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Biomedical subjects

W Buczko

Publications and source records attributed to W Buczko.

At least 163 records · Page 9Linked to original sources

The effect of bovine fibrinopeptides on the central action of chlorpromazine and amphetamine in rats.

A mixture of fibrinopeptides A and B did not evoke any significant central effects when given by intraperitoneal injection, whereas it increased psychomotor activity when injected into a cerebral ventricle. The fibrinopeptides when given by intraperitoneal injection interacted with amphetamine to increase locomotor activity and with chlorpromazine to decrease both locomotor activity and body temperature. It is suggested that the release of fibrinopeptides in various clinical conditions where there is increased fibrinogen-fibrin conversion may lead to an altered sensitivity to centrally acting drugs.

Amphetamine↗

The influence of albumin degradation products on central action of amphetamine and pentetrazol.

Trypsin degradation products of albumin given intraperitoneally and into the brain ventricle decrease psychostimulatory effects of amphetamine as evaluated by Lat's test and stereotypy. Albumin degradation products obtained by trypsin and leukocyte digestion increased the convulsant effects of pentetrazol. These effects are possibly connected with a neurohormonal background in the central nervous system.

Amphetamine↗

Effect of fenfluramine on 5-hydroxytryptamine uptake and release by rat blood platelets.

1. (+)-Flenfluramine reduces the central stores of 5-hydroxytryptamine (5-HT) by a poorly understood mechanism. 2. Rat blood platelets have been used in this study as a simple model for serotoninergic nerve endings. 3. (+)-Fenfluramine shows a dual effect: it inhibits the uptake of (14C)-5-HT by platelets and it releases newly absorbed (14C)-5-HT from platelets. 4. The inhibition of (14C)-5-HT uptake induced by (+)-fenfluramine appears very rapidly, is concentration-dependent and seems not to be competitive. (+)-Fenfluramine is ten times less effective than chloroimipramine but tem times more effective than (+)-amphetamine; (+)-fenfluramine is more active than its (-)isomer or its metabolite norfenfluramine ((+)- or (-)-form). 5. The release of (14C)-5-HT from platelets induced by (+)-fenfluramine is concentration-dependent but increases wtih increased incubation time. Both chloroimipramine and (+)-amphetamine are in comparison very poor release inducers; (+)-fenfluramine is more active than its (-)-isomer or its metabolites. 6. The effect on (14C)-5-HT uptake exerted by (+)-fenfluramine and chloroimipramine in vitro could not be observed in vivo. 7. The observed effect on fenfluramine on the uptake and release of 5-HT may explain the lowering action of fenfluramine on the brain 5-HT level, an effect considered of importance for the anoretic effect on this drug.

Animals↗

Influence of fibrinogen degradation products (FDP) on the central nervous system and on the effects of centrally acting drugs.

Fibrinogen degradation products (FDP) from bovine fibrinogen were obtained in vitro by trypsin digestion for 3 and 120 min, respectively. FDP-120 min applied i.p. and i.v.c. stimulated the CNS, while FDP-3 min did not. The FDP increased the potency of amphetamine, caffeine, thiopental, and chlorpromazine by enhancing their level in the brain. Peptides from 120 min digestion were more effective. A possible mechanism of observed changes has been discussed.

Amphetamine↗

The effect of products of fibrinogen digestion by plasmin (P-FDP) on the central nervous system.

Low molecular peptides, derived from fibrinogen digested by plasmin and injected either intraperitoneally or into the brain lateral ventricle, were found to act depressively on the CNS in active rats, while in fairly active rats they showed stimulatory effects. Fractionation of P-FDP on Sephadex G-25 showed that the most active peptides had a molecular weight lower than 5,000.

Animals↗

Modulation of plasminogen activator inhibitor type-1 biosynthesis in vitro and in vivo with oligo(nucleoside phosphorothioate)s and related constructs.

