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D H Nugteren

Publications and source records attributed to D H Nugteren.

At least 19 recordsLinked to original sources

Evaluation of jojoba oil as a low-energy fat. 2. Intestinal transit time, stomach emptying and digestibility in short-term feeding studies in rats.

The influence of jojoba oil (JO) incorporation in the diet on stomach emptying and intestinal transit time, and the digestion and absorption of JO were investigated in short-term feeding studies in rats. The animals were fed purified diets containing 18% (w/w) fat, of which half consisted of a mixture of lard and sunflower seed oil (SF) supplemented with an equivalent amount of JO. The control animals were fed a mixture of lard and SF (18%). No treatment-related differences were observed in the rate of stomach emptying or the intestinal transit time. Comparative lipid analysis of lymph, intestinal content, intestinal mucosa and faeces indicated that most of the ingested JO was degraded and absorbed. Part of the JO was present as wax ester in the lymph. Hydrolysis of JO was much slower than that of triacylglycerols and continued in the alimentary tract beyond the small intestine due to bacterial processes. JO did not influence the absorption of the conventional fat.

Animal Feed↗

The urinary excretion of prostaglandins E and their corresponding tetranor metabolites by rats fed a diet rich in eicosapentaenoate.

An HPLC method was developed to determine simultaneously in a single analysis prostaglandin E2, prostaglandin E3, tetranor-prostaglandin E1 and delta 17-tetranor-prostaglandin E1 in rat urine. As internal standard omega-nor-prostaglandin E2 was added to the samples at the beginning of the analysis. The assay was applied in feeding experiments in which rats were fed diets with mixtures of (n-6) and (n-3) fatty acids (linoleate, arachidonate, alpha-linolenate and eicosapentaenoate). The level of urinary prostaglandin E2 was not very much affected by the diet and prostaglandin E3 could never be detected in significant amounts. These primary prostaglandins are assumed to reflect prostaglandin biosynthesis in the kidney medulla. Tetranor-prostaglandin E1 is a characteristic urinary metabolite of prostaglandin E2 in the rat; its level increased after feeding arachidonic acid. delta 17-Tetranor-prostaglandin E1 became a major metabolite when the rats received eicosapentaenoic acid. However, we found that the ratio of urinary tetranor-prostaglandin E1/delta 17-tetranor-prostaglandin E1 is not a very reliable measure of the ratio of prostaglandin E2/prostaglandin E3 formed in the body, because prostaglandin E3 is converted to a much greater extent into delta 17-tetranor-prostaglandin E1 than is prostaglandin E2 into tetranor-prostaglandin E1. As a matter of fact, incubations of tissue homogenates of rats resulted always in predominant formation of prostaglandins of the 2-series, even after high eicosapentaenoate diets. We conclude, in agreement with work carried out earlier, that biosynthetic pathways leading to prostaglandins of the 3-series are of minor importance.

Alprostadil↗

Lipid composition of cultured human keratinocytes in relation to their differentiation.

The present study was undertaken to explore the possibility of the use of cultured human keratinocytes for the study of changes in lipid composition in relation to epidermal differentiation. In a submerged culture system, in which the stratification is incomplete, no significant differences have been found between the lipid composition of cells grown either at low calcium concentration (0.06 mM) (at which the keratinocyte differentiation is markedly retarded) or at normal calcium concentration (1.6 mM) (at which some differentiation takes place). Under these conditions the amount of phospholipids and sterols was high and that of ceramides was low. Furthermore, the acylglucosylceramides (AGC) and acylceramides (AC), the latter one known to be involved in water barrier function, were found to be absent. Contrary to this, both AGC and AC were found to be present in significant amounts in an air-exposed model using de-epidermized dermis (DED) as a substrate (in which, as judged from morphologic criteria, the extent of keratinocyte stratification is similar to that seen under the in vivo conditions). Fatty acid analysis revealed significantly lower content of 18:2 and higher content of 16:1 and 18:1 acids with all culture conditions used, as compared to the parent epidermis. This is probably a result of fatty acid levels and composition in fetal calf serum (which was used in the present study) that differ markedly from the in vivo situation. The 20:4 content was similar to that in the epidermis only in cells cultured under the submerged conditions, during which they have been found (Isseroff et al. 1987. J. Lipid Res. 28: 1342-1349) to be able to convert 18:2 to 20:4. In DED cultures, however, the 20:4 content was markedly lower. Under all culture conditions used, the triglyceride content was higher as compared to the non-cultured epidermis. The high content of triglycerides and the fatty acid composition of the various lipid fractions showed a resemblance with what is found in the epidermis in essential fatty acid-deficient animals. This resemblance was confirmed by electron micrographs which revealed the presence of some partially or completely empty lamellar bodies. The results of the present study suggest that the air-exposed culture model, in which the keratinocytes show a high extent of stratification, could be of great value in the study of epidermal lipid metabolism. However, further alterations in culture conditions are necessary to more closely approximate the lipid composition of noncultured epidermis.

