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Biomedical subjects

A Vacek

Publications and source records attributed to A Vacek.

At least 37 records · Page 2Linked to original sources
PubMed1999

Pretreatment with granulocyte colony-stimulating factor reduces myelopoiesis in irradiated mice.

The purpose of this study was to investigate effects of the treatment prior to irradiation with granulocyte colony-stimulating factor (G-CSF) on hematopoiesis in B10CBAF1 mice exposed to a sublethal dose of 6.5 Gy of 60Co gamma radiation. G-CSF was administered in a 4-day regimen (3 microg/day); irradiation followed 3 h after the last injection of G-CSF. Such a treatment was found to stimulate granulopoiesis, as shown by increased counts of granulocyte-macrophage progenitor cells (GM-CFC) and of granulocytic cells in the femoral marrow and spleen at the time of irradiation. However, postirradiation counts of GM-CFC and granulocytic cells in the marrow of mice pretreated with G-CSF were reduced up to day 18 after irradiation. Interestingly, the D0 values for marrow GM-CFC determined 1 h after in vivo irradiation were 1.98 Gy for controls and 2.47 Gy for mice pretreated with G-CSF, indicating a decreased radiosensitivity of these cells after drug treatment. The inhibitory effects of the pretreatment with G-CSF on the postirradiation granulopoiesis could be attributed to the phenomenon of "rebound quiescence" which can occur after cessation of the treatment with growth factors. Postirradiation recovery of erythropoiesis in the spleen of mice pretreated with G-CSF exhibited a dramatic increase and compensated for the decreased erythropoiesis in the marrow at the time of irradiation. This complexity of the hematopoietic response should be taken into account when administering G-CSF in preirradiation regimens.

Animals↗
PubMed1998

Granulocyte colony-stimulating factor and drugs elevating extracellular adenosine synergize to enhance haematopoietic reconstitution in irradiated mice.

The activation of adenosine receptors has recently been demonstrated to stimulate haematopoiesis. In the present study, we investigated the ability of drugs elevating extracellular adenosine to influence curative effects of granulocyte colony-stimulating factor (G-CSF) in mice exposed to a sublethal dose of 4 Gy of 60Co radiation. Elevation of extracellular adenosine in mice was induced by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), an adenosine prodrug. The effects of dipyridamole plus AMP, and G-CSF, administered either alone or in combination, were evaluated. The drugs were injected to mice in a 4-d treatment regimen starting on d 3 after irradiation and the haematopoietic response was evaluated on d 7, 10, 14, 18 and 24 after irradiation. While the effects of G-CSF on the late maturation stages of blood cells, appearing shortly after the completion of the treatment, were not influenced by dipyridamole plus AMP, positive effects of the combination therapy occurred in the post-irradiation recovery phase which is dependent on the repopulation of haematopoietic stem cells. This was indicated by the significant elevation of counts of granulocyte-macrophage progenitor cells (GM-CFC) and granulocytic cells in the bone marrow (d 14), of GM-CFC (d 14), granulocytic and erythroid cells (d 14 and 18) in the spleen, and of neutrophils (d 18), monocytes (d 14 and 18) and platelets (d 18) in the peripheral blood. These effects suggest that the repopulation potential of the combination therapy lies in a common multilineage cell population. The results of this study implicate the promising possibility to enhance the curative effects of G-CSF under conditions of myelosuppressive states induced by radiation exposure.

Adenosine↗
PubMed1997

Stimulation of hemopoietic colony formation from mouse marrow cells in vitro using human dialyzable leukocyte extracts-IMMODIN-SEVAC.

The influence of dialyzable extract from human leukocytes (DLE) on the in vitro growth of the granulocyte-macrophage colony-forming cell (GM-CFC) colonies from progenitors of mouse bone marrow cells was studied. DLE alone did not induce the colony growth but it modulated the number of colonies if administered together with a colony-stimulating factor (CSF). The costimulatory effect prevailed in a broad range of DLE dilution and the index of increase was enhanced with the lowering of the CSF concentration. The costimulatory augmentation of clonal proliferation of GM-CFC with DLE was further strengthened by addition of indomethacin, thus indicating an intervening role of prostaglandins in the modulatory influence of DLE.

