The formation of pneumonitis was accompanied by a pronounced procoagulant shift in the regulation system of the aggregate state of blood. The Xe/O2 inhalations ensured physiologically optimal levels of prothrombin and activated partial thromboplastin time against the background of a moderate decrease in fibrinogen level throughout the experiment. At the same time, the activity of the natural anticoagulant antithrombin III increased from day 5 to day 14.

Xenon-Induced Effects in Relieving Experimental Acute Respiratory Distress Syndrome.

The effects of inhalations of an oxygen-xenon (70%/30%) mixture were studied in two models of acute respiratory distress syndrome caused by intratracheal administration of 0.5 mg/kg LPS or 0.04 ml acidin-pepsin (pH 1.2). Inhalation of the oxygen-xenon mixture inhibited the development and reduced the intensity of the inflammatory process in the lung tissue, which was assessed by the dynamics of lung weight and body weight of animals: the therapeutic exposure decreased both parameters. It was found that the thrombogenic stimulus, pathognomonic for the development of acute respiratory distress syndrome, decreased under the effect of oxygen-xenon inhalations, while the level of natural anticoagulant antithrombin III increased.

Xenon-Induced Recovery of Functional Activity of Pulmonary Surfactant (In Silico Study).

To understand the nature of xenon-induced recovery of the functional activity of pulmonary surfactant during inhalation of a gas mixture of Xe/O2, the mechanisms of the ongoing processes were studied in silico. Impaired ability of pulmonary surfactant to maintain low surface tension preventing alveolar atelectasis occurs due to formation of aggregates of its phospholipids and a decrease in their lateral mobility. Aggregated lipid systems, whose structure can explain the loss of lateral mobility of surfactant phospholipids, were modeled in silico at the molecular level. Changes in the Gibbs energy and enthalpy in the reactions of the formation and decomposition of xenon intermediates with model systems of various compositions/structures were calculated. The simulation was carried out for atomic xenon and for xenon polarized by molecular oxygen in the gas phase and taking into account solvation with water. The loss of lateral mobility of phospholipids can be explained by specific features of electronic structure of hydrophobic hydrocarbon molecules (acyl chains), which, under certain conditions, are capable of forming structured common regions of the electrostatic potential, to which xenon has an affinity. In this case, inclusion coordination compounds of the "guest-host" type are formed, which subsequently decompose due to the nature of the polarization of the Xe atoms. The formation and decomposition of xenon intermediates in these systems lead to recovery of the lateral mobility (fluidity) of phospholipids, which restores functional activity of surfactant films.

Mechanisms of the Effects of Short-Term Inhalations of Xe and O2 Gas Mixture in the Rehabilitation of Post-COVID Ventilation Failure.

The article presents a theoretical rationale and a clinical case of relief of post-COVID ventilation failure by inhalation of Xe and O2 gas mixture. Pneumonitis of coronavirus etiology transforms saturated phospholipids of surfactant into a solid-ordered phase, which disrupts surface tension, alveolar pneumatization, and alveolar-capillary gas exchange. Using molecular modeling (B3LYP/lanl2dz; GAUSSIAN09), we demonstrated that Xe atom due to the van der Waals dispersion interaction increases the distance between the phospholipid acyl chains providing a phase transition from the solid-ordered to liquid phase and restored the surface-active monolayer surfactant film. A clinical case confirmed that short-term inhalations of the Xe and O2 gas mixture relieved manifestations of ventilation insufficiency and increased SpO2 and pneumatization of the terminal parts of the lungs.

[Xenon effects on cells and receptors]. / Vliianie ksenona na kletki i retseptory.

Xenon (Xe) is being more widely used in medicine owing to its unique physical-and-chemical properties of a noble gas. However, the knowledge about the physiological and patho-physiological changes occurring in the organism and in its separate structures during the interaction with Xe is still scanty. The aim of this survey was to briefly describe the presently known Xe biological-and-medical properties and certain mechanisms of Xe impact produced on cells and receptors as well as on the release of mediators and hormones. Besides, the Xe hemodynamic effects are also defined. The conclusion is that the Xe effect can be of a complex nature and can depend on the conditions of the body vital activity (optimal condition, activation, lesion), which predetermine, in their turn, the performance of the structural-and-functional units of various cellular systems.

