Platelets are the smallest blood cells, and yet their total volume and surface area exceed those of all types of leukocytes combined. Platelets are produced by the bone marrow megakaryocytes and megakaryocytes in the lung microvessels. Approximately 50% of all platelets are produced in the lungs, which makes it possible to characterize them as the main site for the production of platelets. In small circuit of blood circulation, there are approximately 30% more platelets than in large circuit. This “excess” of platelets is necessary for the stabilization of the endothelial barrier of the lung vessels regulated by the platelet mediator sphingosine-1-phosphate, a regulator of tight junctions of endothelial cells. The circulating platelets have an amazing ability to “bud” new pro- and pre-platelets, giving rise to new platelets. The removal of platelets from circulation proceeds via their phagocytosis by spleen macrophages (if platelets are covered with IgG or are bound to immune complexes), or Kupffer liver cells and hepatocytes (if platelets have incomplete glycans or desialated proteins). In homeostatic conditions, most of the platelets are removed in liver. Platelet clearance in bacterial infections and sepsis is accelerated because of the activity of bacterial sialidases. Recognition of desialized platelet structures is carried out by the liver cells through the Asgr receptor. Despite DNA absence, the platelets are able to synthesize proteins at mRNAs that are present in majority of platelets. Activation of platelets leads to aggregation and exocytosis of the granule contents, and production of immunomodulating molecules. However, activation of platelets may be incomplete and has various consequences. In a non-classical activation model, platelets can release microparticles that contain about 600 different proteins. About 75% of microparticles in the blood of healthy donors are derived from platelets. Like as immune system cells, platelets are activated by numerous endogenous ligands (alarms), including ADP and ATP, which bind to purinergic receptors P2Y1, P2Y12 andP2X1. Platelets accumulate and retain 99% of the serotonin stored in the body. The platelets contribute to induction of inflammation by releasing proinflammatory cytokines, chemokines, and lipid mediators. In addition, platelets are the source of enzymes that accomplish the capacities of neutrophils and endothelium for production of anti-inflammatory lipid mediators that contribute to tissue repair following acute phase of inflammation.

Changes in the functional activity of the hypothalamo-hypophyseal-adrenocortical system (HHACS) and hypothalamo-hypophyseal-gonadal system (HHGS) in conditions of different levels of stress and the possibility of correcting them using the native DNA formulation Derinat, which has immunomodulatory properties, were studied. The vectors of changes in hormonal reactions in both systems were found to be independent of the intensity of stress: there were increases in corticosterone levels and decreases in testosterone concentrations in different stress models. Intraperitoneal administration of Derinat at doses of 10 and 50 mg/kg increased HHACS and HHGS activity and reversed the stress-induced reduction in the blood testosterone concentration, which may be evidence that Derinat has stress-protecting effects. Administration of Derinat promoted normalization of stress-induced changes in the production of immunomodulatory cytokines among lymphocyte-activating factors with regulatory influences not only on the functioning of the immune system, but also on the HHACS and HHGS functions.

H NMR spectroscopy was used to establish that 7-alkoxyalkyl-3-thia-7-azabicyclo[3.3.1]nonan-9-onesand their decarbonylated derivatives in deuterochloroform solution exist in the double chair conformation. The predominantly formed secondary alcohols isomers have preferred double chair conformation with the hydroxyl group equatorial relative to the plane of the piperidine ring. On the other hand, the epimeric alcohols have predominant boat-chair conformation; the piperidine ring takes the boat form due to intramolecular hydrogen bonding between the unshared electron pair of the nitrogen atom and hydroxyl group proton.Keywords: 7-alkoxyalkyl-3-thia-7-azabicyclo[3.3.1]non-9-one and its derivatives, conformational analysis, 1 H NMR spectra.The study of the three-dimensional structure of bicyclic compounds containing important biogenic elements such as oxygen, nitrogen, and sulfur holds interest not only in regard to the search for new physiologically active compounds but also for the development of conformational analysis and stereochemistry. We have described the synthesis of a series of 7-alkoxyalkyl-3-thia-7-azabicyclo[3.3.1]non-9-ones, their deoxygenated derivatives, and derived secondary alcohols [1]. In the present work, we have determined the three-dimensional structure of these compounds using high resolution 1 H NMR spectroscopy. We studied ketones 1-5 with various substituents at the nitrogen atom, their reduced analogs 6-10, and secondary alcohols 11-14. The chemical shifts and coupling constants for the individual stereoisomers isolated from alcohols 11 and 12 were used to interpret the rather complex spectra of alcohols 13 and 14, each of which is a mixture of two isomers that could not be separated.Bicyclo[3.3.1]nonanes and their 3,7-dihetero analogs exist in solution as one of four forms: double chair (cc), chair-boat (cb), boat-chair (bc), and double boat (bb) or as a mixture in conformational equilibrium [2]. The predominant configuration is determined not only by the overall electronic and steric factors within these __________________________________________________________________________________________

Thrombocytes keep a leading role in conjugating thrombosis, inflammation and congenital immune responses. The platelets provide stable adhesion and interaction with immune cells. Activated platelets express CD40L (CD154), a membrane glycoprotein of tumor necrosis factor (TNF) family. Hence, the platelets are the main source of sCD40L in blood plasma. Platelet CD154 may interact with CD40 receptor on endothelial cells, causing an inflammatory response, and enhancing production of immunoglobulins by B-lymphocytes. Membrane and soluble CD154 of platelets combined with other signals can induce maturation and activation of dendritic cells (DC). The platelets possess functional receptors, e.g., TLR2, TLR4, TLR7 and TLR9 they also bear Fc-receptors, including FcγRIIA, FcεRI and FcαRIA. FcγRIIA on platelets mediate protection against bacteria. Cross-linking of FcαRI on platelets results in production of prothrombotic and pro-inflammatory mediators such as tissue factor and IL-1β. Activation of platelets via FcεR1 causes release of chemokine RANTES and serotonin, which contribute to the pro-inflammatory response of other immune cells. Platelets possess receptors for activated complement components and its fragments (CR2, CR3, CR4, C1q, C1 inhibitor and factors D and H). Activated platelets trigger the complement system through the release of protein kinases and ATP, and also by phosphorylation of C3 and C3b. α-granules of platelets contain chemokines which represent the most numerous group of antimicrobial proteins of platelets (kinocidins), and there is an antimicrobial protein of the defensin family – hBD-1 in the cytoplasm of platelets. Ligand and receptor of the TNF superfamily (TRAIL and LIGHT), the SDF-1 chemokine (CXCL12), the IL-1βinterleukins, IL-8 and the soluble IL-6 receptor (sRIL-6) are recognized as platelet products belonging to the family of cytokines and their receptors. The HMGB-1 protein classified as an inflammatory cytokine, is expressed by activated platelets and causes formation of the extracellular traps by neutrophils. Platelets produce numerous growth factors, including EGF-α and EGF-β1, EGF-β2, TGF-α and TGF-β1, TGF-β2, PDGF, HGF, FGF-β, IGF, pro- and antiangiogenic factors, e.g., VEGF-F and angiopoietins Ang-1 and Ang-2. Fulfillment of immune functions by the platelets is carried out by their interaction with leukocytes, which are attracted to the site of infection and inflammation and retained during the development of an “immune thrombus” under conditions of high shear stress. Platelets can not only maintain and guide the immune response, but also initiate these events. They are able to present the antigen in the context of MHC class I molecules, and activate naїve CD8+T lymphocytes. Potential consequences of platelet interaction with neutrophils, monocytes, dendritic cells and lymphocytes are discussed in the review article.

No abstract