Potentiation of the stimulatory effect of erythropoietin on erythropoiesis by antiserotonin drug during cytostatic myelosuppression.

Combined stimulatory effect of antiserotonin drug and erythropoietin on the bone marrow erythropoiesis was studied under conditions of cytostatic myelosuppression. The stimulatory effect of erythropoietin on regeneration of the hemopoietic erythroid stem increased, if serotonin mediation in the CNS was disordered before induction of cytostatic myelosuppression. The stimulatory effect of a combination of cyproheptadine and epocrine (experimental group) significantly surpassed that of cyproheptadine and epocrine monotherapies. The increase in the content of erythroid elements in the blood system of experimental animals was due to recovery of the structural and functional integrity of the hemopoietic tissue (at the expense of reduction of the suppressive effect of CNS serotonin on the formation of erythroid hemopoietic islets) and simultaneous stimulation of division and maturation of erythroid precursors with epocrine.

Mechanisms of granulocytopoiesis-stimulating activity of immobilized granulocytic colony-stimulating factor in cytostatic myelosuppression.

The hemostimulatory effects of granulocytic CSF, immobilized on polyethyleneglycol using radiation synthesis nanotechnology, were studied on the model of cyclophosphamide-induced myelosuppression. Immobilization of granulocytic CSF led to stimulation of granulomonocytopoiesis by increasing functional activity of granulomonocytic precursors and secretion of humoral factors by elements of hemopoiesis-inducing microenvironment, and due to more intensive formation of hemopoietic islets. The granulocytopoiesis-stimulating effect of immobilized granulocytic CSF was comparable to the effect of standard nonconjugated granulocytic CSF. Specific activity of immobilized granulocytic CSF in oral treatment was demonstrated.

Effect of transplantation of peripheral blood mononuclears obtained using granulocytic colony-stimulating factor and hyaluronidase on regeneration of hemopoietic tissue during myelosuppression.

The mechanisms of hemopoiesis recovery after transplantation of peripheral blood mononuclears obtained using granulocytic CSF and granulocytic CSF in combination with hyaluronidase were studied on the model of cytostatic myelosuppression. It was found that regeneration of the hemopoietic tissue resulted from an increase in the pool of erythroid and granulomonocytic precursors and in their functional activity. The increase in the count of fibroblast precursors in the bone marrow, higher production of hemopoietins by adherent myelokaryocytes, and an increase in the level of humoral factors in the serum were detected after injection of the transplants. A higher therapeutic efficiency of cell material obtained after combined use of granulocytic CSF and hyaluronidase was shown.

Effect of granulocytic colony-stimulating factor on cytostatic-suppressed granulocytopoiesis under conditions of exhausted catecholamine depot.

Exhaustion of catecholamine depot in the CNS before modeling of cytostatic myelosuppression potentiates the stimulatory effect of granulocytic CSF on regeneration of the granulocytic hemopoiesis stem. The increase in granulocyte count in the blood system under these conditions is caused by recovery of the structural and functional organization of the hemopoietic tissue (at the expense of reduction of the suppressive effect of catecholamines on the formation of granulocytic hemopoietic islets) and simultaneous stimulation of division and maturation of granulomonocytic precursors.

Mobilization of progenitor cells into the blood by immobilized granulocytic colony-stimulating factor.

The effects of granulocytic CSF immobilized on polyethylenoxide by nanotechnology on the bone marrow and circulating pools of mesenchymal and hemopoietic precursors were studied. Immobilized granulocytic CSF caused the release of progenitor cells of different classes into the blood. The effect of injected immobilized granulocytic CSF was superior to that of nonconjugated granulocytic CSF. Specific activity of oral immobilized granulocytic CSF after oral administration was demonstrated.

Hemostimualting properties of preparation containing ultralow doses of antibodies to stem cell factor in cytostatic myelosuppression.

Preparation containing ultralow doses of antibodies to stem cell factor considerably activates bone marrow myelopoiesis suppressed by cyclophosphamide. This effect of the preparation is based on stimulation of proliferation of committed hemopoietic precursors and increase in functional activity of adherent elements of hemopoiesis-inducing microenvironment.

Adrenergic regulation of erythropoiesis during cytostatic-induced myelosuppressions.

