Publications by authors named "Capdevila J"

Arachidonic acid (AA) is oxidized via three pathways which result in several series of distinct metabolites. Cyclooxygenase produces prostaglandins (PGs), prostacyclins, and thromboxanes. Lipoxygenase produces hydroperoxy/hydroxyeicosatetraenoic acids (HPETE/HETEs) and leukotrienes.

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Microsomal fractions isolated from rat anterior pituitary glands catalyze the oxygenation of arachidonic acid. By a combination of chromatographic and mass spectrometric techniques, we have identified epoxyeicosatrienoic acids as reaction products and thus documented the presence of an NADPH-dependent arachidonic acid epoxygenase activity in rat adenohypophysis.

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Acute gonococcal urethritis was treated with a single oral dose of 2.5 g of thiamphenicol in 62 patients after diagnosis by gram-staining of urethral smears and/or cultures for Neisseria gonorrhoeae in Thayer-Martin medium. Therapy resulted in bacteriologic and clinical cure in 50 cases.

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Epoxyeicosatrienoic acids have been isolated and purified from the livers of male rats. They were identified by gas chromatography-mass spectrometric techniques. These results expand the list of in vivo-produced eicosanoids.

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The mechanistic plurality of the microsomal cytochrome P-450 enzyme system is illustrated by studies of the oxidative metabolism of benzo[a]pyrene, 3-hydroxybenzo[a]pyrene and arachidonic acid. Rat liver microsomal metabolism of benzo[a]pyrene or 3-hydroxy-benzo[a]pyrene, supported by cumene hydroperoxide, generates benzo[a]pyrene quinones via molecular oxygen-dependent and -independent pathways. Arachidonic acid is metabolized by rat liver microsomal fractions to a variety of oxygenated products, including cis-trans diene conjugated monohydroxy-acids, epoxy-acids as well as omega- and omega-1-oxidation products.

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Metapyrone and eicosatetraynoic acid but not indomethacin are effective inhibitors of the secretory response of isolated rat pancreatic islets to arginine and glucose. Epoxyeicosatrienoic acids, products of the cytochrome P-450-NADPH dependent arachidonic acid epoxygenase activity, are potent and selective mediators for the in vitro release of either insulin or glucagon from preparations of isolated rat pancreatic islets.

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The 5,6-; 8,9-; 11,12- and 14,15-epoxyeicosatrienoic acids and their respective hydration products, the vic-diols, recently reported as metabolites of arachidonic acid in rat liver microsomes, were examined for effect on release of 45Ca from canine aortic smooth muscle microsomes. At 10(-6) M, the diols had no effect, but the 5,6-; 11,12- and 14,15-epoxyacids increased the loss of 45Ca. Further studies with the 14,15-epoxyacid demonstrated a dose-dependent decrease of Ca++ uptake (ATP present) in canine aortic microsomes in 0.

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Adenosine deaminase (ADA) activity was studied in 221 patients with pleuroperitoneal effusions. Patients were subdivided into the following six groups: (1) 48 cases of tuberculosis; (2) 46 with malignancies; (3) 30 postpneumonic effusions; (4) 19 cases of several diseases; (5) 18 patients with pleural effusions of unknown origin; and (6) 60 with acellular transudates. Mean ADA activity was 92.

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Arachidonic acid (AA) stimulates the in vitro release of somatostatin (SRIF) from the hypothalamic median eminence (ME). This effect is inhibited by 5, 8, 11, 14-eicosatetraynoic acid (ETYA) but not by indomethacin (ID). Microsomal fractions from the rat hypothalamus catalyze an NADPH-dependent metabolism of AA to form several oxygenated products of which the major metabolites are 5, 6-epoxyeicosatrienoic acid (5, 6-EET) and its hydration product, 5, 6-dihydroxyeicosatrienoic acid (5, 6-DHET).

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Epoxyeicosatrienoic acids, formed during the cytochrome P-450-catalyzed oxidation of arachidonic acid, react with a liver cytosolic epoxide hydrolase to form vicinal diols of eicosatrienoic acid. The role of this cytosolic enzyme, rather than a microsomal bound type, explains previous results illustrating the ability to accumulate epoxides during the in vitro aerobic steady state of oxidative metabolism of arachidonic acid by liver microsomes. The inability of the 5,6-epoxyeicosatrienoic acid to serve as a suitable substrate for this enzyme is discussed in light of recent studies concerning possible unique physiological functions for this metabolite.

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Anterior pituitary cells were incubated in the presence of luteinizing hormone-releasing hormone and one of three inhibitors of arachidonic acid metabolism:indomethacin, an inhibitor of the cyclooxygenase system; nordihydroguaiaretic acid, an antioxidant that inhibits lipoxygenase; and icosatetraynoic acid, an acetylenic analogue of arachidonic acid that blocks all known pathways of arachidonic acid metabolism. Indomethacin was ineffective in blocking luteinizing hormone-releasing hormone-stimulated luteinizing hormone secretion. Nordihydroguaiaretic acid was only marginally capable of inhibiting luteinizing hormone-releasing hormone-stimulated luteinizing hormone secretion.

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