PubMed Health⌕ Search

Biomedical subjects

Z Jastrzebski

Publications and source records attributed to Z Jastrzebski.

At least 19 recordsLinked to original sources
PubMed1997

Pharmacokinetics of selol, a new agent containing selenium, in rats.

The pharmacokinetic properties of selol, a new organoselenium compound, were evaluated in rats. Each animal was given a single oral or subcutaneous dose of selol 12 mg/kg. The selenium concentration was determined in whole blood and tissues by non flame carbon furnace atomic-absorption spectrometry. The pharmacokinetic parameters Cmax and tmax differed statistically between oral (p.o.) and subcutaneous (s.c.) treatment. The selenium average peak concentrations in the blood were 494 +/- 8 ng/ml after oral and 322 +/- 5 ng/ml after subcutaneous administration. They were reached after 1.9 +/- 0.1 h and 2.4 +/- 0.1 h, respectively. For the AUC0 mean values of 1373 +/- 56 ng.h/ml (p.o.) and 1273 +/- 137 ng.h/ml (s.c.) were found. The mean residence time (MRT) was significantly longer after subcutaneous administration. Selenium distributes quickly to the main organs with prevalence to the adrenal gland. Moreover, its concentrations in the examined organ were evidently higher after subcutaneous treatment as compared to the oral route. Our data suggest that Selol may be used as a possible source of selenium for the treatment of selenium-deficient patients, particularly via the subcutaneous route.

Administration, Oral↗
PubMed1995

Clonidine hypotension in spontaneously hypertensive rats (SHR) depends on the functional state of GABAergic and glutamatergic systems.

The effect of gamma-aminobutyric acid (GABA)A receptors and of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor blockade on clonidine hypotension was studied. The experiments were performed on spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. We found that the blockade of GABAA receptors line significantly (P < 0.01) reduced hypotensive responses to clonidine. Similarly, the NMDA receptor antagonist dizocilpine (MK-801) completely abolished the blood pressure lowering effect of clonidine. Our findings support the conclusion that clonidine hypotension is closely related to the functional state of both inhibitory GABAergic and excitatory glutamatergic systems.

Animals↗
PubMed1995

Activation of GABA-A receptor by hypotensive drugs.

Chronic antihypertensive treatment with clonidine and beta-adrenoceptor blockers leads to a significant increase in GABA-A receptor number in the hypothalamus, the pons-medulla and the striatum. The enhancement of receptor number after two beta-blockers was associated with the decrease of Kd factor in the pons-medulla and the striatum. There was no change in receptor affinity after clonidine. We conclude that neurotransmission via GABA-A receptors is important for the hypotensive effects of clonidine and some beta-adrenoceptor blockers.

Animals↗
PubMed1995

Toxicity studies of a new selenium compound, Selol, in rats.

Selol is a new organoselenium compound synthesized in the Department of Drug Analysis, Warsaw. The general acute and cumulative toxicities of Selol were tested in rats. The compound did not display any toxic effects after parenteral administration up to 500 mg/kg-1 s.c. and 100 mg/kg-1 i.p. However, given orally it exhibited high toxicity. LD50 value after a single oral administration amounted to 100 mg/kg-1 and after administration in an increasing-dose schedule to 80 mg/kg-1. On the basis of these results the authors conclude that Selol may be converted to a more toxic product during digestion. Therefore, Selol as a source of selenium is safer given by the parenteral route.

Administration, Oral↗
PubMed1994

Antihypertensive treatment with beta blockers and gabaergic transmission in rat brain.

The effects of chronic oral administration of propanolol and metoprolol on blood pressure and GABAergic function were investigated in spontaneously hypertensive rats (SHR) and compared with the effect of dihydralazine. Under the experiment conditions employed all drugs reduced significantly (p < 0.01) arterial pressure. The beta blockers elevated GABA turnover in the hypothalamus and the pons-medulla. Dihydralazine, however had not such an effect. Our result suggest that the antihypertensive action of beta blockers may be related in part to the enhanced cerebral GABAergic transmission.

Adrenergic beta-Antagonists↗
PubMed1993

Enhancement of GABAergic system activity by metoprolol in spontaneously hypertensive rats.

