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At least 811 records · Page 45Linked to original sources
PubMed1993

N.m.r. lipid profiles of cells, tissues and body fluids. Neutral, non-acidic and acidic phospholipid analysis of Bond Elut chromatographic fractions.

Although the advantages of in vitro n.m.r. analysis of cellular lipids have been documented, this purely n.m.r. approach also has drawbacks. Rapid and quantitative separation of total lipids into neutral lipids, non-esterified fatty acids, non-acidic phospholipids and acidic phospholipids using Bond Elut ion-exchange columns as demonstrated here permitted a more quantitative and complete n.m.r. analysis of glycerides, cholesterol, saturated and unsaturated sphingolipids and ether lipids, as well as of diacylcholine and ethanolamine lipids. Acidic lipids were also analysed. The fatty acid compositions of the intact lipids in each of the four Bond Elut fractions were determined from the n.m.r. spectrum of each fraction.

Animals↗
PubMed1976

The esterification of exogenous fatty acids by adipose tissue of hypertriglyceridaemic subjects with or without diabetes mellitus.

1. The esterification of exogenous palmitate to diglyceride and triglyceride in adipocytes was studied in obese and diabetic patients with and without hypertriglyceridaemia. The rate of esterification correlated significantly with the triglyceride content of adipocytes. 2. In diabetic patients with hypertriglyceridaemia, the rate of esterification to triglyceride was significantly greater than in diabetic patients with normotriglyceridaemia. This difference could not be attributed to differences in glucose tolerance or to the degree of obesity. 3. Fasting plasma insulin levels were greater in the hypertriglyceridaemic group than in the normotriglyceridaemic group. The difference in esterification rates could have been due to differences in adipocyte size. 4. The esterification of fatty acid in adipose tissue of diabetic patients was lower than in non-diabetic subjects and this difference could not be accounted for by differences in adipocyte size or differences in the intracellular pools of fatty acid in adipose tissue. 5. The role of esterification of exogenous fatty acids in adipose tissue as a possible determinant of the uptake of glyceride fatty acids from plasma is discussed.

Adipose Tissue↗
PubMed1983

Effect of nicotinic acid on acylglycerol metabolism in human adipose tissue.

1. The effect of nicotinic acid on the metabolism of acylglycerols was investigated in human adipose tissue incubated with [U-14C]-glucose. 2. Nicotinic acid caused a 25% inhibition of the conversion of [U-14C]glucose into total lipids of adipose tissue, which was solely attributed to a decrease in the formation of the glyceride-glycerol moiety of triacylglycerols. There was no effect on the conversion of [U-14C]glucose to carbon dioxide by nicotinic acid. The drug inhibited the rate of glycerol release by 50% and significantly reduced the tissue level of diacylglycerols but did not alter the tissue concentration of monoacylglycerols. 3. It is concluded that in human adipose tissue nicotinic acid inhibits both the synthesis and hydrolysis of triacylglycerols and influences the metabolism of diacylglycerols.

Adipose Tissue↗
PubMed1999

An oral formulation of nicotine for release and absorption in the colon: its development and pharmacokinetics.

AIMS: Ulcerative colitis is predominantly a disease of nonsmokers and transdermal nicotine has therapeutic value in active disease; however side-effects are troublesome. The aim of this study was to develop an oral formulation of nicotine which would be slowly released in the colon over 6 h, and to examine its pharmacokinetic profile in 12 healthy volunteers, with measurements of serum nicotine and cotinine, its principal metabolite. METHODS: Nicotine was combined with a polyacrylic carbomer, Carbopol 974P which was incorporated into 13 different vehicles and their release profiles examined in vitro. The polyglycolized glyceride, Gelucire 50/13, was chosen for subsequent kinetic studies because it consistently produced a suitable release pattern which was linear. Capsules containing 3 mg nicotine, combined with carbomer in Gelucire 50/13, were coated with an acrylic resin Eudragit L; this ensured the capsule would remain intact until the ileum. On 2 separate days, 6 and 15 mg nicotine, contained in 2 and 5 capsules, respectively, were administered to 12 subjects, all nonsmokers, mean age 28 years. Serial blood measurements were taken for 36 h, serum nicotine and cotinine concentrations were measured by gas liquid chromatography. RESULTS: There was considerable intersubject variability in the nicotine and cotinine values. Plasma nicotine levels began to rise about 4 h after ingestion of the capsules, corresponding with the oro-caecal transit time. Cmax nicotine values were 2.2 and 5 ng ml-1, obtained 7 h after the ingestion of 6 and 15 mg, respectively, of the formulation. The corresponding Cmax values for cotinine were 37 and 94.4 ng ml-1, occurring after 9-10 h. The mean for elimination half-lives in the 24 studies, including the 6 and 15 mg doses, for nicotine were 4.3+/-2.7 h and for cotinine 16.8+/-7.5 h. With 6 mg nicotine-carbomer, only 1 of 12 volunteers had possible side-effects, but with the 15 mg dose 11 out of the 12 reported adverse effects which were systemic or gastrointestinal in nature-their timing corresponded with peak serum concentrations of nicotine. CONCLUSIONS: An oral formulation of nicotine has been developed; in the ileum and colon, this becomes available for slow linear release over 6 h and delivers high concentrations of nicotine for topical effect on the colon. 6 mg Nicotine was well tolerated, whilst 15 mg gave both systemic and gastrointestinal side-effects. High concentrations of topical nicotine in the colon are achieved with relatively low systemic bioavailablity-reflected by the Cmax and AUC values for nicotine. This, or comparable formulations, may be of therapeutic value in ulcerative colitis.

