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Biomedical subjects

B Descomps

Publications and source records attributed to B Descomps.

At least 19 recordsLinked to original sources
PubMed1995

Differential incorporation of fish-oil eicosapentaenoate and docosahexaenoate into lipids of lipoprotein fractions as related to their glyceryl esterification: a short-term (postprandial) and long-term study in healthy humans.

We investigated how the distribution of eicosapentaenoate (EPA, 20:5n-3) and docosahexaenoate (DHA, 22:6n-3) in the sn-2 and sn-1(3) positions of fish-oil triacylglycerols influenced their respective incorporation into triacylglycerol, cholesterol esters, and phospholipids of two lipoprotein fractions: low- and very-low-density lipoprotein (VL/LDL) and high-density lipoprotein (HDL). Nine healthy volunteers were studied over both a short-term (0-8 h) and a long-term (30 d) postprandial period of daily supplementation with 2 g EPA and 1.3 g DHA given as 11 g fish-oil triacylglycerol in which DHA was predominantly situated in the sn-2 position. Our results strongly suggest that the higher triacylglycerol incorporation of DHA and the higher metabolic availability of EPA compared with DHA for phospholipid accumulation (particularly in the short-term study) depend on their respective preferential sn-2/sn-1(3) positions in fish-oil triacylglycerol, emphasizing the important role of the triacylglycerol structure and its potential manipulation for modulating availability of either or both fatty acids.

Adult↗
PubMed1992

Effect of the progesterone antagonist RU486 on human myometrial spontaneous contractility and PGI2 release.

We studied the effect of antiprogesterone RU 486 on spontaneous uterine contractility and PGI2 release with human myometrial strips superfused "in vitro". A decrease of PGI2 release into the superfusion medium was observed after 20 min superfusion. The inhibition was dose-dependent and reversible. After 20 min washing with tyrode medium without RU 486, the uterine strips recovered their initial rate of release. R5020, a progesterone agonist, did not affect PGI2 release nor dexamethasone and testosterone. Parallel to the decrease of PGI2 observed during RU 486 superfusion, the uterine spontaneous contraction frequency decreased, while the amplitude and duration of contractions increased. The alteration of uterine contractility was also rapid, dose-dependent and reversible. Modification of uterine strip spontaneous contractility, similar to those induced by RU 486, were also observed with superfusions of R5020 at concentrations as low as 10(-9)M, dexamethasone (10(-8)M), but not with superfusions of testosterone. These observations are not in favour of a progesterone-receptor mediated effect of RU 486 in our model. The mechanism of action may be related to the antiprogesterone specific structure i.e. the bulky substituent at the C-11 position. The RU 486 effect on uterine strip contractility, mimicked by other steroids, could point to a non-specific lipid/membrane interaction. However, the fact that testosterone did not affect motility, may indicate a possible specificity of steroids having a 3 oxo pregnene structure.

Adult↗
PubMed1992

[Cyclosporin A metabolism and induction of cytochrome P-450 in orthoptic hepatic transplantation in rats].

The aim of our study were 1) to establish that cyclosporin (CsA) metabolism was correlated with the rate of cytochrome P4503A (cyt.) in Wistar rats induced with dexamethasone (Dex.), 2) to demonstrate that the induction of cyt. with Dex. in liver "rat donor" was transmissible to "recipient rat" after liver transplantation. Sixty rats were divided in 5 groups. In group T, a single dose of CsA (10 mg/kg) was administered intravenously in 10 rats; in group D, 10 rats were treated with Dex (300 mg/kg daily for 4 days) and then received CsA as above; in group BN 5 rats were treated with beta-naphthoflavone. Thirty five rats underwent a liver transplantation either from "non induced donors" (group G, n = 11) or from "induced donors with Dex." (group GD, n = 24) followed by CsA injection the next day. For each rat, CsA plasma levels were determined by radioimmunoassay in 6 samples. Liver microsomes cyt. from samples of the liver of donor rats (group G and GD) or after sacrifice (group T, D, BN) were quantitated by immunoblot analysis and estimated from densitometric analysis of the blot. Mean maximal plasma concentration (Cmax) were 2,822 +/- 997 ng/ml in group T, 1,447 +/- -458 ng/ml in group D, 2,685 +/- 1,383 ng/ml in group G, 1,337 +/- 713 ng/ml in group GD and 3,094 +/- 685 ng/ml in group BN. Considering the Cmax and the ASC (area under curve), there was a significant difference between all groups and separately between groups T and D, G and GD.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Synthesis of nuclear lipids in L2C leukemic lymphocytes.

