Effect of Activated Immunocompetent Cells on the Content of Multipotent Stromal Cells in Splenic Transplants of CBA and CBA/N Mice Administered with Polyvinylpyrrolidone.

One day after intraperitoneal injection of polyvinylpyrrolidone (PVP) to recipient CBA and CBA/N mice, the count of multipotent stromal cells (MSC) in the 4-month-old splenic transplants was minimum in CBA/N→CBA/N group in comparison with the transplants of intact recipients (0.6 from the control level), but increased by 2.3, 3.2, and 3.7 times in CBA/N→CBA, CBA→CBA, and CBA→CBA/N groups, respectively. In the blood serum of recipient CBA/N mice with 4-month splenic transplants of CBA donors, the levels of some cytokines (IL-5, TNFα, and IL-2) was significantly increased 1 and 24 h after PVP injection in contrast to mice with bone marrow transplants, which attests to activation of the innate immunity mechanisms in this (splenic) transplantation variant. Probably, this phenomenon can be explained by the fact that the splenic transplants contain a sufficient number of CD+B-1a lymphocytes that can restore the response of recipient CBA/N mice to PVP. Thus, similar to bone marrow transplants [5], MSC count in splenic transplants increased only in groups, where the recipients were capable of responding to PVP. In other words, after injection of PVP to recipient mice, MSC counts in the spleen and bone marrow at this moment are determined by availability of activated immunocompetent cells. Overall, the novel data attest to close relationships between the stromal tissue of hematopoietic and lymphoid organs, on the one hand, and immune system, on the other.

Simultaneous Administration of NOD-2 (MDP) and TLP-4 (LPS) Ligands to Bone Marrow Donors 24 h before Transplantation Increases the Content of Multipotent Stromal Cells (MSCs) in Bone Marrow Grafts in CBA Mice Compared to the Total Result of Their Isolated Administration.

In 3-month bone marrow transplants of CBA mice from bone marrow donors receiving single injections of TLR-4 ligand (LPS) or NOD-2 ligand (muramyl dipeptide, MDP) 24 h before transplantation, an increase in the total number of MSCs (by 2.6 and 1.9 times, respectively), as well as a slight increase in the number of nuclear cells and the mass of bone capsules (by 1.3 and 1.2 times) were observed. After combined administration of MDР and LPS to donors, the total content of MSCs in the grafts was higher by 1.6 times in comparison with the total result of their isolated administration (and by 7.2 times in comparison with the control). At the same time, the concentration of osteogenic MSCs in the grafts of all groups was almost the same and corresponded to the control level. The number of nuclear cells and the mass of bone capsules of the grafts after combined administration of LPS and MDP were close (~80%) to the sum of the results of their isolated administration. These findings suggest that activation of the stromal tissue and the success of bone marrow transplantation depend on the intensity of innate immune responses. These data can be useful for the development of optimal methods of tissue transplantation.

[Efficacy of combined use of glycosaminoglycan peptide complex for intramuscular administration and oral diacerein in osteoarthritis: evaluation according to an observational multicenter clinical trial].

BACKGROUND: The combined use of intramuscular injection glycosaminoglycan peptide complex (GPC) and oral diacerein can increase the effectiveness of treatment of osteoarthritis (OA). AIM: Compare the effectiveness of combination GPC + diacerein and GPC monotherapy in the treatment of OA in clinical practice. MATERIALS AND METHODS: A retrospective evaluation of the results of a 12-week multicenter observational non-interventional study of the effectiveness of GPC (Rumalon, a course of intramuscular injections 3 times a week, №25) in patients with moderate/severe OA (n=2955) requiring regular administration of nonsteroidal anti-inflammatory drugs (NSAIDs). The analysis identified a group of patients (n=414) who received GPC in combination with diacerein 100 mg/day (Diaflex Rompharm). The therapeutic effect was compared in the groups of GPC monotherapy (n=2541) and the combination of GPC with diacerein. These groups did not differ in average age (61.411.8 and 61.911.3 years), both were dominated by women (76.3 and 70.3%), there was approximately equal intensity of pain during movement and impaired joint function: 6.11.8/6.01.6 and 4.92.1/5.11.8 (according to the numerical rating scale 010). The dynamics of pain intensity, the need for NSAIDs, and the frequency of adverse events (AE) were compared 12 weeks after the start of treatment. RESULTS AND DISCUSSION: In the majority of patients with OA both on the background of GPC monotherapy and combined use of GPC and diacerein, there was a significant improvement. The number of patients with pain reduction 50% was 54.3 and 62.8% (p0.001), NSAID administration was completely stopped in 66.7 and 77.5% (p0.001), respectively. The effectiveness of the combination of GPC and diacerein was significantly higher than that of GPC monotherapy in OA of the knee joint, hip joint, and generalized OA. AE from the gastrointestinal tract was observed in 7.8 and 8.9%, arterial hypertension in 6.3 and 4.6%, allergic reactions in 0.3 and 0.5% of patients (not significant). CONCLUSION: The application of the code of civil procedure is an effective treatment for OA. The combination of GPC and diacerein provides a more significant improvement than GPC monotherapy. GPC and diacerein (including in combination) are well tolerated and rarely cause AE.

