Hepato- and thyreotoxicity of tifemoxone.

The oral toxicity of Tifemoxone, phenoxymethyl-6 tetrahydroxazine-1, 3 thione-2, a new potential antidepressant was studied during 6 months in rats at 30, 85 and 230 mg/kg/d and in beagle dogs at 10, 55 and 300 mg/kg/d. Thyroid hyperplasia and hypoactivity were observed in the rats and dogs plasma triiodothyronine, determined in dogs, was modified. A dose dependent hepatotoxic effect was observed in the rats and dogs. In dogs at low dose, one animal died after B.S.P. test. Water consumption and urinary volume increased, weight loss and anemia appeared at high doses in both rats and dogs. Hair loss was observed in rats and convulsions in dogs. In conclusion, Tifemoxone like tetrahydroxazine thione and some derivatives caused thyreotoxicity, hairlessness and increased in water comsumption and diuresis and in addition it had strong hepatotoxic effect especially in the dog.     

In vivo distribution of carrier protein/67Ga-complexes

The uptake of 67Ga as citrate, chloride and complexed by carrier-proteins (lactoferrin and transferrin) has been studied in tumor- and inflammatory lesion-bearing rats. Different uptake patterns are shown by tumors and lesions. 67Ga-transferrin complexes are taken up to the highest extent by tumors and inflammatory lesions. The comparative distribution studies using normal animals indicate a systemic increase of 67Ga uptake by tumor- and lesion-bearing animals which might be of importance in explaining the mechanism of 67Ga accumulation. The role of ionic environment changes and radioactivity concentration by isomorphous ionic replacement is discussed.     

Percutaneous transluminal angioplasty of stenotic lesions in dialysis vascular accesses

Forty-five stenoses behind arteriovenous fistulas in 35' haemodialysed patients were treated with percutaneous transluminal angioplasty (PTA). Immediate stenoses dilatation results in relation to the AVF type were haemodynamically significant in 40 cases (88%), with poorer results on bovine heterograft stenoses. Dilatation results in relation to the site of the lesion showed haemodynamically efficient angioplasty on stenoses next to the anastomosis (67.5%) but a poor result on distal lesions (4 cases). We observed 4 cases of thrombosis but 2 recovered after treatment, one after local fibrinolytic perfusion one after surgical thrombectomy. Follow-up over a period of one to 18 months (mean 8 months) including angiography and appreciation of the dialysis quality were performed in 30 patients who had a successful dilatation. PTA appears to be a technically feasible and clinically effective method of treating stenoses lying on the venous limb fistula in patients on chronic haemodialysis.     

SPECT analysis of recent cerebral infarction

We measured regional cerebral blood flow and [123I]iodoamphetamine (IMP) uptake in 16 patients with unilateral brain infarcts during the subacute period (Day 3 to Day 50) and again after 3 months. Our results show that the central and peripheral areas described earlier in the chronic period were already differentiated in the subacute period. The central area presented a short phase of luxury perfusion and a longer phase of IMP hyperfixation. The peripheral area showed both a slight regional cerebral blood flow decrease and an early IMP uptake decrease similar to those previously found in the chronic period. Contralateral regional cerebral blood flow during the subacute period, considered normal, was significantly lower than that during the chronic period.     

Complete sequence of a cDNA encoding an active rat choline acetyltransferase: a tool to investigate the plasticity of cholinergic phenotype expression

A cDNA clone encoding the complete sequence of an active rat choline acetyltransferase (ChoAcTase; acetyl-CoA:choline O-acetyltransferase, EC 2.3.1.6) has been isolated. Analysis of the deduced amino acid sequence reveals 85% and 31% identity with the porcine and Drosophila melanogaster enzymes, respectively. To further elucidate the molecular basis of neurotransmitter-related phenotypic plasticity, the expression of ChoAcTase mRNA was compared with that of tyrosine hydroxylase [TH; tyrosine 3-monooxygenase, L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2], in neurons from superior cervical ganglia grown in the following conditions: 1) normal medium, 2) high K+ medium, and 3) normal medium supplemented with 50% muscle-conditioned medium (CM). TH mRNA was expressed in all three media; its level rose in high K+ and decreased strikingly in the presence of CM. ChoAcTase mRNA could be visualized in CM, but fell to undetectable levels in normal and high K+ media. These results suggest that translational or post-translational mechanisms do not play a major role for the modulation of neurotransmitter-associated phenotype.     

Comparative action of fenfluramine on the uptake and release of serotonin and dopamine.

The anorectic agent, fenfluramine, proves to be a good inhibitor of serotonin uptake in vitro, in synaptosomes from rat whole brain (IC50 = 8.5 +/- 0.6 X 10(-7) M). After administration in vivo, its inhibitory activity in vitro equals that of chlorimipramine and in contrast to the latter, its effect is of long duration. Fenfluramine is also effective in promoting the release of serotonin from pre-loaded synaptosomes. In comparison, the structurally related compound, amphetamine, has little activity with respect to these serotonin mechanisms. It is, however, active both in inhibiting the uptake of dopamine and in promoting its release, whereas fenfluramine is inactive. The implication of these mechanisms in the serotonin-depleting capacity as well as in the anorectic activity of fenfluramine is discussed.     

Molecular basis for the use of steroids in psychiatry (author's transl)

In animals, estrogens and progestins modulate food intake, running wheel activity and sexual behavior, androgens stimulate sexual behavior and aggression, and corticoids influence cerebral electrolyte regulation, sleep and memory. In this and other studies, we have established that soluble receptors binding steroid hormones are present, often in high concentration, in various central structures such as hypothalamus, cortex, hippocampus and amygdala and have shown that some of the effects of steroids on behavior can be related to their interaction with these receptors and the resultant biochemical events. Thus, in the rat, the induction of sexual behavior by estrogens and progesterone can be related to the increase in progestin receptor induced in the hypothalamus by estrogens. The action of glucocorticoids has been implicated in memory processes involving protein synthesis and this study shows that glucocorticoids stimulate protein synthesis in the cortex of hypophysectomized rats, a structure rich in glucocorticoid receptors. Since the hormonal specificity of receptor binding is similar in peripheral and central target tissues, it is suggested that competition experiments on a peripheral target tissue can be used as a simple test to select compounds (agonists or antagonists) able to replace endogenous hormones at the receptor site in the treatment of psychiatric disorders due to endocrine dysfunction (hormone deficit or excess).