We previously reported that propiconazole strongly inhibits cholesterol synthesis, but not cell division in a stimulated cell, the human lymphocyte cultured with phytohemagglutinin, showing that newly synthesized cholesterol is not necessary for cell division. In this study we labeled the L2C leukemic guinea pig lymphocyte, a naturally stimulated cell, with [2-14C]acetate, and compared the composition of newly synthesized lipids isolated from nuclei and whole cells (or microsomes). We observed that the proportion of cholesterol in labeled non-saponifiable lipids extracted from nuclei was lower than in non-saponifiable lipids isolated from whole cells, whereas the proportion of squalene and polar lipids was higher. By analyzing total lipid extracts, the polar lipids were identified as alkylglycerols, and the above mentioned distribution of constituents was confirmed. The identification of alkylglycerols was also supported by the comparison of radioactive lipid composition after labeling cells with three different lipid precursors: [2-14C]mevalonate, [2-14C]acetate and [2-14C]stearate. When cells were labeled in the presence of dodecylimidazole, the percentage of squalene and alkylglycerols decreased in nuclear lipids, but was not altered when cells were cultured in the presence of propiconazole, a cholesterol synthesis inhibitor which does not affect cell division of human stimulated lymphocytes. We have shown that dodecylimidazole inhibited alkylglycerol biosynthesis and squalene uptake by the nucleus, suggesting that these compounds could play a role in the regulation of cell division.

Animals↗
PubMed1991

Active cholesterol biosynthesis in cultured aortic smooth muscle cells: evolution during the life-span of the culture.

Cultured aortic smooth muscle cells from rabbit, in synthetic and contractile state, are considered good models for studying pathological and normal cells, respectively, during the atherosclerotic process. Cholesterogenic activity was compared in cells which were obtained in both states of the same subculture and incubated with labeled sodium acetate. This activity (expressed as the percentage of total cell radioactivity uptake transformed into cholesterol) was very high in synthetic cells and comparable to that of cancer cells. Cholesterol synthesis was lower in contractile cells and similar to that observed in a nonpathological cultured cell. During the cell life-span (studied in two cultures) cholesterogenic activity initially increased and then slowly decreased, in the two phenotypic states. Near the end of the culture life, cholesterol production drastically decreased, but this was due to a blocking of the last steps, lanosterol demethylation and C27 sterol transformation into cholesterol, rather than to a sharp decrease in the first steps of the cholesterogenic process. Cells in the synthetic and contractile states released newly synthesized lipids which were essentially late precursors of cholesterol, but accumulation of oxy-sterols was not observed. The excretion of metabolites increased with culture aging.

Animals↗
PubMed1990

Labeling of ethambutol with 99mTc using a new reduction procedure. Pharmacokinetic study in the mouse and rat.

Certain 99mTc-labeled derivatives of ethylene diamine substituted in NN', when labeled with 99mTc, have been proposed for studying renal excretion, and others for brain imaging. Ethambutol, a well known antituberculosis drug, possesses a structure very similar to these derivatives. We prepared a complex of [99mTc]ethambutol using hypophosphorus acid as the reducing agent. The complex was then analyzed by paper and cellulose F chromatography and by FAB mass spectrometry. A pharmacokinetic study in the mouse and rat indicated that the complex is eliminated by the kidney faster than DTPA, slower than [131I]hippuran and without significant renal retention. The [99mTc]ethambutol complex is easy to prepare and shows good stability in water at physiological pH, making it potentially useful in renal excretion studies.

Animals↗
PubMed1990

[Aberrant expression of HLA-DR antigens of the MHC class II in bronchial epithelial cells in asthmatic patients].

The study of cellular events in the bronchi of asthmatic patients shows significant epithelial destruction. The ciliated cells are more often destroyed than others in the respiratory epithelium. Using highly specific monoclonal antibodies, we detected that the epithelial cells were positive for HLA-DR antigen expression, whereas those from healthy subjects were negative. The aberrant expression could be explained by the presence of T lymphocytes in the asthmatic bronchial mucosa. The activated lymphocytes (CD4+) are known to release gamma interferon, which is a lymphokine that induces or enhances the expression of HLA-DR antigens. These cells, which are known to mediate cytotoxicity in an Ag-specific and Ia-restricted way, could take part in the shedding process of epithelial cells in asthma.

