D Alber

University of Franche-Comté, Becoinson, Franche-Comté, France

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Publications (16)15.68 Total impact

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    ABSTRACT: Given the often reported relationships between sleep-wake regulation and the cerebral prostaglandins (PGs), the effect of chronic rapid eye movement (REM) sleep deprivation on brain PGE2 and PGD2 biosynthesis in mouse was evaluated, since they are known to have opposite actions as respectively wake- and sleep-inducing substances. Mice were subjected to 5 and 10 days of REM sleep deprivation by the flower pot technique. After sacrifice, PGE2 and PGD2 were determined in the pituitary, hypothalamus and hippocampus. Except in the pituitary where no changes were shown, the PGE2/PGD2 ratio was significantly enhanced after 5 and 10 days of REM sleep loss, when compared to control. These results showed an alteration of cerebral PGE2 and PGD2 biosynthesis, resulting in a shift from PGD2 toward PGE2. These results were not consistent with a role of PGD2 as a sleep-promoting substance as, if that was the case, it would be increased during the REM sleep deprivation. But they do not rule out its involvement as a facilitating substance.
    Prostaglandins Leukotrienes and Essential Fatty Acids 12/1994; 51(5):369-72. · 1.98 Impact Factor
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    ABSTRACT: To investigate the blood pressure lowering effect of magnesium (Mg2+) in the hypertensive rat, we measured the prostacyclin release (PGI2, as immunoreactive 6-keto-PGF1 alpha) by isolated aortae from normotensive and deoxycorticosterone acetate (DOCA)-salt hypertensive rats fed a control or Mg(2+)-enriched diet. We also studied the in vitro effect of Mg2+ on aortic PGI2 release. The Mg(2+)-enriched diet significantly decreased by 10% blood pressure in DOCA-salt hypertensive rats but not in normotensive rats. The Mg(2+)-enriched diet significantly increased by 122% aortic PGI2 release in DOCA-salt hypertensive rats, but not in normotensive rats. Mg2+ supplementation in the incubation medium (4.8 mM) significantly increased aortic PGI2 release by 94% in DOCA-salt hypertensive rats, but not in normotensive rats. These data suggest that the Mg(2+)-induced attenuation of blood pressure in DOCA-salt hypertensive rats could be linked with the enhanced vascular PGI2 release.
    Prostaglandins Leukotrienes and Essential Fatty Acids 12/1992; 47(3):183-6. · 1.98 Impact Factor
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    ABSTRACT: Devil's Claw (Harpagophytum procumbens), an herbal product being marketed in Canada and in Europe as a home remedy for the relief of arthritic disease, was investigated in healthy humans on eicosanoid production during spontaneously blood clotting. Volunteers took H. procumbens (daily 4 capsules of 500 mg powder containing 3% of total glucoiridoids) for a period of 21 days. The following are the results (mean (SEM)): before H. procumbens intake, prostaglandin (PG)E2 (ng/ml serum): 2.1 (0.4) (n = 25), thromboxane (TX)B2: 147 (27) (n = 25), 6-keto-PGF1 alpha: 4.4 (0.7) (n = 13), leukotriene (LT)B4: 3.4 (0.4) (n = 25); after intake: PGE2: 3.2 (0.6), TXB2: 143 (24), 6-keto-PGF1 alpha: 4.2 (0.9), LTB4: 3.8 (0.6). Each subject serving as her own control, no statistically significant differences were observed between before and after H. procumbens intake. These results indicate that Devil's Claw lacks, at least in healthy humans and under the selected conditions, the biochemical effects on arachidonic acid metabolism of antiarthritic drugs of the non-steroidal antiinflammatory type.
    Prostaglandins Leukotrienes and Essential Fatty Acids 09/1992; 46(4):283-6. · 1.98 Impact Factor
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    ABSTRACT: In order to investigate the contribution of eicosanoids to human oesophageal functions and disorders (gastrooesophageal reflux, GOR and reflux oesophagitis, RO), we have used a selected ion monitoring gas chromatographic/mass spectrometric methodology to quantify the cyclooxygenase and lipoxygenase products biosynthesized in vitro by endoscopic mucosal biopsy specimens. Prostaglandins (PGs) were quantified as MEMOTMS derivatives and HETEs, as hydrogenated methyl ester of tert-butyldimethylsilyl) ether derivatives. PGE2, PGF2 alpha appeared as the major prostanoids, whereas 12HETE seemed to be the major lipoxygenase product. In the case of GOR or RO, biosynthesis of PGE2 was dramatically increased, while no change could be detected for 12HETE. PGE2 increase seems to be related to inflammatory reaction, in which its exact role remains unclear. Moreover, it cannot be excluded that PGE2 is a side product which might be protective to the oesophageal mucosa.