The relevance of the GABAergic system for the antihypertensive action of metoprolol in spontaneously hypertensive rats was studied by comparing the effect of metoprolol with the effect of dihydralazine. Chronic oral treatment with metoprolol produced the maximum effect after 49 days (-delta 34 mm Hg). This effect persisted on the same level for up to 55 days. The measurements of gamma-aminobutyric acid (GABA) synthesis and specific [3H]GABA binding were performed in the hypothalamus, the pons-medulla, the hippocampus and the striatum. Significant stimulation of GABA synthesis and turnover appeared in the hypothalamus and the pons medulla. In contrast, chronic administration of dihydralazine had no influence on GABA synthesis rate. It was also shown that metoprolol elevated significantly (P < 0.01) specific [3H]GABA binding in the hypothalamus and the pons-medulla. In the striatum this effect of metoprolol was less pronounced. Binding constant analysis revealed changes in both the receptor density and affinity. Our results suggest that the hypotensive response to chronic treatment with metoprolol might be attributed to an enhancement of GABAergic system activity.

Analysis of Variance↗
PubMed1993

Intracellular accumulation of cytosine arabinoside in murine normal and neoplastic lymphocytes following their exposure to sodium 2-mercaptoethanesulphonate.

The effect of mesna on intracellular accumulation of cytosine arabinoside (Ara-C) in murine normal and neoplastic lymphocytes was studied. Simultaneous exposure of cells to mesna at concentrations ranging from 0.25 to 1.0 mM and 3H-Ara-C (40.0 nM) resulted in a strong inhibition of Ara-C uptake in normal lymphocytes. Under the same experimental conditions, mesna did not affect the Ara-C uptake in neoplastic cells (cultured L5178Y mouse leukaemia cells and neoplastically transformed thymus cells). It was found that the inhibitory effect of mesna was not cell cycle-dependent, since mesna reduced the Ara-C uptake in both normal quiescent and PHA-stimulated cells. We therefore concluded that mesna may selectively reduce Ara-C uptake by normal cells in vitro.

Animals↗
PubMed1993

Acute systemic toxicity and antihypertensive activity of a novel todralazine analog in rats.

Acute intravenous toxicity and antihypertensive activity of KB1, a novel todralazine analog was investigated and compared with the effects of todralazine (Td) in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. LD50 values were 72 mg.kg-1 for KB1, and 255 mg.kg-1 for Td in WKY and 43 mg.kg-1 or KB1 in SHR. Therefore, the toxicity of KB1 was higher than that of Td and it increased in SHR. The antihypertensive activity of KB1 (ED20% 9.8 mg.kg-1) in WKY was about 9 times less potent in comparison with Td (ED20% 1.1 mg.kg-1). Blood pressure reducing activity of KB1 augmented apparently in SHR (ED20% 2.5 mg.kg-1) whereas Td had not such an effect (ED20% 1.0). Thus, the influence of Td on blood pressure was similar in normotensive and hypertensive animals. Our results indicate that KB1 is capable of reducing blood pressure preferentially in hypertension.

Animals↗
PubMed1993

Systemic toxicity and dermal irritation of Tołpa Peat Preparation.

The systemic toxicity of the peat preparation in rats and rabbits was assessed. Dermal irritation tests were conducted on rabbits. In acute and chronic toxicity studies TPP was well tolerated in both animal species. Laboratory findings revealed no hematologic abnormalities as well as disturbances in liver and kidney function. No local irritancy of TPP was found. The results show that TPP may be considered as practically non toxic.

Amino Acids↗
PubMed1993

Pharmacodynamic interaction of clonidine and muscimol in hypertension.

The effect of the GABA agonist muscimol on the hypotensive action of clonidine in SHR was investigated. Muscimol administered before clonidine significantly (p < 0.01) intensified clonidine-induced reduction of blood pressure. This effect was achieved at muscimol doses which themselves had no influence on blood pressure. Muscimol injected after clonidine was ineffective. Our data suggest that the muscimol-clonidine interaction occurs at the level of GABAergic neurotransmission since both agents have been proved to activate the function of GABAergic neurons.

Analysis of Variance↗
PubMed1992

Increased activity of the GABAergic system in selected brain areas after chronic propranolol treatment in spontaneously hypertensive rats.

The influence of chronically administered propranolol on the functional state of the gamma-aminobutyric acid-ergic (GABAergic) system in spontaneously hypertensive rats was studied and compared with the effect of dihydralazine. GABA content, synthesis and turnover rate in selected brain areas were assessed. Hypotensive activity of propranolol and dihydralazine after injection of GABA antagonist pictrotoxin was examined in acute experiment. Prolonged administration of propranolol increased GABA content, synthesis and turnover rate in the hypothalamus and the pons-medulla. After chronic injections of dihydralazine there was no change in GABA indices. Antihypertensive activity of dihydralazine in picrotoxin-treated animals remained unchanged. On the contrary, picrotoxin suppressed the propranolol-induced decrease in blood pressure. Our results indicate that propranolol increases GABAergic system activity. Therefore, we conclude that down-regulation of the GABAergic system in hypertension may be compensated by the regulatory action of propranolol.

