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At least 973 records · Page 54Linked to original sources
PubMed1984

Arachidonic acid metabolism in gonadotroph-enriched pituitary cells.

Control of pituitary hormone secretion by hypothalamic-releasing peptides appears to involve unidentified products of the cyclooxygenase and lipoxygenase pathways, as well as the adenylate cyclase system. To identify the patterns of arachidonic acid metabolism in specific pituitary cell types, the labeled products formed from [14C]-arachidonic acid were analyzed in rat pituitary cells separated by centrifugal elutriation into fractions enriched in gonadotrophs, somatotrophs and lactotrophs. Gonadotroph-enriched cell fractions metabolized arachidonic acid to 11-, 12- and 15-HETE, HHT, PGD2, PGE2 and TXB2. The products were characterized by high performance liquid and thin-layer chromatography, together with gas chromatographic-mass spectrometric identification of 12- and 15-HETE. In cells preincubated with indomethacin, the formation of 11-HETE, HHT, PGD2, PGE2 and TXB2 was markedly reduced. In gonadotroph-enriched cell fractions, the production of cyclooxygenase metabolites was 3 to 4 times greater than that of lipoxygenase products. The somatotroph- and lactotroph-enriched cell fractions produced only very small amounts of oxygenated arachidonic acid metabolites under the conditions studied, but all cell fractions incorporated [14C]-arachidonate into mono-, di- and tri-glycerides, as well as into phospholipids. These results demonstrate the differential capacities of the individual pituitary cell populations for metabolizing arachidonic acid, and emphasize the relative prominence of the oxidation pathways for arachidonate metabolism in the gonadotroph-enriched cell fraction of the rat pituitary gland.

Animals↗
PubMed1996

Evaluation of local toxicity after repeated intranasal vaccination of guinea-pigs.

In intranasal vaccination it is important that the adjuvant does not have any toxic effect on the sensitive nasal mucosa. In this study a histological and clinical evaluation of the effects of two different adjuvants in a vaccine containing detoxified diphtheria (DT) and tetanus toxoid (TT) in guinea pigs was done. The guinea pigs were divided in four groups and treated daily for 14 days with different formulations. Group I with saline, Groups 2 and 3 with the vaccines in a non-ionic surfactant formulation containing glycerides and Group 4 with tetraethyleneglycol formulation containing glycofurol. The guinea pigs in Groups 1, 2 and 4 were sacrificed on day 15 and Group 3, 1 week later and the tissues processed for histological examination. The animals remained healthy during the treatment and minor clinical signs, such as nose-blowing, decreased with time. The histological appearance, including the development of lymphoid tissue, was comparable in all groups. A specific toxic effect on the nasal mucosa by the different vaccine and adjuvant formulations was not observed.

Adjuvants, Immunologic↗
PubMed1996

Relationship between hepatic fatty acid desaturation and lipid secretion in the estrogenized chicken.

Desaturation of fatty acids is thought to facilitate their incorporation into glyceride and their subsequent secretion as lipoproteins. However, in the laying hen, the dramatic increase in hepatic lipogenesis is often paralleled by a liver steatosis that may affect egg production and even result in death. The balance between lipid secretion and storage, in relation to the fatty acid desaturation process, was therefore investigated in young male estrogenized chicken. Estrogen stimulation resulted in a dramatic increase in VLDL concentration (40.4 mg/ml versus 0.158 mg/ml in control) and hepatic lipid content (8.61 g/liver versus 1.47 g/liver in control). In estrogenized chickens, VLDL, total liver, and microsomes contained relatively more monounsaturated and less saturated and polyunsaturated fatty acids, whereas hepatic delta 9 desaturase activity was twofold higher. Moreover, in these birds, the proportion of monoenoic fatty acids was greater in VLDL (55%) than in the liver (50%), which was indicative of their preferential secretion. Therefore, under the influence of estrogen, fatty acid synthesis and desaturation are associated with and increased VLDL secretion, which limits the degree of hepatic accumulation of triglyceride and the risk of subsequent steatosis.

Animals↗
PubMed1979

Cyclic AMP and lipogenesis in fat cells from thyroidectomized rats.