    Biomedical & environmental mass spectrometry 11/1988; 16(1-12):299-304.
  • C Moussard, D Alber, J C Henry
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    ABSTRACT: In an attempt to elucidate the possible involvements of eicosanoids in esophageal functions and disorders, we have investigated the formation of both cyclooxygenase and lipoxygenase metabolites from 14C-arachidonic acid by rabbit esophageal tissues. Homogenates of rabbit esophageal mucosa and muscularis were incubated with 14C-arachidonic acid and after ether extraction eicosanoids were separated and quantified by reverse phase high performance liquid chromatography. The predominant cyclooxygenase products were 6-keto-PGF1 alpha, PGF2 alpha, and PGE2 for mucosa and 6-keto-PGF1 alpha, and PGE2 for muscularis. The formation of these products was inhibited both by indomethacin and the dual pathway inhibitor, nordihydrogualaretic acid (NDGA). In mucosa the major eicosanoid was 12-HETE (12-hydroxyeicosatetraenoic acid) which was inhibited by NDGA but not by indomethacin which on the contrary enhanced its formation. Additionally four polar products were synthesized which appeared to be lipoxygenase-dependent as their formation was inhibited by NDGA but not by indomethacin. Muscularis produced as a minor lipoxygenase product only 12-HETE, which was inhibited by NDGA but unchanged in the presence of indomethacin. In addition, both tissues, but mucosa more than muscularis, possessed large prostaglandin catabolizing capacity. The present findings indicate that rabbit esophageal tissues can convert 14C-arachidonic acid into lipoxygenase as well cyclo-oxygenase products which may have a role in esophageal physiology and pathophysiology.
    Prostaglandins Leukotrienes and Essential Fatty Acids 02/1988; 31(1):31-9. · 1.98 Impact Factor
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    ABSTRACT: In vivo prostaglandin E2 (PGE2) levels were measured in esophageal mucosa excised from 9 normal subjects, 11 patients with gastroesophageal reflux without esophagitis (GER) and 8 patients with reflux esophagitis (RE). Severity of GER was quantified by postcibal pH monitoring. A manometric study was also performed. No difference was found in PGE2 levels between healthy mucosa in controls (41.7 +/- 9.3 ng/g of wet tissue, at 15 cm above the lower esophageal sphincter (LES)) and healthy mucosa in GER (37.8 +/- 11.2 ng/g) or in RE (34.3 +/- 9.0 ng/l). However, PGE2 levels were significantly enhanced within the inflammatory mucosa in RE (290.4 +/- 45.7 ng/g). No difference was found in basal LES pressure between the 3 groups. These results suggest that PGE2 in the esophagus may be involved in pathogenesis of inflammation. Therefore PGE2 might not have the same cytoprotective function as in stomach or duodenum. No correlation was found between PGE2 levels in the esophagitis lesion or basal LES pressure. These data are not consistent with a possible relationship between LES pressure and the PGE2 content of the distal esophagus.
    Prostaglandins Leukotrienes and Medicine 11/1987; 29(2-3):141-51.
  • C Moussard, D Alber, J C Henry
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    ABSTRACT: In the present study we investigated the arachidonic acid metabolism in guinea pig placenta during the last third of gestation. Homogenates were incubated with 14C-labeled substrate, and eicosanoid formation was determined using rp HPLC. Arachidonic acid was substantially converted to cyclooxygenase products i.e 6-keto-PGF1 alpha, TxB2, PGF2 alpha, PGE2, PGD2 and 12-HHT. Lipoxygenase activity was also found but of a much lower degree and represented by the mono-hydroxy acids 12-HETE and 15-HETE. The total conversion of arachidonic acid exhibited a progressive rise from day 50 to term, due principally to the increasing part of TxB2, PGE2 and 12-HHT throughout this gestational period and in addition, near term, of 6-keto-PGF1 alpha and PGF2 alpha. These results suggest that there is an increasing concentration and/or activity of cyclooxygenase system enzymes with placental development in guinea pig, which may contribute to the augmented intrauterine availability of prostanoids near parturition. Additional experiments were performed to compare the metabolism of exogenously added 14C-arachidonic acid and endogenously present 12C-arachidonic acid during placental homogenate incubation by means of isotope dilution GC-MS. Although the 14C- and 12C-prostanoid patterns were comparable, the 14C/12C ratios of the prostanoids formed during incubation were significantly different. These data indicate that exogenous arachidonic acid and endogenous arachidonic acid in placental homogenate do not follow up exactly the same metabolic pathway so that the assumption of biochemical identity between exogenous radio-tracer and studied endogenous substrate is not quite true.