Animals↗
PubMed1996

Micropreparation of hemopoietic stem cells from the mouse bone marrow suspension by gravitational field-flow fractionation.

Gravitational field-flow fractionation is a relatively simple experimental technique. This method was used for the characterization of stem cells from mouse bone marrow. Because these cells are bigger than the other cells in bone marrow, it is possible to separate them from the mixture. The fractions collected after passing through the separation channel were characterized using a Coulter Counter and used for transplantation into irradiated mice.

Animals↗
PubMed1996

The effect of DLE fractions on GM-progenitors of haematopoietic stem cells in vitro.

Dialysable leucocyte extract (DLE) prepared from buffy coats of human blood, potentiates the effect of Colony-stimulating factor (CSF) on the growth of granulocyte-macrophage colony forming cell (GM-CFC) colonies in vitro. This relative increase of the number of colonies is apparent when diluted CSF (present in lung conditioning medium) as a control, and DLE, in a wide range of concentrations are added to the culture of mouse bone marrow cells. Fractionation of DLE on Amicon membranes revealed that the activity resides in molecules of 0-5 kD. Molecules 5-10 kD have no potentiating effect. DLE and its fractions (0-5 kD, 0-1 kD), except fractions 0-500 D and 5-10 kD, when added undiluted i.e. at the initial concentration, exerted a suppressive effect: colonies are not formed despite the presence of CSF. In a pilot experiment, it was shown that DLE is able to stimulate colony-forming activity of earlier progenitors of erythroid cells (BFUe), under the influence of erythropoietin.

Animals↗
PubMed1993

Hematopoietic recovery in repeatedly irradiated mice can be enhanced by a repeatedly administered combination of diclofenac and glucan.

A combination of diclofenac and glucan administered repeatedly in a protective regimen in the course of repeated gamma irradiation of mice (6 x 2 Gy during 3 weeks) enhanced granulopoiesis and other indices of hematopoietic recovery investigated from 3 to 7 days after the last radiation exposure. Repeated administration of diclofenac or glucan alone or treatment of the mice with the diclofenac-glucan combination given once before the first or the last radiation exposure did not induce such effects. The protective effect of the repeatedly administered combination of the drugs was realized despite the fact that the response of the serum colony-stimulating activity to the repeated combined drug administration was decreased at the end of the treatment regimen compared to that of mice given this drug combination only once. The combined treatment is supposed to act via increased proliferation of the hematopoietic stem or progenitor cells. Additivity or even synergism of the hematostimulatory action of glucan and of the strengthening of positive control of cell proliferation achieved by removing negatively acting prostaglandins (diclofenac action) may account for the radioprotective effects observed.

Animals↗
PubMed1993

Noradrenaline reduces cardiovascular effects of the combined dipyridamole and AMP administration but preserves radioprotective effects of these drugs on hematopoiesis in mice.

Recent results of the authors have demonstrated that the elevation of extracellular adenosine induced by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), a soluble adenosine prodrug, mediates radioprotective effects in mice. Furthermore, it has been shown that this action is induced by at least two mechanisms: (1) protection by hypoxia as a result of the effects of treatment on the cardiovascular system (bradycardia, vasodilation), and (2) an enhanced regeneration of the radiation-perturbed hematopoiesis. Here, it was ascertained that the joint use of an optimal dose of noradrenaline given with dipyridamole and AMP combination eliminates the hypothermic and hypoxic effects of the treatment, but preserves the radioprotective action of dipyridamole and AMP combination in terms of hematopoietic recovery and partially also survival enhancing effects of the drugs in gamma-irradiated mice. These findings might be of importance for attempts to obtain available and tolerable radioprotective pharmacological prescriptions for clinical use.

Adenosine Monophosphate↗
PubMed1993

Hyporesponsiveness of murine myeloid progenitor cells to glucan following its repeated administration.