Thyroid hormones regulate lipid metabolism by affecting lipogenesis as well as lipolysis. The present paper discusses the way thyroidectomy induced an enhancement in lipogenesis in rat fat cells. The doubling in the conversion of glucose to CO2 and fatty acids seen after thyroidectomy was found to be due to a modification in the actual pathway of glucose metabolism: there was a preferential stimulation of the conversion of glucose to CO2 by the pentose cycle (utilisation of [1-14C]glucose) while the production of fatty acids and glyceride-glycerol proceeded, respectively, much more, or only slightly more, via the pathway of [6-14C]glucose metabolism. Studies employing the phosphodiesterase inhibitor MIX, or the cyclic AMP analogue, DBcAMP showed that the lipogenic process depends on cyclic AMP. As the stimulatory effect of thyroidectomy was not abolished, however, lipogenesis must be under the independent control of both cyclic AMP and absence of thyroid hormones. Insulin, a further mediator of lipogenesis was found to further enhance the already preexisting high conversion of glucose to CO2 in fat cells from thyroidectomized rats. It is concluded that at least three factors modify lipogenesis: thyroidectomy, cyclic AMP and insulin; each achieving its effect in an independent manner.

1-Methyl-3-isobutylxanthine↗
PubMed1987

Lipid metabolic pathways operating in amphibian full-grown oocytes.

The utilization of (2-3H)-glycerol in lipid biosynthesis was analyzed in Bufo arenarum and Xenopus laevis full-grown oocytes. The precursor was more actively incorporated in Xenopus laevis oocytes. Neutral glycerides were the lipids displaying the highest levels of radioactivity followed by phosphatidylcholine and phosphatidylethanolamine. After reincubation of prelabeled oocytes in a saline buffer solution, a net fall in labeled phosphatidic acid concomitant with an increase in phosphatidylcholine were detected. The present findings establish that glycerolipid biosynthesis is operative in full-grown oocytes. In addition, Xenopus laevis oocytes seem to be metabolically more active.

Amphibians↗
PubMed1991

Lipogenesis depending on sexual maturity in female Japanese quail (Coturnix coturnix japonica).

1. Lipid biosynthesis in the liver as well as transport into the follicles in Japanese quail were investigated depending on sexual maturity at 5, 7, 9 and 11 weeks of age. Lipogenesis of the liver and incorporation of lipid into the follicles were determined by administering [1-14C]sodium acetate. 2. Body weight increased up to 9 weeks of age, whereas the weight of the liver and follicle did not alter after 7 weeks of age. 3. Fatty acid synthesis in the liver was at its highest at 7 weeks of age. Incorporation of 14C into non-saponifiable lipid and glyceride-glycerol fractions in the liver was not influenced by aging. 4. The labelled fatty acids in the follicle increased linearly as the birds became sexually mature.

Acetates↗
PubMed1993

Changes in photon dose distributions due to breast prostheses.

PURPOSE: Subcutaneous prosthetic implants had been routinely used for cosmetic augmentation and for tissue replacement following mastectomy over the last 15 years. The implants come in many forms as the gel filler material and surrounding shell material(s) vary significantly. METHODS AND MATERIALS: This study uses a thin window parallel-plate chamber and thermoluminescent dosimeters to quantify and dosimetric changes to surrounding breast tissue due to the presence of the prosthesis. A mammographic phantom was compared to four commercial prostheses, namely two silicon gel fillers within two different shells (silicon or silicon/polyurethane), a tri-glyceride within silicon and a bio-oncotic gel within silicon/polyurethane. The latter two implants were designed with a low-Z fill for diagnostic imaging benefits. RESULTS: Ion chamber results indicate no significant alteration of depth doses away from the implant with only minor canceling (parallel opposed) interface perturbations for all implants. In addition the physical changes to the irradiated prostheses were quantified by tonometry testing and qualified by color change. Each implant exhibited color change following 50 Gy, and the bio-oncotic gel became significantly less formable following irradiation, and even less formable 6 weeks postirradiation. CONCLUSION: The data indicates that prostheses do not affect the photon beam distribution, but radiation does affect the prostheses.

Breast↗
PubMed1976

Sustained administration of cyclazocine for antagonism of morphine.

The plasma levels, distribution and excretion of tritium were determined after administration of a single or sustained dose of 3H-cyclazocine to naive and morphine-addicted rats. The plasma levels reached and maintainat animals tolerant to morphine were cross-tolerant to cyclazocine. Although only half the administered radioactivity was excreted after either a single dose or a continuous administration, no appreciable concentration was found in any of the organs studied. The behavior of a single or sustained dose of cyclazocine was also determined in rabbits to evaluate the effect of the implant site on the drugs release rate and tissue biocompatibility. The release-rate of 3H-cyclazocine from a glyceride matrix implanted subcutaneously or intramuscularly could be controlled by modification of the matrix itself or by manipulation of the drug concentration within the matrix. Durations of action between a few days and a month were obtained by these means from devices that were both biodegradable and tissue compatible. The results indicate that the procedures used here may provide a practical means for administering narcotic antagonists to addicts.