    Prostaglandins 08/1987; 34(1):79-90.
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    ABSTRACT: It is well established that prostaglandin catabolism involves sequential actions of a 15-hydroxyprostaglandin dehydrogenase, a 15-keto-prostaglandin delta 13-reductase and a 15-ketoprostaglandin reductase. This pathway must be confirmed in never investigated tissues before any enzyme assay is carried out. We have developed a new, simple, rapid and reliable method to investigate catabolizing sequence of prostaglandins based on the tritium kinetic isotope effect which occurs during the oxidation of the 15-hydroxyl group of the prostaglandin into a 15-keto group.
    Prostaglandins 04/1986; 31(3):501-8.
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    ABSTRACT: Although numerous data exist concerning tritium kinetic isotope effect in enzymic reactions, little is related to the metabolism of tritiated prostaglandins. The present study reports an evaluation of the kinetic isotope effect which occurs during the oxidation of 15-hydroxyl group of tritium-labeled prostaglandins E2 and F2 alpha by the 15-hydroxyprostaglandin dehydrogenase and during the oxidation of 9-hydroxyl group of tritium-labeled prostaglandin F2 alpha by the 9-hydroxyprostaglandin dehydrogenase. The large kinetic isotope effect tends to limit the validity of the dehydrogenase assay using tritium-labeled prostaglandins as substrate. However these assays can be considered to be an indication of relative enzyme activity.
    Prostaglandins 04/1986; 31(3):489-500.
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    ABSTRACT: Peritoneal fluid levels of 6-keto-PGF1 alpha, TxB2, PGE2 and PGF2 alpha were measured in 62 infertile women undergoing coelioscopy. In 10 patients with mild endometriosis, the levels of all prostanoids were significantly enhanced as compared to control group (15 infertile patients without pelvic lesion). In 5 patients with moderate endometriosis, only PGF2 alpha exhibited a significant enhancement. The results confirmed the prostanoid component alteration of peritoneal fluid in infertile women with mild or moderate endometriosis, which however not has been found by all authors. In 6 patients with chronic salpingitis, no difference was found in prostanoid levels as compared to control group. The 26 patients with pelvic adhesions were distributed in 3 groups on the criterion of easy lysed or not adhesions. In group I (not lysed adhesions, 7 patients), no difference was found in prostanoid levels as compared to control group. In group II (mixed adhesions, 13 patients), the levels of all prostanoids, particularly 6-keto-PGF1 alpha, were significantly higher than that found in control group. In group III (easy lysed adhesions, 6 patients), the levels of 6-keto-PGF1 alpha, TxB2 and particularly PGF2 alpha were significantly enhanced as compared to control group. The results of this study suggest that prostanoids are implicated in physiopathology of endometriosis and pelvic adhesions and perhaps in mechanism of the associated infertility.
    Pathologie Biologie 03/1986; 34(2):101-7. · 1.07 Impact Factor
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    ABSTRACT: Prostanoids are thought to take a prominent part in gestation and parturition physiology. Experiments were designed to determine the chronological alterations in placental synthesis and metabolism of prostanoids during the third trimester of gestation in the guinea-pig. Placental obtained at days 50, 55, 60, at term and after delivery were assayed (RIA and/or GC/MS) for PGE2, PGF2 alpha and TxB2 before (in vivo levels) or after 1 hour incubation (in vitro levels) for PGE2, PGF2 alpha, PGD2, TxB2, 6-keto-PGF1 alpha and PGF1 alpha. In addition, PGE2 and PGF2 alpha metabolism was measured by radiochromatography assay. No differences with gestational age were found in PGE2 and TxB2 in vivo levels but PGF2 alpha showed a slight increase around day 60. In contrast, in vitro levels of PGF2 alpha, TxB2 and PGE2 (in decreasing order of production) exhibited a marked increase from day 50 to delivery, whereas the other prostanoids showed no changes. Moreover, PGE2 and PGF2 alpha metabolism by the 15-hydroxyprostaglandin dehydrogenase was found to decrease during the same gestational period. These results are consistent with the idea that placenta in guinea-pig may be an important source of endogenous prostanoids and may contribute to the augmented intrauterine availability of prostanoids near parturition. The implications of these findings in relation to the mechanisms controlling synthesis and metabolism of prostanoids are discussed.