[Control of pain in the early post-traumatic period in the outpatient practice. Results of the multi-center observational study RAPTOR (Rational Analgesia PostTraumatic: an Observational Research)].

AIM: Evaluate the frequency, nature and course of PTP, as well as the effectiveness and safety of NSAIDs in PTP in real clinical practice. MATERIALS AND METHODS: The assessment of the condition and need for NSAIDs (original meloxicam) in 1115 outpatient patients who suffered a fracture of the radius (32.2%), injury to the knee (35.2%) or ligaments of the ankle (32.6%); women/men 51.5 and 48.5%, average age 46.915.5 years. We evaluated the dynamics of pain intensity (on a numerical rating scale NRS 010) at rest and during movement, the preservation of moderate and severe pain, as well as the development of adverse drugs reactions (ADR) to NSAIDs 48 weeks after injury. RESULTS: The average intensity of pain during movement decreased from 7.031.66 to 2.211.38 (p0.001), at rest from 4.462.07 to 0.710.989 (p0.001). The number of people with pain severity 4 in the NRS in 48 weeks after the radius fracture, injury of the knee and ligaments of ankle was 21.0, 16.9 and 11.9%, with moderate or severe impairment of the injured limb 40.4, 26.2 and 16.3%, respectively. The need for taking NSAIDs up to 7 days was noted in 43.3%, 714 days-in 41.8%, more than 2 weeks or constantly in 14.9% of patients. Weak or moderate ADR were observed in 20.8% of patients, mainly dyspepsia and hypertension. Discontinuation of NSAIDs due to ADR was required in only 2.6% of patients. Pain retention 4 in NRS was associated with initially expressed pain (7 in NRS) OR 2.75 (95% CI 0.834.13; p0.001) and the presence of osteoarthritis of knee and/or hip OR 1.56 (95% CI 1.032.34; p=0.039). CONCLUSION: PTP decreases rapidly in most patients after a radius fracture, injury of the knee, and ankle ligament injury while taking the original meloxicam. However, in a significant part of patients, moderate or severe PTP persists after 48 weeks, which requires prolonged analgesic therapy and active rehabilitation.

Combined Administration of TLR4 (LPS) and TLR3 (Poly I:C) Ligands to CBA Mice Elevates the Content of Osteogenic MSC by 1.6 Times and Increases Content of Bone Marrow MSC to Intermediate Level between Values Attained by Their Individual Administration.

In 1 and 24 h after combined administration of TLR4 (LPS) and TLR3 (Poly I:C) ligands to CBA mice, the content of MSC in bone marrow increased to intermediate value between the levels attained by their individual injections. The content of osteogenic MSC assessed in 24 h postinjection corresponded to the control level in Poly I:C group, decreased in LPS group by 2.5 times relatively to the control, and increased by 1.6 times (relatively to control) after combined administration of the ligands. In 3 h after combined addition of LPS and Poly I:C in vitro to 12-day-old primary culture of mouse bone marrow stromal cells, the concentration of TNFα in culture medium was intermediate between the levels attained by their individual application. The data revealed dependence of activation of stromal tissue on intensity of innate immunity reactions; they also attested to marked elevation of osteogenicity of MSC pool after costimulation with Poly I:C and LPS, which can underlie augmented calcification of the tissues during combined viral and bacterial infections.