Cell-based therapy of chronic degenerative diseases of the central nervous system.

The traditional methods of pharmacotherapy of the degenerative diseases of the central nervous system do not frequently allow one to achieve the desired clinical effect. The fundamentally new approach for the treatment of severe neurological diseases is provided by the methods of biological medicine, in particular, transplantation of a complex of fetal tissues. Cell-based therapy was used to treat patients with multiple sclerosis; ante-, intra- and postnatal lesions; consequences of hemorrhagic and ischemic apoplexies; neuritis of facial nerve; sclerosis; Parkinson's disease; Alzheimer's disease; epilepsy and other types of pathologic process. The source material for obtaining a suspension of cells was the fetuses of allogenic origin. The suspension of brain cells in amounts of up to 1.5 x 10(8) cells and vitality not less than 40% was administered to the patients into liquor spaces using the method of endolumbar puncture. The total number of transplantations was 1900. Practically in all the cases FT was tolerated well. Positive clinical and immunologic changes were observed in the majority of the patients, thus, remission induction (in the patients with the progressive course of multiple sclerosis) for a period over 12 months was registered in 87.5% of the cases. Noteworthy that considerable changes were observed in immunograms: depression of antibody levels to brain-specific proteins, native and denatured DNA; quantitative and qualitative improvement of lymphocyte subpopulation indices, positive changes in the immunoregulatory index. Clinically, in 69% of the cases there was an improvement in more than one neurological defect and a change in the values of the Kurtzke scale towards a decrease by 2-3 points. The conduct of cell therapy with the MS patients under the acute process conditions after liquorosorption allowed the arresting of clinical manifestations and the creation of preconditions for further restoration. The retrobulbar transplantations provided a quick arrest of the retrobulbar neuritis clinical symptoms and in one case an almost complete restoration of vision in the patient with amaurosis (blindness). The remission duration has a marked direct dependence on the number of courses of endolumbar transplantations. Thus, the method of cell therapy with the use of human tissue transplantations is safe and can be used for different neurodegenerative lesions of the central nervous system. The high efficacy of the method suggests the possibility and necessity of using this method as an alternative of classical pharmacological therapy. An important element of cell therapy is the control after the state of the patient's immunity system.

[Salivary lysozyme in the screening for stomach cancer]. / Lizotsim sliuny v skrininge na rak zheludka.

The study was concerned with measurement of lysozyme activity of saliva in healthy subjects and patients with different pathologies of the stomach including precancer and cancer. It established a considerable decrease in this parameter in cancer and precancer as compared with healthy controls. Assay of saliva lysozyme activity was found to yield more specific and prognostic data than clinical symptoms and examination of the patient. This procedure proved highly valuable in forming groups at risk for stomach cancer, due to providing significant differences in saliva lysozyme activity indices between "healthy subjects--stomach pathology" and "precancer--precancerous changes--stomach cancer" groups.

[The oxidative metabolism of the blood neutrophilic granulocytes in precancer and cancer of the stomach]. / Okislitel'nyi metabolizm neitrofil'nykh granulotsitov krovi pri predrake i rake zheludka.

The results of investigation of blood polymorphonuclear leukocytes oxidative metabolism by nitroblue tetrazolium (NBT) test and luminol-dependent chemiluminescence in patients with gastric precancer and cancer are presented. Chemiluminescence was increased in the patients of both groups as compared with control. Disturbances in oxidative metabolism of neutrophils was detectable by NBT test when functional test was used.

[The activation of the early chemiluminescent response of human neutrophils by joint treatment with tumor necrosis factor (TNF-alpha) and the calcium ionophore A-23187]. / Aktivatsiia rannego khemiliuminestsentnogo otveta neitrofilov cheloveka sovmestnoi obrabotkoi faktorom nekroza opukholi (FNO-al'fa) i kal'tsievym ionoforom A23187.

