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At least 649 records · Page 36Linked to original sources
PubMed2006

Examination of the impact of a range of Pluronic surfactants on the in-vitro solubilisation behaviour and oral bioavailability of lipidic formulations of atovaquone.

Exogenous surfactants are increasingly used to enhance the dispersion properties of lipid-based formulations of poorly water-soluble drugs, yet their possible effects on formulation digestion and oral bioavailability in-vivo are not well documented. In this study, in-vitro dispersion and digestion experiments were conducted using formulations comprising a blend of long-chain glycerides, ethanol, a model poorly water-soluble drug (atovaquone), and a series of surfactants including Cremophor EL and a range of Pluronic surfactants (Pluronics L121, L61, L72, L43 and F68). Inclusion of Cremophor EL, a surfactant with a high hydrophilic-lipophilic balance (HLB), promoted complete digestion of the formulation and effective dispersion and solubilisation of the lipolytic products and co-administered drug. Surprisingly, formulations containing the Pluronic (L121) with the lowest HLB (0.5) equally effectively promoted digestion and drug solubilisation and a trend towards decreased digestion and drug solubilisation was observed with Pluronics of increasing HLB values. All formulations effectively prevented drug precipitation, suggesting possible utility in-vivo, and no correlation was evident between the ability of the formulations to self-emulsify on dispersion and to promote drug solubilisation on digestion. Subsequent assessment of the oral bioavailability of atovaquone after administration of formulations containing Cremophor EL or Pluronic L121 or a simple solution of atovaquone in long-chain glycerides confirmed the utility of lipid-based formulations for enhancing the oral bioavailability of poorly water-soluble drugs such as atovaquone, but also indicated that in some cases microemulsion preconcentrate formulations may not provide additional bioavailability benefits beyond that achievable using simple lipid solutions.

Administration, Oral↗
PubMed1994

Lipid interference with fluorometric assay of DNA in adipose tissues under various conditions.

Interference by lipids with fluorometric assay of DNA in adipose tissues using Hoechst 33258 was investigated. Mixed glycerides shifted the emission maximum of standard DNA and induced a dose-dependent increase in fluorescence intensity. Glycerides in the samples containing a known concentration of DNA yielded erroneously higher DNA concentrations. The DNA concentrations obtained from acetone-defatted white and brown adipose tissues (WAT and BAT) were lower than those of non-defatted ones, while DNA content did not differ in low lipid-containing skeletal muscle between defatted and non-defatted samples, indicating that large amounts of lipids interfere with DNA measurement using Hoechst 33258 and that acetone defatting is a simple method to avoid this interference. Using this defatting method, the cellularity of WAT and BAT was estimated in rats under various experimental conditions. Cold-acclimation and repetitive immobilization stress decreased the body weight gain and the epididymal WAT weight. Sucrose overfeeding increased WAT weight but not body weight. These treatments of 4 weeks' duration did not induce any significant difference in WAT cell number from controls, while cold-acclimation increased the tissue cell number as well as the BAT weight.

Acetone↗
PubMed2002

Duodenal infusion of glucose decreases milk fat production in grass silage-fed dairy cows.

Four lactating dairy cows were arranged in a 4 x 4 Latin square design to study the effect of intestinal glucose supply on milk fat synthesis. Glucose (0, 443, 963, and 2398 g/d) was continuously infused in the duodenum over 14-d periods. Grass silage-based diets were formulated to be isoenergetic and isonitrogenous and met 100 and 110% of energy and protein requirements according to INRA (1989). Mammary uptake of nutrients was estimated through assay of arteriovenous differences and blood flow measurements. Glucose infusions decreased arterial concentrations of acetate, beta-hydroxybutyrate, and nonesterified fatty acids linearly and total glycerides curvilinearly. Milk fat yield was slightly decreased (- 52 g/d) between 0 and 963 g/d of glucose and milk fatty acid composition was modified by a marked decrease in long-chain fatty acids and an increase in de novo synthesis. The decrease in long-chain fatty acids, related to the decreased mammary uptake of plasma total glycerides, was likely due to a decrease in lipoprotein lipase and esterification activities. In regards to the evolution of metabolite concentrations in milk, the enhanced de novo synthesis and chain elongation was probably allowed by a greater availability of NADPH synthesized through pentose phosphate pathway. The greatest dose of glucose clearly decreased milk fat yield (-234 g/d). A mammary cell mediated intracellular reaction likely caused a homothetic decrease in milk fatty acids. However, reduced synthesis was not due to a shortage of glycerol-3-phosphate because its milk concentration remained unchanged. In conclusion, changes in exogenous glucose supply, in cows fed a grass silage-based diet, decreased milk fat production and modified milk fatty acid composition.

