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Physiological studies on the utilization of oleic acid by Saccharomyces cerevisiae in relation to microbody development.

We studied the influence of specific growth conditions on the induction of beta-oxidation enzymes and rate of microbody proliferation in S. cerevisiae by oleic acid. Of all conditions tested, highest enzyme levels and microbody numbers were achieved in glucose-limited continuous cultures, supplemented with oleic acids second carbon source. Comparable enzyme levels were observed in identical cultures of peroxisome-deficient (pas) mutants of S. cerevisiae. These experiments showed chemostat cultures on glucose/oleic acid mixtures to be a method of choice for future studies on microbody biogenesis/assembly in constructed, conditional pas mutants.

Cell Division↗

Effect of oleic acid on canine gastroduodenal motility, pyloric diameter and gastric emptying.

The motility of the antrum, duodenum and pylorus was recorded with strain gauge transducers and induction coils in conscious beagle dogs. The effect of oleic acid on gastroduodenal motility and on the pyloric diameter was studied in the interdigestive state and during emptying of a mashed potato meal. The flow of digesta was observed fluoroscopically. Gastric emptying was measured by planimetry of the radiopaque gastric silhouette. The intraduodenal injection of oleic acid reduced the diameter of the pylorus in the empty stomach. In the digestive state oleic acid diminished gastric emptying of the potato meal. The antral motility was significantly diminished (amplitudes from 100 +/- 39.2 to 93 +/- 41.2 mV, contractile frequency from 4.3 +/- 0.6 to 3.8 +/- 1.5 min-1, motility index from 435 +/- 197 to 345 +/- 213 V, n = 3400-4700 contractions), whereas the duodenal motility was enhanced (amplitudes from 100 +/- 49.6 to 106 +/- 58.6 mV, motility index from 548 +/- 296 to 567 +/- 377 V, n = 5800-6400 contractions). The diameter of the pyloric opening during the phase of relaxation was about 25% less in comparison to the control meal. The weaker antral contractions and the less opening of the pylorus diminished gastric evacuation and enhanced retropulsion of the gastric chyme. A higher incidence of segmental duodenal contractions produced a slower transfer of digesta. Results demonstrated that gastric emptying was regulated by several co-operating factors. The pylorus was involved by producing different resistances to flow during its phase of relaxation.

Animals↗

Amrinone improves right ventricular ejection fraction and oxygen delivery without deterioration of extravascular lung water in canine oleic acid pulmonary injury.

Fourteen mongrel dogs were anaesthetized and mechanically ventilated with oxygen. After oleic acid was administered intravenously, amrinone 1 mg/kg was intravenously administered to one group followed by a continuous infusion of 10 micrograms/kg/min for one hour (amrinone group, n = 7). Isovolumetric saline was administered to the control group (n = 7). Amrinone slightly lowered PaO2 but significantly increased oxygen delivery and improved gastric intramucosal pH (pHi) during the first 30 minutes (7.33 +/- 0.13) compared with the control group (7.21 +/- 0.06, P < 0.05). The pHi remained higher in the amrinone group (7.30 +/- 0.15) than in the control group (7.16 +/- 0.06, P < 0.05) after the drug was withdrawn. Extravascular lung water was significantly augmented after oleic acid injection and sustained in all animals for the remainder of the study.

Amrinone↗

Comparative metabolism of erucic and oleic acid in hepatocytes from rats fed partially hydrogenated marine oil or palm oil.

