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Biomedical subjects

A Chodkowska

Publications and source records attributed to A Chodkowska.

At least 19 recordsLinked to original sources

Six-week treatment with Ukrain in rabbits. Part I: Morphological parameters.

This study was performed to evaluate the effect of 6-week treatment with Ukrain in doses of 0.3, 1.5 and 3.0 mg/kg i.v. on the morphological and biochemical parameters of peripheral blood and morphology of body organs in rabbits. Ukrain application did not change the body organs and total body weight. The drug did not affect biochemical parameters of peripheral blood, except for a minor reduction in the total plasma level and increases in serum uric acid and urea indicating enhanced catabolism of proteins. The peripheral erythrocyte and leukocyte counts were not altered, whereas the percentages of lymphocytes, monocytes, and eozynophils were increased after higher doses of Ukrain. An increase in rod neutrophils and a decrease in the percentage of segmented neutrophils were also noted. These observations indicate a lack of organ toxicity following long-term treatment with Ukrain.

Alkaloids↗

Six-week treatment with Ukrain in rabbits. Part II: Serum levels of gonadal hormones.

The effect of 6-week treatment with Ukrain at doses of 0.3, 1.5, and 3.0 mg/kg i.v. on the serum levels of steroid hormones, i.e., estradiol, testosterone, and progesterone, was studied in rabbits of both sexes. It is demonstrated that Ukrain treatment exerts minor changes in serum hormone levels. The level of estradiol was increased in the serum of male rabbits following Ukrain treatment only at the dose of 1.5 mg/kg i.v. Similarly, the estradiol serum level was increased after Ukrain given at 1.5 mg/kg i.v. in female rabbits. In male rabbits Ukrain application at 0.3 mg/kg i.v. increased the serum testosterone level. Serum testosterone levels were not altered following Ukrain administration up to 3.0 mg/kg i.v. in female rabbits. Ukrain raised the serum progesterone levels in male rabbits at the doses of 0.3 and 3.0 mg/kg i.v. in females, only the highest dose of Ukrain produced a significant increase of serum progesterone.

Alkaloids↗

Six-week treatment with Ukrain in rabbits. Part III: Serum levels of thyroid hormones.

The influence of 6-week treatment with Ukrain at doses of 0.3, 1.5 and 3.0 mg/kg i.v. on serum levels of thyroid hormones, i.e., thyroxine and triiodothyronine, was studied in rabbits of both sexes. Ukrain affected the serum levels of both hormones in males. An increase in the thyroxine level was found after Ukrain used at a dose of 1.5 and 3.0 mg/kg i.v., whereas increased triiodothyronine was noted when Ukrain was given at all studied doses. In females the thyroxine level was not altered by Ukrain administration, whereas the triiodothyronine concentration was increased following Ukrain at 0.3, 1.5 and 3.0 mg/kg i.v. it is probable the altered thyroid hormone levels as a result of Ukrain application may contribute to the drug's potent immunomodulatory action.

Adjuvants, Immunologic↗

Preliminary pharmacokinetic studies of Ukrain in rats.

Ukrain (thiophosphoric acid derivative of Chelidonium majus L. alkaloids) was administered to rats i.p. at a dose of 28 mg/kg (equivalent to 0.1 LD50). A high performance liquid chromatography (HPLC) method for rapid determination of Ukrain in plasma has been described. It was found that Ukrain rapidly penetrated into the plasma of the rats and the elimination of the drug from the plasma was slower. The results obtained were as follows: absorption rate constant ka = 0.0432 [min-1]; elimination rate constant K = 0.0113 [min-1]; drug half-life t1/2 = 61.32 min; actual concentration of Ukrain in the plasma C = 33 e-0.0113t - 39 e-0.0432t [microgram/ml]; and delay in drug absorption T0 = 5.23 min.

Alkaloids↗

Modification of antinociceptive action of Ukrain by endogenous nitric oxide in the writhing syndrome test in mice.

The effects of L-arginine, the physiological precursor of nitric oxide (NO), and inhibitors of NO-synthase on the antinociceptive action of Ukrain (4.75, 9.5, and 19.0 mg/kg i.p.) were investigated using the writhing syndrome test in mice. It was found that L-arginine (0.1 or 1.0 mg/kg i.p.) significantly decreased or enhanced the antinociceptive effect of Ukrain, depending on the combination administered. In addition, the inhibitors of NO-synthase NG-nitro-L-arginine methyl ester (L-NAME) (1.0 and 10 mg/kg i.p.), 7-nitroindazole (1.0 mg/kg i.p.) and NG-monomethyl-L-arginine acetate (L-NMMA) (1.0 mg/kg i.p.) significantly enhanced Ukrain-induced antinociception. These results suggest that endogenous NO can modify the antinociceptive effect of Ukrain.

Alkaloids↗

Effect of six-month treatment with Ukrain on early osteoporosis induced by ovariectomy in rats. Part I: Preliminary studies of bone parameters.

