Search

Start Over Creator Znojil, V.

2. Effects of Stable Adenosine Receptor Agonists on Bone Marrow Hematopoietic Cells as Inferred from the Cytotoxic Action of 5-Fluorouracil

Creator:
Pospíšil, M., Hofer, M., Vacek, A., Znojil, V., and Pipalová, I.
Type:
article, model:article, and TEXT
Subject:
Adenosine receptor agonists, Hematopoiesis, and 5-Fluorouracil
Language:
English
Description:
The aim of the study was to investigate the effects of stable adenosine receptor agonists on bone marrow hematopoiesis by utilizing the model of hematopoietic damage induced by 5-fluorouracil (5-FU), a cycle-specific cytotoxic agent. Effects of a non-selective agonist NECA activating all the known adenosine receptors (A1, A2A, A2B, A3) and of the selective agonists for A1 (CPA), A2A (CGS 21680), and A3 (IB-MECA) adenosine receptors were investigated. Experiments were performed with B10CBAF1 mice under in vivo conditions. Adenosine receptor agonists were given in single injections before 5-FU administration and the effects were determined 4 days later. The numbers of femoral marrow nucleated cells and hematopoietic progenitor cells (CFC-GM and BFU-E) were taken as indices of the effects. The non-selective agonist NECA given at a dose of 200 nmol/kg induced biphasic time-dependent effects, i.e. protection and sensitization, when given 10 h and 22 h before 5-FU administration, respectively. The use of isomolar doses of selective receptor agonists indicated that the protective effects of NECA were induced by activation of A2A and A2B receptors, while the sensitizing action of NECA was mediated via A3 receptors. In addition, it was observed that A1 receptors induced protection when activated by administration of CPA 22 h before 5-FU. These findings are discussed with respect to the action of adenosine receptor agonists on the cell cycle state and on the cell cycle-independent cellular protective mechanisms.
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

3. Enhancement of haemopoietic spleen colony formation by drugs elevating extracellular adenosine: effects of repeated in vivo treatment

Creator:
Hofer, M., Pospíšil, M., Netíková, J., Znojil, V., and Vácha, J.
Type:
article, model:article, and TEXT
Subject:
haemopoietic stem cells, dipyridamole, and adenosine monophosphate
Language:
English
Description:
The potential role of adenosine receptor signalling in the amplification of haemopoietic stem cells in vivo was investigated. Elevation of extracellular adenosine in mice was induced by the joint administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate, an adenosine prodrug. The response of haemopoietic stem cells to the drug treatment was measured by endogenous spleen colony-forming assay in sublethally gamma-irradiated animals. The combination of drugs was administered before irradiation either singly or repeatedly at 24 h intervals. The results demonstrated the possibility of enhancing the spleen colony formation by the drug treatment. The highest stimulatory effect on spleen colony counts and on the colony sizes occurred after 3-4 injections of the drugs. Higher spleen colony responses were observed under injection regimens terminated 3 h before irradiation, as compared to those terminated 24 h before the radiation exposure. The results are interpreted as an evidence of the expansion of the stem cell pool. A tolerance to this stimulatory action developed after more than 3 injections of the drugs.
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

4. Morphometric characteristics of cardiac hypertrophy induced by long-term inhibition of NO synthase

Creator:
Sládek, T., Gerová, M., Znojil, V., and Devát, L.
Type:
article, model:article, and TEXT
Subject:
NO deficiency, hypertension, morphometry, cardiac hypertrophy, myocyte, and capillary domain
Language:
English
Description:
Morphometry of cardiomyocytes and capillary domains in the left ventricle myocardium was performed in control rats and in rats treated with nitro-L-arginine methyl ester 50 mg/kg/day p.o. for a period of 8 weeks. The myocardial hypertrophy accompanying the NO-deficient hypertension induced by chronic inhibition of NO synthase is characterized by an increase in thickness of myocardial fibres and by relative rarefaction of the capillary bed, e.g. an alteration in myocardial structure which is typical for pressure overload hypertrophy.
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

5. Radioprotective efficacy of dipyridamole and AMP combination in fractionated radiation regimen, and its dependence on the time of administration of the drugs prior to irradiation

Creator:
Hofer, M., Pospíšil, M., Netíková, J., Znojil, V., Vácha, J., and Holá, J.
Type:
article, model:article, and TEXT
Subject:
radioprotection, fractionated irradiation, haemopoiesis, adenosine monophosphate, and dipyridamole
Language:
English
Description:
We have recently demonstrated that the combined administration of dipyridamole and adenosine monophospate to mice induces radioprotective effects in terms of postirradiation haemopoietic recovery in animals irradiated with a single dose. The aim of the present experiments was to investigate the radioprotective ability of the drug combination under conditions of fractionated radiation treatment. It has been shown that administration of drugs either 15 or 60 min before each of the five daily 3-Gy doses of gamma-radiation enhances haemopoietic recovery and survival of mice exposed to an additional "top-up" dose of 3.5 Gy. Furthermore, it has been ascertained that the regimen using administration of the drugs 60 min prior to irradiation is more effective than administration of the drugs 15 min prior to irradiation. Due to the evidence that administration of the drugs 15 min prior to irradiation protects the organism mainly via mechanisms of systemic hypoxia while the pretreatment 60 min before irradiation avoids the role of hypoxia and mainly induces cell proliferation effects, our results suggest a more effective protective role of mechanisms stimulating haemopoiesis under conditions of fractionated radiation. The data may provide a basis for more rational use of radioprotection in fractionated radiation regimens.
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public