Absorption↗
PubMed1981

Changes in rat liver and adipose tissue lipogenesis in the course of continuous gamma radiation.

Lipogenesis in liver of continuously irradiated rats (dose rate of 0.57 Gy per day for up to 25 or 30 days) was increased, in comparison with control animals, between 7 and 30 days. In the liver of fed rats it was approximately five times higher than animals fasted for 16 hours before sacrifice. Lipogenesis in adipose tissue was decreased on the third day of irradiation and its value was higher than in controls between 7 and 25 days. Glyceride glycerol synthesis in irradiated rats was increased compared with controls on the first, seventh and between 21 and 25 days of continuous irradiation. We suggest that the increase in lipogenesis in the liver of continuously irradiated rats is an important factor in lipid metabolism disorders caused by the continuous irradiation.

Adipose Tissue↗
PubMed2004

Study of in-vitro release characteristics of carbamazepine extended release semisolid matrix filled capsules based on Gelucires.

Various extended release carbamazepine (CBZ) formulations have been developed previously, in order to reduce the frequency of dosing in chronic therapy and to decrease the variability in drug plasma concentration. In the present study, the suitability of different grades of Gelucires (G, glyceride based excipients) to formulate CBZ extended release capsules by the application of semisolid matrix (SSM) filling capsule technology was investigated. The possible modification of CBZ release kinetics by using Gelucire blends or inclusion of hydrophilic additives in the SSM was studied. The effect of ageing on some selected formulations was also evaluated, using scanning electron microscopy and differential thermal analysis. Twenty-one capsule formulations were prepared and assessed for their release characteristics. The mechanism of drug release from the test formulations was studied. The following results were obtained: a) Release data could not be correlated to the melting point (mp) of Gelucires used, pointing to relative lipophilicity of the base as a more important determinant of drug release. Among Gelucire grades having melting points higher than 37 degrees C, the release rate proved to be highly dependent on the HLB value and matrix composition. b) CBZ release occurred by different mechanisms, including matrix disintegration, diffusion and or erosion depending on the vehicle employed. c) Zero order release profiles of CBZ were obtained from SSM-based on G50/13, G53/10 and their blends in ratios higher than 1:1 and G53/10 containing croscarmellose sodium. d) The ageing study revealed that these latter formulations, except those based on G50/13, also showed high dissolution stability during one year of shelf ageing. e) PVP, as a polymorphic transformation inhibitor, can be used to reduce the storage-induced changes of some grades of Gelucires. From the above data, it can be concluded that different grades of Gelucires and their blends as well as hydrophilic additives could be successfully used to formulate CBZ extended release SSM filled capsules with various release kinetics.

Capsules↗
PubMed1967

Lipid synthesis, intracellular transport, storage, and secretion. I. Electron microscopic radioautographic study of liver after injection of tritiated palmitate or glycerol in fasted and ethanol-treated rats.

A time sequence study of intracellular movement of labeled lipid in the liver was carried out on fasted and ethanol-treated rats injected with either palmitate-(3)H or glycerol-(3)H by electron microscopic radioautography. The elimination of water-soluble lipid precursors during specimen preparation was checked and found to be complete. The labeled lipid product in the tissue was identified as mostly triglyceride. A dehydration procedure was adapted to minimize the loss of lipid during specimen preparation. At 2 min after injection, the earliest time interval studied, both precursors were found to have penetrated the liver cells, and the label was found over both rough and smooth elements of the endoplasmic reticulum, which is the site of glyceride esterification. From 5 min on, in fasted and especially in ethanol-treated rats, the label was seen also over lipid droplets 0.5-2.0 micro in diameter, which represent "storage lipid" (slowly turning over compartment). Mitochondria became labeled mostly at later time intervals after injection. From 10 min on, concentration of label was seen over the Golgi apparatus, containing small osmiophilic particles. Association of label with groups of particles in smooth-surfaced vesicles and vacuoles in and near the Golgi apparatus and in the vicinity of the sinusoidal border was seen, both after palmitate-(3)H and glycerol-(3)H. It is proposed that these particles represent lipoproteins which are formed in the endoplasmic reticulum, "processed" in the Golgi apparatus, and transported in vacuoles to the sinusoid surface to be discharged into the circulation.