Involvement of Bone Marrow Multipotent Stromal Cells in the Processes Presumably Provoking Vascular Calcification.

During serial transplantation of bone marrow derived from young and aged donor CBA mice to 5-month-old recipients, the counts of multipotent stromal cells (MSC) in transplants from young donors assessed at each passage surpassed those of aged donors by 3.2, 7.8, 3.0, and 2.2 times attesting to the age-related decrease of active pool of bone marrow MSC. The medullary curettage in mouse femur increased the total number of MSC and the number of osteogenic MSC both in the contralateral femur and in the bone marrow transplants attesting to spread of the effects of osteogenic factors after bone injury onto the bone tissue of the body even if this tissue if not topographically related to the skeleton. Combined and simultaneous administration of antigenic complex of S. typhimurium (or LPS) with BMP-2 markedly increased the count of osteogenic medullary MSC by 3.6 or 4.6 times in comparison with intact control or by 2.1 and 2.7 times in comparison with administration of BMP-2 alone, which probably resulted from enlargement of the pool of osteogenesis-inducible MSC due to inflammation. Addition of BMP-2 to the culture of splenic stromal cells where osteogenesis does not occur under normal conditions provoked appearance of MSC colonies with alkaline phosphatase activity attesting to involvement of inducible osteogenic MSC in vascular calcification. It can be hypothesized that the reaction to the age-related changes in the bone tissue and osteoporosis is similar to the reaction to bone marrow injury and includes initiation of systemic inflammation and elevation of blood BMP-2, both of which are prerequisite for vascular calcification.

Ligands of NOD2 (Muramyl Dipeptide) and TLR4 (LPS) in 24 h after Combined In Vivo Administration Produce a Synergistic Increase in the Content of Multipotent Stromal Cells in the Bone Marrow and Peritoneal Exudate of CBA Mice.

In 24 h after combined administration of ligands of NOD2 (muramyl dipeptide) and TLR4 (LPS) receptors to CBA mice, a synergistic increase (by 10 times compared to the intact control) in cloning efficiency and content of multipotent stromal cells was observed in the bone marrow in comparison with the total effects of their individual administration (by 2.1 and 4.1 times, respectively). A similar effect was also observed in the peritoneal exudate. When ligands were administered simultaneously, the concentration of osteogenic multipotent stromal cells in the bone marrow decreased to a greater extent than in case of individual injections of the ligands, but did not drop below 7% of the control, which is apparently indicative of a decline threshold. In 3 h after simultaneous addition of the ligands in vitro to 12-day primary cultures of mouse bone marrow stromal cells, a synergistic increase in TNFα concentration was observed (32-fold increase from the level of intact control), while IL-10 concentration did not differ from the control, which is indicative of the proinflammatory nature of the process and the absence of immunosuppressive effect. These results suggest that activation of the stromal tissue depends on the intensity of innate immunity reactions.

Effect of Activated Immunocompetent Cells on the Number of Multipotent Stromal Cells in Bone Marrow Transplants of CBA and CBA/N Mice in a Short Time after Polyvinylpyrrolidone Administration to Animals.

One hour after polyvinylpyrrolidone administration, the content of multipotent stromal cells in the spleen of CBA and CBA/N mice increased almost equally (by 2.5 and 2.9 times, respectively), but in 24 h, the effectiveness of multipotent stromal cell cloning in the spleen of CBA/N mice decreased almost to the control level, whereas in CBA mice, the number of multipotent stromal cells continued to increase. Serum concentration of IL-5, TNFα, and IL-2 in both lines was elevated in 1 h after polyvinylpyrrolidone administration, which is likely to reflect activation of the innate immunity. One day after polyvinylpyrrolidone administration, the number of multipotent stromal cells in bone marrow transplants in the CBA/N→CBA/N and CBA→CBA/N groups remained practically unchanged, while in groups CBA→CBA and CBA/N→CBA it was equally increased (by 3.6 and 3.4 times, respectively). Thus, the number of multipotent stromal cells in bone marrow transplants after 1 day was increased only in groups where recipients (CBA mice) were capable of responding to polyvinylpyrrolidone administration, i.e. the number of stromal cells by this term, was apparently determined by the presence of activated immunocompetent cells. These findings also indicate that activation of the stromal tissue dur ing immune response can have a two-phasic pattern: the first phase (1 h after antigen adminis tration) can be determined by activation of innate immunity receptors (in multipotent stromal cells or other cells) observed in CBA and CBA/N mice, and the second phase occurs during further development of the immune response (that was observed in CBA mice, but not in CBA/N mice due to absence of CD+B-1a lymphocytes). The findings attest to close interactions between the stromal tissue and the immune system.

