[The effect of fenoterol (partusisten) on cAMP and cGMP concentrations, acetylcholine esterase and choline acetyltransferase activities in rat placenta]. / Wplyw podawania fenoterolu (partusisten) na stezenie cAMP i cGMP, aktywnosci acetylotransferazy cholinowej i esterazy acetylocholinowej w lozysku szczura.

Several observations indicate a possible role of the placental cholinergic system in the modulation and maintenance of placental function and subsequently fetal growth and development. We have investigated the effect of Partusisten (1 mg/kg p.o., twice daily, since the 15th to the 20th day of gestation) on cAMP and cGMP concentrations, acetylcholine esterase and choline acetyltransferase activities in rat placenta. The obtained results show that Partusisten increased cAMP concentration and decreased cGMP concentration (see Tab. 1; Fig. 1, 2). Choline acetyltransferase activity was elevated (Tab. 2; Fig. 3) whereas Partusisten had no effect on acetylcholine esterase activity (see Tab. 2; Fig. 4). The results indicate disorders in placental cholinergic system after chronic Partusisten administration to pregnant rats. On the other hand, the marked increase in choline acetyltransferase activity suggested the high adaptability of placenta.

[Pharmacokinetics of 6-mercaptopurine in rats during postnatal development]. / Farmakokinetyka 6-merkaptopuryny u szczurów w czasie rozwoju osobniczego.

It was shown that 6-MP pharmacokinetics in rats was age-dependent. The distribution processes were mainly influenced by age of animals. 6-MP total distribution volume (VD) increased from 26.4 ml in 2 week old animals to 60.2 ml and 55.5 ml in 4-week-old and adult rats, respectively. However, the relative volume of distribution (delta, per cent of body weight) decreased from 1019 ml/kg in 2 week old rats to 317 ml/kg in adult rats. Similar relationships between total body clearance and the age of animals were observed. One may suspect that the changes in the distribution processes are connected both with the increased extracellular water content and the changed protein binding in young animals.

[Pharmacokinetics of nitrofurantoin in the bodies of pregnant rats]. / Farmakokinetyka nitrofurantoiny (NTF) w ustroju szczurów ciezarnych.

The investigation of nitrofurantoin (NTF) pharmacokinetics in pregnant rats was undertaken to estimate its cumulation in the fetus unit. It was found that pharmacokinetics of NTF is dose-dependent in non-pregnant rats. The biological half-life time increased from 0.24 to 0.41 and 0.72 h for NTF doses 10.20 and 40 mg/kg, respectively. The elimination of NTF was diminished in pregnant rats. The pharmacokinetic analysis revealed a possibility of strong NTF accumulation in the pregnant rats (increased K12/K21 ratio). Taking into account increased renal function in pregnancy, one may suspect that decreased elimination of NTF was rather caused by its significant cumulation in the changed tissue compartment.

[Serotonin concentration in the rat fetal brain in experimental intrauterine dystrophy]. / Stezenie serotoniny w mózgu plodów szczura w doswiadczalnie wywolanej dystrofii wewnatrzmacicznej.

The concentration of serotonin (5-hydroxytryptamine, 5-HT) was determined in the brain of fetal rats with experimental intrauterine growth retardation (IUGR). IUGR was induced using the procedure of Wigglesworth. On the 17th day of gestation, the uterine artery supplying one uterine horn was ligated. The artery of the opposite uterine horn was left untouched (control). On the 22nd day the fetuses were delivered by C-section. 5-HT was determined by fluorometric method. Statistical analysis employed the paired Student t-test. The average body weight of the IUGR fetuses was 3.15 g, whereas control fetuses 4,50 g. The mean concentration of 5-HT was 10,4% lower in IUGR fetal brains. The mean 5-HT brain concentration in IUGR was 155 micrograms/g of tissue, whereas in control the mean concentration was 173 micrograms/g of tissue. The difference between these brain concentrations was significant (p less than 0,005). We conclude that reduction in maternofetal blood flow in the 3rd trimester of gestation results in decreased concentration in the brain of 5-HT.

[Chloramphenicol metabolism in the tissues of newborn and adult rabbits]. / Metabolizm chloramfenikolu w tkankach królika nowo narodzonego i doroslego.

The in vitro studies on the metabolism of chloramphenicol in the liver, kidney and lung of 5 days old and adult rabbit as well as in the placenta (20-23 day of gestation) have been performed. The metabolites have been identified by thin-layer chromatography technique. Nonmetabolized chloramphenicol and reduction product were estimated by spectrophotometric method. The obtained results showed that in adult rabbit chloramphenicol was metabolized in the liver and lung, but no nitroreduction seems to occur in none of these tissues. In contrast to the adult animal the metabolism of chloramphenicol occurred in the all investigated organs of 5 days old rabbit. Each of the examined tissues of newborn animal showed the activity of nitroreductase. The biotransformation, including nitroreduction, of chloramphenicol occurred also in placenta. The thin-layer chromatography technique showed the presence of the product of hydrolysis of amide linkage in the liver of adult rabbit and in the placenta, and in the placenta additionally the product of hydrolysis of amide linkage without aliphatic amine group.

[Effect of drugs on cyclic AMP levels in the tissues of animals at different stages of ontogenesis. I. Experimental studies on the effect of adrenomimetic drugs on cyclic AMP concentration in the brain of 7-day-old and adult rats]. / Wplyw leków na stezenie cyklicznego AMP w tkankach zwierzat w róznych okresach rozwoju osobniczego. I. Badania doswiadczalne nad wplywem leków adrenomimetycznych na stezenie cyklicznego AMP w mózgu szczurów 7-dniowych i doroslych.