Adipose Tissue↗
PubMed1971

Plasma and phagosome membranes of Acanthamoeba castellanii.

Plasma membranes were isolated from the ameba Acanthamoeba castellanii by low-speed velocity centrifugation followed by equilibrium centrifugation in a sucrose gradient. The isolated membranes had a high ratio of sterol to phospholipid (0.98 moles/mole) and of phospholipid to protein (0.43 mg/mg). The plasma membranes had very low concentrations of DNA, RNA, lipid inositol, and glycerides. Glycolipids and glycoproteins were enriched in the plasma membranes relative to their concentrations in the whole cell. The plasma membranes were also judged to be of high purity by the absence, or very low level, of enzymatic activities considered to be indicative of other cell membranes, and by electron microscope examination. Alkaline phosphatase and 5'-nucleotidase activities were enriched in the plasma membranes 13-fold relative to the whole homogenate and had higher specific activities in the plasma membranes than in any other cell fractions. A Mg(++) adenosine triphosphatase (ATPase) was enriched sixfold in the plasma membranes relative to the whole homogenate. The phospholipids of the plasma membranes contained more phosphatidylethanolamine and phosphatidylserine and less phosphatidylcholine than did the phospholipids of the whole cells. There were differences in the fatty acid compositions of corresponding phospholipids in the plasma membranes and whole cells but no difference in the ratios of total saturated to unsaturated fatty acids. The membranes of phagosomes isolated from amebae that had ingested polystyrene latex had essentially the same phospholipid, sterol, and enzymatic composition as plasma membranes.

Adenosine Triphosphatases↗
PubMed1967

The formation and continuous turnover of a fraction of phosphatidic acid on stimulation of NaC1 secretion by acetylcholine in the salt gland.

Acetylcholine, which stimulates NaCl secretion in the avian salt gland, causes the rapid formation of a fraction of phosphatidic acid, as measured by (32)P incorporation, which amounts maximally to about 0.18 micromoles per g of fresh tissue. This does not appear to involve synthesis of the diglyceride moiety of phosphatidic acid, as measured by glycerol-1-(14)C incorporation. It presumably involves formation of phosphatidic acid by the diglyceride kinase pathway from preformed diglyceride and ATP. The specific activity of the AT(32)P of the tissue is not increased in the presence of acetylcholine. At time intervals after addition of acetylcholine during which a full response, measured as increased O(2) uptake, may be observed, phosphatidic acid appears to be the only phosphatide which shows any increase either in total (32)P radioactivity or in net specific acitvity. This responsive fraction of phosphatidic acid undergoes continuous turnover of its phosphate moiety. There is no evidence that this turnover is due to the phosphatidic acid acting as a pool of intermediate for the synthesis of other phospholipids or glycerides. The responsive fraction amounts to not more than 20% of the total phosphatidic acid of the tissue; it does not mix with the other (non-responsive) phosphatidic acid of the tissue. The observations suggest that this phosphatidic acid plays some role in the over-all secretory process.

Acetylcholine↗
PubMed1975

Effect of micelle formation on the absorption of neutral fat and fatty acids by the chicken.

Experiments were conducted to determine the absorption of various dietary fatty acids and glycerides singly and in mixtures. Chickens with or without cannulated bile ducts or ligated pancreatic ducts were used to evaluate the absorption of fatty acids or mixtures of fatty acids and the absorption patterns of several classes of lipids and their effect on the absorption of palmitic acid under in vivo conditions. In spite of wide melting point differences, isomers of various monoglycerides or 18-carbon unsaturated fatty acids exhibited identical absorption and solubility patterns. A homologous series of saturated monoglycerides showed a maximum absorption value for the monoglycerides with fatty acids of 12 and 14 carbons. Absorption decreased with increasing chain lengths of the fatty acid in the monoglyceride. Conversely, the absorption of palmitic acid when fed with the various monoglycerides progressively increased to a maximum in the mixture containing monomyristin and then decreased when fed with monopalmitin or monostearin.