    Prostaglandins Leukotrienes and Medicine 02/1986; 21(1):37-49.
  • Gastroentérologie Clinique et Biologique 06/1984; 8(5):484-5. · 1.14 Impact Factor
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    ABSTRACT: Prostaglandins are involved in different stages of reproduction. In respect to the placental metabolism of prostaglandins in the Guinea pig, we have studied the composition of Guinea pig placenta in free and total fatty acids. The arachidonic and dihomo-gamma-linolenic acids, precursors of prostaglandins of series 2 and 1, and the linoleic acid were quantified at different gestational ages using a gas-chromatography capillary column technique. Only the linoleic acid shows a significant increase at the end of gestation.
    Comptes rendus des séances de la Société de biologie et de ses filiales 02/1984; 178(4):474-80.
  • D. Alber, J. C. Henry
    International Journal of Mass Spectrometry and Ion Physics 01/1983; 48:257-260.
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    ABSTRACT: Concentrations of N-acetyl-beta-D-glucosaminidase (NAG), alanine-amino-peptidase (AAP) and beta-2-microglobulin (beta 2M) were determined daily in the urine of 28 patients treated with gentamicin (2-3 mg . kg-1 . day-1) for a mean of 15 days. All had normal renal function. Increased activity in NAG and AAP was observed for all patients, either immediately or after 2 or 3 days of treatment. The results were compared with serum creatinine concentrations and urinary beta 2M levels. This study indicates a relationship between the nephrotoxicity of gentamicin and initial urinary enzymic activity(NAGi) prior to any treatment. The degree of NAG response during the first ten days of treatment appeared as a second prognostic factor. Renal failure was observed for one out of the 12 patients with normal NAGi (NAGi less than 200 mumol/day). Seven of them showed a marked enzyme activity response (greater than 1500 mumol/day) with an increase in beta 2M activity. Eleven out of the 16 patients with elevated NAGi (NAGi greater than 200 mumol/day) developed renal failure and showed an elevated maximal response. The concentration of AAP appears to be of little prognostic value. The variation in individual maximal urinary enzyme responses observed among the 28 patients during the first ten days of treatment points to the existence of individual sensitivities to gentamicin, the exact mechanism of which remains unclear.
    Clinica Chimica Acta 10/1981; 116(1):25-34. · 2.76 Impact Factor
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    ABSTRACT: Concentrations of (NAG), alanine-aminopeptidase (AAP) and beta-2-microglobulin (β2M) were determined daily in the urine of 28 patients treated with gentamicin (2–3 mg·kg−1· day−1 ) for a mean of 15 days. All had normal renal function. Increased activity in NAG and AAP was observed for all patients, either immediately or after 2 or 3 days of treatment. The results were compared with serum creatinine concentrations and urinary β2M levels. This study indicates a relationship between the nephrotoxicity of gentamicin and initial urinary enzymic activity (NAGi) prior to any treatment. The degree of NAG response during the first ten days of treatment appeared as a second prognostic factor. Renal failure was observed for one out of the 12 patients with normal NAGi (NAGi < 200 μmol/day). Seven of them showed a marked enzyme activity response (> 1500 μmol/day) with an increase in β2M activity. Eleven out of the 16 patients with elevated NAGi (NAGi> 200 μmol/day) developed renal failure and showed an elevated maximal response. The concentration of AAP appears to be of little prognostic value.The variation in individual maximal urinary enzyme responses observed among the 28 patients during the first ten days of treatment points to the existence of individual sensitivities to gentamicin, the exact mechanism of which remains unclear.
    Clinica Chimica Acta 10/1981; · 2.76 Impact Factor