Rats were fed for 8 weeks high fat diets containing 20% of either palm oil (PO) or linoleic-supplemented partially hydrogenated marine oil (PHMO). Hepatocytes were isolated from rats fasted overnight. Incubations were performed with albumin bound [10-14C] oleic acid and [14-14C] erucic acid, respectively, for 15 or 60 min. The cell viability was better than 90% after 60 min of incubation. The incorporation of radioactive metabolites into lipids of the cells and of the secreted products was determined. The uptake and channelling of 18:1 and 22:1 into various lipid classes in the hepatocytes were different, but were little influenced by the diets. Erucic acid disappeared more rapidly from the incubation medium than 18:1 at both incubation times and for both dietary groups, and was mainly incorporated into the hepatocyte triglycerides and found in the free fatty acid pool, whereas only small amounts of labelling were detected in the phospholipids. Oleic acid, however, was readily incorporated into both phospholipids and triglycerides, and little was found in the free fatty acid pool. For both the triglycerides and the free fatty acids more than 90% of the radioactivity was represented by the incubation fatty acid. Chain-shortened products were found in the phospholipids, especially after incubation with 22:1. The chain-shortening capacity was somewhat higher in the PHMO group, relative to the PO group. At both incubation times, the major part (80-90%) of the total radioactivity was found in the lipid-soluble fraction of the incubation medium, and for both groups 60-80% still as the original incubation fatty acid. 20-30% of the radioactivity was found in the triglycerides secreted from the cells. Phospholipids were secreted in minor amounts (1-5%). Water soluble products constituted 3-7% at 15 min of incubation, increasing to 10-12% at 60 min, highest when incubating with 22:1 and similar for both dietary groups.

Animals↗

Negative mesenteric effects of lung recruitment maneuvers in oleic acid lung injury are transient and short lasting.

OBJECTIVE: To test the hypothesis that repeated recruitment maneuvers (RMs) have sustained negative effects on mesenteric circulation, metabolism, and oxygenation 60 mins after RMs in pigs with oleic acid lung injury. Further, we aimed to test the hypothesis that an infusion of prostacyclin (PC) at 33 ng.kg.min would attenuate such possible negative mesenteric effects. DESIGN: Randomized, experimental, controlled study. SETTING: University hospital animal laboratory. SUBJECTS: A total of 31 anesthetized, fluid-resuscitated pigs with oleic acid lung injury. INTERVENTIONS: : Animals were randomized to one of the following four groups: a control group (n = 7) that received no intervention, recruitment group (n = 8) that underwent the RM sequence, a prostacyclin group (n = 8) that received an infusion of PC, and a recruitment-prostacyclin group (n = 8) that received an infusion of PC and concomitant RM sequence. MEASUREMENTS AND MAIN RESULTS: We measured systemic and mesenteric hemodynamic variables, jejunal mucosal perfusion, mesenteric lactate flux, jejunal tissue oxygen tension, and mesenteric oxygen delivery, uptake, and extraction ratio. Five minutes after RMs, mesenteric oxygen extraction ratio and mesenteric lactate flux were more prominently increased in the recruitment group, giving evidence of worsened mesenteric conditions after RMs. These signs of worsened conditions were further supported by more decreased jejunal tissue oxygen tension and portal vein oxygen saturation in the recruitment group. PC preserved mesenteric oxygenation, as indicated by less of a decrease in portal vein oxygen saturation at the time corresponding to 5 mins after RM and less of a decrease in mesenteric oxygen delivery at the time corresponding to 15 mins after RM. PC preserved mesenteric oxygenation as indicated by less of a decrease in portal vein oxygen saturation at 5 mins after RM and an attenuated increase in mesenteric oxygen extraction ratio at 5 mins after RM. There was a trend toward worsened jejunal mucosal perfusion, although not significant. CONCLUSIONS: In an oleic acid lung injury model, three repeated RMs did not improve systemic oxygenation or lung mechanics. Negative effects on mesenteric oxygenation and metabolism were transient and short lasting. The intestinal effects of PC during RMs were minor and opposing, showing preserved oxygenation but a trend toward worsened mucosal perfusion.

Animals↗

Evaluation of an oleic acid water-in-oil-in-water-type multiple emulsion as potential drug carrier via the enteral route.

A water-in-oil-in-water (W/O/W) emulsion composed of oleic acid was used as a carrier of carboxyfluorescein (CF) via the enteral route, as a model for future drug transport. The absorption of CF in the small intestine of rats given the emulsion (W/O/W group) was compared with the absorption in a group administered CF alone (CF group), and a group administered a mixed micelle of oleic acid and a surface-active agent in CF solution (MM group). Higher amounts of CF were absorbed in the W/O/W and MM groups than in the CF group. At 120 min, the amount of CF remaining in the intestinal tract was smaller in the MM group than in the W/O/W group. In the early period, CF excretion into bile was higher in the MM group than in the W/O/W group, but from 120 to 360 min, CF excretion in the W/O/W group was higher than in the MM group (non-specific). The blood CF level was significantly higher at 240 and 360 min in the W/O/W group than in the other two groups. The highest concentration in lymph was found in the W/O/W group. The W/O/W emulsion was considered superior to the micelles because it maintained a higher blood level of CF over long periods and transferred it to the lymph. This suggests that the W/O/W emulsion is applicable as a drug carrier via the enteral route.