Asthma↗
PubMed1990

Radioimmunological determination of total thyroxin by antibodies immobilized on polystyrene tubes coated with styrene-maleic anhydride copolymers.

In this new technique for preparing activated polystyrene tubes for assay of human thyroxin (T4) we coated plastic with styrene-maleic anhydride copolymers. The quantity of antibodies immobilized on these tubes was considerably greater than on non-activated polystyrene tubes, and the time required for immobilization was shortened. Calibration curves were plotted, and determination of total T4 in 200 serum samples confirmed the expected increase in sensitivity as compared with a commercial (Gammacoat) method. The manufacturing procedure is simple and could easily be automated. Thus, such copolymer-coated tubes constitute an advantageous and reliable component in the assay of total T4 that can be used to improve the sensitivity of this and various other radioimmunological determinations.

Antibodies↗
PubMed1989

Direct in vivo characterization of delta 5 desaturase activity in humans by deuterium labeling: effect of insulin.

The conversion of dihomogamma linolenic acid (DHLA) into arachidonic acid (AA) was compared in normal subjects and diabetic patients before and after treatment with insulin. The kinetics of the incorporation of deuterium-labeled DHLA and its conversion product, deuterium-labeled AA, was determined in plasma triglycerides, plasma phospholipids, and platelet lipids of subjects after ingestion of 2 g of the labeled precursor. Analysis was performed by gas liquid chromatography-mass spectrometry using multiple ion detection. In normal subjects, the deuterium-labeled DHLA concentration rose to 24 to 69 mg/L in plasma triglycerides four to nine hours after ingestion and to 20 to 34 mg/L in plasma phospholipids about four hours later. Deuterium-labeled AA appeared at 12 hours, rose to 2.4 to 3.8 mg/L between 48 and 72 hours in plasma phospholipids, but remained at the limit of detection in plasma triglycerides and was undetectable in platelet lipids. In diabetic patients both before and after insulin treatment, the deuterium-labeled DHLA concentration in plasma triglycerides and in plasma phospholipids followed the same pattern as in normal subjects. However, the deuterium-labeled arachidonic acid concentration was below 1 mg/L in plasma phospholipids before insulin. After insulin treatment the patients recovered normal DHLA metabolism because deuterium-labeled AA rose in phospholipids to a mean value of 3.5 mg/L, which is in the same range as that observed in normal subjects (3.2 mg/L). The present data provide direct evidence for the conversion of DHLA into AA in humans. The effect of insulin and the data from the literature of animal studies suggest insulin dependence of delta 5 desaturase in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

8,11,14-Eicosatrienoic Acid↗
PubMed1988

Effect of estradiol and antiestrogens on cholesterol biosynthesis in hormone-dependent and -independent breast cancer cell lines.

The effects of estradiol and/or antiestrogens on cholesterol biosynthesis were studied in two breast cancer cell lines. Cholesterogenic activity was evaluated after labeling cells with sodium [14C]acetate for increasing periods of time (up to 24 h) and measuring the incorporation of the radioactivity into nonsaponifiable lipids and into cholesterol, after separation from other labeled metabolites. We compared the effects of estradiol on cholesterogenesis with the well-known effects of this hormone on cell proliferation: estradiol stimulated both cholesterol synthesis and cell growth in MCF-7 cells, but stimulated neither in BT20 cells. The stimulation affected both the 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase step and the post-HMGCoA steps. Only the key enzyme step appeared to be mediated by the estrogen receptor. The hydroxytamoxifen and LY 117018 antiestrogens strongly inhibited cellular cholesterol production in both cell lines. Under the same conditions, cell growth is affected in MCF-7 cells, but not in BT20 (as shown by groups from other laboratories). This demonstrates that de novo synthesis of cholesterol is not essential for cell growth when cells are cultured in the presence of whole serum. The inhibition of cholesterol synthesis by antiestrogens mainly affected the lanosterol demethylation step and the C-27 sterol to cholesterol conversion. This inhibiting effect of antiestrogens was not mediated by the estrogen receptor.

