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Biomedical subjects

E Nowakowska

Publications and source records attributed to E Nowakowska.

At least 19 recordsLinked to original sources

[Amiodarone for long term treatment of arrhythmia in children].

Amiodarone was used in 37 pediatric subjects aging 1 day--16 years. Very high efficiency of long-term treatment (mean 8 months) was found in the cases of supraventricular as well as ventricular tachyarrhythmias (paroxysmal and nonparoxysmal) including complex life-threatening ones. The treatment was not effective only in three subjects. In the other cases normal heart rhythm was achieved or duration time and number of tachycardia attacks was reduced. The class of arrhythmia improved. It was often recommended to use amiodarone together with digitalis preparation in order to obtain its antiarrhythmic activity. Our usual amiodarone dose was 10-20 mg/kg of body mass/24 h intravenously (in order to interrupt the attack) or 10 mg/kg/24 h per os in saturation period. Then the daily dose was reduced to the mean equal 5 mg/kg. Amiodarone side effects were observed in rather high percentage of subjects (24%) during long-term treatment. There were abnormal laboratory tests or laboratory and clinical abnormalities of thyroid function observed in 3 cases. In 4 other ones amiodarone deposits in cornea were found. They disappeared in 2 cases after drug dose reduction. In 1 child the symptoms of lung fibrosis and in the other one of sunshine hypersensitivity were observed. Thus, because of side effects treatment had to be interrupted in 7 cases (19%). It is concluded that amiodarone is exceptionally effective antiarrhythmic drug, very useful also in the youngest pediatric patients. On the other hand it is concluded, that the treated subjects must remain under careful medical control because of high rate of amiodarone side effects.

Adolescent↗

[Genetic polymorphism of glutathione s-transferase as a factor predisposing to allergic dermatitis].

In the inductive phase of contact allergic dermatitis, simple chemical compounds (haptens) produce together with epidermic proteins adducts presented by Langerhans cells to T lymphocytes. Binding to protein carrier is a necessary condition of transforming a low-molecular allergen into immunogenic one and evoking immunological reaction. The production of allergen adducts with proteins is conditioned by the presence of electrophilic groups in their molecules, or their acquiring during biotransformation phase I. Active allergen metabolites undergo further alterations during biotransformation phase II which leads most frequently to the decline in their chemical activity and more rapid excretion from the body. The number of reactive metabolites (reactive allergens) available for producing adducts with proteins keeps the balance between activation and deactivation reactions. Glutathione S-transferases play a particular role in the allergens (or their metabolites) deactivation process in biotransformation phase II. These enzymes catalyse reactions responsible for the declined electrophilic potential of allergens (or their metabolites), and thus for the decrease in the number of allergen molecules able to produce protein covalent bindings (adducts). Glutathione S-transferases, occurring in the human cellular cytoplasm belong to five classes: alpha(GST A), mu(GST M), theta(GST P), pi(GST T) and Z(GST Z), as well as to one class present in microsomes. The study indicated the presence of isoenzymes GST T1 and GST M1 in the skin. Both isoforms participate in the process of low-molecular allergen biotransformation. Carriers of defective genes GST T1 and/or GST M1 are more vulnerable to allergenic effect of some allergens, e.g. thimerosal, which is associated with the absence of or decrease in the activity of isoenzymes GST T1 and GST M1.

Allergens↗

Investigating potential anxiolytic, antidepressant and memory enhancing activity of deprenyl.

L-deprenyl in the dose of 0.25 mg/kg (the dose with no effect on locomotor activity) was administered to Wistar rats in single and prolonged treatment (21 days). In the same manner carboxymethyl cellulose was given to the control group. In the forced swimming test the rats from the deprenyl group showed reduced immobility time only once, after 7 days of treatment, as compared with the control group. In the Crawley's test one parameter was increased after deprenyl--the white square entries (WSE), showing that the rats were emboldened to move more freely in the white, lighted area. In the maze test the most important observations were that deprenyl shortened the food finding time and significantly counteracted the elongation of this time after scopolamine. The authors discuss the possibility that deprenyl has a modulatory effect on learning and memory and this effect depends on the dose used. It seems also that the increase of monoamine and cholinergic transmission may be involved. The small antidepressant and anxiolytic effect may be due to the metabolites of deprenyl of the amphetamine group.

Animals↗

Synthesis, structure and antiaggregatory effects of some N-(4,5-dihydro-1H-imidazol-2-yl)indoles.