Administration, Oral↗

Nutritive value of high-oleic acid sunflower seed for broiler chickens.

Two experiments were conducted to evaluate the use of high-oleic acid sunflower seed (HOASS) in broiler diets. In the first experiment, HOASS was included in a basal diet at 80, 160, 240, and 320 g/kg at the expense of the energy-yielding ingredients, and the AMEn values of the experimental diets were determined. The linear regression equation of AMEn values on rate of inclusion was calculated. Extrapolation value for the AMEn of HOASS at 100% inclusion was 4224 +/- 77 kcal/kg. In the second experiment, diets containing up to 200 g of HOASS/kg were given to broilers (Cobb) from 0 to 42 d, and performance parameters, nutrient digestibility, and AMEn value were determined at 12 and 42 d of age. Birds fed the diets containing 100 and 200 g HOASS/kg gained less weight (P < 0.001) than those fed the diet containing no HOASS at both ages. Differences in feed-to-gain ratio were only significant for the diet with the highest concentration of HOASS. Apparent digestibility of nutrients and dietary AMEn contents of diets increased with age; thus, the mean digestibility of diets for amino acid N and for total fatty acids increased from 82.1 and 68.0% at 12 d to 86.7 and 84.7% at 42 d, respectively, and AMEn content was improved by 6.5%. Inclusion of HOASS in the diet decreased the digestibilities of fat, oleic acid, and total fatty acids. A decrease in the digestibility of aspartic acid, threonine, tyrosine, valine, isoleucine, and AMEn with increasing inclusion level was also observed at 12 d of age.

Aging↗

[Cardiocirculatory effects of halothane and isoflurane in respiratory distress caused by oleic acid].

INTRODUCTION: When lungs are damaged or affected by edema they behave differently from healthy lungs in the presence of drugs that can modify vascular reactivity. OBJECTIVES: To determine the effects of halothane and isoflurane on pulmonary edema induced by oleic acid in dogs. MATERIAL AND METHODS: Eighteen dogs were anesthetized with sodium pentothal. Hemodynamic and lung parameters as well as end-tidal gases were monitored. Pulmonary edema was induced with an injection of oleic acid (0.1 ml/kg). Five periods were studied: 1) before injection of oleic acid; 2) 90 min after injection; 3) 20 min after ventilation with 1 MAC halothane or isoflurane; 4) 20 min after 2 MAC ventilation with the assigned anesthetic, and 5) 20 min after withdrawal of anesthetic. RESULTS: With halothane, cardiac output and arterial blood pressure decreased significantly. With isoflurane, arterial pressure decreased by way of changes in vascular resistance. Neither anesthetic affected hypoxic pulmonary vasoconstriction. CONCLUSIONS: Neither anesthetic worsens arterial oxygenation in a model of pulmonary edema that is similar to adult respiratory distress.

Anesthetics, Inhalation↗

Protective effect of cobra venom factor on pulmonary injury induced by oleic acid.

The protective effect of cobra venom factor (CVF), separated from the venom of Naja naja atra, on pulmonary injury induced by oleic acid was reported. The blood gas tensions, tidal volume, transthoracic pressure and pulmonary arterial pressure in anaesthetized dogs were continually monitored. The experimental results showed that CVF, given 20 h before the dosage depleting complements exceed 95%, significantly attenuated oleic acid-induced pulmonary dysfunction, including hypoxemia, increasing veno-arterial shunt and P(A-a)O2 and decreasing dynamic compliance and pulmonary blood flow. Histological examination of lung tissues after the experiment also showed improvement of hyaline membrane formation, alveolar haemorrhage and pulmonary arteriolar thrombosis. It was evident that the depletion of serum complements by CVF inhibited the development of lung injury induced by oleic acid. CVF might be a potentially useful drug for the treatment of respiratory distress syndrome in the near future.