Acetates↗
PubMed1988

Antibody immobilization on swollen polystyrene tubes for the radioimmunological determination of total human serum IgE.

A new technique for preparing activated polystyrene tubes was developed involving the controlled swelling of plastic. The quantity of antibodies immobilized on these tubes, and consequently the quantity of bound IgE, was considerably increased. Calibration curves were plotted and the determination of total IgE in 200 serum samples confirmed the expected increase in sensitivity compared to a standard method. The manufacturing procedure was simple and could easily be automated. Thus, swollen polystyrene tubes constitute an advantageous solid stage in the assay of total IgE, which can improve the sensitivity of various radioimmunological determinations.

Antibodies↗
PubMed1988

Role of estrogen receptors and antiestrogen binding sites in an early effect of antiestrogens, the inhibition of cholesterol biosynthesis.

The effects of estradiol (E2), 4-hydroxy-tamoxifen (OH-Tam), and LY117018 on cholesterogenesis were investigated in two human breast cancer cell lines (MCF-7 and BT20), and in rat hepatoma (HTC) and fibroblastic (NRK-49F) cell lines. It was found that 10(-10) M E2 stimulated and 10(-8) M OH-Tam inhibited cholesterol synthesis in the estrogen-sensitive MCF-7 cell line. The OH-Tam effect occurred in less than 15 min whereas E2 only stimulated after 8 h. The inhibition of cholesterol synthesis was not reversed by E2. E2 was without effect in the HTC and estrogen-resistant BT20 cell lines whereas OH-Tam was as effective as in the MCF-7 cells. LY117018 had nearly as much effect on cholesterol synthesis as OH-Tam, in both MCF-7 and BT20 cells. Neither E2 nor OH-Tam had any effect on the NRK-49F cell line, even at micromolar concentrations. The three lines (MCF-7, BT20, HTC), whose cholesterol synthesis has been shown to be OH-Tam sensitive, appeared to contain high-affinity antiestrogen binding sites (AEBS); since the OH-Tam-resistant line (NRK) only contained low-affinity AEBS, there appears to be some relationship between OH-Tam sensitivity and high-affinity AEBS content. This suggests that the cholesterogenesis inhibition induced by antiestrogens is ER-independent and may involve AEBS. The cholesterogenesis stimulation induced by E2 occurred via a different pathway that appears to be related to the presence of ER in the cells.

Animals↗
PubMed1988

Correlations between free plasma estradiol and estrogens determined by bioluminescence in saliva, plasma, and urine during spontaneous and FSH stimulated cycles in women.

Estrone and estradiol (E1 + E2) concentrations in saliva were compared with four other parameters of estrogen status in five normal ovulatory women and ten FSH stimulated women selected for an in vitro fertilization program. E1 + E2 in saliva, plasma, and urine were assessed by a rapid, specific and sensitive enzymatic assay using bioluminescence. The free fraction of plasma estradiol was determined by equilibrium dialysis and total plasma estradiol by conventional radioimmunoassay. The pattern of E1 + E2 variation in saliva was similar to that of free plasma estradiol and the two parameters were correlated in both spontaneous and stimulated cycles. However, the lower correlation coefficient (r = 0.52, P less than 0.001) in spontaneous cycles compared with the high (r = 0.96, P less than 0.001) in the stimulated cycles shows that salivary E1 + E2 could be representative of plasma free estradiol in stimulated cycles but not in normal cycles. The free fraction of plasma estradiol reproduced the variation of total plasma estradiol in spontaneous as well as in FSH stimulated cycles and both parameters were strongly correlated (r = 0.91, P less than 0.001 and r = 0.90, P less than 0.001), respectively. The data show that salivary E1 + E2 concentrations are highly representative of the free fraction of E2 in plasma and at a lesser extend (r = 0.72, P less than 0.001) of total plasma E2 in FSH stimulated cycles.

Adult↗
PubMed1987

Enteral absorption in man of eicosapentaenoic acid in different chemical forms.