Ukrain, thiophosphoric acid alkaloid derivatives from Chelidonium majus L. was administered intraperitoneally in a dose of 28 mg/kg (equivalent to 0.1 LD50) every other day for six months to female rats with ovariectomy-induced early osteoporosis. Administration of Ukrain was started on the second day after the surgical operation. At the end of the long-term treatment with Ukrain each rat was tested for the strength of both humeri and some parameters of rat femur were measured. The body weight of ovariectomized rats was also examined. The present results show that the decrease in the mechanical strength of the humeral bones and some changes in the femur caused by ovariectomy were prevented by the six-month treatment with Ukrain. However, in both ovariectomized groups and in ovariectomized rats pretreated with Ukrain an increase of body weight was observed.

Alkaloids↗

Effect of six-month treatment with Ukrain on early osteoporosis induced by ovariectomy in rats. Part II: Preliminary studies of peripheral blood parameters.

Studies on Wistar rats have demonstrated that six months after ovariectomy no changes were observed in peripheral blood morphology other than a decreased leukocyte count. A similar effect was noted in the sham-operated group. The present results show that Ukrain treatment started on the second postoperative day and continued every other day for six months significantly increased leukocyte count in comparison with the untreated ovariectomized and sham-operated groups. The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also estimated in this study. In none of the groups studied was any change of ALT activity noted. The activity of AST was significantly increased in the sham-operated and untreated ovariectomized rats. After six-month treatment with Ukrain, the activity of this enzyme was significantly decreased in the serum of untreated ovariectomized rats. In rats pretreated with Ukrain some of the studied parameters of peripheral blood were similar to those of the control group.

Alanine Transaminase↗

Antinociceptive effect of ten day administration of Ukrain in mice and interaction of the treatment with morphine.

The present study shows that Ukrain, administered i.c. in doses of 9.5 and 19 mg/kg once daily for 10 days in mice, produced evident antinociceptive action in the writhing syndrome and hot-plate tests. Moreover, we found that as a result of 10-day treatment with Ukrain the antinociceptive action of morphine (0.1 mg/kg s.c. administered after the last dose of Ukrain) was significantly decreased. These results and the observed interaction between Ukrain and morphine seem to be contra-indications to their combined usage.

Alkaloids↗

Interaction between Ukrain and morphine in their ten-day treatment in mice in the writhing syndrome test.

The antinociceptive properties of Ukrain and of morphine in their 10 day treatment in mice were studied by the writhing syndrome test. It was found that the antinociceptive action of Ukrain after 10 days of treatment was similar to that of morphine (0.1 mg/kg s.c.) in the same period. Results indicate that the combined treatment with Ukrain and morphine for 10 days completely reduced their antinociceptive action.

Alkaloids↗

The influence of antineoplaston A5 on particular subtypes of central dopaminergic receptors.

A new therapeutic strategy for the treatment of Parkinson's disease (PD) is based on providing trophic support for degenerating dopaminergic (DA) neurons. It can be accomplished by administration of neurotrophic factors, or inducing astrocytes to differentiate and produce such factors. Antineoplaston A5 (A5), which is a naturally-occurring cytodifferentiating agent, may induce astrocytes to undergo normal differetiation, produce neurotrophic factors and alleviate the symptoms of PD. This paper describes studies on the influence of A5 on subtypes of central DA receptors by measuring the potency of haloperidol catalepsy in rats. A5, D1 agonist, and D1 D2 antagonists were given i.p. and D2 agonist s.c. for three consecutive days. Haloperidol catalepsy was measured by the method of Costall and Nylor. The degree of catalepsy was assessed every 30 min for 24 h and statistically evaluated using the Student's t-test. The results confirmed that A5 significantly attenuated catalepsy and stimulates dopamine D2 receptors. It reverses catalepsy induced by haloperidol and D2 antagonists, but increases cataleptogenic activity if given in combination with the D2 agonist. This leads to the conclusion that A5 as a naturally-occurring agent neutralizes both hyper- and hypoactivity of central dopaminergic structures. Besides possible use as an antiparkinsonism agent, A5 may find application in the treatment of other disturbances of dopaminergic transmission.

Animals↗

The influence of antineoplaston A5 on the central dopaminergic structures.

Antineoplastons are naturally occurring cytodifferentiating agents. Chemically, antineoplastons are medium and small sized peptides, amino acid derivatives and organic acids which exist in blood, tissues and urine. In clinical trials in advanced cancer, in addition to the anticancer activity it was observed that patients suffering from both cancer and Parkinson's disease exhibited marked improvement in parkinsonian symtomatology when treated with antineoplaston A5. The present study was designed to analyse the influence of A5 on central dopaminergic structures. Mice and rats were given A5 intraperitoneally at three different dosage levels. Experiments conducted included spontaneous locomotor activity, amphetamine-induced yawning and erections, catalepsy, the effect on the level and utilization of noradrenaline and dopamine in the brain and the influence of prolonged and chronic treatment on the haloperidol-induced catalepsy. It has been demonstrated that A5 stimulates the central dopaminergic receptors. It diminishes the cataleptic response to haloperidol and enhances the incidence of apomorphine-induced yawning. Biochemical studies demonstrated increased concentration of dopamine and noradrenaline in the brain and diminished utilization of both catecholamines.