Animals↗

Formation of conjugated delta8,delta10-double bonds by delta12-oleic-acid desaturase-related enzymes: biosynthetic origin of calendic acid.

Divergent forms of the plant Delta(12)-oleic-acid desaturase (FAD2) have previously been shown to catalyze the formation of acetylenic bonds, epoxy groups, and conjugated Delta(11),Delta(13)-double bonds by modification of an existing Delta(12)-double bond in C(18) fatty acids. Here, we report a class of FAD2-related enzymes that modifies a Delta(9)-double bond to produce the conjugated trans-Delta(8),trans-Delta(10)-double bonds found in calendic acid (18:3Delta(8trans,10trans,12cis)), the major component of the seed oil of Calendula officinalis. Using an expressed sequence tag approach, cDNAs for two closely related FAD2-like enzymes, designated CoFADX-1 and CoFADX-2, were identified from a C. officinalis developing seed cDNA library. The deduced amino acid sequences of these polypeptides share 40-50% identity with those of other FAD2 and FAD2-related enzymes. Expression of either CoFADX-1 or CoFADX-2 in somatic soybean embryos resulted in the production of calendic acid. In embryos expressing CoFADX-2, calendic acid accumulated to as high as 22% (w/w) of the total fatty acids. In addition, expression of CoFADX-1 and CoFADX-2 in Saccharomyces cerevisiae was accompanied by calendic acid accumulation when induced cells were supplied exogenous linoleic acid (18:2Delta(9cis,12cis)). These results are thus consistent with a route of calendic acid synthesis involving modification of the Delta(9)-double bond of linoleic acid. Regiospecificity for Delta(9)-double bonds is unprecedented among FAD2-related enzymes and further expands the functional diversity found in this family of enzymes.

Amino Acid Sequence↗

Effects of dietary oleic-rich oils (virgin olive and high-oleic-acid sunflower) on vascular reactivity in Wistar-Kyoto and spontaneously hypertensive rats.

The effects of two monounsaturated fatty acid (MUFA)-rich diets, containing virgin olive oil (OO) and high-oleic-acid sunflower oil (HOSO), on development of vascular response from isolated thoracic rat aorta and lipid composition and fatty acid composition were studied and compared with samples from rats fed on a control diet. Dietary MUFA oils were fed for 6 weeks to spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats from 4 weeks of age. The maximum contraction of aortic ring preparations in response to phenylephrine (10(-6) m) was significantly decreased in SHR rats fed with OO (0.81 (sem 0.05) v. 1.18 (sem 0.09) g, and treatment with HOSO did not alter the phenylephrine-induced contractions. The relaxant responses to acetylcholine (10(-5) m) were significantly enhanced (30.03 (sem 0.70) v. 18.47 (sem 0.28) %, in the rings from SHR rats treated with OO, and were more pronounced than in WKY rats In the same way, OO attenuated the dose-response curves induced by phenylephrine (10(-8)-10(-5) m) from SHR rats, accompanied with a slower contraction. These results suggest that only the chronic feeding of OO diet was able to attenuate the vascular response of rat aorta. In addition, an increase in phospholipid content (186.7 (sd 3.2) v. 159.1 (sd 11.3) g/kg, and changes in the fatty acid composition of aorta (mainly a decrease in arachidonic acid) could contribute to improving endothelial function. Therefore, the effects can not be attributed exclusively to the content of MUFA (mainly oleic acid). Other components of OO, such as polyphenols, not present in HOSO, may help to explain the vascular protective effect of OO consumption.

Acetylcholine↗

Secretion of lipids, apolipoproteins, and lipoproteins by human hepatoma cell line, HepG2: effects of oleic acid and insulin.