The role of central adrenergic structures in the regulation of the erythroid hematopoietic stem was studied during administration of cyclophosphamide and 5-fluorouracil. The central nervous system contributed to suppression of erythropoiesis during cytostatic treatment. The suppressive effect of brain adrenergic structures on the erythron after treatment with cyclophosphamide and 5-fluorouracil was related to dysfunction of adherent cells in the hemopoiesis-inducing microenvironment (formation of hemopoietic islets and secretion of erythropoietic activity) and production of growth factors by myelokaryocytes, respectively. Brain norepinephrine had an inhibitory effect on proliferative activity and differentiation of erythroid precursors that were associated with the erythropoietin and peripheral alpha-adrenergic structures. However, stimulation of beta-adrenergic structures was followed by an increase in the rate of erythroid cell maturation.

[Type-specific antibodies to hepatitis C virus in sera from patients with various hematologic diseases]. / Tipospetsificheskie antitela k virusu gepatita C v syvorotkakh bol'nykh s razlichnymi zabolevaniiami krovi.

The reactivity of 100 sera taken from patients with different blood diseases and donors with respect to synthesized peptides in the variable area of protein NS4 of hepatitis C virus was studied. The presence of type-specific antibodies in the blood sera of patients with hepatitis C was shown. Two antigenic determinant corresponding to 1683-1705 and 1711-1732 amino acid residues in the protein area under study were detected. In hematological patients undergoing frequent blood transfusions mixed infection with different types of hepatitis C virus was registered; these types could be reliably determined with the use of synthetic peptides. The serotype determined with the use of peptides corresponded to the type of the circulating virus.

[Detection of antibodies to the nucleocapsid protein of Hepatitis C virus by immunoenzyme analysis using synthetic peptides of nucleocapsid N-terminal part]. / Opredelenie antitel k nucleokapsidnomu belku virusa gepatita C metodom immunofermentnogo analiza na osnove sinteticheskikh peptidov iz N-kontsevoi chastinukleokapsidnogo peptida.

Solid-phase synthesis of 7 linear peptides overlapping the immunodominant N-terminal region of hepatitis C virus (HCV) core protein (aa 7-75) was carried out. Their antigen reactivity was studied by non-competitive ELISA with sera from patients with chronic HCV infection. Three B-epitopes located within aa 7-19, 20-34, and 39-75 appeared to be the most immunoreactive. Use of the set of synthetic peptides in ELISA detected anti-HCV core antibodies with 93% efficiency in comparison with ELISA and commercial anti-HCV Recomblot based on the use of commercial recombinant HCV core protein.

[Use of synthetic peptides as additional antigens for detecting antibodies to hepatitis C virus]. / Ispol'zovanie sinteticheskikh peptidov kak dopolnitel'nykh antigenov dlia vyiavleniia antitel k virusu gepatita C.

Peptide fragments of hepatitis C virus (HCV) nonstructural protein NS4 capable of reacting with anti-HCV in enzyme immunoassay are synthesized. Addition of synthetic peptides to recombinant nucleocapsid HCV antigen absorbed on solid phase notably improves the efficacy of detection of antibodies to HCV in the sera of patients with hepatitis C.

[Synthesis and antigenic activity of peptides from the C-terminal part of the NS4-protein of the hepatitis A virus]. / Sintez i antigennaia aktivnost' peptidov iz C-kontsevoi chasti nestrukturnogo NS4-belka virusa gepatita C.

A set of four peptides from the HCV NS4-protein C-terminal region (aa 1921-1940) were obtained by solid-phase synthesis using activated esters and symmetrical anhydrides of Boc-amino acids. Peptide 1921-1940 has demonstrated a positive reaction in ELISA with individual anti-HCV-positive sera from patients with acute and chronic hepatitis C (80% and 56%, respectively). We analysed the antigenic properties of the peptide 1921-1940 and its fragments and suggested at least two antibody recognizing sites to be contained in this region.

[Synthesis and antigenic activity of peptides from core- and NS3-proteins of hepatitis C virus]. / Sintez i antigennaia aktivnost' peptidov iz sostava core- i NS3- belkov virusa gepatita C.

We synthesized the 20-34 and 22-34 fragments of the core and 1269-1282 fragment of the NS3 protein of the hepatitis C virus. The peptides were prepared by the solid-phase synthesis using activated esters and symmetrical anhydrides of Boc-amino acids. Peptide 20-34 demonstrated positive reaction in ELISA with all individual sera from HCV chronic patients. Peptide 1269-1282 reacted with 33% patients sera.