Browsing by Author "Varagic, V.M. (7006591279)"

Tourniquet trauma produced a decrease in the noradrenaline content in the heart of the rats through the period of tourniquet application (up to 4 hr). In the same period, the content of adrenaline was significantly increased. This relationship between noradrenaline and adrenaline remained the same in the posttraumatic period. Parallel to the observed changes in the catecholamine content of the heart, a significant decrease in the number of the beta-adrenergic receptors (B(max)) and an increase in their affinity (a decrease in K(D)) was also found in the hearts of rats exposed to tourniquet trauma. These changes remained throughout the posttraumatic period, with one exception: no change 30 min after trauma has been observed. Reapplication of tourniquet was associated with a restoration of the beta-adrenergic receptors and complete survival of the animals. The decrease in the beta-receptors density after trauma might be due to down-regulation produced by increased concentration of adrenaline, a beta-receptor agonist. Meanwhile, some other factors, particularly ischaemia, might also contribute to the observed changes in the beta-adrenergic binding sites.

1. The effect of L-N6-phenylisopropyladenosine (L-PIA) on the maximum tension developed (Td) and the maximum rate of rise of tension (dT/dt max) of the isolated hemidiaphragm of the rat was investigated during direct electrical stimulation. 2. L-PIA itself (0.07-5.5 μmol l-1) did not produce significant changes in either Td or dT/dt max. 3. In the presence of a standard concentration of dipyridamole (26.4 μmol l-1), L-PIA produced a significant and concentration-dependent increase in both Td and dT/dt max. 4. In the presence of a standard concentration of aminophylline (640 μmol l-1), L-PIA produced a small and insignificant, but concentration-dependent decrease of both Td and dT/dt max. 5. In the presence of both dipyridamole (26.4 μmol l-1) and of aminophylline (640 μmol l-1), L-PIA (0.07-5.5 μmol l-1) produced a small and insignificant potentiation of the isometric contraction of the isolated hemidiaphragm. 6. It is concluded that antagonistic action between L-PIA and aminophylline probably takes place at A1-receptors. The inhibitory action of L-PIA, observed after blockade of adenosine receptors by aminophylline, is presumably realized through some other mechanism(s) independent of adenosine receptor sites.

1. The effect of L-N6-phenylisopropyladenosine (L-PIA) on the maximum tension developed (Td) and the maximum rate of rise of tension (dT/dt max) of the isolated hemidiaphragm of the rat was investigated during direct electrical stimulation. 2. L-PIA itself (0.07-5.5 μmol l-1) did not produce significant changes in either Td or dT/dt max. 3. In the presence of a standard concentration of dipyridamole (26.4 μmol l-1), L-PIA produced a significant and concentration-dependent increase in both Td and dT/dt max. 4. In the presence of a standard concentration of aminophylline (640 μmol l-1), L-PIA produced a small and insignificant, but concentration-dependent decrease of both Td and dT/dt max. 5. In the presence of both dipyridamole (26.4 μmol l-1) and of aminophylline (640 μmol l-1), L-PIA (0.07-5.5 μmol l-1) produced a small and insignificant potentiation of the isometric contraction of the isolated hemidiaphragm. 6. It is concluded that antagonistic action between L-PIA and aminophylline probably takes place at A1-receptors. The inhibitory action of L-PIA, observed after blockade of adenosine receptors by aminophylline, is presumably realized through some other mechanism(s) independent of adenosine receptor sites.

As part of an investigation of phenobarbital (PB) pharmacokinetics in patients with status epilepticus (SE), urinary excretion of PB and its main metabolite, hydroxyphenobarbital (HPB), was studied in patients who had an episode of SE, as well as in non-convulsing ones. Eleven in-patients were studied: (group 1) five patients (4 M + 1 F; 48 ± 28 years old; 64 ± 6 kg body weight; mean ± SD) with convulsive status epilepticus, and (group 2) six patients (5 M + 1 F; 37 ± 13 years old; 71 ± 15 kg body weight) with epilepsy, seizure-free at the moment of PB administration and without established anti-epileptic therapy. All subjects received a single intravenous dose of PB (15 mg/kg) at a rate of 100 mg/min. PB and HPB concentrations were measured by high performance liquid chromatography with UV detection at 220 nm in urine samples collected throughout 24 h. The comparison of pharmacokinetic parameters of urinary excretion of PB and HPB showed a statistically significant difference in the values of recovery of HPB and total barbiturate (higher values in the patients with SE) in 24 h urine. Differences in the excretion of PB between the two groups of patients - higher values in the patients who had had an episode of SE, and in urine flow - slightly elevated volumes in the same group, failed to reach statistical significance, probably due to the small number of participants in the study.