The purpose of the investigations was the comparison of the adrenergic receptors excitability in brain of 7-days-old and adult rats after adrenaline and isoprenaline administration. The excitation was evaluated biochemically by measurement of the beta receptor-mediated increase in brain cAMP concentration. There was no significant difference in brain tissue cAMP concentration of 7-days-old and adult rats in physiological conditions. The concentration of cAMP in brain of adult rats was not affected after administration both adrenaline and isoprenaline. On the contrary, the concentration of cAMP in brain of 7-days-old rats was significantly increased after each of two examined drugs, indicating that blood-brain barrier is permeable for catecholamines at this age.

Experimental and clinical pharmacokinetics of nitrofurantoin in the early period of life.

The investigation of pharmacokinetics showed age-dependent rate of nitrofurantoin elimination in rats. Nitrofurantoin half-life of 0.41 hr in adults was prolonged to 0.95 hr in 2-weeks-old rats. Nitrofurantoin excretion rate was decreased in children younger than 2 years. Older children excreted in urine 44.32 +/- 16.07 and younger 25.07 +/- 5.7 per cent of the given dose of nitrofurantoin, indicating the lower capacity for nitrofurantoin elimination via kidneys.

[The effect of biseptol and sodium salicylate administration on the concentration of serotonin and histamine and mono- and diamine oxidase activities in rat placenta]. / Wplyw podawania biseptolu i salicylanu sodu na stezenie serotoniny i histaminy oraz na aktywnosc oksydazy monoaminowej i dwuaminowej w lozysku szczura.

It is known that two biogenic amines:serotonin and histamine, as well as the enzymes connected with their metabolism (mono- and diamine oxidase), play very important role in human and animal fetal development. We have investigated the effect of Biseptol and sodium salicylate administered to pregnant rats on the concentrations of serotonin and histamine and activities of the above mentioned enzymes in placenta. The obtained results showed that the administration of Biseptol has no influence on the serotonin concentration, whereas the administration of sodium salicylate caused slight increase of serotonin concentration in rat placenta. The activity of monoamine oxidase was elevated after administration of both drugs (Tabl. I, Fig. 1). The administration of Biseptol decreased the histamine concentration and caused the marked increase of DAO activity. The sodium salicylate administration to the pregnant rats didn't influence on the histamine concentration, whereas it caused parallel twofold increase of DAO activity (Tabl. II, Fig. 2).

[Sulfamethoxazole concentration in the homogenate of the human embryo]. / Stezenie sulfametoksazolu w homogenacie ludzkiego jaja plodowego.

The investigations on the extent of placental drug transfer has conventionally been based on determining drug concentration in cord blood at delivery. There is, however, data that levels in cord blood at delivery may provide misleading information on the extent of drug transfer in utero. It is due to the fact that not every drug reaches the fetus in pharmacologically active form. Hence, the evaluation of placental drug transfer requires determination of free drug concentration in fetal tissues. Seven women with indications for interruption of pregnancy for social reasons have taken Biseptol 480--Polfa (400 mg sulfamethoxazole and 80 mg trimethoprim) for 4-5 days before the operation. Each woman received 1,92 g of drug (4 tablets) a day in two divided doses. In the tissues obtained during abortion, the concentration of sulfamethoxazole was estimated by the modified method of Bratton and Marchall . The obtained results show that in the first trimester of gestation sulfamethoxazole crosses human placental barrier; it is detectable in embryo in a great amount. This fact indicates that administration of Biseptol to the pregnant mother may be harmful for the embryo. Our investigations have not permitted yet on for the statement that there is the correlation between the sulfamethoxazole concentration and week of gestation during the first trimester.

[Binding capacity of some drugs to plasma proteins of newborns in comparison with adults (author's transl)]. / Bindungskapazität der Serumeiweisskörper von Neugeborenen und Erwachsenen für einige Arzneimittel.

Comparative studies on binding capacity of some drugs to plasma proteins of newborns and adults were carried out. Plasma from the newborn and adult rabbits as well as human from 4 sources: a) from healthy adults, b) from cord blood, c) from 5 days old newborns, and 6 month old infants were used for the experiments. For methodological reasons in the first part of our studies we have chosen: two sulfonamides - sulfamethazine and sulfamethoxasole, chlorpromazine and sodium salicylate. In the experiments two different techniques were used 1) equilibrium dialysis, 2) ultrafiltration. On the basis of the results obtained in animals as well as in human beings it was noted that the degree of drug binding to plasma proteins in newborns was different from that observed in adults, it may be higher or lower according to the drug used. The knowledge of this fact is of great importance, and should be taken into consideration in the calculation of proper dosage of various drugs in the newborns and infants.

[Influence of reserpine on the libration of catecholamines in the brain and heart of rats in ontogenetic development (author's transl)]. / Wplyw rezerpiny na uwalnianie amin katecholowych z mózgu i serca szczura w rozwoju ontogenetycznym

The influence of reserpine on the level of noradrenaline and dopamine in the brain, and that of noradrenaline in the heart of rats in various age groups were investigated. It was found that the level of catecholamines in the brain and heart of young rats decreases much more rapidly and to a greater extent than in adult rats.