B Acad Nat Med Paris
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B Acad Nat Med Paris · Jan 1998
Review[Interactions between central opioidergic and cholecystokininergic systems in rats: possible significance for the development of of opioid tolerance].
Numerous data suggest that cholecystokinin (CCK) acts as an opioid-modulating peptide. Because pharmacological and behavioural studies have shown that CCK reduces the analgesic effects of opioids, an opioid-mediated activation of CCK-containing neurones has been proposed to be responsible for the development of opioid tolerance. In an attempt to directly assess this hypothesis, we have examined, in naive or morphine-tolerant/dependent rats, the possible influence of opioid-receptor ligands on--1 the release of CCK from spinal cord slices and--2 the extracellular levels of CCK in the frontal cortex in awake, freely moving animals. ⋯ In contrast, the delta 2-mediated increase in CCK release persisted. Thus, in morphine-tolerant/dependent rats, opioids apparently retain only their excitatory effects on CCK-containing neurones. These data support the idea that morphine exerts an excitatory influence on central CCKergic neurones, which could tend to reduce the analgesic action of the alkaloid, and are in line with the hypothesis that morphine tolerance/dependence is associated with an activation of CCK-containing neurones.
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B Acad Nat Med Paris · Jan 1998
Review[Arsenic and retinoic acid, towards targeted treatments of acute promyelocytic leukemia?].
Acute promyelocytic leukaemia is a key model system in cancer biology. Its exquisite sensitivity to retinoic acid constitutes the first example of differentiation therapy. ⋯ The fusion protein also delocalizes PML and other nuclear body antigens and this alteration of nuclear protein traffic seems to play a role in growth control and apoptosis. The clinical response of this disease to retinoids and arsenic trioxide, both of which induce the degradation of the fusion protein, constitute the first example of a therapy directly targeted to a specific genetic lesion in a human cancer.
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B Acad Nat Med Paris · Jan 1998
Case Reports[A new inherited metabolic disease: delta1-pyrroline 5-carboxylate synthetase deficiency].
delta 1-pyrroline 5-carboxylate synthetase (P5C synthetase) catalyzes the ATP and the NAD(P)H-dependent conversion of L-glutamate to glutamate semialdehyde (GSA) which is the metabolic precursor for proline biosynthesis. We described in two siblings a paradoxical hyperammonemia with hypoprolinemia and hypoornithinemia associated to bilateral cataract, mental retardation, joint laxity and skin hyperelasticity. ⋯ Both patients are homozygous for an L396S substitution, this amino acid being highly conserved across species. This is the first report of a P5C synthetase deficiency in human.