As part of an investigation of phenobarbital (PB) pharmacokinetics in patients with status epilepticus (SE), urinary excretion of PB and its main metabolite, hydroxyphenobarbital (HPB), was studied in patients who had an episode of SE, as well as in non-convulsing ones. Eleven in-patients were studied: (group 1) five patients (4 M + 1 F; 48 ± 28 years old; 64 ± 6 kg body weight; mean ± SD) with convulsive status epilepticus, and (group 2) six patients (5 M + 1 F; 37 ± 13 years old; 71 ± 15 kg body weight) with epilepsy, seizure-free at the moment of PB administration and without established anti-epileptic therapy. All subjects received a single intravenous dose of PB (15 mg/kg) at a rate of 100 mg/min. PB and HPB concentrations were measured by high performance liquid chromatography with UV detection at 220 nm in urine samples collected throughout 24 h. The comparison of pharmacokinetic parameters of urinary excretion of PB and HPB showed a statistically significant difference in the values of recovery of HPB and total barbiturate (higher values in the patients with SE) in 24 h urine. Differences in the excretion of PB between the two groups of patients - higher values in the patients who had had an episode of SE, and in urine flow - slightly elevated volumes in the same group, failed to reach statistical significance, probably due to the small number of participants in the study.

In our previous experiments, we demonstrated that xylazine, an α 2 -adrenergic agonist, stimulated proliferation of thymocytes triggered by concanavalin A. In contrast, higher concentrations of xylazine were inhibitory. In this work, we studied the mechanisms involved in immunosuppression of xylazine and found that the compound at concentrations between 100 μM and 500 μM induced apoptosis of rat thymocytes in vitro. In addition, xylazine at concentrations higher than 50 μM also induced apoptosis of a thymocyte hybridoma (BWRT8) and increased apoptosis of the line triggered by T cell receptor (TCR) cross-linking. Apoptosis was confirmed by morphological analysis staining with merocyanine 540 and propidium iodide and in cases of BWRT8 by fragmentation of DNA. The mechanisms of xylazine-induced apoptosis of the BWRT8 hybridoma were further examined. We demonstrated that the process in both nonactivated and activated (TCR cross-linking) BWRT8 cells was not prevented by yohimbine (a selective α-adrenergic antagonist) and by antibodies to Fas and Fas-L. In contrast, cell death was completely blocked by a caspase inhibitor, z-Val-Ala-Asp (OMe)-CH2F. Cyclosporine, a calcineurin blocker, partly inhibited the xylazine-induced apoptosis of activated BWRT8 cells. © 2003 Prous Science. All rights reserved.

In our previous experiments, we demonstrated that xylazine, an α 2 -adrenergic agonist, stimulated proliferation of thymocytes triggered by concanavalin A. In contrast, higher concentrations of xylazine were inhibitory. In this work, we studied the mechanisms involved in immunosuppression of xylazine and found that the compound at concentrations between 100 μM and 500 μM induced apoptosis of rat thymocytes in vitro. In addition, xylazine at concentrations higher than 50 μM also induced apoptosis of a thymocyte hybridoma (BWRT8) and increased apoptosis of the line triggered by T cell receptor (TCR) cross-linking. Apoptosis was confirmed by morphological analysis staining with merocyanine 540 and propidium iodide and in cases of BWRT8 by fragmentation of DNA. The mechanisms of xylazine-induced apoptosis of the BWRT8 hybridoma were further examined. We demonstrated that the process in both nonactivated and activated (TCR cross-linking) BWRT8 cells was not prevented by yohimbine (a selective α-adrenergic antagonist) and by antibodies to Fas and Fas-L. In contrast, cell death was completely blocked by a caspase inhibitor, z-Val-Ala-Asp (OMe)-CH2F. Cyclosporine, a calcineurin blocker, partly inhibited the xylazine-induced apoptosis of activated BWRT8 cells. © 2003 Prous Science. All rights reserved.