Browsing by Author "Mitrovic, Dusan M. (57207601763)"

The brain vascular perfusion method, with a multiple-time brain uptake analysis, has been employed to study the effects of chronic amphetamine intoxication on the kinetics of entry of 2 inert polar molecules, d-[14C]mannitol (mol.wt. 180) and [3H]polyethylene glycol (PEG, mol.wt. 4000) into the forebrain of the guinea pig. The unidirectional transfer constants, Kin, determined from graphic analysis 14 and 20 days after chronic amphetamine treatment (5 mg/kg daily, i.p.) showed a marked time-dependent progressive enhancement of transfer for both molecules. The kinetic features of this entry suggest the opening up of pathways through the blood-brain barrier (BBB) which allows mannitol and PEG to pass into the brain at rates which are irrespective of their molecular size and/or lipophilia and these changes cannot be attributed to simple mechanical factors such as hypertension. This opening of the BBB was associated with changes in behaviour (increased locomotor activity, stereotypy, hypervigilance, social withdrawal, and loss of weight) seen in 14- and 20-day amphetamine-treated animals. At 7 and 28 days after the withdrawal of the amphetamine treatment, the behavioural manifestations were absent, and the Kin values for both molecules were not significantly different from those measured in normal control animals which had been treated with placebo injections. The present results suggest a reversible dysfunction of the BBB as a consequence of the chronic amphetamine intoxication which correlates with the behavioural syndrome induced in the guinea pig. © 1989.

The brain vascular perfusion method, with a multiple-time brain uptake analysis, has been employed to study the effects of chronic amphetamine intoxication on the kinetics of entry of 2 inert polar molecules, d-[14C]mannitol (mol.wt. 180) and [3H]polyethylene glycol (PEG, mol.wt. 4000) into the forebrain of the guinea pig. The unidirectional transfer constants, Kin, determined from graphic analysis 14 and 20 days after chronic amphetamine treatment (5 mg/kg daily, i.p.) showed a marked time-dependent progressive enhancement of transfer for both molecules. The kinetic features of this entry suggest the opening up of pathways through the blood-brain barrier (BBB) which allows mannitol and PEG to pass into the brain at rates which are irrespective of their molecular size and/or lipophilia and these changes cannot be attributed to simple mechanical factors such as hypertension. This opening of the BBB was associated with changes in behaviour (increased locomotor activity, stereotypy, hypervigilance, social withdrawal, and loss of weight) seen in 14- and 20-day amphetamine-treated animals. At 7 and 28 days after the withdrawal of the amphetamine treatment, the behavioural manifestations were absent, and the Kin values for both molecules were not significantly different from those measured in normal control animals which had been treated with placebo injections. The present results suggest a reversible dysfunction of the BBB as a consequence of the chronic amphetamine intoxication which correlates with the behavioural syndrome induced in the guinea pig. © 1989.

Tiazofurin is a nucleoside analog with potent antitumor activity. The objective of this study was to define the kinetic parameters of tiazofurin transport from blood into the guinea pig brain. The second aim was to define kinetic parameters of tiazofurin transport inhibition by adenosine (K(i) and K(d)a), as well as whether tiazofurin blood-to-brain transport was performed in countertransport with Na+. In order to determine these parameters, the in situ method of perfusion of guinea pig brain was used. Addition of increasing concentrations of unlabelled tiazofurin to perfusing medium (0.05-2.7 mmol/l) caused progressive decrease of [3H]-tiazofurin brain clearance with K(m) values ranging from 119.57 ± 40.12 to 150.17 ± 51.68 x 10-6 mol/l. Maximal transport capacity ranged from 325.03 ± 113.93 to 417.50 ± 151.53 pmol/min/g. Introduction of adenosine into the perfusing medium (0.005-0.2 mmol/l) caused similar but more rapid decrease of [3H]-tiazofurin brain clearance (K(i) = 6.36 ± 3.14 x 10-6 mol/l for nucleus caudate and 11.74 ± 4.85 x 10-6 mol/l for cerebral cortex). Therefore, it seems that transport system for adenosine plays the main role in tiazofurin brain uptake, but another transport mechanism is also involved in this process. Depletion of perfusing medium from sodium ions did not cause significant change in volume of distribution values for [3H]-tiazofurin in guinea pig cerebral cortex.

Tiazofurin is a nucleoside analog with potent antitumor activity. The objective of this study was to define the kinetic parameters of tiazofurin transport from blood into the guinea pig brain. The second aim was to define kinetic parameters of tiazofurin transport inhibition by adenosine (K(i) and K(d)a), as well as whether tiazofurin blood-to-brain transport was performed in countertransport with Na+. In order to determine these parameters, the in situ method of perfusion of guinea pig brain was used. Addition of increasing concentrations of unlabelled tiazofurin to perfusing medium (0.05-2.7 mmol/l) caused progressive decrease of [3H]-tiazofurin brain clearance with K(m) values ranging from 119.57 ± 40.12 to 150.17 ± 51.68 x 10-6 mol/l. Maximal transport capacity ranged from 325.03 ± 113.93 to 417.50 ± 151.53 pmol/min/g. Introduction of adenosine into the perfusing medium (0.005-0.2 mmol/l) caused similar but more rapid decrease of [3H]-tiazofurin brain clearance (K(i) = 6.36 ± 3.14 x 10-6 mol/l for nucleus caudate and 11.74 ± 4.85 x 10-6 mol/l for cerebral cortex). Therefore, it seems that transport system for adenosine plays the main role in tiazofurin brain uptake, but another transport mechanism is also involved in this process. Depletion of perfusing medium from sodium ions did not cause significant change in volume of distribution values for [3H]-tiazofurin in guinea pig cerebral cortex.

The aim of this study was to determine the mechanism of transport of 14C-thiamin in the hearts of healthy (non-alcoholic) and chronically alcoholic guinea pigs. We used the single-pass, paired-tracer dilution method on isolated and retrogradely perfused guinea pig hearts. The maximal cellular uptake (Umax) and total cellular uptake (Utot) of 14C-thiamin were determined under control conditions and under influence of possible modifiers. We tested how the presence of unlabeled thiamin, metabolic inhibitors, or absence of sodium ions influence the transport of 14C-thiamin. The results of our experiments show that the transport of 14C-thiamin is specific and energy-dependent and that its properties are significantly changed under the influence of chronic alcoholism. The latter effect occurs by increase in both Umax and Utot, as a manifestation of a compensatory mechanism in thiamin deficiency. © 2008 NRC.

The aim of this study was to determine the mechanism of transport of 14C-thiamin in the hearts of healthy (non-alcoholic) and chronically alcoholic guinea pigs. We used the single-pass, paired-tracer dilution method on isolated and retrogradely perfused guinea pig hearts. The maximal cellular uptake (Umax) and total cellular uptake (Utot) of 14C-thiamin were determined under control conditions and under influence of possible modifiers. We tested how the presence of unlabeled thiamin, metabolic inhibitors, or absence of sodium ions influence the transport of 14C-thiamin. The results of our experiments show that the transport of 14C-thiamin is specific and energy-dependent and that its properties are significantly changed under the influence of chronic alcoholism. The latter effect occurs by increase in both Umax and Utot, as a manifestation of a compensatory mechanism in thiamin deficiency. © 2008 NRC.