Individual Low-Energy Toroidal Dipole State in

The low-energy dipole excitations in ^{24}Mg are investigated within the Skyrme quasiparticle random phase approximation for axial nuclei. The calculations with the force SLy6 reveal a remarkable feature: the lowest I^{π}K=1^{-}1 excitation (E=7.92 MeV) in ^{24}Mg is a vortical toroidal state (TS) representing a specific vortex-antivortex realization of the well-known spherical Hill's vortex in a strongly deformed axial confinement. This is a striking example of an individual TS which can be much more easily discriminated in experiment than the toroidal dipole resonance embracing many states. The TS acquires the lowest energy due to the huge prolate axial deformation in ^{24}Mg. The result persists for different Skyrme parametrizations (SLy6, SVbas, SkM*). We analyze spectroscopic properties of the TS and its relation with the cluster structure of ^{24}Mg. Similar TSs could exist in other highly prolate light nuclei. They could serve as promising tests for various reactions to probe a vortical (toroidal) nuclear flow.

NLR2 and TLR3, TLR4, TLR5 Ligands, Injected In Vivo, Improve after 1 h the Efficiency of Cloning and Proliferative Activity of Bone Marrow Multipotent Stromal Cells and Reduce the Content of Osteogenic Multipotent Stromal Cells in CBA Mice.

Ligands NLR2 (muramyldipeptide) and TLR (bacterial LPS, flagellin, CpG-dinucleotide, and Poly I:C) and S. typhimurium antigenic complex by 1.5-3-fold increase the efficiency of cloning and content of multipotent stromal cells (MSC) in the bone marrow of CBA mice as soon as 1 h postinjection. The counts of large colonies (150-500 cells) increased by 2.5-3.3 times in comparison with intact bone marrow cultures at the expense of a decrease in the number of smaller colonies, which attests to enhanced proliferation of stromal cells in the colonies. The efficiency of cloning and hence, MSC content in the femoral bone decreased by 1.2-1.9 times after 3 h and increased again after 24 h to the level 1.3-1.5 times higher than the level 1 h postinjection (LPS, Poly I:C, and S. typhimurium antigenic complex). The dynamics of bone marrow MSC cloning efficiency after 1-3 h corresponded to the dynamics of serum cytokine concentrations during the same period. However, the levels of serum cytokines after 24 h in general were similar to those in intact mice or were lower. The concentrations of osteogenic multipotent stromal cells in the bone marrow decreased 2-3-fold after 3 h and thus persisted by 24 h postinjection. Twofold (at 24-h interval) and a single injection of S. typhimurium antigenic complex to mice led to a significant increase of cloning efficiency, observed as early as just 1 h postinjection (1.9 and 1.5 times, respectively). The same picture was observed for serum cytokines. On the whole, injections of TLR and NLR ligands and of S. typhimurium antigenic complex led to stromal tissue activation within 1 h postinjection, this activation consisting in a significant increase of the efficiency of cloning and of MSC count in the bone marrow, and also in an increase in their proliferative activity and a decrease (after 3 h) of osteogenic MSC concentration.

Counts of MSC in the Bone Marrow of Young and Old CBA Mice after a Single Exposure to Osteogenic Stimuli (Curettage, BMP-2 Injection) or Antigens (S. typhimurium Antigenic Complex) and in Heterotopic Bone Marrow Transplants.