Animal Nutritional Physiological Phenomena↗
PubMed1979

Monoglyceryl acetoacetate: a ketone body-carbohydrate substrate for parenteral feeding of the rat.

The monoglyceride of acetoacetate was prepared from diketene and glycerol. The resulting mixture was composed of nearly equal amounts of 1- and 2-monoacetoacetin. This mixture was tested as a parenteral energy substrate by continuous intravenous infusion into the rat. This glyceride provided 71% of the daily energy for 7 consecutive days. Other groups were either fed ad libitum or fed ad libitum and supplemented with intravenous glucose isoenergetic to monoacetoacetin. All three groups had similar daily non-protein energy intake, and the two supplemented groups ate less protein than normal rats. All three groups gained weight similarly although the glucose group tended to gain fastest and the monoacetoacetin group tended to gain slowest. The rates were not significantly different. At the end of 7 days, the glucose group was hyperglycemic and the monoacetoacetin group was hyperketonemic compared to normal fed rats. The only significant differences among the livers was the small size found for the glucose group. Hepatic compositions were similar. It was concluded from these data that intravenous monoacetoacetin can support weight gain in rats and is a potential alternative to glucose as an energy source in parenteral nutrition.

Acetoacetates↗
PubMed1981

Absence of impaired glucose utilization in adipocytes from rats fed a carbohydrate-free, high protein diet.

Glucose utilization was studied in isolated adipocytes from rats fed a mixed (51% carbohydrate, 30% fat, 19% protein), high fat (81% fat, 19% protein) or high protein diet (30% fat, 70% protein). Despite similar food intake, rats on the high protein (HP) diet had smaller epididymal fat pads than the other two groups. The reduction in fat pad size was caused by small and variable reductions in both cell size and cell number. Fat cells from rats on the high fat (HF) diet had the previously reported reduction in pentose phosphate shunt activity in the absence and presence of insulin, and marked diminution of de novo fatty acid synthesis. Lactate release was elevated in the absence of insulin. There was no insulin stimulation of glucose uptake, CO2 production, glyceride-glycerol production or lactate release in these adipocytes. However, significant stimulation of fatty acid synthesis was seen. There was no impairment of glucose uptake or utilization in cells from rats on the HP diet despite the absence of dietary carbohydrate. Indeed, 14CO2 produced from glucose-l-14CO2 produced from glucose-1-14C was increased in these adipocytes. Thus the impaired glucose utilization in rats on the high fat, carbohydrate-free diet is due solely to the fat content of the diet.

Adipose Tissue↗
PubMed1977

Studies on adrenaline-induced lipolysis in artificial lipid micelles.

Lipid micelles were prepared by incubating a mixture of glycerides (triolein, diolein, and monoolein), and lecithin in Krebs-Ringer phosphate buffer at 37 degrees C for 30 min. It was found that adrenaline stimulated the release of free fatty acids in a lipolytic system consisting of the lipid micelles and adipose tissue lipase. Adrenaline did not increase the cyclic AMP content of the reaction mixture. Dibutyryl cyclic AMP, theophylline, and phospholipase C increased the rate of lipolysis in the system but cyclic AMP and phospholipase D did not.

Bucladesine↗
PubMed1978

Water-soluble lipoproteins from yolk granules in sea urchin eggs. I. Isolation and general properties.

Most of the water-soluble lipoproteins in sea urchin eggs (Hemicentrotus pulcherrimus) were localized within yolk granules. Under hypotonic conditions, yolk granules released lipoproteins and a 24S protein species as high molecular weight components; the lipoproteins constituted about 40% of the total materials released. Three yolk lipoproteins(YLP-1, 2, and 3, in order of quantity) were isolated by ultracentrifugation and gel filtration. The hydrated densities of YLP-1, 2, and 3 were 1.027, 1.062, and 1.009 g/cm(3), respectively. YLP-1, 2, and 3 contained glyceride as a major lipid in quantities of 3.1, 1.8, and 4.3 times the amount of each protein, respectively. These lipoproteins contained large amounts of carbohydrate. Sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed four major periodic acid-Schiff (PAS) positive polypeptide bands common to the three lipoproteins. All the constituent polypeptides of the 24S protein were also PAS positive. Electron microscopy of negatively stained YLP-1, 2, and 3 revealed the average diameters to be 36, 29, and 48nm, respectively. The 24S protein appeared to be cylindrical in shape with average exterior dimensions of 10--20 nm. Thin-section micrographs showed that yolk granules are packed with particles around 30 nm in diameter, suggesting that these particles are not the 24S proteins but the lipoprotein particles.