Oligonucleotides with a nucleotide sequence complementary to various regions of human plasminogen activator inhibitor type-1 (PAI-1) mRNA have been studied as antisense inhibitors of expression of PAI-1 protein in cultured cells [human umbilical vein endothelial cells (HUVEC), human aortic smooth muscle cells, human hybrid endothelial cells]. Hexadeca(deoxyribonucleoside phosphorothioate) 13 complementary to a fragment of a signal peptide PAI-1 mRNA was found to be most active, giving ca. 70% inhibition of PAI-1 release in a time- and dose-dependent way. The stereo-regular All-S(P) and All-R(P) diastereomers of 13 were studied and found to inhibit PAI-1 synthesis in HUVEC in a stereo-dependent manner, with the All-S(P) diastereomer considerably more active than the stereo-random construct and All-R(P) isomer. The observed stereo-dependent activity of oligonucleotide phosphorothioate constructs is presumably governed by their resistance to nucleases. The corresponding phosphodiester analogue of 13 was not active unless covalently bound at its 5'-end to a lipophilic alcohol residue (menthol, heptadecanol). The observed antisense activity of phosphodiester oligonucleotide bioconjugates in cultured human hybrid endothelial cells was paralleled by their increased stability in human plasma with respect to unconjugated oligonucleotide. The oligo(deoxyribonucleoside phosphorothioate) complementary to the same signal peptide region of rat PAI-1 mRNA was found to reduce the PAI-1 level in blood plasma of rats after intravenous administration into the tail vein. The effect was both time- and dose-dependent. The same oligonucleotide was found to protect against arterial thrombus formation in the rat (lower incidence of venous thrombosis, lower thrombus weight, and increased occlusion time in experimentally induced thrombosis). An anti-PAI-1 inhibitory activity has been independently reported for a 20-mer oligo(2'-O-methyl-ribonucleoside phosphorothioate) complementary to a 3'-untranslated region of human PAI-1 mRNA in cultured HUVEC and human aortic smooth muscle cells.

Animals↗

Attenuation of the acute amnestic effect of ethanol by ifenprodil: comparison with ondansetron and dizocilpine.

The aim of the present study was to examine the influence of ifenprodil, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist which also blocks 5-HT3 receptors, on the amnestic effect of ethanol in a passive avoidance task in mice. The anti-amnestic action of ifenprodil was compared with the effects of the 5-HT3 receptor antagonist ondansetron and the non-competitive NMDA-receptor antagonist dizocilpine (MK-801). Ethanol, 2 g/kg and dizocilpine 0.1 mg/kg significantly impaired the passive avoidance response. In contrast, ifenprodil (0.1-10 mg/kg), ondansetron (0.03-0.3 mg/kg) and dizocilpine (0.01 and 0.03 mg/kg) did not alter passive avoidance by themselves. Dizocilpine did not diminish the amnestic action of ethanol when administered at doses of 0.03-0.1 mg/kg. However, the amnestic effect of ethanol was partially restored towards normal by ifenprodil 0.3 mg/kg and by ondansetron 0.03 mg/kg (alone or together with dizocilpine 0.01 mg/kg) but it was not affected by other doses of ifenprodil (0.1, 1 and 10 mg/kg) and ondansetron (0.1 and 0.3 mg/kg). In conclusion, ifenprodil at an appropriate dose reduced ethanol-induced amnesia in a step-through passive avoidance task. The results are compatible with the assumption that the anti-amnestic action of ifenprodil may be (at least partially) due to an antagonism at 5-HT3 receptors.

Acute Disease↗

Influence of fibrinogen degradation products (FDP) on the central action of acetylcholine.

Depressive behavioral effects of acetylcholine (10 mug ivtr) and physostigmine (0.3 mg/kg ip), and prolongation of the duration of electrogenic seizures produced by the drugs were prevented by intraperitoneal or intraventricular administration of FDP (0.5 mg/kg or 5 mug resp.). The peptides did not affect the brain acetylcholine level and did not influence the inhibitory effect of physostygmine on AChE activity.

Acetylcholine↗