A moderate marrow granulocytic hyperplasia developed after 4 injections of glucan (soluble derivative carboxymethylglucan) administered to mice at 3-4-day intervals. However, when evaluating the response of the marrow granulocyte-macrophage colony-forming cells (GM-CFC) to the fifth glucan injection given in the repetitive treatment schedule, the development of hyporesponsiveness of these cells was found, contrary to the stimulatory action of a single glucan injection. In addition, the prompt increase in serum granulocyte-macrophage colony-stimulating activity occurring after a single glucan injection, and proposed to upregulate myelopoiesis, was absent in mice treated with glucan repeatedly. A joint administration of glucan with diclofenac, an inhibitor of prostaglandin synthesis, was able to enhance the GM-CFC response to a single glucan injection, probably due to the removal of the downregulation action of prostaglandins on these progenitor cells. However, a repeated administration of diclofenac with glucan did not reduce substantially the development of GM-CFC hyporesponsiveness. Thus, the results suggest that the GM-CFC hyporesponsiveness or tolerance to repeated glucan injections was induced by weakening the mechanisms of positive control mediated by the serum colony-stimulating activity.

Adjuvants, Immunologic↗
PubMed1993

Elevation of extracellular adenosine induces radioprotective effects in mice.

The radioprotective effectiveness of the elevation of extracellular adenosine induced in mice by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate, a soluble adenosine pro-drug, was evaluated. Based on survival studies, endogenous hemopoietic spleen colony formation, and the postirradiation behavior of bone marrow granulocyte-macrophage colony-forming cells (GM-CFC), it was demonstrated that the combined administration of dipyridamole and AMP protects mice when given either 15 or 60 min before irradiation. It could be deduced that the radioprotective action is induced by at least two independent mechanisms: (1) protection by hypoxia as a result of the effect of the treatment on the cardiovascular system, and (2) and enhanced regeneration of the hemopoietic stem cells due to either enhanced postirradiation repair or an increased proliferation of the hemopoietic stem cells. Both of these protective mechanisms, which are able to increase the regeneration of hemopoiesis, seemed to be effective in enhancing the survival of mice given single radiation exposures, with a dose reduction factor for the LD50/30 of 1.11. The protective efficiency of the mechanisms enhancing the postirradiation recovery of hemopoiesis was also evident in experiments evaluating the survival of mice subjected to fractionated irradiation and a repeated administration of the protective agents.

Adenosine↗
PubMed1992

Investigation of red blood cell fractionation by gravitational field-flow fractionation.

Gravitational field-flow fractionation is used for the separation of particles according to their sizes in the range 1-100 microns: larger particles elute before smaller ones. This phenomenon can be explained as a result of the steric exclusion of the particles from the vicinity of the channel walls, and/or hydrodynamic effects supposedly associated with the inertia of the liquid. The method was used for the investigation of red blood cells. The dependence of the retention ratio on the flow-rate, sample volume, concentration of blood and relaxation time was studied. Analysis of fifteen individual fractions by Coulter counter and reinjection of three other fractions were studied in order to verify fractionation of red blood cells.

Cell Separation↗
PubMed1992

Protection of early cellular damage in 1 Gy-irradiated mice by the elevation of extracellular adenosine.

In whole-body 1Gy-irradiated mice a modification of early cellular damage by means of preirradiation dipyridamole and adenosine monophosphate (AMP) treatment was investigated. Both drugs were given either alone or in combination, AMP being administered i.p. at doses of 5, 10 and 15 mg, dipyridamole s.c. at the dose of 2 mg, 20 min before AMP. The thymidine level in plasma and the amount of free polynucleotides in the thymus and spleen, both estimated at the interval of 4 h after irradiation, were used as indices of early cellular damage in vivo. The elevated level of thymidine observed in the plasma of irradiated controls decreased significantly after the administration of AMP (5 mg) alone to 71%, after the combination of dipyridamole and AMP a still deeper significant fall to 60% was observed. Such a protective effect was observed when injecting AMP 15 min before irradiation. Using the interval of 65 min between AMP administration and irradiation, no protection was detected. The higher doses of AMP (10, 15 mg) enhanced the protective effect manifested in plasma thymidine level only moderately. The amount of free polynucleotides, elevated in the thymus and spleen of irradiated mice, was significantly decreased in the thymus of mice pretreated with the combination of dipyridamole and AMP. The results suggest that the treatment used decreases the radiation damage of the sensitive thymocyte population. It is proposed that the joint use of AMP, an adenosine prodrug, and dipyridamole, a drug inhibiting adenosine uptake by cells, leads to an elevation in extracellular adenosine which activates cell surface adenosine receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1992

Amelioration of radiation damage to haemopoiesis by Ivastimul, given after irradiation to mice protected by peroral cystamine.