The influence of recombinant human tumor necrosis factor-alpha (TNF-alpha) and calcium ionophore A23187 on luminol- and lucigenin-dependent chemiluminescence capacity (CL) of human polymorphonuclear leukocytes (PMN) has been studied. The CL response of TNF-alpha treated PMN is amplified by lucigenin, but not luminol. TNF-alpha and A23287 synergistically induced both the luminol- and lucigenin-dependent early CL response. The combination of A23187 and activator of protein kinase C--phorbol (myristoyl-13-acetyl)--also provoked early CL response. While the combination of TNF-alpha and A23187 decreased late CL response compared to A23187 alone. The obtained results suggests that synergistic CL response of PMN induced by TNF-alpha and A23187 is connected with activation of protein kinase by TNF-alpha.

[Changes in the profile of cytotoxic mediator monocytes in patients with cancer and precancerous conditions of the stomach]. / Izmenenie profilia tsitotoksicheskikh mediatorov monotsitov u bol'nykh rakom i predrakovymi sostoianiiami zheludka.

Peripheral blood monocytes from healthy subjects, patients with gastric precancer disease (chronic gastric ulcer, stomach polyps and chronic atrophic gastritis) and different stages of gastric cancer were used. Spontaneous and lipopolysaccharide (LPS)-stimulated TNF-like factors production by monocytes was significantly higher in the precancer gastric disease patients than in the healthy subjects. At the same time the spontaneous capacity of monocytes to produce NTF-like factors was 2.5 lower in the gastric cancer patients compared to the healthy subjects. Moreover, in 5/13 of the gastric cancer patients in TNF-like factors production by the LPS-stimulated and non-stimulated monocytes was 1 unit/ml less. Spontaneous and reactive CL indexes were higher in the cancer patients monocytes than in the healthy subjects. The obtained results suggest that reactive oxygen species production can be an alternative mechanism by which a cytotoxic action of monocytes is regulated.

Decreased luminol-dependent chemiluminescence response of neutrophils to recombinant human tumour necrosis factor in patients with gastric cancer.

Production of reactive oxygen species by neutrophils was analyzed by a chemiluminometric method in the presence of luminol in ten healthy donors, eight patients with gastric cancer and ten patients with gastric precancer. The neutrophil chemiluminominescence response to recombinant tumour necrosis factor (rTNF) was almost five times lower in the gastric patients when compared with healthy donors and precancer patients. The chemiluminescence response to zymosan was decreased only in the gastric cancer patients with chemiluminescence index activation (CTNF) less than 1. The observed changes of neutrophil functions are thought to result in a decrease of neutrophil cytotoxic activity in gastric cancer patients.

[The potentials of low-intensity laser radiation in treating precancerous diseases of the stomach]. / Vozmozhnosti nizkoénergeticheskogo lazernogo izlucheniia v lechenii predopukholevykh zabolevanii zheludka.

The beneficial effect of low-energy laser radiation on the natural course of disease, morphologic characteristics of gastric mucosa and key elements of systemic hemostasis was observed in 98 patients with precancer of the stomach (gastric ulcer and chronic atrophic-hyperplastic gastritis with epithelial dysplasia). A correlation between clinical response and normalization of morphologic appearance and homeostasis makes the above-mentioned treatment modality promising and worth further development.

[Study of reserve possibilities of antiaggregation activities of the vascular wall]. / Issledovanie rezervnykh vozmozhnostei antiagregatsionnoi aktivnosti sosudistoi stenki.

The effects of various schedules of local hypoxia of the upper limb on the vascular wall antiaggregation activity have been studied in healthy volunteers. A double 5-minute local hypoxia with a 30 min interval, as well as a single occlusion of the limb vessels permit a judgement on the antiaggregation activity of the vessel wall; therefore this test may be recommended for the assessment of the vascular wall anti-aggregation activity.