The efficiency of cloning and the content of multipotent stromal cells (MSC) in the femoral bone marrow of intact CBA mice was 1.5 times less in old mice (24-36 months) than in young ones (2-3 months). The concentration of osteogenic MSC was higher in old vs. young mice (42±3 vs. 22±2%, respectively). Changes in the total counts of MSC and concentrations of osteogenic MSC in response to osteogenic (curettage, BMP-2) and immunogenic stimuli (S. typhimurium antigenic complex) were similar in young and old mice in comparison with intact controls of respective age. The counts of the total pool of bone marrow MSC and pool of osteogenic MSC in response to osteogenic stimuli were 1.5-2 times less in old vs. young mice. This difference seemed to be a result of age-specific decrease of their bone marrow count but not of age-specific decrease of the MSC functional activity, this leading to a decrease in the transplantability of bone marrow stromal tissue of old mice. Comparison of transplantations "old donor - young recipient" vs. "young donor - young recipient" demonstrated a decrease in the count of nuclear cells (1.8 times), size of bone capsule (2-fold), efficiency of MSC cloning (1.6 times), count of MSC per transplant (2.9 times), and count of osteogenic MSC per transplant (3.3 times). The concentrations of osteogenic MSC in transplants from young and old donors leveled in young recipients, that is, seemed to be regulated by the host. Serum concentrations of IL-10 and TNF-α in intact old mice were at least 2.9 and 2 times higher than in young animals, while the concentrations of almost all the rest studied cytokines (IL-2, IL-5, GM-CSF, IFN-γ, IL-4, IL-12) were lower. Presumably, the decrease in the content of bone marrow MSC and in transplantability of bone marrow stromal tissue in old mice were caused by exhaustion of the MSC pool as a result of age-specific chronic inflammation. These data indicated a close relationship between age-specific changes in the stromal tissue and immune system.

Local and Systemic Functional Responses of Mouse Macrophages to Intravaginal Infection with Type 2 Herpes Simplex Virus and Vaccination.

Activity of cathepsin D and phagocytosis of macrophages from vaginal lavage fluid, peritoneal exudation, and spleen were studied in mice of sensitive (DBA/2) and resistant (BALB/c) lines after intravaginal infection with type 2 herpes simplex virus and vaccination. Activity of cathepsin D and intensity of phagocytosis (irrespective of the macrophage source) and their ratio in BALB/c mice in early terms after infection were close to the control levels taken as a unit. In DBA/2 mice, these parameters and their balance were shifted and changes in cathepsin D activity depended on the time after challenge. Activities of cellular and extracellular cathepsin D increased sharply on day 1 postinfection under conditions of local virus interaction with the vaginal mucosa and activation of the pathological process. Later, after generalization of the infection, activity of cathepsin D decreased, while phagocytosis increased in all the studied macrophage populations. Vaccination corrected the cathepsin D/phagocytosis imbalance and created conditions for rapid elimination of the virus.

The Content of Multipotent Stromal Cells in 3-4.5-Month Heterotopic Bone Marrow Transplants of CBA Mice Subjected to a Single Exposure to Osteogenic Stimuli (Curettage, BMP-2) or Antigens (S. typhimurium antigenic complex, LPS).

At the early stages of development (3 months), transplants from bone marrow donors subjected to single in vivo stimulation (curettage, administration of BMP-2 or antigenic complex of S. typhimurium) 1 day before transplantation were characterized by significantly elevated content of nucleated cells (by 1.4, 1.9 and 2.9 times, respectively), efficiency of cloning of multipotent stromal cells (by 3.8, 3.8 and 7.2 times), and total number of multipotent stromal cells (by 5, 7 and 21 times) and osteogenic multipotent stromal cells (by 5, 9 and 15 times) in comparison with the control (intact donors); more rapid increase in the weight of bone capsules was also noted. At later terms, the difference by these parameters between the control and experimental groups became less pronounced, but even in 4.5 months, the total number of multipotent stromal cells in the transplant in experimental groups exceeded the control values by 1.4-1.7 times and osteogenic multipotent stromal cells by 2 times. In donors exposed to the specified stimulations, the content of multipotent stromal cells in the femoral bone marrow in 1 day increased by 2.1 times (curettage), 2.6 times (administration of S. typhimurium antigens), and 3.3 times (LPS); administration of BMP-2 reduced this value by 50%. The content of osteogenic bone marrow multipotent stromal cells at this term increased by 1.7 times (BMP-2) and 5.5 times (curettage), after administration of S. typhimurium antigens, this parameter corresponded to the control. The concentration of osteogenic multipotent stromal cells in the bone marrow of intact donors was 22%; the maximum values were observed after curettage (57%) and BMP-2 administration (74%) and minimum after treatment with S. typhimurium antigens (8%). However, this parameter in all groups of transplants little differed and leveled as soon as by 3-4 months, which can be due to regulatory influences of the recipient body. The initial advantage in the content of bone marrow multipotent stromal cells in donors exposed to osteogenic stimuli and administration of antigens ensured considerably more rapid growth of the transplants in comparison with the control. These results can be useful for the development of optimal protocols of tissue grafting.

