Effects of drug administration in pregnancy on children's school behaviour.

Files with prescription data were used to assess possible behavioural changes in children, whose mothers used benzodiazepines or neuroleptic drugs during the second half of their pregnancy. Prescriptions, bearing the identification number of women resident in one district of Prague, filed in pharmacies during 1974 and the first three months of 1975 represent the first part of the data. During 1984, children born in the appropriate earlier period were searched and linked with the earlier prescription data. A group of 68 children with possible exposure to neuroleptics and a group of 15 children possibly exposed to diazepam during the second half of their intrauterine development were found. Two groups of 55 and 7 children, respectively, born of mothers without exposure to these drugs, were chosen as controls. The teachers of classes attended by these children were addressed by a letter and asked to evaluate their behaviour at school. This was done by means of a form containing analogue scales evaluating different features of behaviour. Each child was compared with its control. The statistical evaluation with Student's t-test, regression analysis and analysis of variance did not reveal any significant difference between both groups and their controls.

Transport of calcium across the dually perfused placenta of the rat.

1. A rat placenta was dually perfused in situ with modified Krebs fluid. Perfusion was carried out through the femoral artery on the maternal side and through the umbilical artery on the fetal side. 2. Transfer of 45Ca2+ and [3H]L-glucose across the placenta was measured in the maternal-fetal direction. The transcellular component of the maternal-fetal transport of Ca2+, Jmf,tc, was estimated from transfer rates of the two tracers and from Ca2+ concentration in maternal perfusate, [Ca2+]m. 3. At [Ca2+]m of 1.1 mM (physiological concentration of Ca2+ in plasma) Jmf,tc was 92.4 +/- 13.7 nmol min-1 (mean +/- S.D.), which is about 90% of the transport expected in an intact placenta. The permeability-surface area product (PS) of the placenta to [3H]L-glucose was 13.8 +/- 3.9 microliters min-1, about 4 times higher than that expected in intact placenta. 4. Transport of 45Ca2+ changed rapidly when [Ca2+]m was varied. Kinetic constants of the transcellular transport of Ca2+ are the Michaelis constant, Km, = 0.45 mM and the maximum rate of transport, Vmax, = 116 nmol min-1. It follows from this that at physiological levels of Ca2+, transport of Ca2+ to the fetus is relatively independent of changes in [Ca2+]m. 5. Strontium and barium (SrCl2 and BaCl2, 1 mM) decreased Jmf,tc; the response was prompt and reversible. Magnesium (2 mM) had no effect. Maternal-fetal transport of 85Sr2+ and 133Ba2+ was decreased rapidly and reversibly by elevating [Ca2+]m from 0.35 to 2 mM. These observations suggest that Sr2+ and Ba2+ are transported across the placenta by the Ca2+ transport system. This means that the transport is not substrate specific. 6. Cadmium (1 mM-CdCl2) decreased Jmf,tc irreversibly with some latency. The slowness of the response suggests a non-competitive inhibition. Cadmium (0.02 mM-CdCl2) was without effect on Jmf,tc. 7. A Ca2+ channel blocker, nifedipine (10 microM), administered to the maternal side had no effect on Jmf,tc.

Cardiovascular drugs in Czechoslovakia--registration and consumption data.

Data on registration and consumption of cardiovascular drugs in Czechoslovakia were sorted from the computerized Drug Information System (DIS) for a detailed analysis. Cardiovascular drugs (including antiarrhythmics, cardiac glycosides, diuretics, antihypertensive agents and vasodilators) represent at present 10% of all registered drugs in Czechoslovakia with an ever increasing trend over the last ten years. For economical analysis of consumption of cardiovascular drugs, three methodological approaches (expenditure figures, material units--number of packages and DDD (Defined Daily Dosis), as a technical unit of measurement) were chosen. In the period of 7 years (1980-1986) all three methodologies confirmed the increasing trend of cardiovascular drugs consumption in Czechoslovakia. However, an international comparison of consumption data between Czechoslovakia and Sweden revealed lower levels in Czechoslovakia in this respect.

Extraction of radioactive rubidium and D-glucose from the artificially perfused intervillous space of the human placenta.

Extraction (Et) of 86Rb and [14C]D-glucose from the artificially perfused intervillous space of the human placenta was measured using [3H]L-glucose as a reference tracer. E. of 86Rb increased slowly from initial values near zero to a late maximum, which indicates that Et was greatly influenced by heterogeneity of indicator transit times through the intervillous space. The ascending part of the plot of -1n(I-Et) against time (t) of 86Rb was approximately linear. In each experiment the time corresponding to zero extraction was estimated by linear extrapolation of the plot. The mean of the times obtained in the individual experiments corresponded to the most frequent transit time of the indicators through the system outside the placenta. These observations suggest that 86Rb is taken up by the trophoblast from the entire space perfused. Under such conditions the rate of the trophoblast uptake can be estimated from the slope of the above plot. Unlike that of 86Rb, Et of [14C]D-glucose increased rapidly to a relatively steady level. This time course of Et may result from combined effects of transit time heterogeneity and rapid back-flux of the tracer.

Uptake of inorganic phosphate by the maternal border of the guinea pig placenta.