Animals↗
PubMed1989

Systematic isolation and identification of membrane lipid oxidation products.

This report discusses the analytical procedure by which it is possible to isolate and identify the oxidation products of cellular and subcellular membrane lipids. The key point of this procedure is the method used for the transmethylation of the lipid material isolated from the tissues. In effect, both the conversion of the glycerides into methyl esters and the reduction of the hydroperoxyl groups into the corresponding hydroxyl groups is performed in one step, without breaking any oxirane rings that may be present. The methyl esters containing functional groups introduced by oxidative processes are separated from the non-modified ones by preparative TLC and are identified by GLC and GC-MS.

Chromatography, Thin Layer↗
PubMed2004

Synthesis and characterization of vegetable oil derived esters: evaluation for their diesel additive properties.

Trans-esterification of four vegetable oils; canola oil, greenseed canola oil from heat-damaged seeds, processed waste fryer grease and unprocessed waste fryer grease, was carried out using methanol, and KOH as catalyst. The methyl esters of the corresponding oils were separated from the crude glycerol, purified, and characterized by various methods to evaluate their densities, viscosities, iodine values, acid numbers, cloud points, pour points and gross heat of combustion, fatty acid and lipid compositions, lubricity properties, and thermal properties. The fatty acid composition suggests that 80-85% of the ester was from unsaturated acids. Substantial decrease in density and viscosity of the methyl esters compared to their corresponding oils suggested that the oils were in their mono or di glyceride form. The lubricity of the methyl esters, when blended at 1 vol% treat rate with ISOPAR M reference fuel, showed that the canola methyl ester enhanced the fuel's lubricity number. From the analyses performed, it was determined that the ester with the most potential for being an additive or a substitute for diesel fuel is the canola methyl ester, whose physical and chemical characteristics are similar to diesel fuel.

Calorimetry, Differential Scanning↗
PubMed2006

Application of emulsifiers/stabilizers in dairy products of high rheology.

The role played by low molecular weight emulsifiers (mono- and di-glycerides) and non-dairy stabilizers (alginates, carrageenans, gums and gelatins) in the formation and stabilization of liquid milk (and specifically a functionalized milk containing omega-3), yoghurt and ice cream has been reviewed. Attention is given to the interactions that may occur between the reactive sites on polysaccharide stabilizers and milk proteins and other milk components, and to the desirable characteristics, e.g., viscosity/consistency, appearance and mouthfeel, body and texture, imparted to yoghurt and ice cream by addition of emulsifiers and gums.

Dairy Products↗
PubMed2005

Physicochemical behavior of oil-in-water emulsions: influence of milk protein mixtures, glycerol ester mixtures and fat characteristics.

Different emulsions based on two protein mixtures (skim milk powder (SMP) and functional dairy proteins (FDP)), two mono-di-glyceride mixtures (MDG) (saturated and partially unsaturated), three fats (hydrogenated and refined coconut oils and refined palm oil) were studied to investigate the interactions occurring between the oil phase, low molecular weight emulsifiers and proteins. Immediately following the emulsification process, high diameters of fat globules were obtained in FDP-based systems, relevant of an aggregation phenomenon. At this stage, the fat globule size characteristics were dependent on the emulsifier and fat types present in the formulation. In contrast, SMP-based emulsions were characterized by low proportions of aggregated particles regardless the formulations. Ageing (24 h at 4 degrees C) promoted disaggregation in FDP formulations, while SMP emulsions were well stabilized. Just after the homogenization step, less proteins were required to stabilize the globule interface in FDP systems as compared to SMP ones. Only with SMP, the amount of protein load at the fat globule surface was influenced by the oil nature and/or by the emulsifier type. A competitive adsorption of caseins, over whey proteins, was demonstrated in the case of FDP. The ageing period promoted a displacement of the proteins adsorbed at the oil droplet interface, suggesting a disruption of the interfacial protein interactions. This disruption was more marked with SMP than with FDP and, in both cases, was more or less influenced by the emulsifier and oil phase natures. The variations of the viscosity and rheological parameters (elastic and viscous moduli) were not dependent on one specific component of the formulation.

Chemical Phenomena↗
PubMed2003

Lipid drug delivery and rational formulation design for lipophilic drugs with low oral bioavailability, applied to cyclosporine.