Cell Differentiation↗

Conversion of linoleic acid and arachidonic acid by skin epidermal lipoxygenases.

Two different lipoxygenases have been identified in human and rat epidermis. One lipoxygenase has a (n-9)-specificity, converts arachidonic acid into 12-hydroxyeicosatetraenoic acid (12-HETE), and has been described by several investigators. Linoleic acid is not a substrate for this enzyme. The other lipoxygenase, with (n-6)-specificity, converts arachidonic acid into 15-HETE and linoleic acid into 13-hydroxyoctadecadienoic acid (13-HOD). Especially the latter lipoxygenase is thought to be involved in the regulation of the differentiation of the skin cells into a proper water-barrier layer. Linoleate is supposed to be the physiological substrate; this fatty acid is especially present in characteristic sphingolipids with unique structures.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Naturally occurring conjugated octadecatrienoic acids are strong inhibitors of prostaglandin biosynthesis.

Fatty acids from natural sources (mostly seed oils) were isolated and assayed for their effect on the bioconversion of arachidonic acid into prostaglandin E2, using sheep vesicular gland microsomes. Homologues and isomers of the naturally occurring fatty acids, obtained by chemical modification and/or organic synthetic methods, were also tested. Two very active cyclooxygenase inhibitors were discovered, namely jacarandic acid (8Z, 10E, 12Z-octadecatrienoic acid), isolated from Jacaranda mimosifolia, the concentration which gives 50% inhibition ([I]50) being 2.4 microM and the synthetic 8Z, 10E, 12E-octadecatrienoic acid, having an [I]50 of 1.0 microM. Under the conditions of the assay (75 microM substrate), earlier described potent inhibitors showed the following [I]50's: indomethacin: 1.3 microM; 9,12-octadecadiynoic acid: 1.3 microM, 8Z, 12E, 14Z-eicosatrienoic acid: 2.7 microM; 5,8,11,14-eicosatetraynoic acid: 4.4 microM. At a concentration of about half that of the substrate, the following naturally occurring fatty acids revealed inhibition ([I]50): columbinic acid (29 microM), calendulic acid (31 microM), liagoric acid (31 microM), ximenynic acid (39 microM), crepenynic acid (40 microM) and timnodonic acid (43 microM). Other fatty acids, and some of the above acids, were converted themselves more or less rapidly, mostly into conjugated monohydroxy fatty acids.

Animals↗

Metabolic profile of linoleic acid in porcine leukocytes through the lipoxygenase pathway.

Porcine neutrophilic leukocytes were found to contain a lipoxygenase which converted linoleic acid into 13-hydroxy-9,11-octadecadienoic acid (n-6 specificity), arachidonic acid into 12-hydroxy-5,8,10,14-eicosatetraenoic acid (n - 9 specificity) and 5-hydroxy-6,8,11,14-eicosatetraenoic acid into 5,12-dihydroxy-6,8,10,14-eicosatetraenoic acid. This lipoxygenase was partially purified and it appeared that its substrate specificity and other properties were quite different from the 12-lipoxygenase of blood platelets. Incubations of intact or broken porcine leukocytes with added linoleic acid revealed the formation of not only 13-hydroxy-9,11-octadecadienoic acid but also of substantial amounts of epoxyhydroxy and trihydroxy isomers. These products from linoleate, collectively described by the name 'octadecanoids' were characterized in detail by a combination of chemical, chromatographic and mass spectrometric techniques. The phospholipids of porcine leukocytes contain more than twice as much linoleate than arachidonate (22 vs. 8%). In accordance with this fatty acid composition we found that in the stimulated neutrophil the endogenous production of octadecanoids often surpassed that of the eicosanoids. Lipoxygenation of endogenously liberated linoleic acid was especially pronounced when a suspension of leukocytes in citrated plasma was recalcified and allowed to clot.

Animals↗

Identification, isolation and characterization of epidermal lipids containing linoleic acid.

Three specific linoleate-rich lipids have been identified in pig epidermis and are referred to as O-acylglucosyl ceramide, O-acyl ceramide, and O-acyl acid. The acid moiety is up to 70% linoleic acid and linked via the hydroxyl group of a omega-OH long-chain fatty acid, which itself is linked to sphingosine or glucosyl sphingosine. The identification of O-acyl ceramide confirmed the findings of another group, whereas the structural configuration of the O-acylglucosyl ceramide is different to previous reports. The identification of an O-acyl acid in epidermis is novel. Our evidence allows us to speculate that a hydroxylated derivative of the O-acyl ceramide may be intimately involved in the permeability barrier of skin, perhaps providing sufficient polarity to maintain a lamellar phase in the intercellular space of the lower stratum corneum region, and that it is specifically in this form that linoleic acid is involved in skin barrier function. Alternatively, or concurrently, this species may act as a signal for late keratinisation events.