Animals↗
PubMed1998

Platelet- and macrophage-derived endogenous cannabinoids are involved in endotoxin-induced hypotension.

Macrophages are the primary cellular targets of bacterial lipopolysaccharide (LPS), but the role of macrophage-derived cytokines in LPS-induced septic shock is uncertain. Recent evidence indicates that activation of peripheral CB1 cannabinoid receptors contributes to hemorrhagic hypotension and that macrophage-derived anandamide as well as unidentified platelet-derived substances may be contributing factors. Here we demonstrate that rat platelets contain the endogenous cannabinoid 2-arachidonyl glyceride (2-AG), as identified by reverse phase high-performance liquid chromatography, gas chromatography, and mass spectrometry, and that in vitro exposure of platelets to LPS (200 microg/ml) markedly increases 2-AG levels. LPS-stimulated, but not control, macrophages contain anandamide, which is undetectable in either control or LPS-stimulated platelets. Prolonged hypotension and tachycardia are elicited in urethane-anesthetized rats treated 1) with LPS (15 mg/kg i.v.); 2) with macrophages plus platelets isolated from 3 ml of blood from an LPS-treated donor rat; or 3) with rat macrophages or 4) platelets preincubated in vitro with LPS (200 microg/ml). In all four cases, the hypotension but not the tachycardia is prevented by pretreatment of the recipient rat with the CB1 receptor antagonist SR141716A (3 mg/kg i.v.), which also inhibits the hypotensive response to anandamide or 2-AG. The hypotension elicited by LPS-treated macrophages or platelets remains unchanged in the absence of sympathetic tone or after blockade of nitric oxide synthase. These findings indicate that platelets and macrophages generate different endogenous cannabinoids, and that both 2-AG and anandamide may be paracrine mediators of endotoxin-induced hypotension via activation of vascular CB1 receptors.

Animals↗
PubMed1975

Modification of the membrane composition of Mycoplasma mycoides subsp. capri by the growth medium.

Mycoplasma mycoides subsp. capri was grown in different media. The amounts of the lipids in these media were varied, resulting in altered lipid compositions of the cells. Lowering the amounts of cholesterol in the media resulted in less cholesterol incorporation into the cell lipid, with a concomitant decrease in the amount of phospholipid. The changes in the phospholipid/cholesterol ratio in the mycoplasmas were very small compared with the large changes in the amounts of cholesterol which occurred when the cholesterol content in the medium was altered. Changes in the amounts of glycolipid and glyceride in the cell lipid also resulted from alterations of the cholesterol concentration in the media. Under these conditions cell with reduced cholesterol contents were more sensitive to lysis by digitonin. No changes were observed in the polyacrylamide gel electrophoretic pattern of cellular or membrane proteins when the cholesterol was replaced by other sterols.

Bacterial Proteins↗
PubMed1997

Effect of formulation on the rheology of theophylline compound suspensions in Gelucires.

The theophylline derivatives, etofylline, diprophylline and proxyphylline, which exhibit increasing aqueous solubility, were used to prepare suspensions in seven saturated polyglycolyzed glycerides (Gelucires) characterized by their rising hydrophilic-lipophilic balance (HLB). Drug concentration was set at 25% w/w and the production temperature was set at the Gelucire melting point plus 30 degrees C in order to obtain suitable suspensions. Various formulation factors were studied. Ostwald flow indices revealed that the suspensions had a thixotropic shear-thinning behaviour and a relative viscosity which increased as drug aqueous solubility rose and Gelucire HLB decreased. These rheological properties could be explained by the chemical composition of Gelucires and drugs used. A microstructure was proposed for the liquid suspension such that colloidal particles and aggregates formed in these suspensions directly influenced the observed rheological properties. Observation of solidified suspensions by scanning electron microscopy confirmed this hypothesis. Moreover, a correlation between the relative viscosity of drug suspensions on the one hand and drug concentration, drug solubility and Gelucire HLB on the other allowed for the calculation of the required concentration of each theophylline derivative in each Gelucire to obtain a given viscosity.

Chemistry, Pharmaceutical↗
PubMed1972

Triacylglycerols characteristic of porpoise acoustic tissues: molecular structures of diisovaleroylglycerides.

More than two-thirds of the triacylglycerols from the acoustic tissues of the porpoise (Tursiops gilli) consist of 2 moles of isovaleric acid for every 1 mole of long-chain acids. Cranial blubber, which has no distinct acoustic function, does not contain these unusual glycerides. The presence of large amounts of diisovaleroylisopentadecanoylglycerol suggests that this structure may be particularly important in sound transmission through lipid-protein matrices.

Acoustics↗