Taste perception with age: generic or specific losses in threshold sensitivity to the five basic tastes?

Detection thresholds for NaCl, KCl, sucrose, aspartame, acetic acid, citric acid, caffeine, quinine HCl, monosodium glutamate (MSG) and inosine 5'-monophosphate (IMP) were assessed in 21 young (19-33 years) and 21 elderly (60-75 years) persons by taking the average of six ascending two-alternative forced choice tests. A significant overall effect was found for age, but not for gender. However, an interaction effect of age and gender was found. The older men were less sensitive than the young men and women for acetic acid, sucrose, citric acid, sodium and potassium chloride and IMP. To detect the compound dissolved in water they needed a 1.32 (aspartame) to 5.70 times (IMP) higher concentration than the younger subjects. A significant decline in thresholds with replication was shown. The age effect found could be attributed predominantly to a generic taste loss.

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.

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.

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.

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.

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.

Purification and characterisation of prostaglandin endoperoxide D-isomerase, a cytoplasmic, glutathione-requiring enzyme.

Prostaglandin endoperoxide D-isomerase in rat spleen was purified until homogeneity. This cytoplasmic enzyme occurs in many organs of the rat and also in other species, and requires specifically glutathione for its action. The molecular weight is 30 000 and the isoelectric point pI 5.2.

Isolation and properties of enzymes involved in prostaglandin biosynthesis.

Prostaglandin (PG) endoperoxide synthetase was purified until homogeneity had been attained. The pure enzyme displays both cyclooxygenase and peroxidase activity, in accordance with the work of MIYAMOTO et al. (J. biol. Chem. 252, 2629--2636 (1976)). This enzyme therefore converts arachidonic acid into PGH2. Glutathione S-transferases, in the presence of glutathione, convert PGH2 into a mixture of PGF2alpha, PGE2 and PGD2. A new transferase in sheep lung gives mainly PGF2alpha and PGD2. Isolation and properties of these enzymes will be discussed. Finally, progress will be reported on the isolation of a soluble enzyme from various rat organs such as lung and spleen, which forms almost exclusively prostaglandin D.

Conversions of prostaglandin endoperoxides by glutathione-S-transferases and serum albumins.

Serum albumins of certain animal species (cow, sheep, pig) accelerate the decomposition of prostaglandin endoperoxides, with formation of large amounts of prostaglandin D. The reaction is inhibited by arachidonic acid, which suggests an interaction of the endoperoxide with the fatty acid binding sites of serum albumin. Glutathione-S-transferases, in the presence of glutathione, convert the endoperoxide into a mixture of prostaglandin F2alpha, E2 and D2. The prostaglandin D/E-ratio depends on the transferase used. The known rat liver transferases give mainly prostaglandin F2alpha and E2, but a new transferase in sheep lung was discovered which gives rise to large quantities of prostaglandin F2alpha and D2. The sheep lung transferase was purified to homogeneity. Two iso-enzymes with identical enzymic activity were obtained. The major component (transferase SL 2, an iso-enzyme of glutathione-S-transferase, EC 2.5.1.18) has a molecular weight of 45 000 and consists of two subunits. Its isoelectric point is 9,8-9.9. These properties, as well as the amino acid composition and the substrate specificity for typical transferase substrates, indicate a close resemblance to transferase B (ligandin), a major binding protein of rat liver. Although purified glutathione peroxidase from erythrocytes is very active in catalysing the reduction of the 15-hydroperoxy group of prostaglandins, it does not have any effect on the decomposition of the endoperoxide group.