The relation of the accumulation of cadmium in human placenta to the intake of high-fibre grains and maternal iron status.

Exposure to cadmium via the diet is known to depend to a large extent on the intake of cereal grains, particularly the high-fibre fractions of wheat. Subjects with low iron status absorb more cadmium than those with better iron status. The purpose of the present study was to determine to what extent cadmium accumulation in human placenta is affected by the intake of grain fibre and maternal iron status during pregnancy. Thirty-nine pregnant women participated in the study. In each trimester the women were requested to complete a dietary history and to allow blood samples to be taken for haemoglobin, serum ferritin and serum thiocyanate determinations, the latter as a marker for smoking. At delivery the whole placenta was taken for the determination of the cadmium concentration. The 32 women who had serum thiocyanate levels less than 70 mumol/l, who had completed at least one dietary history and from whom a blood sample was obtained in the third trimester, were included in the final statistical analyses. In the group of women who consumed less than the median intake of grain fibre and had more than 15 micrograms ferritin/l serum in the third trimester, the placenta cadmium concentration was nearly half that in the placentae of women who had consumed more grain fibre or had lower iron status in late pregnancy.     

Studies on Propafenone-type Modulators of Multidrug-Resistance IV: Synthesis and Pharmacological Activity of 5-Hydroxy and 5-Benzyloxy Derivatives

A series of 5-hydroxy and 5-benzyloxy analogs of the antiarrhythmic and multidrug resistance (MDR) modulating drug propafenone was synthesized and the MDR-modulating activity of the compounds was evaluated using a daunomycin efflux assay system. The key step of the synthesis is the selective reduction of the double bond in 1 without cleavage of the benzyl group thus leading to the phenol 3 . Alkylation with epichlorohydrine followed by nucleophilic epoxide ring opening gave the benzylated target compounds 5a–d . Subsequent cleavage of the benzyl group gave the 5-hydroxy analogs 6a–d . Structure activity relationship studies showed, that the 5-hydroxy derivates 6a–d fit the log P/log potency correlation line previously established for a series of propafenone analogs. In contrast, all four 5-benzyloxy analogs 5a–d showed almost identical EC₅₀ values, independent of their log P value.     

Electro-encephalographic disturbances due to chronic toxin abuse in young people, with special reference to glue-sniffing

A study was carried out in order to document any abnormalities in the electro-encephalogram (EEG) that might appear in young adolescents who have deliberately inhaled the range of volatile substances loosely referred to as 'glue'. The EEGs of a group of 'street children' being assisted in a Johannesburg shelter were examined. The records were analysed for any clinical abnormalities and also subjected to spectral analysis in order to examine the overall characteristics of frequency, power and spatial distribution. The EEGs clearly revealed that, although at the time of the examination the subjects were ostensibly abstinent, both clinical and normative evidence of continuing brain disturbance was present. It was concluded that glue sniffing is likely to have long term electrocerebral sequelae.     

5-HT-receptor-induced changes of the intracellular cAMP level monitored by a hyperpolarization-activated cation channel

The HvCNG channel from the moth Heliothis virescens is highly sensitive to cAMP concentrations ranging between 0.1 microM and 5 microM. This HvCNG channel was over-expressed in Spodoptera frugiperda (Sf.9) cells to measure endogenous cAMP levels. Hyperpolarization-activated inward currents were measured in the whole-cell patch-clamp configuration with pipettes filled with different cAMP concentrations to calibrate the system. Varying the cAMP concentration between 0 microM and 100 microM in the pipette, the half-maximal activation voltage ( V1/2) was shifted by +28.5+/-1.7 mV. The activation time constant (tau(a)) was used as a parameter for cAMP quantification because it was independent of the expression level of HvCNG channels. tau(a) changed from 1106+/-60 ms at 0 microM cAMP to 265+/-7 ms at a saturating concentration of 1 mM cAMP. A dose-response relationship yielded values of 0.6 microM for the half-maximal cAMP concentration and 1.5 for the Hill coefficient. Activation of endogenous adenylyl cyclases by 50 microM forskolin induced an elevation of the cAMP level by about 1.6+/-0.2 microM. Co-expressions of HvCNG channels in combination with the mouse 5-HT4a- or 5-HT1A- receptors and the corresponding Gs- or Gi-proteins were successful and allowed us to also verify receptor-induced changes of the cAMP level. Stimulation of m5-HT4a-receptors by 0.1 microM 5-HT induced an increase of cAMP of about 4.6+/-1.5 microM, whereas cAMP levels decreased from a control value of 1+/-0.2 microM to 0.41+/-0.1 microM after stimulation of the m5-HT1A-receptors.