3-Hydroxybutyric Acid↗
PubMed1984

Roles of acetate and its interactions with glucose and lactate in cow mammary tissue.

Slices from mammary glands from six lactating Holstein cows were incubated in Krebs-Ringer bicarbonate-based media in the presence of varying concentrations of acetate, glucose, and lactate. Conversions of acetate to carbon dioxide, fatty acids, citrate, glyceride-glycerol, and lactose were determined. Specific effects of beta-hydroxybutyrate and stearate availability also were evaluated. Utilization of acetate for all functions usually followed Michaelis-Menten kinetics with apparent affinities in the physiological concentration range of acetate. Availability of glucose had a large "permissive" effect on acetate to conversion to fatty acids. However, acetate metabolism was independent of the availability of lactate. Conversion of acetate to glyceride-glycerol was significant. This indicates the possibility of bidirectional glycolytic flux, which could limit glucose conversion to fatty acids. Addition of stearate caused general increases of acetate metabolism. Conversion of acetate to fatty acids, carbon dioxide, and citrate was elevated in the absence of beta-hydroxybutyrate. The latter observation indicates beta-hydroxybutyrate may not be a required initiator of fatty acid synthesis in mammary tissue.

Acetates↗
PubMed1985

Roles of lactate and its interactions with acetate in maintenance and biosynthesis in bovine mammary tissue.

Mammary gland tissue slices from three lactating Holstein cows were incubated in Krebs-Ringer bicarbonate-based media with varying concentrations of lactate and other substrates. Conversions of 1- and 2-carbon-14 of lactate to carbon dioxide, fatty acids, citrate, glyceride glycerol, and lactose were determined. Effects of acetate, glucose, beta-hydroxybutyrate, stearate, and pyruvate on lactate metabolism were evaluated. Oxidation of lactate increased asymptotically with lactate concentration. Low acetate concentration stimulated oxidation of carbon 2 of lactate slightly while higher acetate availability inhibited lactate oxidation. Conversion of lactate to fatty acids increased linearly with lactate concentration. This conversion of lactate was inhibited strongly by acetate. Significant conversion of carbon 2 of lactate to glyceride-glycerol but not lactose was detected. Bovine mammary glands have the capacity of utilize sizeable quantities of lactate for oxidation and lipogenesis. Both phenomena are highly dependent on availability of acetate. Pyruvate dehydrogenase and citrate lyase could represent important regulatory sites in vivo for determination of tissue preference for acetate over lactate. Results indicate factors other than an inactive malate transhydrogenation cycle likely limit glucose conversion to fatty acids.

Acetates↗
PubMed1996

Intestinal uptake and metabolism of fatty acids in the chick.

Uptake and metabolism of fatty acids in the duodenal mucosa of the chick was studied. In vitro incubations of a mucosal homogenate with 14C-oleic acid indicated that together with glycerides, water-soluble 14C compounds and 14CO2 were formed; the latter comprised approximately one quarter of metabolites formed. Studies in chickens introducing 14C-oleic acid into the duodenum and determining appearance of label in the cannulated pancreaticoduodenal vein and brachial artery indicated that similar processes occur in vivo, with both labeled glycerides and water-soluble compounds appearing in the blood. Quantitatively, metabolism of 14C-oleic acid to nonlipid compounds amounted to some 15% of the dose after 60 min. These findings suggest that a considerable portion of ingested fatty acids are metabolized before transport to the circulation.

Animals↗
PubMedDate not supplied

[Effect of diet with high fat content on lipogenesis in the liver, lipid composition and lipoprotein spectrum of blood].