By using a rational formulation approach, we have tried to find the general characteristics for promising self-emulsifying drug delivery systems (SEDDS) based on natural lipid components, for the oral delivery of lipophilic drugs. Galactolipids, which are polar lipids commonly found in the chloroplast membranes of green plants, and a natural part of the human diet, were the main surfactants in these formulations. This was done in three clinical studies: a screening study, followed by a prediction study and, finally, a confirmatory study; in all 17 experimental formulations were investigated. The clinical trials were performed in healthy volunteers. Cyclosporine, a well-known lipophilic peptide, was incorporated in different SEDDS, and administered orally, followed by the measurement of the blood concentration of the drug over time. The pharmacokinetic parameters, which describe the rate and extent of absorption, were estimated. We found that fractionated oat oil (FOO) and medium chain monoglycerides (60:30:10 mono-, di- and tri-glycerides) promoted absorption, and resulted in a formulation with absorption characteristics nearly equal to the commercial formulation of cyclosporine, Sandimmun Neoral.

Adult↗
PubMed2006

Plasmalogens in the retina: in situ hybridization of dihydroxyacetone phosphate acyltransferase (DHAP-AT)--the first enzyme involved in their biosynthesis--and comparative study of retinal and retinal pigment epithelial lipid composition.

Plasmalogens (Pls) are phospholipids containing a vinyl-ether bond in the sn-1 position of the glycerol backbone. The physiological role of Pls is still enigmatic, especially within the eye where their deficiency leads to developmental abnormalities. In order to learn more about the functions of Pls in the posterior eye, we evaluated retinal Pl content as well as the expression of the first enzyme involved in Pls biosynthesis, dihydroxyacetone phosphate acyltransferase (DHAP-AT) in the retina. In situ hybridization of DHAP-AT mRNA was performed on rat eye sections. The Pl contents of calf retina and retinal pigment epithelium (RPE) samples were determined by high-performance liquid chromatography, thin-layer chromatography, and gas chromatography. DHAP-AT was highly expressed in the inner segment of photoreceptors and in the RPE, suggesting two distinct sites for Pl biosynthesis. Plasmenyl-ethanolamine was the prominent class of Pls in both neural retina and RPE (28-29% of the total phospho-ethanolamine-glycerides). According to the nature of the alkenyl residue linked to the sn-1 position of Pls, the most striking finding was the greater proportion of octadecanal-aldehyde in the sn-1 position of plasmenyl-ethanolamine of the neural retina compared to all the other classes of Pls in the neural retina and the RPE. These findings might be relevant to the biological functions of Pls against oxidative stress and in the formation of lipid rafts.

Acyltransferases↗
PubMed2006

Toxicology and pharmacology of sodium ricinoleate.

Ricinoleic acid constitutes approximately 90% of the fatty acid content of castor oil. Castor oil is known for its purgative effects and can be used to induce labor. Both castor oil and ricinoleic acid are approved for use in food. The mechanistic basis for purgative actions likely includes the membrane-disruptive effects of detergent-like molecules, such as sodium ricinoleate (a 'soap'). These effects have been shown to be dose-related and to exhibit a threshold below which no laxative response was evident, in both animals and in humans. Castor oil was not toxic in subchronic feeding studies in rodents at doses ranging up to 10-20% of the diet. Sodium ricinoleate, as a surfactant, demonstrates predictable skin and mucus membrane irritant effects, and may induce a Type IV dermal sensitization response in those previously sensitized to it. However, food-grade castor oil and sodium ricinoleate are prepared in such a manner as to be free of the castor bean constituents that have been proven to be the source of reported Type I immediate hypersensitivity responses. Feeding studies with castor oil in rodents provide a basis for a no observable adverse effect level (NOAEL) estimate of 7,500 mg/kg/day and 5,000 mg/kg/day in mice and rats, respectively (). Applying an uncertainty factor of 100 to the lesser of these NOAELs, one can thus estimate an acceptable daily intake (ADI) in man to be 50 mg/kg, or 3,000 mg of castor oil per day in an average 60 kg person. As ricinoleic acid constitutes approximately 90% of castor oil, applying this calculation to the 3,000 mg/day estimated ADI in humans for castor oil (given the rapid hydrolysis of castor oil glyceride in the gastrointestinal tract), the acceptable daily intake of ricinoleic acid may be as high as 2,400 mg/person.