After administering the equivalent of 1 g of eicosapentaenoic acid (EPA) in four different chemical forms, the kinetics of EPA incorporation into plasma triglycerides (TG) were compared by gas liquid chromatography on a capillary column following separation of the lipid fraction by thin layer chromatography. EPA incorporation into plasma TG was markedly smaller and later when EPA was administered as an ethyl ester rather than as EPA free fatty acid, EPA arginine salt or 1,3-dioctanoyl-2-eicosapentaenoyl glycerol (2-EPA). Our results and the data in the literature are compatible with the hypothesis that 2-EPA is absorbed with minimum hydrolysis and escapes random distribution between the other positions of the glycerol molecule during the absorption process.

Adult↗
PubMed1987

Bioluminescence: an improvement in the enzymatic assay of dehydroepiandrosterone sulfate in biological fluids.

Dehydroepiandrosterone sulfate (DHEAS) determination in biological fluids was carried out by enzymatic hydrolysis and conversion into estrogens [estrone (E1) and estradiol (E2)] by the multienzyme system of human placental microsomes. The enzymatic complex consists of sulfatase, 3 beta-hydroxysteroid oxido reductase and 5en----4en isomerase which converts DHEAS into androstenedione (A); the latter component is further converted into estrogens by the aromatase. The resulting estrogens were determined from the NADH formed by the transhydrogenation reactions of human placental dehydrogenase. NADH was measured by bioluminescence. As little as 4 pg was assayable by this rapid enzymatic method, with a coefficient of variation of 8%. The results are in good agreement with radioimmunoassay and the method is suitable for routine use.

Dehydroepiandrosterone↗
PubMed1986

Characterization of oxysterol-binding protein in rat embryo fibroblasts and variations as a function of the cell cycle.

A cell-free system assay involving cell freeze-thawing and protein fractionation by ammonium sulfate precipitation was developed to characterize a cytosol binding protein specific for oxysterols in rat embryo fibroblasts. This protein shared common characteristics with the oxysterol-binding protein described in L cells and in normal human lymphocytes: 8 S sedimentation coefficient, sterol-protein complex of Mr 160 600, saturability, high affinity (Kd in the range of 10(-9) M) and specificity for cholesterol derivatives oxidized on the side chain. These compounds were better inhibitors of DNA synthesis than the compounds oxidized on the nucleus, whereas no difference was found between sterols oxygenated either on the side chain or on the nucleus, as far as inhibition of hydroxymethylglutaryl-CoA reductase (HMG-CoA reductase) was concerned. Macromolecular components capable of specifically binding 25-hydroxycholesterol were also detected in the fibroblast nucleus. The cytosol oxysterol-binding protein showed a sharp increase (5-fold) in the G2M phase of the cell cycle and in exponentially growing cells (maximal binding site number/cell: 43 500, versus 8850 in confluent cells). Neither the affinity nor the sedimentation coefficient of the protein changed in either situation. The quantitative (but not qualitative) variations of oxysterol-binding protein could be related to the inhibitory effect of 25-hydroxycholesterol on DNA synthesis, which becomes critical when this sterol is added in the G2M phase of the cell cycle.

Animals↗
PubMed1986

Stimulation of aromatase activity by dihydrotestosterone in human skin fibroblasts.

In order to study the regulation of aromatase activity by androgens in cultured fibroblasts derived from genital skin of normal prepubertal boys, aromatase activity was evaluated in the presence of various concentrations of non-aromatizable androgen DHT(5 alpha-dihydrotestosterone). The estrogen formation was assayed by an enzymatic method, after 24 h incubation of the cells with 10(-6) M androstenedione. Aromatase activity was stimulated 3- to 20-fold by DHT at concentrations 10(-10) and 10(-9) M. It was necessary to preincubate the cells with DHT for 48 h in order to bring about this stimulation. The stimulatory effect was not significant after preincubation for only 24 h. The basal value of aromatase activity was in the range of 8 +/- 1.2 pmol/mg protein/day (mean +/- SEM), while the maximal stimulation 1043 +/- 46 pmol/mg protein/day was obtained at the concentration of 10(-8) M DHT. This stimulation was partially blocked with cyproterone acetate at level of 20 +/- 4 pmol/mg protein/day; stimulation of aromatase activity by DHT could thus be mediated by the androgen receptor. This stimulatory effect was prevented by incubation of the cells with cycloheximide or actinomycin D, suggesting that DHT acts to increase aromatase activity in cultured fibroblasts by inducing the synthesis of new proteinaceous material. In vitro regulation of aromatase activity by androgens could contribute to a new approach to the extraglandular formation of estrogen.

Aromatase↗