Content of lipids and lipoprotein composition in blood did not reflect the intensity of lipogenesis in liver tissue of rats, which were kept on diets with high content of vegetable or animal fats. Both diets with excess of fat increased the rate of acetylation reaction in synthesis of glycerides and esterification of free cholesterol in liver tissue. In this case secretion of synthesized lipids into blood was decreased. Excess of vegetable oil, as distinct from animal fat, decreased the content of glycerides, pre-beta and beta-lipoproteins in blood and activated the synthesis of free cholesterol in liver tissue.

Acetates↗
PubMedDate not supplied

[The effect of excess amounts of qualitatively differing fats on liver lipogenesis].

Tests conducted with rats receiving for 30 days isocaloric with control rations containing an elevated amount of animal or vegetable fats (lard, sunflower oil) demonstrated that the influence of the said fat-rich rations on the lipogenesis in the liver presents certain peculiarities that find their expression in a different intensity with which the components of the carbohydrate, fat and interstitial metabolism behave in reactions of the lipids synthesis. Both rations tend to slightly bring down the rate of the endogenous fatty acids formation but contribute to a more intensive synthesis of glycerides and fatty acids cholesterol ethers. The vegetable oils, where are prevalent polysaturated fatty acids, provoke an accelerated utilization of carbohydrates in the synthesis of the glycerin structure of glycerides and phospholipids, as well as of the palimitic acid metabolites and the C-2 fragments in the liver cholesterol synthesis.

Animals↗
PubMed1975

[Irregularities in the lipid composition of muscle tissue in Duchenne's myodystrophy].

A study is made of the phospholipid content, glycerides and cholesterine in the muscular tissue of 20 patients with Duchene's myodystrophy. It was established that there is an increase in the relative content of sphingomyelin and a drop in phosphatidilcholine. The study shows an increase of glycerides and cholesterine per gm, of raw weight and in the content of the noncollagen protein.

Child↗
PubMed1972

Calculation of lipolysis and esterification from glycerol metabolism in rat adipose tissue.

Pieces of epididymal fat pad from fed and 48-hr-fasted rats were incubated for various periods of time in Krebs-Ringer bicarbonate containing [1-(14)C]glycerol. The radioactive substrate taken up by the tissue increased linearly with time in both groups and was mainly converted to glyceride-glycerol and CO(2). The slopes of the regressions of (14)C-labeled glyceride-glycerol with time were not different between the groups, while those of (14)CO(2) were smaller in the fasted than in the fed animals. Because the radioactive glycerol in the medium is being continuously diluted with the glycerol coming out of the tissue, it is necessary to take account of this factor in calculating the actual amount of glycerol utilized by the tissue. The glycerol produced by the tissues is higher in the fasted than in the fed animals, and in both groups it increases hyperbolically with time. As negligible amounts of the (14)C-labeled glycerol taken up by the tissue recirculates to the medium, the rates of glycerol release (lipolysis), esterification, and oxidation to CO(2) were calculated.

Adipose Tissue↗
PubMed1979

The insulin-like effect of hydrogen peroxide on pathways of lipid synthesis in rat adipocytes.

In addition to the well known insulin-like effects of certain concentrations of H2O2 on glucose transport and oxidation in isolated rat adipocytes, the present work demonstrates that lipid synthesis from glucose is also enhanced over a narrow range of H2O2 concentrations (0.15 to 0.5 mM) added to the incubation medium. As in the case of insulin, H2O2 was found to stimulate greater glucose incorporation into glyceride-fatty acid than incorporation into glyceride-glycerol. As part of a multifaceted regulation of lipogenesis, H2O2, like insulin, increased the amount of pyruvate dehydrogenase in the active form without increasing the total amount of pyruvate dehydrogenase. Pyruvate dehydrogenase activity increased within 5 min of H2O2 incubation, reached a maximum at 15 min and declined thereafter as the H2O2 disappeared from the incubation medium. While medium glucose per se was found to activate the enzyme, it is unlikely that the effect of H2O2 was mediated by the known enhancement of glucose transport since the effects on the enzyme were maximal in the absence of glucose in the incubation medium. These findings add to the growing list of insulin effects that are reproduced by H2O2, and strengthen the hypothesis that assigns H2O2 the role of "second messenger" of insulin.