Aminooxyacetic Acid↗
PubMed1992

Pharmacological effects of Ukrain in rats and rabbits.

The effect of Ukrain administered in various doses on mean blood pressure (MAP) and breathing rate in rats and rabbits was evaluated. It was found that MAP was reduced and breathing rate increased significantly in both animal species. Maximum tolerated dose (MTD) of Ukrain was 10-fold higher in rats than in rabbits, and it amounted to 3.5 mg x kg(-1) and 0.35 mg x kg(-1), respectively. Possible clinical implications of these findings were discussed.

Alkaloids↗
PubMed1991

Effect of clonidine on blood pressure and GABAergic mechanisms in spontaneously hypertensive rats.

The action of clonidine on blood pressure and on the functional state of the gamma-aminobutyric acid-ergic (GABAergic) system was studied. A single injection of clonidine (1, 5, 10, 20 micrograms.kg-1) induced a dose-dependent decrease of blood pressure. Chronic administration of clonidine, 10 micrograms.kg-1, produced the maximum effect after the third injection. The effect was maintained for the duration of the study. Single or chronic clonidine injections, at the dose of 10 micrograms.kg-1 enhanced the GABA content in the brain and hypothalamus. This effect was less pronounced in the hippocampus. The drug administered according to the same regimen stimulated glutamic acid decarboxylase activity only in the hypothalamus. Clonidine caused a marked enhancement of specific [3H]GABA binding in the hypothalamus. These data suggest that the hypotensive action of clonidine is related to stimulation of the GABAergic system.

Animals↗
PubMed1991

Propranolol effect on GABA synthesis rate estimated by two different methods.

The propranolol effect on GABA synthesis rate in some brain structures using two different method was assessed. Both methods gave comparable results. Evaluation of the synthesis rate in vivo after inhibition of GABA degradation supplied more adequate information indicating that the availability of GABA precursor in the hypothalamus and the hippocampus is limited.

Animals↗
PubMed1991

Modulation of anticancer drug toxicity by solcoseryl.

The studies of the effect of solcoseryl on toxicity of selected anticancer drugs were performed in mice. The observed differential influence of solcoseryl was dependent on the type of anticancer drug as well as on the schedule of solcoseryl administration. The protective effect of the biostimulator was noticed exclusively against 5-FU toxicity. The results of our studies could provide possible implications for therapeutic approach.

Actihaemyl↗
PubMed1991

Effect of solcoseryl on antitumour action and acute toxicity of some antineoplastic drugs.

The in vivo effect of Solcoseryl on the antitumour activity and acute toxicity of some antineoplastic drugs was examined. It was found that Solcoseryl does not inhibit the antineoplastic effectiveness of the drugs against transplantable P 388 leukaemia in mice. Studies of the effect of Solcoseryl on acute toxicity of selected antineoplastic drugs in mice revealed that the biostimulator could exert a modifying influence. The prior administration of Solcoseryl significantly decreases the acute toxicity of methotrexate but has no effect on acute toxicity of 5-fluorouracil, increases the acute toxicity of bleomycin and vinblastine and has no effect on acute toxicity of methotrexate and mitoxantron. On the other hand, Solcoseryl administered simultaneously with the antineoplastic drugs increases acute toxicity of 5-fluorouracil, bleomycin and mitoxantron. The protective effect of the biostimulator noted exclusively against acute toxicity of 5-fluorouracil was also observed after multiple administration of this anticancer drug.

Actihaemyl↗
PubMed1988

The effect of sodium-2-mercaptoethane-sulphonate, N-acetylcysteine and cysteine on the uptake of cytosine arabinoside by normal and neoplastic thymus cells of mice.

The effect of some sulfhydryl compounds on the uptake of cytosine arabinoside (Ara-C) by normal and neoplastically transformed mouse thymus cells was studied. Sodium 2-mercaptoethanesulphonate (Mesna) was found to greatly inhibit (in 80%) the uptake of Ara-C by normal cells. Two other SH-compounds (cysteine and N-acetyl-cysteine) displayed no such effect. None of the three compounds reduced the uptake of Ara-C by neoplastic thymus cells. The possible pharmacological implications of these findings are discussed.

Acetylcysteine↗