Animals↗

Metabolism of linoleic acid and other essential fatty acids in the epidermis of the rat.

Essential fatty acids are absolutely necessary for maintaining the proper condition of the water barrier (stratum compactum) in the skin. Even direct topical application of linoleic acid or any other Z,Z-(n-6, n-9)-fatty acid to the skin restores the barrier in essential fatty acid-deficient animals. In order to investigate the mechanism by which these polyunsaturated fatty acids exert their activity, radioactively labelled fatty acids were applied to the skin of the live animal and the epidermal lipids were analysed after 1-4 days. Much radioactivity was incorporated into two peculiar lipids, viz. acyl ceramide and acyl acid, which are characteristic of the barrier, in which linoleate was esterified to the end-position of very-long-chain (C30-34) unsaturated omega-hydroxy fatty acids. Strong evidence was obtained which showed that these lipids carry linoleate into the barrier layer where it is converted, probably by lipoxygenase(s), into a series of peroxidated lipids. The lipoxygenase inhibitor, eicosatetraynoic acid, prevents both oxygenation of the polyunsaturated fatty acid and the formation of a healthy skin. This peroxidation may supply the mediators which induce the proper differentiation of the epidermal cells into an effective stratum compactum and a horny layer.

Animals↗

Characterization of monohydroxylated lipoxygenase metabolites of arachidonic and linoleic acid in rabbit peritoneal tissue.

Rabbit peritoneal tissue contains a lipoxygenase which converts arachidonic acid preferentially into 15-hydroxy-5,8,11,13-eicosatetraenoic acid. Stereochemical analysis of the menthyloxycarbonyl derivative of this metabolite by means of a high-pressure liquid chromatography method, involving the use of a Ag+ -loaded cation-exchange column, indicated that it has mainly the 15-Ls-hydroxy configuration. The biosynthesis of 15-hydroxy-5,8,11,13-eicosatetraenoic acid could be confirmed during examination of the monohydroxy acids obtained without addition of fatty acids, thus formed from endogenously released substrate. However, the 9-and 13-hydroxy derivatives of linoleic acid were also formed and in quantities exceeding those of 15-hydroxy-5,8,11,13-eicosatetraenoic acid.

Animals↗

15-Hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE) formation by rabbit peritoneal tissue.

The capacity of rabbit peritoneal tissue to produce lipoxygenase metabolites from exogenous arachidonic acid has been studied. The lipoxygenase pathway of arachidonic acid in this tissue is mainly directed to 15-HETE. Preliminary experiments with peritoneal macrophages indicate that these cells, just like PMN leukocytes, may contribute to the 15-HETE formation observed in peritoneal tissue.

Animals↗

Prostacyclin is not a circulating hormone.

Gas chromatography with electron-capture detection of the extensively purified pentafluorobenzyl derivative of 6-oxo-PGF1 alpha was used to determine prostacyclin in blood. Neither human peripheral plasma or whole blood, nor blood drawn directly from the human heart (blood from the right and left atrium which is comparable to pulmonary artery and vein blood), contained any detectable prostacyclin (less than 20 pg/ml). Even hyperventilation did not result in detectable PGI2-formation. During intravenous infusion of PGI2 into one arm, large amounts were found in blood drawn from the other arm. Increased levels were also found during severe infection and in endotoxin shock. These results lend no support to theories based on the concept that prostacyclin is a circulating hormone under normal conditions.

Animals↗

Fish oil feeding lowers thromboxane- and prostacyclin production by rat platelets and aorta and does not result in the formation of prostaglandin I3.

It is demonstrated that feeding cod-liver oil to rats leads to a considerable reduction in the formation of platelet TxA2 and of vascular PGI2. No appreciable formation of TxA3 and PGI3 is observed, although arterial thrombosis is depressed and bleeding time is prolonged. These findings contradict the suggested role of prostaglandins of the 3-series in thromboregulation.

Animals↗

Lack of prostacyclin biosynthesis by aortic tissue of the chicken.

The capacity of chicken aorta to produce prostaglandins both from exogenous and endogenous arachidonic acid has been evaluated. The metabolism of arachidonic acid in this tissue is mainly directed to PGE2 and, in contrast to mammalian species, virtually no prostacyclin synthetase is present. However, the capacity of chicken thrombocytes to generate thromboxane A2 and 12-L-hydroxy-5, 8, 10, 14-eicosatetraenoic acid is similar to that observed for the mammalian blood platelets.

Animals↗