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J P Petit

Publications and source records attributed to J P Petit.

At least 19 recordsLinked to original sources

Regulation of bone resorption and osteoclast survival by nitric oxide: possible involvement of NMDA-receptor.

Nitric oxide has been shown to play an important role in regulation of bone resorption. However, the role of endogenous nitric oxide on osteoclast activity remains still controversial. In this work, using RT-PCR amplification, we demonstrated that rabbit mature osteoclasts express mRNA encoding for neuronal nitric oxide synthase suggesting that this enzyme could be involved in basal nitric oxide production in these cells. Then we assessed the effect of carboxy-PTIO, a nitric oxide scavenger, on in vitro bone resorption and osteoclast survival. Carboxy-PTIO (10-100 microM) inhibited osteoclastic bone resorption in a dose dependent manner and induced osteoclast apoptosis by a mechanism involving caspase 3 activation. These results suggest that basal concentration of endogenous nitric oxide may be essential for normal bone resorption by supporting osteoclast survival. Because osteoclasts express N-methyl-d-aspartate-receptor (NMDA-R), we hypothesized that in osteoclasts NMDA-R may be involved in nitric oxide production as in neuronal cells. We confirmed that blockade of NMDA-R with specific non-competitive antagonists, MK801 and DEP, strongly inhibited bone resorption. As for carboxy-PTIO, we showed that blockade of NMDA-R by both antagonists induced osteoclast apoptosis in a dose dependent manner by a mechanism dependent on caspase 3 activation. Intracellular calcium concentration in osteoclasts decreased within minutes in the presence of both antagonists. Finally, MK801-induced osteoclast apoptosis was partially reversed in the presence of small amount of SNAP (100 nM), a nitric oxide donor, suggesting that the effect of NMDA-R on osteoclast apoptotic cell death could be due to a decrease in nitric oxide production. Taken together, our results are consistent with the hypothesis that NMDA-R on osteoclasts could have a similar function as those in neuronal cells, i.e., to allow a calcium influx, which in turn activates a constitutive neuronal nitric oxide synthase. Nitric oxide generated by this pathway may be essential for osteoclast survival and hence for normal bone resorption.

Animals↗

Asymmetric synthesis of novel isoindolines: azasaccharide mimics as potential enzyme inhibitors.

2',3'-Dideoxy-2',3'-didehydronucleosides and azasaccharides are known to possess antiviral activity. The synthesized 1-methoxyisoindoline system (10), which is related to the above nucleosides, is potentially stable in-vivo. The 1-methoxyisoindoline was synthesized from the achiral phthalaldehyde in 10 steps via an enantiomerically pure diol obtained by Sharpless asymmetric dihydroxylation. The new heterocyclic compound is an azosaccharide mimic which provides an access to a new series of nucleoside analogues with potential as antiretroviral agents (anti-HIV) and as glycosidase inhibitors.

Dideoxynucleosides↗

[Functioning of an organ procurement center in Bordeau].

The ever increasing practice of transplantation requires the creation of units specialized in the reception of potential organ donors. The functioning of the organ procurement centre at Bordeaux is described, and the results of 100 procurements performed over a 27-month period are reported. The technical support (electroencephalography, laboratories, etc.) ensures that the donors are under permanent care. Recipients chosen in priority are "super-emergencies" and local patients. One half of the 100 donors came from the Gironde department and the others from 6 neighbouring departments. Procurement takes place 6 hours on average after the 2nd inactive electroencephalogram, and it is multiple in 87 per cent of the cases. Two hundred and fifty-two organs were obtained, including 166 kidneys (8 of which were not utilized), 50 hearts and 36 livers; 55 per cent remained in Bordeaux and 45 per cent were sent to other parts of France or abroad. The cerebral death reception centre must be self-sufficient, independent and permanently accessible. Ideally, local co-ordination is ensured by a physician. Procurements in peripheral hospital are possible but difficult to organize. A greater sensitization, a better regional collaboration and a widening of the criteria used in the selection of donors should result in a further increase in the number of multiple organ procurements.

Adolescent↗

Effects of amine pretreatment on ketamine catatonia in pinealectomized or hypophysectomized animals.

The present studies were designed to clarify the role of catecholamines and pineal idolamines on ketamine-induced catatonia in the intact, pinealectomized or hypophysectomized chick and rat. In the pinealectomized chick, pretreatment with dopamine increased the duration of catatonia (DOC) after ketamine, but pretreatment with norepinephrine did not. The pineal indolamines exhibited mixed actions. Serotonin and N-acetyl serotonin which augmented ketamine DOC, did not do so in the absence of the pineal gland, whereas melatonin potentiated the ketamine DOC in both the intact and pinealectomized chick. Ketamine was more potent in the hypophysectomized chick and the circadian rhythm noted in the intact chick was absent; furthermore, melatonin did not augment the ketamine DOC whereas dopamine continued to do so. This study did not demonstrate a species difference regarding the role of the amines on the pineal in spite of the immature blood-brain barrier in the young chick and the intact barrier in the rat. In addition, these data indicate a direct role of the pituitary in the augmentation of ketamine DOC induced by melatonin. Furthermore, dopamine appeared to act on systems more closely involved with the induction of ketamine catatonia rather than directly on the pituitary.

Amines↗