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J Fontagné

Publications and source records attributed to J Fontagné.

At least 19 recordsLinked to original sources

Ornithine alpha-ketoglutarate counteracts the decrease of liver cytochrome P-450 content in burned rats.

The effect of ornithine alpha-ketoglutarate (OKG) on cytochrome P-450 enzyme activities was studied in a well-defined model of injury (burn followed by fasting then subsequent hypocaloric diet) administered to young rats for 3 d. Hepatic microsomes were prepared by ultracentrifugation and levels of cytochromes P-450 were determined spectrophotometrically. The activities of ethoxy-resorufin-O-deethylase (EROD), benzyloxy-resorufin-O-dealkylase (BROD), and erythromycin demethylase were measured as markers of P-450 1A, 2A, and 3A isotypes respectively. The level of total hepatic microsomal proteins (8 mg/mL) remained constant. The level of cytochrome P-450 (1.14+/-0.08 nmol/mg microsomal proteins) was decreased by a hypocaloric diet (23%, P = 0.003) and burn further enhanced this phenomenon (15%, P = 0.03). Both healthy and burned rats receiving OKG showed the same level of cytochrome P-450 as the rats fed ad libitum. OKG supplementation counteracted the enhancement (40%) of EROD activity induced by hypocaloric diet but did not influence BROD and erythromycin demethylase activities. OKG sustained cytochrome P-450 levels in rats fed a hypocaloric diet, even after burning. These findings indicate that OKG may favor drug metabolism in this injured population.

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Immunomodulatory effects of ornithine alpha-ketoglutarate in rats with burn injuries.

OBJECTIVE: To investigate the influence of enterally administered ornithine alpha-ketoglutarate (OKG) on muscular amino acid content, eicosanoid release, and polymorphonuclear leukocyte responsiveness after induction of burn injury in rats. DESIGN: Experimental trial. MATERIALS AND METHODS: Four groups of rats were considered: (1) healthy rats that received a standard diet supplemented with 5 g/kg per day of OKG; (2) rats with burn injuries that received the same nutrition as group 1; (3) healthy rats that received standard diet supplemented with glycine in an isonitrogenous amount relative to OKG; and (4) rats with burn injuries that received the same nutrition as group 3. The thymus and 1 skeletal muscle were weighed. The oxidative metabolism of pleural polymorphonuclear leukocytes was measured by means of superoxide generation (O2-) and the chemiluminescent response to opsonized zymosan. Prostaglandin E2 and 6-keto-prostaglandin F1 alpha were measured in the supernatants of pleural and peritoneal cells. RESULTS: The weights of the thymus and the muscle from healthy rats were similar. Those of rats from group 4 were significantly lower (P < .05), whereas those of rats from group 2 were not. Metabolism of OKG led to enhanced amounts of arginine and glutamine in skeletal muscle. The metabolic bursts of polymorphonuclear leukocytes from healthy rats were similar. Those of glycine-treated rats with burn injuries were significantly depressed (P < .05), whereas those of the OKG-treated group were not. Pleural and peritoneal cells from the rats with burn injuries that received OKG generated significantly more prostaglandins (P < .01) than did cells from the other groups of rats. CONCLUSION: Ornithine alpha-ketoglutarate administered to rats with burn injuries displays immunomodulatory properties that can enhance host-defense mechanisms in animals that are affected by a severe injury.

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Studies on in vitro colony formation by mouse bone marrow cells using different inflammatory pleural exudates. Relation to colony stimulating factor (CSF).

An inflammatory exudate obtained in Swiss mice 3 hours after intrapleural injection of dextran was able to increase the number of cultivated peritoneal macrophages in S phase. This exudate was also able to stimulate the formation of colonies from mice bone marrow progenitors of macrophages and granulocytes in methylcellulose culture. The stimulating activity of this acute inflammatory exudate was compared with that of colony stimulating factor (GM.CSF). The qualitative and quantitative results showed that the biological activity of the mitogenic factor of this inflammatory exudate, inflammatory mitogenic factor (IMF) was very close to GM.CSF at optimal concentration, but when used at the same concentration, the exudate was less active than GM.CSF. A stimulating activity was also found with another inflammatory pleural exudate induced by calcium pyrophosphate. The comparative kinetics of the action of the two exudates on CFUc appeared alike but the rise was earlier with calcium pyrophosphate. These results suggest the release of a growth factor for monocyte-macrophage in different acute inflammatory exudates.