Adipose Tissue↗
PubMed1970

Studies on the compartmentation of lipid in adipose cells. I. Subcellular distribution, composition, and transport of newly synthesized lipid: liposomes.

The subcellular distribution and composition of endogenously synthesized lipid in isolated white adipose cells were studied to determine the nature and extent of lipid compartmentation. After brief incubation of cells with labeled glucose, acetate, or palmitic acid, over 90% of newly synthesized triglyceride was localized in the bulk-lipid phase, indicating rapid intracellular transport and storage. From 13 to 20% of the newly formed lipid was diglyceride, and over 95% of it was localized in the central lipid-storage vacuole rather than in organelle systems concerned with esterification, thus indicating intracellular segregation of newly synthesized partial glycerides. Most of the newly synthesized phosphatides partitioned with membranous organelles. Synthesis of cholesterol or cholesteryl ester was negligible. After brief incubation of cells with labeled glucose, the relative specific activity of organelle triglyceride was mitochondria >> microsomes > liposomes > soluble supernatant > bulk lipid. In pulse-chase studies the specific activity of organelle triglyceride decreased and that of the bulk fraction increased reflecting intracellular lipid transport. The data suggest that a significant proportion of newly formed lipid is transferred from mitochondrial membranes into the storage vacuole by direct lipid-lipid interaction. Liposomes, which consist of small enclosed lipid droplets resembling chylomicrons, contained triglycerides of specific activity similar to microsomal triglyceride. While the evidence that liposome triglyceride may be microsomal in origin is indirect, the results do indicate that the liposome fraction represents a phase in the transport and(or) storage of new glyceride. At least two forms of compartmentation of newly synthesized lipids occurred. The first, termed "structural," refers to localization of lipids to organelle fractions. The second type of compartmentation, termed "chemical," concerns the intracellular segregation of a specific lipid class. The accumulation and segregation of newly synthesized diglyceride in the bulk storage pool are examples of the latter form of compartmentation.

Acetates↗
PubMed1976

Retention of lipolytic products in chylomicrons incubated with lipoprotein lipase: electron microscope study.

Early effects of lipolysis on the structure of chylomicrons in vitro were studied in rat chylomicrons incubated with purified bovine mild lipoprotein lipase at pH 8.1. The amount of the albumin added to the incubation medium was limited so that free fatty acids (FFA) and partial glycerides formed during lipolysis would accumulate in the chylomicrons. The structures visualized in lipolyzed chylomicrons was found to be affected by pH during preparation of specimens for microscopy, whether fixed with OsO4 and sectioned, or stained with sodium phosphotungstate and examined as whole mounts. Circular aqueous spaces were present in the triglyceride core of lipolyzed chylomicrons processed at pH 8.1 and 7.4. Sometimes the spaces contained aggregates of osmiophilic material and whorls of bilayered lamellae. The spaces were replaced by lamellar structures having a periodicity of 40 A, in chylomicrons processed at pH 5.5, and the spaces and lamellae were both absent at pH 3.0. The findings indicate that these spaces were lined by a lipid monolayer which formed bilayered lamellae under certain conditions. It is concluded that the monolayer lining the aqueous spaces is an inward extension of the chylomicron surface film produced by the accumulation and movement of lipolytic products, FFA and partial glycerides, in the interfacial plane between core triglyceride and water.

Animals↗
PubMed1968

Composition and synthesis of fatty acids in atherosclerotic aortas of the pigeon.

The composition, synthesis, and esterification of fatty acids were studied in aortas of White Carneau and Show Racer pigeons after perfusion of the aortas with a medium containing acetate-1-(14)C. For both breeds of pigeons the principal change in aortic fatty acids, in response to an atherogenic diet, was a marked increase in the percentage of oleic acid in the cholesteryl ester fraction. In atherosclerotic aortas incorporation of acetate-1-(14)C into the phospholipid and glyceride fractions increased 2-fold, while a much greater increase (up to 10-fold) was seen in incorporation into cholesteryl esters. In those birds receiving the atherogenic diet, palmitic acid accounted for approximately 50% of the fatty acid radioactivity, compared with approximately 25% from control aortas. Calculation of fatty acid synthesis showed the major newly synthesized fatty acids to be stearic acid in the phospholipid fraction; stearic, palmitic, and oleic acids in the glycerides; and oleic acid in the cholesteryl esters. The pattern of fatty acid synthesis was closely similar to the actual fatty acid composition of the aorta. In atherosclerotic aortas an increased synthesis of all fatty acids was seen, but the greatest increase was seen in the synthesis of oleic acid and its esterification to cholesterol.

