Characterization at the individual cell level and in whole blood samples of shear stress preventing red blood cells aggregation.

The aggregation of red blood cells (RBC) is an intrinsic feature of blood that has a strong impact on its microcirculation. For a number of years it has been attracting a great attention in basic research and clinical studies. Here, we study a relationship between the RBC aggregation parameters measured at the individual cell level and in a whole blood sample. The home made optical tweezers were used to measure the aggregating and disaggregating forces for a pair of interacting RBCs, at the individual cell level, in order to evaluate the corresponding shear stresses. The RheoScan aggregometer was used for the measurements of critical shear stress (CSS) in whole blood samples. The correlation between CSS and the shear stress required to stop an RBC pair from aggregating was found. The shear stress required to disaggregate a pair of RBCs using the double channel optical tweezers appeared to be about 10 times higher than CSS. The correlation between shear stresses required to prevent RBCs from aggregation at the individual cell level and in whole blood samples was estimated and assessed quantitatively. The experimental approach developed has a high potential for advancing hemorheological studies.

[Criteria of systemic inflammatory response syndrome are unacceptable in the diagnosis of sepsis in patients with leukopenia]. / Kriterii sindroma sistemnogo vospalitel'nogo otveta nepriemlemy dlia diagnostiki sepsisa u bol'nykh s leikopeniei.

Twenty-two patients with hemoblastosis were examined in order to evaluate the possibility of using the criteria of the total system's inflammatory response syndrome (TSIRS) for the diagnosis of sepsis in hemoblastosis patients with leukopenia. The patients were examined before and after chemotherapy. Twelve patients with myelotoxic leukopenia developed TSIRS in response to a concomitant infection. No intensive care and resuscitation were needed in 9 of them; antibiotic therapy rapidly improved the clinical status. Three of these patients had to be transferred to intensive care wards. These patients differed from patients with TSIRS who needed no intensive care and from patients without TSIRS by higher fever (39.6 +/- 0.9, 39.1 +/- 0.4, and 36.5 +/- 0.7 degrees C, respectively), tachycardia (114.1 +/- 19.1, 105.3 +/- 12.8, and 84.0 +/- 10.0 stroke/min, respectively), thrombocytopenia (35.4 +/- 33.2.10(9), 55.1 +/- 34.5.10(9), and 89.2 +/- 95.1.10(9)/liter, respectively), prolongation of XIIa-dependent fibrinolysis (161.0 +/- 67.5. 64.7 +/- 57.0, and 46.2 +/- 45.8 min, respectively), decreased content of antithrombin III (79.6 +/- 8.1, 102.0 +/- 16.2, and 98.9 +/- 11.9%, respectively), and a more grave status according to the APACHEII score (20.4 +/- 5.2, 15 +/- 2.0, and 10.8 +/- 3.2, respectively). The APACHEII score and XIIa-dependent fibrinolysis were in direct correlation. We consider that the TSIRS/sepsis criteria are highly sensitive but not specific. They just permit singling out the group of patients part of whom may have sepsis.

Changes in TNF and IL-6 production after diphtheria toxoid vaccination: drug modulation of the cytokine levels.

The effect of vaccination with diphtheria toxoid (AD-M) on TNF and IL-6 production has been studied in humans. In the present study it was demonstrated that immunization with AD-M resulted in changes of in vitro TNF and IL-6 production by peripheral blood mononuclear cells. TNF release was suppressed but IL-6 production was stimulated. On the other hand, serum levels of TNF were markedly increased over a period of 3 weeks. It was also demonstrated that the postvaccinal cytokine production disturbances may be corrected by pretreatment with a new synthetic hexapeptid (Imunofan((R))). It is possible that the imunofan treatment could prevent some postvaccinal complications.

[Mechanisms of inhibiting production of tumor necrosis factor alpha by the synthetic hexapeptide--immunophane]. / Mekhanizmy ingibitsii porduktsii faktora nekroza opukhloi alph sinteticheskim geksapeptidom--immunofanom.

The authors examined the human blood mononuclear-induced tumor necrosis factor production using the new drug--the synthetic hexapeptide Immunophan. The levels of tumor necrosis factor in the supernatant liquid were measured by the enzyme immunoassay and the cytotoxic test using L-929 fibroblastoid cells. Following 2-8 hours of short-term incubation of mononuclear cells with Immunophan, there was a reduction in spontaneous or lipopolysaccharide - or ionophore A23187-induced production of tumor necrosis factor. As high as 5-20% of plastic-nonadherent cells treated with Immunophan in a concentration of 0.25 mu/ml were found to produce the same effect. Two-four hours after Immunophan activation, the cells produced into the supernatant liquid soluble factors with a molecular weight of 70-85 kD that suppressed the production and activity of tumor necrosis factor. Thus, the modulating effect of Immunophan against tumor necrosis factor production is associated with the induction of regulatory cells producing the soluble receptors of tumor necrosis factor. It is suggested that extrabody pharmacological induction of the cells that regulate the production of tumor necrosis factor, followed by their subsequent administration into the autologic organism might be used while developing new variants of extracorporeal treatments of the diseases which are characterized by the pathogenetically significant hyperproduction of the inflammatory cytokins,--tumor necrosis factor, interleukin-1, interleukin-6.