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Effect of in vitro treatment with indomethacin on mouse granulocyte-macrophage colony-forming cells in culture (CFUC). Possible role of prostaglandins.

The effect of indomethacin (6 mg/kg daily orally for 2, 3 or 4 days) on myelopoiesis was studied in mice by estimating 1) differential cell counts of bone marrow, 2) proliferation of the CFUC in presence of GM-CSF, 3) proliferative state of CFUC after tritiated thymidine suicide. After 4 days of treatment, a rise in the recognizable myeloid precursors, an increase of both the colony forming capacity and the number of CFUC in S-phase were observed. These data suggest that indomethacin produced an hyperplasia of the committed stem cell compartment. The decrease of PGE2 amounts in bone marrow cells following treatment with indomethacin could explain the hyperplasia observed. These in vivo results are in accordance with the in vitro data which show that PG could control the proliferation and differentiation of myeloid progenitor cells.

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Effect of human chorionic gonadotrophin on phagocytic activity and proliferative capacity of rat peritoneal macrophages in culture.

Human chorionic gonadotrophic hormone (hCG) decreased phagocytosis of rat peritoneal macrophages in culture and also inhibited their capacity to be stimulated by an inflammatory exudate. Both effects were related to the concentration used. These experimental results suggest that elevated levels of hCG may play a role in the prevention of the rejection of the foetal allograft by the maternal host.

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[Stimulation of the growth of murine bone marrow colonies in vitro by an acute inflammatory exudate. Comparison with colony stimulating factor CSF)].

Formation of colonies from mice bone marrow progenitors of macrophages and granulocytes in methylcellulose culture was induced by an inflammatory pleural exudate obtained from mice injected with dextran. Mitogenic activity of this acute inflammatory exudate was compared with that of colony stimulating factor (CSF). It was found that colony and cluster counts, during 10 days of culture, were similar with the two types of stimulating factors. When used at the same dose, exudate was less active than CSF. It was concluded that inflammatory exudate showed an activity similar to that of CSF but contained a smaller amount of stimulating factor. Further cytochemical studies are necessary to specify whether or not the two factors induced the same type of colonies (monocytic or granulocytic).

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[Modification of chromatin condensation in cultured macrophages during induction of cell division by an inflammatory exudate].

The determination of chromatin condensation in rat peritoneal macrophages in culture showed a predominance of heterochromatin with low transcriptory activity. After induction of division in rat peritoneal macrophages in culture by an acute inflammatory exudate, a decrease of heterochromatin and an increase of euchromatin were observed. This result brings further evidence to support previous observations according to which this type of exudate shows mitogenic properties.

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Induction of DNA synthesis in rat peritoneal macrophages in culture by a pleural inflammatory exudate.

Peritoneal macrophages in culture are blocked in the G0 phase of the cell cycle, but retain many of their functional characteristics such as phagocytic ability. Peritoneal macrophages have been thought to be a terminal cell type. It has been investigated whether such properties could be modified by a substance released in acute inflammatory exudates. For this purpose a pleural exudate obtained from rats injected with dextran (40,000) 4 hours before, was centrifuged to eliminate cells, sterilized by filtration on Millipore filter 0.22 mum and diluted 50% with 199 medium culture. This medium was used to treat normal and activated peritoneal macrophages in culture. The effects were observed 24, 48, 72, 96 hours after the beginning of treatment. An enhancement of spreading and capacity of phagocytosis was observed 24 hours after the beginning of treatment. After 48 hours, the number of cells incorporating tritiated thymidine increased and became highest 4 days later. These phenomena were also obtained with pleural exudate of inbred rats (Lewis, Wag) treating macrophages of the same strain and with rat pleural exudate treating mouse macrophages. No effects were observed with dextran alone. The chemical nature of the stimulatory factor remains to be elucidated.

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[The effect of prostaglandins E1 and A2 on the proliferation and phagocytosis of mouse peritoneal macrophages in culture].

The action of prostaglandins E1 and A2 was studied on the proliferation and the phagocytosis of mouse peritoneal macrophages in culture. The proliferation was not stimulated by prostaglandins E1 and A2, but the phagocytosis was increased by prostaglandin A2 and decreased by prostaglandin E1. These actions could be correlated with the regulatory role of prostaglandins.

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