A series of 1-(4,5-dihydro-1H-imidazol-2-yl)indole derivatives was prepared in order to evaluate their antiaggregatory activity in human platelets. The compounds 4a-m were prepared by reacting N-aryl-N-(4,5-dihydro-1H-imidazol-2-yl)hydroxylamines (2a-d) with monosubstituted acetylene derivatives 3a-b. Imidazoline derivatives 4 were further acetylated or sulfonylated to give amides 5a-c and sulfonamides 6a-c and 7a-c, respectively. Eight compounds were taken as representative aryliminoimidazoline analogs. Among them only one, 4m, showed a good concentration-dependent action against the primary or alpha 2-adrenoreceptor mediated phase of noradrenaline-induced aggregation in platelets.

Crystallography, X-Ray↗

Behavioural effects of fluoxetine and tianeptine, two antidepressants with opposite action mechanisms, in rats.

The behavioural effects of two antidepressants with opposite molecular mechanisms, tianeptine 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin - 11-yl)amino]heptanoic acid S,S-dioxide, CAS 66981-73-5) 5 mg/kg p.o., a serotonin reuptake enhancer, and fluoxetine (+/-)-N-methyl-3-phenyl-3-[(alpha, alpha, alpha-trifluoro-p- tolyl)oxy]propylamine, CAS 54910-89-3) 5 mg/kg p.o., a serotonin reuptake inhibitor, were compared after single and prolonged administration (7 and 14 days) once daily). In all experiments the drug effects were noted at the peak activity time: 30 min after tianeptine and 60 min after fluoxetine administration. In the immobility time test both drugs had a shortening effect on immobility time only after prolonged administration or, in single treatment, after joint administration. A different pattern was observed in the two compartment test: both antidepressants showed anxiolytic effects after single and prolonged treatment. However, when the drugs were given in joint administration, the anxiolytic effects were entirely abolished after single as well as prolonged treatment. In reference spatial memory test (food finding time in the maze) tianeptine had no effect, whereas fluoxetine caused, after single and prolonged treatment, a very marked improvement of reference memory. Joint administration of both drugs resulted in worsening the effects on memory in comparison to fluoxetine alone, but the results were still significantly better vs. control. In the test for sedative action (in the Activity Meter AM-1, where the movements of the animals are counted electronically) only after prolonged treatment with tianeptine a diminished locomotor activity could be observed. It is concluded that in the action of the drugs (beside the effect on serotonin uptake) other mechanisms must play an important role. The diminished locomotor activity after tianeptine suggests an influence on the dopaminergic or GABA-Receptor system.

Animals↗

Long-term effects of acute exposure to chlorphenvinphos on behavioural responsiveness to amphetamine and scopolamine in rats.

We investigated the effect of acute exposure to chlorphenvinphos (CVP) (2-chloro-1 (2,4-dichlorophenyl)-vinyl-diethyl-phosphate), an organophosphate anticholinesterase, on the amphetamine- and scopolamine-induced open-field locomotion in Wistar rats. CVP was administered at a single i.p. dose of 1.0 mg/kg (1/10 of LD50). In part of the rats cholinesterase (ChE) was determined. Three hours after CVP injection, the ChE activity decreased by about 27%. It returned to the preinjection level within 14 days after the exposure. In the behavioural part of the experiment, the animals were challenged with 1.0 mg/kg amphetamine or 0.75 mg/kg scopolamine three weeks after CVP exposure, i.e. after a period of time sufficient for cholinesterase recovery. It has been found that in the CVP-exposed rats, the behavioural responses to amphetamine or scopolamine challenge (the increase in locomotor activity) was significantly reduced compared to the controls. This suggests that acute exposure to CVP produced an increase in cholinergic activity which persisted long after ChE activity had returned to normal.

Amphetamine↗

[Soluble tumor necrosis factor receptors--their properties and role in diagnosis and therapy of acute and chronic diseases].

The review presents the properties and significance of soluble forms of tumor necrosis factor-alpha receptors in physiology and pathology of human organism. Special attention was turned to the possibility of practical application of those forms of the receptors in the therapy of diseases caused by excessive activity of TNF-alpha. The significance of the soluble receptors as prognostic factors of disease progression and outcome was stressed.

Acute Disease↗

Some behavioural effects of risperidone in rats: comparison with haloperidol.

Risperidone is a dopaminergic as well as a 5-HT2 antagonist. The drug was found to exert beneficial effects on both positive and negative symptoms of schizophrenia. Since recently, schizophrenia is regarded as a composite of not only positive and negative but also affective and cognitive symptoms, in this study the effects of risperidone compared with typical neuroleptic haloperidol, on affective and cognitive functions were investigated in rats (anxiolytic, antidepressive and memory tests). We found, that in contrast to haloperidol, risperidone had antidepressive, anxiolytic and memory enhancing effects. The results obtained correspond with favourable effects of risperidone on mood disturbances and cognitive functions of schizophrenic patients observed under clinical conditions.