Mechanism of uptake of inorganic phosphate (Pi) by the maternal border of the dually perfused guinea pig placenta was studied using the paired-tracer dilution technique with 32P-phosphate and 14C-sucrose being the tracers. Placental uptake of radioactive phosphate increased when the concentration of Pi in the perfusion fluid was reduced, and it decreased during anoxia, in presence of CN or during perfusion with low-Na or Na-free fluids. Iodoacetate was without effect. These observations are consistent with placental uptake of Pi being effected by a carrier mediated process dependent on external Na and, partly, on placental metabolism. Unidirectional flux of Pi from the maternal vascular space into the cell compartment of the placenta, estimated from the values of instantaneous extraction of 32P, correlated significantly with foetal weight. The flux per unit weight of the foetus was 17.0 +/- 1.0 nmol X min-1 g-1.

Effects of isoprenaline and orciprenaline on the vascular bed of the mouse placenta.

High doses of isoprenaline or orciprenaline decreased the rate of transfer of tritium-labelled water from mother to fetus. The effect was blocked by propranolol. Maternal blood spaces of the placental labyrinth in the treated animals were congested with masses of red blood cells. These observations suggest that the placental circulation is impaired by high doses of beta-sympathomimetic drugs.

Electrical potential difference across the mid-term human placenta.

Electrical potential difference across the mid-term human placenta was recorded during hysterotomy. The average value registered was 2.7 mV (S.E. of mean=0.4 mV, n=7), fetus negative. From this value and the concentrations of Na, K, Ca, Cl and inorganic phosphate in maternal and fetal plasma the possible mechanisms of net transport from mother to fetus are inferred. It is concluded that of the above ions only the transport of Na is compatible with simple diffusion.

Placental transport of sodium in the guinea-pig.

1. The mechanism of placental transport of Na was studied in guinea-pigs in placentae with intact umbilical blood circulation or in the preparation of the placenta perfused in situ. 2. A constant level of 22Na was maintained in maternal plasma for 60 min, and from the quantity of 22Na recovered from the foetus at the end of this period the influx of Na from mother to foetus was calculated. Ligation of the omphalomesenteric vessels (supplying the everted yolk sac with blood) had no effect on the influx, the corresponding values of influx in the control and treated foetuses being 0-235 +/- 0-020 and 0-247 +/- 0-029 micron-mole/min. g foetal weight (n = 6, the limits are S.E. of mean). The specific activity of Na in amniotic fluid was below that of the maternal or foetal plasma Na by two orders of magnitude. These observations indicate that the extraplacental transport of Na into the foetus is negligibly low. 3. The electrical potential difference (p.d.) and unidirectional fluxes of Na across the placenta perfused in situ were measured by means of 22Na and 24Na administered to the opposite sides of the placental barrier. The fluxes varied with the weight of the foetuses whose placentae were perfused. The flux from the maternal to the foetal side was 0-270 +/- 0-017 micronmole/min.g foetal weight, the flux from the foetal to the maternal side was 0-340 +/- 0-018 micronmole/min.g foetal weight (n = 38). The corresponding p.d. was - 20-7 +/- 1-2 mV (foetal side negative). 4. The active component of Na transport across the placenta was calculated from the unidirectional fluxes and the p.d. The active transport was directed from the foetal to the maternal side, and its rate was 0-211 +/- 0-015 micronmole/min.g foetal weight (n = 38). During perfusion of the placenta with KCN (10(-3) M) the active transport decreased by approximately one third. 5. The flux of Na from the foetal to the maternal side of the perfused placenta was higher than the flux from the maternal to the foetal side. A similar asymmetry of Na fluxes was observed in the non-perfused placenta, the flux from mother to foetus being 0-180 +/- 0-013 micronmole/min.g foetal weight and the flux from foetus to mother 0-235 +/- 0-024 micronmole/min.g foetal weight (n = 12). This indicates that the asymmetry of Na fluxes is caused by the anaesthesia and/or by the trauma of the operation rather than by the perfusion of the placenta. 6. The permeabilities of the perfused placenta to Na and sucrose measured simultaneously from the maternal to the foetal side were 0-0767 +/- 0-0183 and 0-324 +/- 0-0094 cm3/min (n = 7y, respectively. The permeability values bear the same relation to each other as the respective coefficients of free diffusion in water, suggesting that the passive transport of Na across the placenta takes place as simple diffusion through wide aqueous channels. 6...

Effects of potassium cyanide, strophanthin or sodium-free perfusion fluid on the electrical potential difference across the guinea-pig placenta perfused in situ.

1. The possible role of active transport of Na in generating the transplacental potential difference (p.d.) was studied in the guinea-pig placenta perfused in situ by testing the effects of strophanthin or KCN added to the perfusate or of Na-free perfusion fluid.2. The p.d. across the perfused placenta was about -20 mV, and was relatively steady during perfusion.3. Strophanthin (10(-5)M) slightly increased the p.d. In a concentration of 2 x 10(-6)M strophanthin was without significant effect.4. KCN (10(-3)M) decreased the p.d. When KCN was removed after a 30 min treatment the p.d. increased significantly exceeding the initial level. KCN (10(-4)M) slightly increased the p.d.5. Perfusion with Na-free fluid decreased the p.d. to a steady level of about 50-60% of the control values.6. Perfusion with Na-free fluid containing KCN (10(-3)M) for 30 min decreased the p.d. However, the effect did not seem different from the effect of KCN (10(-3)M) or Na-free fluid alone. When KCN was removed the p.d. significantly increased in spite of continued perfusion with Na-free fluid.7. Excepting the effect of KCN (10(-4)M), which could not be explained, the observations were found to be consistent with active transport of Na from foetal to maternal side of the placenta as a source of the p.d. The Na transport could account for about 40-50% of the p.d.