Antiretroviral Activity Of a Novel Pyrimidyl-Di(Diazaspiroalkane) Derivative.

A novel compound, 3,3'-(5-nitropyrimidine-4,6-diyl)bis-3,12-diaza-6,9-diazoniadispiro[5.2.5.2]hexadecane tetrachloride dihydrochloride, was synthesized. The compound was found to inhibit the replication of various viral families by blocking specific heparan sulfate receptors on the host cell's surface. In experiments, the compound was found to be highly effective against several strains of HIV retroviruses.

Prediction of Intraoperative Blood Loss during Total Knee Arthroplasty in HCV+ and HCV- Patients with Hemophilia A.

We examined HCV+ and HCV- hemophilia A patients with knee arthropathy and hematocrit above 38.5%. The mean density of erythrocytes was studied by the phthalate method, intraoperative blood loss was assessed gravimetrically. The volume of blood loss in HCV+ patients with manifest adhesive process and chronic synovitis varied from 300 to 1900 ml, in patients with moderate adhesive process from 400 to 1500 ml. The volume of blood loss in HCV- patients was 300-800 ml. A positive correlation between the blood loss volume and mean density of erythrocytes was detected. Blood loss >1000 ml during total knee arthroplasty can be expected in patients with hemophilia A with HCV and high mean density of erythrocytes. Blood loss >1000 ml is unlikely in HCV- and HCV+ patients with the mean density of erythrocytes not surpassing the normal values.

[Peculiarities of diagnosis and treatment of kidney cancer in the central military hospital].

tumor based on analysis of the treatment of patients with kidney cancer in 1339 received. Studied the characteristics such as the stepwise distribution of patients, incidence of histological types of kidney cancer, and varying degrees of tumor differentiation, the proportion of organ and organ-resecting interventions, methods of drug treatment, adoptive immunotherapy. The information about the features of.

MORPHOLOGICAL ANALYSIS OF HEPATITIS B VIRUS WITH ESCAPE MUTATIONS IN S-gene G145R AND S143L.

BACKGROUND: In terms of serological properties and immunization, the wild type of HBsAg HBV and its G145R mutant behave as different antigens. This testifies to serious structural changes, which presumably could have a significant impact on the morphogenesis of virions and subviral particles. Nevertheless, morphological and ultrastructural investigations of HBV with G145R mutation have not been carried yet. OBJECTIVES: Research of structural and morphological organization of HBV in the presence of the G145R escape mutation. METHODS: Studies of sera, purified viruses and recombinant HBsAg were carried out by transmission electron microscopy by the method of negative staining and indirect reaction of immunelabeling using monoclonal antibodies of different specificity. Specimens of wild type HBV and HBV with S143L mutation obtained in an identical manner were used as the control. RESULTS: The presence of typical virus particles of HBV was shown in the specimens of wild strain and HBV with S143L mutation. Specimens of HBV with G145R mutation were characterized by expressed morphological heterogeneity. In the initial serum and in the specimen of purified virus containing G145R mutant, large oval particles 60-70 nm and up to 200 nm in size, respectively, were found. The presence of antigen structures of HBV in all heterogeneous forms was confirmed. It was shown that forming of subviral particles in the process of expression of the recombinant HBsAg with G145R mutation depends on conditions of expression and purification of the protein. They can vary from well-formed circular and oval particles to practically unstructured fine-grained masses. CONCLUSION: Direct data on the impact of G145R escape-mutation in S-gene, in contrast to S143L mutation, on the morphogenesis of virions and subviral particles of HBV were obtained.

