Browsing by Author "Redzic, Z.B. (6602453895)"

The aim of this study was to investigate the transport of tiazofurin (2-β-D-ribofuranosyl thiazole-4-carboxamide) across the blood-brain barrier (BBB) using brain vascular perfusion and capillary depletion method in the guinea pig. Values for volume of distribution of [3H] tiazofurin in brain increased slowly and almost linearly in time, from 1% of its plasma concentration at 1 min to 5% after 15 min of perfusion. Unidirectional transport constant K(in) was 2.61 ± 0.21 x 10-3 ml/min/g. According to these results, it is evident that tiazofurin slowly penetrates the BBB. Addition of unlabeled tiazofurin to the perfusing medium caused a significant decrease in the uptake of [3H] labeled tiazofurin (K(in) = 0.77 ± 0.1 x 10-3 ml/min/g). Therefore, penetration of tiazofurin from blood into brain seems to be a saturable process. Presence of potential inhibitors of tiazofurin blood-to-brain transport (adenosine and dipyridamole) did not cause complete inhibition of tiazofurin brain uptake. Thus, it could be assumed that transport of tiazofurin from blood into brain is only partially mediated by the nucleosides transport system. The results obtained using capillary depletion method show that tiazofurin that passes across the BBB is accumulated mostly in the brain tissue and not in brain capillaries endothelial cells.

The aim of this study was to investigate the transport of tiazofurin (2-β-D-ribofuranosyl thiazole-4-carboxamide) across the blood-brain barrier (BBB) using brain vascular perfusion and capillary depletion method in the guinea pig. Values for volume of distribution of [3H] tiazofurin in brain increased slowly and almost linearly in time, from 1% of its plasma concentration at 1 min to 5% after 15 min of perfusion. Unidirectional transport constant K(in) was 2.61 ± 0.21 x 10-3 ml/min/g. According to these results, it is evident that tiazofurin slowly penetrates the BBB. Addition of unlabeled tiazofurin to the perfusing medium caused a significant decrease in the uptake of [3H] labeled tiazofurin (K(in) = 0.77 ± 0.1 x 10-3 ml/min/g). Therefore, penetration of tiazofurin from blood into brain seems to be a saturable process. Presence of potential inhibitors of tiazofurin blood-to-brain transport (adenosine and dipyridamole) did not cause complete inhibition of tiazofurin brain uptake. Thus, it could be assumed that transport of tiazofurin from blood into brain is only partially mediated by the nucleosides transport system. The results obtained using capillary depletion method show that tiazofurin that passes across the BBB is accumulated mostly in the brain tissue and not in brain capillaries endothelial cells.

Tiazofurin (TZF- beta-D-ribofuranosyl thiazole-4-carboxamide, NSC- 286193) is a synthetic nucleoside analog with potent antitumor activity. Isolated choroid plexuses (CP) of sheep were perfused in situ and the uptake of [ 3 H]-tiazofurin was determined in relation to the recovery of [ 14 C]- mannitol by means of the paired indicator dilution technique. The maximal uptake of tiazofurin was 8.29 ± 0.84% and was shown to be both carrier- mediated, sodium-dependent and inhibited by adenosine which suggests that it uses the carrier for endogenous nucleosides. However, the total tiazofurin uptake into the choroid plexus was negligible (0.93 ± 1.97%) as a result of a high backflux, indicating that tiazofurin is not trapped within the cells of the CP to any significant degree. The kinetics for the uptake into the CP were more favorable than for its passage across the blood-brain barrier with a K(m) 7.71 ± 1.42 μM, a V(max) of 1.30 ± 0.05 μM/min/g and a negligible constant of a free diffusion (K(2)) which suggests that the CP/CSF route may act as an alternative pathway into the brain. (C) 2000 Prous Science.

Tiazofurin (TZF- beta-D-ribofuranosyl thiazole-4-carboxamide, NSC- 286193) is a synthetic nucleoside analog with potent antitumor activity. Isolated choroid plexuses (CP) of sheep were perfused in situ and the uptake of [ 3 H]-tiazofurin was determined in relation to the recovery of [ 14 C]- mannitol by means of the paired indicator dilution technique. The maximal uptake of tiazofurin was 8.29 ± 0.84% and was shown to be both carrier- mediated, sodium-dependent and inhibited by adenosine which suggests that it uses the carrier for endogenous nucleosides. However, the total tiazofurin uptake into the choroid plexus was negligible (0.93 ± 1.97%) as a result of a high backflux, indicating that tiazofurin is not trapped within the cells of the CP to any significant degree. The kinetics for the uptake into the CP were more favorable than for its passage across the blood-brain barrier with a K(m) 7.71 ± 1.42 μM, a V(max) of 1.30 ± 0.05 μM/min/g and a negligible constant of a free diffusion (K(2)) which suggests that the CP/CSF route may act as an alternative pathway into the brain. (C) 2000 Prous Science.

Tiazofurine is a selective inhibitor of the enzyme inosine monophosphate dehydrogenase, and exhibits potent antitumor activity. Considering the potential side effects on the heart, [3H] tiazofurine uptake into the cardiomyocytes, as well as the mechanism of trans­port, were studied in the isolated perfused guinea pig heart, using the rapid single circulation, paired-tracer technique. The maximal cellular uptake (Umax) of [3H] tiazofurine ranged from 19% to 25% of the injected dose, with total cellular uptake (Utot) ranging 12.1­15.6%. The addition of unlabeled tiazofurine caused inhibition of [3H] tiazofurine uptake, with a Umax value of 9.06 ± 4.6%. Therefore, the uptake of tiazofurine into cardiomyocytes could be considered a saturable process. The inhibition of [3H] tiazofurine uptake caused by adenosine and dipyridamole was of the same degree as the inhibition by unlabeled tiazofurine. Thus, it can be assumed that nucleosides’ transport system(s) are involved in transport of tiazofurine into myocardial cells. © 1995 E.I.F.T. srl - Firenze.

Tiazofurine is a selective inhibitor of the enzyme inosine monophosphate dehydrogenase, and exhibits potent antitumor activity. Considering the potential side effects on the heart, [3H] tiazofurine uptake into the cardiomyocytes, as well as the mechanism of trans­port, were studied in the isolated perfused guinea pig heart, using the rapid single circulation, paired-tracer technique. The maximal cellular uptake (Umax) of [3H] tiazofurine ranged from 19% to 25% of the injected dose, with total cellular uptake (Utot) ranging 12.1­15.6%. The addition of unlabeled tiazofurine caused inhibition of [3H] tiazofurine uptake, with a Umax value of 9.06 ± 4.6%. Therefore, the uptake of tiazofurine into cardiomyocytes could be considered a saturable process. The inhibition of [3H] tiazofurine uptake caused by adenosine and dipyridamole was of the same degree as the inhibition by unlabeled tiazofurine. Thus, it can be assumed that nucleosides’ transport system(s) are involved in transport of tiazofurine into myocardial cells. © 1995 E.I.F.T. srl - Firenze.