The aim of this study was to determine the effect of oleic acid and insulin on the secretion of lipoproteins by HepG2 cells grown in minimum essential medium. Triglycerides were the major neutral lipid (57% of total) and apoB was the predominant apolipoprotein (56% of total) secreted by these cells. The addition of oleate resulted in a two-fold increase in the concentration of neutral lipids but only a slight to moderate increase in the apolipoprotein (A-I, A-II, B, and E) levels. The secretion of very low density lipoproteins (VLDL) was stimulated by 425%, low density lipoproteins (LDL) by 77%, and high density lipoproteins (HDL) by 68%. Whereas neutral lipid composition of LDL was unchanged, the VLDL particles contained a significantly higher percentage of triglyceride and lower percentages of cholesterol and cholesteryl esters compared with VLDL secreted in the absence of oleate. Oleate had no significant effect on the composition of apolipoproteins in VLDL, LDL and HDL. In basal medium, insulin caused a significant decrease in the secretion of neutral lipids and apolipoproteins, particularly triglycerides and apoB. In addition to a 60-68% reduction in the total concentration of VLDL and LDL, insulin altered their composition by producing particles that had a significantly lower content of triglycerides, contained less apoB, and were deficient in apoE. There were no major changes in the concentration or composition of HDL particles. Insulin had a similar but less pronounced effect on the concentration and composition of lipoproteins secreted in the presence of oleate. The increased accumulation of triglycerides in the HepG2 cells concomitant with their reduced levels in the medium suggests that insulin may affect the secretion rather than synthesis of triglyceride-rich lipoproteins.

Apolipoproteins↗

Liposomes enriched in oleic acid are less susceptible to oxidation and have less proinflammatory activity when exposed to oxidizing conditions.

As there is frequently a reciprocal relationship between oleic acid and linoleic acid content in LDL after dietary supplementation, it is difficult to determine the independent effects of oleic and linoleic acid on LDL oxidation. It is also unknown whether monounsaturated fatty acid enrichment might reduce the generation of proinflammatory products that occur when the polyunsaturated fatty acid-rich phospholipids within lipoproteins undergo mild oxidation. To address these issues, we exposed liposomes containing variable amounts of oleic, linoleic, and arachidonic acid to oxidizing conditions. Liposomes enriched in oleic acid but with constant amounts of linoleic acid were less susceptible to oxidation and had significantly greater lag times and time to half maximum conjugated diene formation. When mildly oxidized, liposomes containing either linoleic acid or arachadonic acid increased monocyte chemotaxis and monocyte adhesion to endothelial cells nearly 5-fold, demonstrating that oxidation products of both these polyunsaturated fatty acids are bioactive. The addition of a platelet activating factor receptor antagonist to endothelial cells inhibited stimulation of monocyte adhesion by oxidized liposomes, suggesting that some bioactive oxidation products of polyunsaturated fatty acids may resemble platelet activating factor in structure. In contrast, when liposomes were enriched in oleic acid, monocyte chemotaxis and monocyte adhesion were nearly completely inhibited. These results suggest that enriching lipoproteins with oleic acid may reduce oxidation both by a direct "antioxidant"-like effect and by reducing the amount of linoleic acid available for oxidation as well as reduce the generation of bioactive particles that occur during mild oxidation.

Animals↗

Alveolar permeability enhancement by oleic acid and related fatty acids: evidence for a calcium-dependent mechanism.

Pulmonary exposure to oleic acid (OA) is associated with permeability alterations and cellular damage; however, the exact relationship between these two effects has not been clearly established. Using cultured alveolar epithelial monolayers, we demonstrated that OA and some other fatty acids (< or = 50 microM) can induce permeability changes without detectable cellular damage. At higher concentrations, however, OA caused severe membrane damage and leakage to solute flux. The permeability enhancing effect of OA was observed with both the paracellular marker 3H-mannitol and the lipophilic transcellular indicator 14C-progesterone. While the effect of OA on transcellular permeability may be attributed to its known effect on membrane fluidity, the paracellular promoting effect of OA and its mechanism are not well established. We postulated that OA may increase paracellular permeability through a Ca(2+)-dependent tight junction mechanism. Using dual-excitation fluorescence microscopy, we demonstrated that OA can increase intracellular calcium, [Ca2+]i, in a dose-dependent manner. This effect was transient at low OA concentrations (< or = 50 microM) but became more pronounced and sustained at higher concentrations. Free hydroxyl and unsaturated groups were required for this activation since esterified OA (oleic methyl ester) and stearic acid (a saturated fatty acid with equal chain length) had much reduced effects on both the [Ca2+]i and the permeability alterations. Degree of unsaturation was unimportant since linolenic acid (18:3), linoleic acid (18:2), and OA (18:1) had similar and comparable effects on the two parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ion-pairing interactions between 99MTc-based myocardial imaging agents and oleic acid.