Acetates↗
PubMed1969

Separation of mono- and diglycerides by gas--liquid chromatography.

The parameters affecting the separation and quantification of trimethylsilyl ethers of mono- and diglycerides have been investigated by gas-liquid chromatography with QF-1 and SE-30 as stationary phases and a flame ionization detector. Results have been compared with those obtained earlier for triglycerides. The isothermal characteristics of a range of trimethylsilyl ethers of mono- and diglycerides on both stationary phases showed that log retention volume was directly proportional to carbon number and inversely proportional to absolute temperature. However, glyceride derivatives with lower carbon numbers deviated from these relationships. By using various rates of programmed temperature rise, we have determined the elution temperatures (Kelvin scale) of the mono- and diglyceride trimethylsilyl ethers relative to that of glycerol trilaurate. The "carbon equivalent of a trimethylsilyl group" is defined and shown to be useful in comparing the chromatographic properties of different glyceride classes. Weight and molar correction factors have been obtained and used to analyze diglycerides derived from egg and bovine brain lecithins.

Animals↗
PubMed1966

Lipid transfer between human serum high density lipoproteins and egg yolk lipoproteins in incubation mixtures.

Ultracentrifugally isolated human serum high density lipoproteins of d 1.063-1.21 (HDL) were incubated with egg yolk lipoproteins of d < 1.006 for up to 24 hr at various concentrations. Transfer of HDL cholesterol esters to egg yolk lipoproteins occurred simultaneously with transfer of glycerides from egg yolk lipoproteins to HDL. These observations show that exchange of lipids can take place between lipoproteins in the absence of other serum proteins and enzymes. The mole ratios of HDL cholesterol esters to glycerides approached an integral value of 1 : 1 during the course of the incubation. These results suggest that lipid components form complexes within the HDL structure.

Adult↗
PubMed1984

Mono-, di- and triglycerides in serum of spontaneously hypertensive and normotensive rats in relation to age.

Serum triglycerides appeared significantly lower in spontaneously hypertensive as compared to normotensive rats except in 8-week-old animals. Tri-, di and monoglycerides decreased continuously with age in the former but revealed only a transient fall in the latter. The remarkably high portion of partial glycerides (about 30% of total glycerides) in serum should be considered in all studies on lipolysis in rats.

Aging↗
PubMed1994

Free radical-induced alterations in endothelial cell function.

Free radical-induced injury to the arterial wall has been implicated in the pathogenesis and progression of atherosclerosis. To model the in vitro effects of free radicals on endothelial cell function, protein and lipid synthesis were measured after exposing cells to a superoxide generating system of xanthine (X = 100 microM) and xanthine oxidase (XO = 0.2 units). Total protein synthesis, measured by [35S]methionine uptake, decreased by 87.65 +/- 2.04% over 4 hr compared to controls (P < 0.05). Examination of lipid synthesis by high-performance liquid chromatography in cells prelabeled with either [3H]oleic acid or [3H]sodium acetate revealed alterations in all lipid classes. Phospholipid and neutral glyceride synthesis significantly decreased in a time- and dose-dependent fashion compared to controls (two-way ANOVA). In contrast, cholesterol synthesis and lipid peroxidation increased in a time- and dose-dependent fashion. When X = 200 microM and XO = 0.3 units, there was a statistically significant increase in cholesterol synthesis and lipid peroxidation within 24 hr (Tukey's HSD). We conclude that there is evidence of endothelial cell injury as measured by decreases in protein, glyceride, and phospholipid synthesis. The concurrent increases in lipid peroxidation and cholesterol synthesis may explain the relationship between free radical injury and the pathogenesis of atherosclerosis.

Acetates↗