Animals↗
PubMed2004

Hydration of an amphiphilic excipient, Gelucire 44/14.

The incorporation of drugs into Gelucires has been reported to increase the dissolution rate of poorly soluble drugs, often leading to improved drug bioavailability. In pharmaceutical applications, it is important to know how the excipient interacts with the drug, and how the mixture behaves during manufacturing, storage as well as during administration. The uptake of water by an amphiphilic excipient, Gelucire 44/14, has been investigated in two ways: storage in humid air and addition of liquid water. During exposure to humid air, the uptake goes in stages that correspond to the dissolution of the components of the excipient, starting with the most hydrophilic ones: glycerol, then polyethylene glycol (PEG), PEG esters (PEG monolaurate and PEG dilaurate), and finally glycerides (trilaurin). At each stage, the remaining crystals are in equilibrium with an interstitial solution made of water and the dissolved components. In this range of hydrations, the total uptake is close to the sum of the equilibrium hydrations of the components. In the pharmaceutical formulation, the active ingredient could dissolve in the liquid phase. At larger hydrations, obtained through addition of liquid water, the state of Gelucire 44/14 differs from those of its components. Gelucire 44/14 forms a lamellar phase and this phase melts at 30 degrees C whereas the pure PEG esters form hexagonal and cubic mesophases. The cubic mesophases do not melt until the temperature exceeds 40 degrees C. At body temperature, all crystals in Gelucire 44/14 melt to an isotropic fluid as soon as the total water content exceeds 5%. Therefore the formulation of amphiphilic excipients can be optimized to avoid the formation of mesophases that impede dissolution of the excipient at body temperature.

Body Fluids↗
PubMed2004

Effect of adsorbents on the absorption of lansoprazole with surfactant.

Lansoprazole (LPZ) is a representative drug that shows a high inter-subject variation of bioavailability (BA). Solid preparation composed of surfactant, adsorbent and LPZ were prepared to improve the dissolution and absorption of LPZ, and the BA of LPZ was measured in rats and dogs. As surfactant, Tween 80, polyoxy 60 hydrogenated caster oil derivative (HCO-60) and PEG-8 caprylic/capric glycerides (Labrasol) were used. As adsorbant, porous silicon dioxide (Sylysia 550, 320), magnesium aluminometa silicate (Neusilin S2, NS2N, US2) and porous calcium silicate (Florite RE) were used. After small intestinal administration of LPZ, 5.0 mg/kg, solution with HCO-60 showed the highest plasma LPZ concentration versus time curve of which C(max) and AUC was 0.46+/-0.01 microg/mL and 0.73+/-0.03 microgh/mL. By comparing to that after i.v. injection of LPZ solution, 2.0 mg/kg, the BA of LPZ from HCO-60 solution was 39.0%, which was about seven times higher than that of LPZ powder. To solidify the LPZ solution with HCO-60, adsorbents were used and the obtained solid preparations were used for in vitro release experiment. Sylysia 320, Neusilin S2 and Neusilin NS2 showed the T50% of about 1h. To evaluate the BA of these solid preparations, absorption study was performed in rats. Sylysia 550 system showed the higher AUC than other systems, showing the BA of 28.1%. Sylysia 550 system was filled in an enteric capsule and was orally administered to dogs and BA was compared with enteric tablet. The AUC of Sylysia 550 system was 2.16+/-0.26 microgh/mL and was greater than enteric tablet and the BA of 71.7% was obtained. Solid system composed of LPZ, surfactant and adsorbent has suggested the possibility as a good tool to improve the BA of LPZ.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2005

Significance of lipid matrix aging on in vitro release and in vivo bioavailability.

A polyglycolised glyceride carrier, Gelucire 50/13, was incorporated with paracetamol as a model drug, filled into hard gelatin capsules and stored at three different temperatures for various lengths of time. The resultant solidified matrix within the capsule was subjected to thermal analysis using differential scanning calorimetry (DSC) to ascertain its supramolecular structure. Polymorphic transformations towards more stable gelucire forms were observed upon aging the matrices, with samples stored at a temperature near the melting range of the lower temperature gelucire melting fraction showing the most profound changes. The increase in the rate of drug release from aged samples could be correlated to the alterations to the supramolecular structure of the gelucire. Accelerated drug release from aged samples could also be seen from in vivo studies using healthy human volunteers, although the extent of absorption was not affected. Therefore, even though the sustainability of release may be compromised by aging the gelucire matrices, the bioavailability of the incorporated drug is unlikely to be affected.

Acetaminophen↗