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Genes regulated by arachidonic and oleic acids in Raji cells.

FA are known to modulate immune function in conditions such as arthritis and lupus erythematosus. The effects of arachidonic (AA) and oleic acids (OA) on function and pleiotropic gene expression of Raji cells were investigated. The following parameters were evaluated: cytotoxicity as assessed by loss of membrane integrity and DNA fragmentation; proliferation as measured by [14C]thymidine incorporation; production of interleukin (IL)-10, interferon (INF)-gamma, and tumor necrosis factor (TNF)-alpha; and expression of pleiotropic genes by a macroarray technique (83 genes in total). AA was more toxic to Raji cells than OA. Both FA promoted an increase in Raji cell proliferation at 75 microM, whereas OA at high concentrations (200 microM) decreased proliferation. AA reduced the production of IL-10, TNF-alpha, and INF-gamma. On the other hand, OA provoked an increase of INF-gamma production but did not affect the production of IL-10 and TNF-alpha. The proportions of genes with altered expression were 27% for AA and 35% for OA. The FA affected the expression of genes clustered as: cytokines, signal transduction pathways, transcription factors, cell cycle, defense and repair, apoptosis, DNA synthesis, cell adhesion, cytoskeleton, and hormone receptors. The most remarkable changes were observed in the genes of signal transduction pathways. These results led us to conclude that the effect of these FA on B-lymphocytes includes regulation of gene expression. Thus, diets enriched with fat containing OA or AA may affect B lymphocyte function in vivo.

Arachidonic Acid↗

Cryo-TEM investigation of phase behaviour and aggregate structure in dilute dispersions of monoolein and oleic acid.

Cryo-transmission electron microscopy (cryo-TEM) was used to image the microstructure in dilute sonicated dispersions of monoolein and oleic acid. The aim of the study was to explore how different experimental parameters, such as sample composition, total lipid concentration, pH, and ageing affect the phase behaviour and aggregate structure. Our investigations show that a rich variety of lamellar and non-lamellar structures, including liposomes and particles of cubic and inverted hexagonal phase, may form depending on the experimental conditions. The results are analyzed and discussed in relation to existing phase diagrams and earlier investigations concerning phase- and structural behaviour in monoolein/oleic acid/water systems.

Colloids↗

Selected lobar injury after infusion of oleic acid.

A model of respiratory distress has been developed using sheep in which an isolated lobar injury is induced by infusion of oleic acid into a selected lobar artery. The directed insult permits acute and chronic phase study without the requirement of intensive pulmonary support. One hour after selective lobar injury the affected pulmonary venous oxygenation (Ppvo2) was reduced from greater than 310 to 66-90 Torr. Ppvo2 was most impaired at 48 h (40-55 Torr), but showed improvement by 96 h postinjury. Radionuclide estimates of lobar ventilation and perfusion demonstrated an initial fall in ventilation by 51% and corresponding 41% reduction in perfusion. By 24 h the depression of perfusion matched that of ventilation. Sequential light and scanning electron microscopy demonstrated the presence of a nonhomogeneous injury with areas of both complete parenchymal replacement by fibrous tissue and those with minimal architectural distortion. The selective injury model offers a useful methodology for the evaluation of the effects of various agents on the acute and chronic response of the lung to injury.

Acute Disease↗

[Comparison in genetically hyperlipoproteinemic and normal rats of the secretion of lipids synthesized by isolated livers perfused with isotopic oleic acid and glycerol at high concentrations].

After perfusing isolated livers of Zucker fa/fa ad Fa/- rats with loads of [9,10-3H2] oleic acid (346 mumol) and [1-14C] glycerol (115 mumol), glycerol inhibited the hepatic secretion of triacylglycerol and phospholipids in the two groups of rats. However, the amount of acylglycerols synthetized from these exogenous substrates is slightly higher in the obese rats than in the normal rats. These results suggest that glycerol, present in high amounts in blood of fa/fa rats, failed to regulate triacylglycerols and phospholipids secretion.

Animals↗

Temporal response of lung impedance after i.v. oleic acid in dogs.

We measured total and regional lung impedances in six anaesthetized, paralysed dogs every min for 1 hour immediately following i.v. oleic acid administration. Total lung impedance was assessed from pressure and flow data collected at the airway opening during conventional mechanical ventilation. We obtained regional lung impedance at two sites simultaneously using our recently developed alveolar capsule oscillator technique (Davey, B.L.K. and J.H.T. Bates, 1993, Respir. Physiol. 91:165-182). We found that total lung resistance (RL) increased for the first 15 min in a manner suggestive of an initial bronchoconstrictive event, and then remained stable for the remainder of the hour. EL continued to increase throughout the entire period. In contrast, regional alveolar resistance (RA) increased initially and then returned to baseline, while regional alveolar elastance (EA) remained unchanged. We interpret these results as reflecting an initial transient bronchoconstriction together with a progressive accumulation of oedema in the dependent regions of the lung. This implies that the changes in EL were due mostly to increased heterogeneity of regional ventilation, and that non-dependent lung regions may remain virtually unaffected mechanically even when the overall oedematous changes in lung mechanics are severe.

Airway Resistance↗

A standardized method of oleic acid infusion in experimental acute respiratory failure.