Animals↗

An anxiolytic-like effect of ondansetron disappears in oxazepam-tolerant rats.

In our experiments a drug from the group of 5-HT3 antagonists--ondansetron (OND)--has been used in rats developing tolerance to oxazepam (OXZ). After 7 days of oxazepam administration (5 mg/kg i.p.) a significant decrease in the anxiolytic behavior was observed in the Crawley test. In the rats already partly tolerant to oxazepam, an undiminished anxiolytic-like effect of ondansetron (single injection of 0.1 mg/kg i.p., seventh day) was observed. After 14 days of oxazepam administration its anxiolytic activity was even more diminished. A single injection of ondansetron 0.1 mg/kg restored the anxiolytic behavior: rise of BWT (black-white transition) and WSE (white square entrance). After 21 days the anxiolytic activity of oxazepam was totally abolished and the single injection of ondansetron did not restore the state of anxiolysis. The results show that the anxiolytic effects of ondansetron were not influenced in the first stages of tolerance development to oxazepam, but the drug was not able to produce an anxiolytic effect in the state of full tolerance to oxazepam (after 3 weeks).

Animals↗

[Kava-kava preparations--alternative anxiolytics].

Since Cook's world cruises (1772-1775) there is written evidence of the use of kava-kava by the inhabitants of the Pacific Islands. In last decades kava-kava, an extract of the plant Piper methysticum was used in several European countries (drugs like Laitan, Antares, Viocava, Mosaro etc.). In the presented paper the authors describe the pharmacology, toxicology and pharmacokinetics of the active compounds of kava-kava the kavapyrones. The discussion concerning the therapeutic value of kavapyrones ends with the conclusion of the authors, that kava-kava may be a useful alternative for synthetic anxiolytics.

Animals↗

Anxiolytic and memory improving effects of moclobemide.

The anxiolytic and memory enhancing effects of moclobemide (p-chloro-N-(2-morphinoethyl)benzamide, CAS 71320-77-9, Ro 11-1163), a reversible and selective monoamine A oxidase inhibitor, were investigated in rats. It was found that the drug had an anxiolytic activity lasting in chronic experiments over 2 weeks. The used dose of the drug did not change animal locomotion in activity cages. In memory experiments (food finding time in maze), moclobemide exerted a favorable effect only after a single administration. In rats with scopolamine-impaired memory, moclobemide attenuated the effects of scopolamine in single and chronic experiments.

Animals↗

[Inhibitory monoamine oxidases of the new generation].

This review deals with the new generation of selective and partly reversible monoamine oxidase (MAO) inhibitors. In contrast to the non selective inhibitors, used in the year 1957-1970, the selective inhibitors bind to and block only one of the two isoenzymes, MAO-A or MAO-B. The MAO-A inhibitors and part of the MAO-B inhibitors differ also from the classic drugs by their reversibility. The inhibition of MAO-A cause the rise of norepinephrine, dopamine and serotonin in the synaptic cleft, of MAO-B only of dopamine. The new inhibitors diminish also to some extent the reuptake of monoamines. The molecular action mechanism of the new drug generation is the same as in the non-selective drugs: increase of monoamines, near to the receptor, leads, after a number of intermediate steps, to activation of functional proteins in the cell. The selective block of one of the isoenzymes does not stop the metabolism of tyramine (from cheese, red wine), because this toxic compound is metabolised by both isoenzymes. The control of therapy with MAO-A inhibitors is easier, because of their reversibility. Selective inhibitors of MAO have found a secure place in therapy of depression (inh. of MAO-A, esp. Moclobemide) and Parkinson's disease (inh. of MAO-B, at this time mainly selegiline). Discussed is possible use of selective MAO-inhibitors for achieving an increase in cognitive function and protections of neurone cells from biochemical lesions.

Animals↗

Pharmacological activity of fluoxetine.

Some SSRIs like fluvoxamine and zimeldine have already been investigated for their memory improving activity in humans and animals, with positive results. The purpose of this paper is to observe some activities of fluoxetine the known antidepressant on some control neuron system functions [3].

Animals↗

Studies on the involvement of opioid mechanism in the locomotor effects of benzodiazepines in rats.

The influence of the opioid receptor antagonist naloxone upon the reduced locomotor activity after administration of nitrazepam (NTZ) and upon the increased locomotion after chronic nitrazepam administration was tested. It was found that a single dose of naloxone counteracted both the reduced locomotion after acute administration of nitrazepam as well as the augmented locomotor activity after chronic application of nitrazepam. It is assumed that opioid mechanisms are involved in the locomotor effects of benzodiazepines.

Animals↗