Differential scanning calorimetry study of the interaction of antidepressant drugs, noradrenaline, and 5-hydroxytryptamine with a membrane model.

Differential scanning calorimetry was used to study the interaction of a membrane model with two neuromediators [noradrenaline and 5-hydroxytryptamine (Serotonin)] and four antidepressant drugs (imipramine, indalpine, citalopram, and milnacipran), known to be uptake inhibitors of these neuromediators. The study was carried out on dipalmitoyl phosphatidylcholine liposomes, a bilayer phospholipid system taken as a simplified model of biological membranes. Analysis of the thermograms led us to classify the molecules according to their lipophilic action, as in the conventional measurement of the water-octanol partition coefficient, and also enabled us to precisely determine their location along the phospholipid bilayer. A hypothesis based on this localization is put forward concerning the competitive, or otherwise, character of the blocking of uptake of the neuromediators. The extreme cases of interaction and localization of imipramine and milnacipran, a new antidepressant, relative to the bilayer are also analyzed in terms of side effects.

Influence of cadmium on the chain dynamics of collagen in rat tail tendon.

The molecular mobility of the chain dynamics of collagen was investigated by the thermally stimulated creep method on rat tail tendon after oral administration of cadmium (8 mg.kg-1.day-1) for six weeks. The high resolving power of the technique shows two manifestations of the pseudolathyrogen effect of cadmium: the polar side-chains of collagen, mobile in the immature specimen, which are cross-linked and so immobile in the mature specimen, remain mobile in the cadmium-treated mature specimen. There is also a subsequent decrease in the number of water molecules linked by two hydrogen atoms bound to the tropocollagen molecules. Probably these molecular modifications inhibit mineralization of the organic matrix and so osteogenesis.

Alkaline phosphatase and bone calcium parameters.

Effects of cadmium, an alkaline phosphatase inhibitor, on the calcium content of rat bone were investigated in vivo by a radioisotopic method. Disturbance of bone metabolism is observed in both the superficial (delta) and slow exchanges (Ve), which are also significantly decreased. The crystallized calcium bone compartment (E) is also strongly affected. It appears that changes in the superficial calcium exchanges cause the observed decrease in the crystallized calcium mass. The slowing of osteogenesis is confirmed by the decrease of serum alkaline phosphatase activity. A statistical examination of the correlation coefficient reveals a close link (P less than 0.01) between serum alkaline phosphatase activity and the influx of superficial calcium (Vo+) and, as a result, the crystallized bone calcium parameters. These results show that cadmium can be used to study the relationship between alkaline phosphatase and calcification. The present observations allow us to consider the possibility that alkaline phosphatase may play a role in determining the calcium content of the crystallized phases in deep bone through its action on the tissue surface.

Intestinal calcium absorption in the rat after oral Tween 80 administration.

Calcium absorption into rat intestine was investigated in vitro and in vivo after oral administration of Tween 80 (Polyoxyethylene (20) sorbitan monooleate). The in vivo study showed a significant decrease in serum calcium and in the quantity of calcium excreted by the intestine. In vitro, measurement of calcium influx into slices of intestine taken from Tween 80 treated animals showed that passive calcium diffusion was unchanged and that a decrease in the active transport alone is responsible for reduction in total calcium influx. Lineweaver-Burk analysis of the saturable component of calcium flux showed that the main variation was not due to a change of affinity of the system for the calcium but a decrease of the maximal calcium influx. Thus there are some arguments in favor of non-specific modifications of intestinal medium affecting calcium bioavailability rather than a specific action on the carrier.

Effects of 1.25 dihydroxyvitamin D3 on calcium metabolism in rats exposed to cadmium.

The radioisotopic study of calcium metabolism in the rat after chronic oral administration of cadmium (8 mg/kg) has shown two different effects: a) in the intestine cadmium inhibits the absorption of calcium by active transport; b) in the deep bone compartment, the decrease of the bone calcium used for the crystallization goes together with a reduction of the exchange rates between this compartment and the central compartment (serum extracellular and soft tissues calcium). The simultaneous oral administration of 1.25 dihydroxyvitamin D3 (80 ng/kg) even though it increases significantly the calcium intestinal absorption factor does not allow the various parameters of bone calcium metabolism to stay within normal values. In spite of the arrest of osteolysis and of an strong increase of osteogenesis (superficial bone balances and alkaline phosphatases) the loss of calcium caused by cadmium in the deep bone is not compensated.

[Influence of cadmium on calcium metabolism. Effect on cytochrome P450 (author's transl)]. / Infuence du cadmium sur le métabolisme du calcium. Action sur le cytochrome P450.

Oral administration of cadmium to female rats for 6 weeks does not reduce the microsomal cytochrome P450 levels in the liver and kidneys, nor the cytochrome P450 content in the renal mitochondria.

Effects of 1.25 dihydroxyvitamin D3 on calcium uptake, into rat intestine after chronic oral cadmium administration.

Calcium influx into rat intestine was investigated, in vitro, after cadmium chronic oral exposure. In active calcium transport, pretreatment by 1.25 dihydroxyvitamin D3 prevents the effect of cadmium on the maximal influx value Jm and leads to an increase of the half-saturation constant Kt.

[Determination of bone calcium: correlation between results of compartmental analysis and neutron activation analysis]. / Mesure du calcium osseux: corrélation entre les résultats de la détermination par analyse compartimentale et du dosage par activation neutronique.

In cadmium exposed Rats correlation analysis of calcium deep bone assessed by compartimental analysis and results of bone calcium determination by neutron activation shows a significative relationship between both values.