Amphetamine↗

Synthesis and pharmacological properties of some new 3-(2-N,N-dialkylaminoethyl)-pyrido [2,3-d]-pyrymidin-4-ones.

The following new derivatives of pyrido [2,3-d]-pyrimidin-4(3H)-one were synthesized: 3-(2-N,N-dimethylaminoethyl), 3-(2-N-pyrolidynylethyl), 3-(2-piperidinylethyl) and 3-(2-N-morpholidinylethyl). Their chemical structures were confirmed by MS, IR and 1H NMR spectroscopic data. Newly synthesized compounds were investigated pharmacologically for their central properties in mice and rats. It was shown that compound [III] showed anxiolytic action in the four-plate test and two compounds produced analgesic effects in mice.

Analgesics↗

Some pharmacological properties of prolonged administration of Ukrain in rodents.

Some pharmacological properties of Ukrain administered intraperitoneally (i.p.) once daily for three months in mice and rats of both sexes were studied. A three month treatment with Ukrain significantly depressed the spontaneous locomotor activity and did not affect the motor coordination of mice and rats of both sexes. Ukrain did not affect the body weight gain as well as the mass of internal organs; the exception was an increase in the mass of the spleen in rats. Biochemical studies indicated that a three month treatment with Ukrain depressed the whole brain dopamine (DA) concentrations and did not affect the noradrenaline (NA) concentrations. Long-term administration of Ukrain showed no characteristic changes in the concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the whole brain. The observed changes after three months' treatment with Ukrain are similar in mice and rats of both sexes.

Alkaloids↗

Modification of antinociceptive action of morphine by Ukrain in rodents.

Morphine-induced (0.1 mg/kg s.c.)antinociceptive action was determined in rodents by using the writhing syndrome, hot plate and tail-flick tests. Ukrain given i.p. in doses equivalent to 0.05 and 0.1 LD50 did not affect the reactivity of the mice in the writhing syndrome test. Only in a dose of 0.1 LD50 did Ukrain produce an antinociceptive effect in the hot-plate and tail-flick tests. Ukrain significantly enhanced the antinociceptive effect of morphine in the hot-plate and tail-flick tests. The action of morphine was significantly suppressed by Ukrain in the writhing syndrome test in mice. These results indicated that Ukrain modified the antinociceptive action of morphine.

Acetates↗

Effect of Ukrain on the efficacy of anti-epileptic drugs against maximal electroshock-induced seizures in mice.

It has been found that Ukrain, given intraperitoneally (i.p.), did not influence the threshold for maximal electroconvulsions in mice. Ukrain in doses of 9.5 and 19 mg/kg significantly enhanced the protective efficacy of valproate, decreasing the ED50 values. However, Ukrain had no effect on the protection provided by diazepam, carbamazepine, diphenylhydantoin and phenobarbital. The combined treatment with Ukrain and anti-epileptic drugs did not cause any signs of toxicity.

Alkaloids↗

Interaction between Ukrain and aminophenazone in analgesic tests in rodents.

The effect of Ukrain on the analgesic activity of aminophenazone was studied in mice and rats. Antinociceptive action induced by aminophenazone in doses of 50 or 100 mg/kg intraperitoneally (i.p.) was determined by using the writhing syndrome, hot-plate tests and tail-flick latency. The action of aminophenazone was significantly enhanced by Ukrain in the writhing syndrome test and in the tail-flick test. Antinociceptive action of aminophenazone was decreased by Ukrain in the hot-plate test in mice. These results suggest that Ukrain, given simultaneously with aminophenazone, changes susceptibility of animals to nociceptive reaction in the tests performed.

Acetates↗

Effects of calcium channel inhibitors upon the efficacy of common antiepileptic drugs.

Diltiazem and nifedipine (both 1.25 mg/kg) markedly potentiated the protective action of carbamazepine and diphenylhydantoin against maximal electroshock-induced seizures in mice. These calcium channel inhibitors retained their activity at lower doses. Diltiazem and nifedipine (2.5 mg/kg) also moderately potentiated the efficacy of phenobarbital and valproate. Verapamil (up to 10 mg/kg) was not effective against the action carbamazepine, diphenylhydantoin, phenobarbital, and valproate. None of the calcium channel inhibitors used (up to 40 mg/kg) influenced aminophylline-induced convulsions and mortality. Moreover, the anti-aminophylline activity of valproate and phenobarbital was not potentiated by the calcium channel inhibitors in doses up to 10 mg/kg. Further, combination of carbamazepine, ethosuximide, and trimethadione with the calcium channel inhibitors (up to 10 mg/kg) did not offer any protection against aminophylline-induced convulsions. It can be concluded that calcium channel inhibitors enhance the protective efficacy of some antiepileptics against electroconvulsions. A pharmacokinetic interaction does not seem to be responsible for this effect.

Aminophylline↗