Effect of Hematocrit and Erythrocyte Density on Intraoperative Blood Loss in Hemophilia A Patients During Total Knee Arthroplasty.

Intraoperative blood loss during total knee arthroplasty in patients with hemophilia varies over a wide range (from 300 to 3000 ml). The reasons have not been clarified yet. We studied the dependence of intraoperative blood loss during total knee arthroplasty in patients with hemophilia A on hematocrit and mean erythrocyte density. Intraoperational blood loss ≥1000 ml was observed in patients with hematocrit <38.5%. In patients with hematocrit >38.5% this parameter depended on the mean erythrocyte density: in patients with increased erythrocyte density, the risk of intraoperational blood loss ≥1000 ml was higher. The increase in erythrocyte density can serve as an indicator of pathological processes, including the processes modulating hemostasis. It can also be assumed that erythrocytes with higher density change blood flow, which affects platelet adhesion to the damaged endothelium. Hematocrit below the threshold level and mean density of erythrocytes above the normal level can be regarded as risk factor for increased intraoperational blood loss.

Successive Administration of Streptococcus Type 5 Group A Antigens and S. typhimurium Antigenic Complex Corrects Elevation of Serum Cytokine Concentration and Number of Bone Marrow Stromal Pluripotent Cells in CBA Mice Induced by Each Antigen Separately.

Administration of bacterial antigens to CBA mice induced an increase in serum concentration of virtually all cytokines with a peak in 4 h after administration of S. typhimurium antigens and in 7 h after administration of streptococcus antigens. In 20 h, cytokine concentrations returned to the control level or were slightly below it. In 4 h after administration of S. typhimurium antigens preceded 3 h before by administration of streptococcus antigens, we observed a significant decrease in serum concentrations of IFN-γ, IL-10, GM-CSF, IL-12, and TNF-α, in comparison with injection S. typhimurium antigens alone and IL-5, IL-10, GM-CSF, and TNF-α in comparison with injection of streptococcus antigens alone; the concentrations of IL-2 and IFN-γ, in contrast, increased by 1.5 times in this case. In 20 h after administration of S. typhimurium antigens, the number of multipotential stromal cells (MSC) in the bone marrow and their cloning efficiency (ECF-MSC) increased by 4.8 and 4.4 times, respectively, in comparison with the control, while after administration of streptococcus antigens by 2.6 and 2.4 times, respectively. In 20 h after administration of S. typhimurium antigens preceded 3 h before by administration of streptococcus antigens, these parameters increased by 3.2 and 2.9 times, respectively, in comparison with the control, i.e. the observed increase in the level of MSC count and ECF-MSC is more consistent with the response of the stromal tissue to streptococcus antigens. Thus, successive administration of two bacterial antigens corrected both serum cytokine profiles and MSC response to administration of each antigen separately, which indicates changeability of the stromal tissue in response to changes in the immune response.

Attenuation of short strongly nonlinear stress pulses in dissipative granular chains.

Attenuation of short, strongly nonlinear stress pulses in chains of spheres and cylinders was investigated experimentally and numerically for two ratios of their masses keeping their contacts identical. The chain with mass ratio 0.98 supports solitary waves and another one (with mass ratio 0.55) supports nonstationary pulses, which preserve their identity only on relatively short distances, but attenuate on longer distances because of radiation of small amplitude tails generated by oscillating small mass particles. Pulse attenuation in experiments in the chain with mass ratio 0.55 was faster at the same number of the particles from the entrance than in the chain with mass ratio 0.98. It is in quantitative agreement with results of numerical calculations with effective damping coefficient 6 kg/s. This level of damping was critical for eliminating the gap openings between particles in the system with mass ratio 0.55 present at lower or no damping. With increase of dissipation numerical results show that the chain with mass ratio 0.98 provides faster attenuation than the chain with mass ratio 0.55 due to the fact that the former system supports the narrower pulse with the larger difference between velocities of neighboring particles. The investigated chains demonstrated similar behavior at large damping coefficient 100 kg/s.