PURPOSE: The purpose was to test the hypothesis that ion-paired facilitated transport is of importance in successful myocardial uptake of cationic imaging complexes. In vitro ion-pairing interactions between oleic acid and seven cationic technetium-99m complexes based on the ligands 1,2-bis[bis(2-ethoxyethyl) phosphino ethane] (tetrofosmin), 1,2-bis(dimethyl phosphino ethane) (DMPE) and 1,2-bis(diethyl phosphino ethane) (DEPE) has been studied. The complexes studied were: [99mTc O2 (tetrafosmin)2]+ (commercially available as myocardial perfusion imaging kit, Myoview), [99mTc O2 (DMPE)2]+, [99mTc O2 (DEPE)2]+, [99mTc Cl2 (DMPE)2]+, [99mTc Cl2 (DEPE)2]+, [99mTc (DMPE)3]+ and [99mTc (DEPE)3]+. METHODS: Ion-pairing interactions were monitored using a rotating diffusion cell containing a solid supported liquid membrane and by formation of lipid monolayers. RESULTS: Depletion of complex from the donor phase into an isopropyl myristate model membrane was generally in proportion to distribution coefficient and transfer to the receptor compartment was in all cases very small. However, by the inclusion of 5% w/v oleic acid, which is used in myocardial metabolism, partitioning was enhanced by amounts which varied depending on the tendency to form complex/oleate ion-pairs. Transfer to the receptor compartment was increased for most complexes when given sufficient time to diffuse through the membrane. The complex [99mTc O2 (tetrofosmin)2]+ appeared to form particularly stable ion-pairs with oleic acid. Monolayer formation also indicated ion-pairing interactions. CONCLUSIONS: The results suggested that whether or not a complex is taken up by the myocyte may depend on its ability to 'hitch a ride' by ion-pairing with the myocytes energy source--a molecule of long chain fatty acid.

Cations↗

Sensitivity of scintigraphy for detection of pulmonary capillary albumin leak in canine oleic acid ARDS.

Computerized gamma scintigraphy was shown in this study to be a sensitive technique for the detection and kinetic analysis of a pulmonary capillary protein leak. A rising lung:heart radioactivity of 'slope of injury' was found at each dose of intravenous oleic acid in dogs from 0.01 to 0.20 ml/kg (p less than 0.01). This 'slope of injury' was proportional to the dose of oleic acid (r = +0.97; p less than 0.004) and was more sensitive than changes in arterial oxygen tension, standard chest radiography, bloodless wet:dry lung weight, or alveolar epithelial membrane permeability. Only standard light microscopy and right lymphatic duct flow were able to document the leakage of protein detected by gamma scintigraphy at 0.01 ml/kg oleic acid.

Albumins↗

Continuous negative extrathoracic pressure ventilation, lung water volume, and central blood volume. Studies in dogs with pulmonary edema induced by oleic acid.

The effect of continuous positive-pressure ventilation (CPPV) on extravascular lung water volume has been investigated, but there is only one report which studied the effect of continuous negative extrathoracic pressure ventilation (CNETPV). The effect of CNETPV on central blood volume (CBV) has not been studied. Changes in intrathoracic pressure by CNETPV may alter lung water volume and CBV. In this study the effects of CNETPV on lung water volume and CBV were compared with those of intermittent positive-pressure ventilation (IPPV) and CPPV in dogs with pulmonary edema induced by oleic acid. Nine mongrel dogs were anesthetized and given oleic acid at 0.06 ml/kg intravenously to induce pulmonary edema; CNETPV was applied with a cuirass and a negative thoracic pressure ventilator (Kimura OKT-100) for 1 h. Extravascular lung water volume (as extravascular thermal volume [EVTV]) and CBV were estimated with the double-indicator dilution method using thermal-sodium; PEEP and continuous negative extrathoracic pressure were matched to produce the same increments in FRC. The EVTV increased during CNETPV but did not change during CPPV. The CBV decreased during CPPV but did not change during CNETPV. An increase of transmural pulmonary microvascular pressure was thought to be one of the reasons for the increase in EVTV with CNETPV.

Animals↗