UNLABELLED: Commonly, acute respiratory failure (ARF) in laboratory animals is induced through the intravenous infusion of oleic acid (OA). The methods by which OA is infused, and the methods by which droplets are generated, differ greatly among investigators. The resulting ARF, and the distribution of the underlying pulmonary pathology, are not highly reproducible. A method was developed that generated a reproducible, known spectrum of OA microdroplets. This method was applied to infuse a known volume of OA into the vena cava superior (VCS) in sheep, to induce ARF. In vitro studies were conducted in an observation chamber filled with saline or plasma. The distal end was cut off a 7F Swan Ganz catheter. The catheter was immersed in an observation chamber. Through one of the channels OA was infused at a low flow rate while saline was infused at variable high flow rates through a second channel. The size and the distribution spectrum of the so generated OA droplets were determined from flash photographic studies. The distribution and the size of the microdroplets depended on the media in the observation chamber, and on the saline infusion rate. In vivo studies were conducted in six anesthetized and ventilated sheep. We chose in our in vivo studies a saline flow rate of 126 mL/min and at an OA flow rate of 3 mL/min, that generated OA microdroplets 125 +/- 32 microm SD in size. OA microdroplets were generated in situ in the VCS and where then embolized into small pulmonary vessels. A total dose of 0.06 mL/kg of OA was administered in three separate doses of 0.02 mL/kg, each 10 min apart. The evolving ARF was manifested by a progressive deterioration in arterial blood gases, and a uniform opacification of all lung fields on chest X-ray films. At autopsy the lungs were diffusely consolidated. CONCLUSION: A method was developed to standardize the infusion of OA in laboratory animals that resulted in diffuse involvement of the all lungs, with a predictable and reproducible severe acute respiratory failure.

Acute Disease↗

Reversal of altered intestinal mucosal immunity in rats fed elemental diet by supplementation of oleic acid.

We have previously demonstrated that elemental diet (ED) induces decreased lymphocyte transport in intestinal lymph and significant changes in T cell subsets and the number of IgA-containing cells in gut-associated lymphoid tissues of rats. In order to examine whether the low fat content contributes to the induction of immunological changes in gut-associated lymphoid tissues, the effects of additional fatty acid in the ED were investigated. Rats were divided into four groups: elemental diet alone, elemental diet supplemented with 5% oleic acid (OA), elemental diet with 10% OA and conventional diet as a control. These diets were given at the same daily calorie intake for 4 weeks. The flow rate of intestinal lymph showed no significant difference between the four groups. However, lymphocyte flux as well as the percentage of CD3+ and CD4+ cells were significantly greater in the control and the 10% OA groups than in the ED and 5% OA groups. Intestinal lymph showed decreased concentrations of IgG and IgA in the ED group, whereas the addition of 10% OA significantly attenuated the decrease in these levels. In mesenteric lymph nodes, the CD4+/CD8+ ratio was significantly decreased in the ED group, but 10% OA reversed this change. Immunohistochemical analysis of the ileal mucosa showed that in the ED group the population of CD4+ cells was decreased, while the number of CD8+ cells was increased. Supplementation of OA to ED produced similar stepwise attenuation of the changes in lymphocyte subpopulations in the lamina propria, while the 10% OA group reached levels that were not statistically different from controls. In the elemental diet group, there was a significant decrease in immunoglobulin-containing cells of the IgA class in the lamina propria of the intestine. Similarly, the addition of OA induced dose-dependent recovery in the number of IgA-containing cells. These results suggest that a low dietary concentration of fat may be closely related to changes in lymphocyte transport in intestinal lymph and mucosal immunity of intestinal mucosa induced by the feeding of a long-term ED.

Animals↗

Enhancement of the oral bioavailability of cinnarizine in oleic acid in beagle dogs.

The present study was an attempt to develop a new dosage form of cinnarizine, which is slightly soluble in water, using lipid as a vehicle. The solubility of cinnarizine in several organic solvents was determined. It was found that cinnarizine dissolved well in oleic and linoleic acids. The bioavailability of cinnarizine from the oral administration of an oleic acid solution in a hard capsule was investigated and compared with that of a cinnarizine tablet, using beagle dogs. When cinnarizine was administered in a capsule, the bioavailability was greatly enhanced [i.e., the maximum concentration (Cmax) and AUC values were 2.9 and 4.0 times larger than those of a cinnarizine tablet, respectively]. Meanwhile, the tmax value (the time to reach Cmax) was unchanged. The absorption of cinnarizine from an oleic acid solution was considered to depend on the action of bile salts. This was supported by the results of a dissolution test using a bile salts solution as the dissolution test medium.

Animals↗

Potentiating effects of oxygen in lungs damaged by methylcyclopentadienyl manganese tricarbonyl, cadmium chloride, oleic acid, and antitumor drugs.

The intraperitoneal administration of methylcyclopentadienyl manganese tricarbonyl (MMT) and cyclophosphamide, exposure to an aerosol of cadmium chloride, intravenous administration of oleic acid, and intratracheal instillation of bleomycin to young female BALB/c mice or CD/CR rats result in acute lung injury. Pulmonary morphology and lung collagen content were examined in animals treated with these chemicals alone or in combination with an elevated oxygen concentration (80%) in the inspired air. In mice, the development of fibrosis could be significantly enhanced if animals treated with MMT, cadmium chloride, cyclophosphamide, or bleomycin were exposed to 80% oxygen immediately following exposure to these agents. In rats only cyclophosphamide- and bleomycin-induced acute lung injury was potentiated by hyperoxia, resulting in significant enhancement of lung collagen content. The pathogenesis responsible for this differential species response of pulmonary injury to hyperoxia remains to be investigated.

Animals↗