The combined radioprotection by preirradiation peroral cystamine and postirradiation Ivastimul treatment was examined in sublethally and lethally whole-body gamma-irradiated mice. The enhancement of haemopoietic recovery and increased survival of irradiated mice was demonstrated when a single dose of Ivastimul was administered after irradiation. Ameliorative influence of combined radioprotection may be explained by the haemopoietic stem cell protection by cystamine and haemopoietic stimulation mediated by Ivastimul.

Animals↗
PubMed1991

[Radioprotective effects of DDP].

The authors studied the effect of various DDP applications (sodium salt of dimethyl-dioxopiperazine thiosulfonate) in a dose of 45 mg/kg w. administered 10 min before irradiation, on the survival of female mice C57 and (CBA x C57BL/F1 after a single whole-body exposure to a sublethal dose of gamma rays (LD50/5 = magnitude of 15.495 +/- 0.781 magnitude of Gy and LD50/30 = magnitude of 7.864 +/- 0.018 magnitude of Gy). The depth of DDP protection effect on the haemopoietic stem cells was studied using the method of endogenous spleen colonies (ESC) of haemopoietic tissue. DDP radioprotective effect was also demonstrated after s. c. and i. m. application of this substance 10 min before 6 Gy of gamma radiation; it was shown by a prolongation of the survival time of experimental animals and by an increase in the number of individuals surviving till the 30th day after irradiation. Higher ESC numbers in the animals with DDP protection demonstrate survival of higher number of the haemopoietic stem cells and indicate that DDP is the biological active substance and contributes to the repair of haematopoiesis damaged by radiation and to the survival of irradiated animals.

Animals↗
PubMed1991

Radioprotective effect of dextran sulphate and aerogenic hypoxia on intestinal crypt stem cells in mice.

A single intraperitoneal injection of dextran sulphate given 6 h before irradiation produced higher numbers of microcolonies of intestinal crypt stem cells in whole-body irradiated mice than injection of saline in control mice. If dextran sulphate and hypoxia are combined, the radioprotective effect of hypoxia on intestinal crypt stem cells depends on the time interval between irradiation and administration of dextran sulphate.

Animals↗
PubMed1991

Decrease in the number of progenitors of erythrocytes (BFUe, CFUe), granulocytes and macrophages (GM-CFC) in bone marrow of rats after a 14-day flight onboard the Cosmos-2044 Biosatellite.

A decrease in the number of progenitors of erythrocytes (BFUe, CFUe) and of granulocytes and macrophages (GM-CFC) in bone marrow was found in rats exposed to microgravitation during a 14-day flight onboard the Cosmos-2044 biosatellite when compared to control rats maintained under conditions of gravitation on the ground. The number of progenitors of both lineages of haemopoiesis was also decreased in synchronous control rats, thus suggesting that the pool of progenitors is influenced also by the action of the nonspecific space flight factors.

Animals↗
PubMed1990

Hydroxyurea as a suppressor of the radioprotective effect of dextran sulfate on bone marrow hemopoietic stem cells in mice.

The changes in hemopoiesis of mice following intraperitoneal administration of dextran sulfate (DS) 24 h before irradiation, as well as the effect of injecting them with hydroxyurea (HU), were analyzed. DS increased the proliferation activity and number of hemopoietic stem cells (CFUs) in the bone marrow. The content of CFUs in the bone marrow and the number of endogenous spleen colonies (ESC) of hemopoietic tissue were higher after irradiation in mice treated with DS than in control groups. The survival rate following a lethal radiation dose was also higher. Injection with HU decreased the number of CFUs in animals injected with DS to the level of controls and suppressed its radioprotective effect.

Animals↗