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At least 973 records · Page 54Linked to original sources
PubMed2004

A nanometer lipid emulsion, lipid nano-sphere (LNS), as a parenteral drug carrier for passive drug targeting.

We attempted to develop an artificial lipoprotein-like particle, lipid nano-sphere (LNS), incorporating dexamethasone palmitate (DMP). LNS is 25-50 nm in diameter and is composed of soybean oil and egg lecithin. Potential drug carriers were compared with a conventional fat emulsion for intravenous nutrition, lipid microsphere (LM, d=200-300 nm), which is already used clinically. LM easily entered reticuloendothelial systems, such as the liver, and was rapidly cleared from the circulation. However, LNS showed much higher plasma levels of DMP after intravenous administration to rats and recovered more than 80% of the injected dose in the perfusate in single-pass rat liver perfusion. The calculated volume for the distribution of the lipid emulsion within the liver showed that LNS underwent fenestration and was distributed into the Disse space in the liver. Because of the lower uptake of LNS particles by the liver, LNS showed good recovery from the liver and prolonged the plasma half-life of DMP after intravenous injection. In addition, higher efficiency in the targeting of DMP into inflammation sites and higher anti-inflammatory efficacy were observed in LNS. Thus, LNS easily and selectively passed through the leaky capillary wall by passive diffusion depending on the plasma concentration. Nanometer-sized lipid emulsion particles, LNS, seem to be a promising carrier system for passive drug targeting of lipophilic drugs.

Animals↗
PubMed2003

Transfection properties of stabilized plasmid-lipid particles containing cationic PEG lipids.

Recent work has shown that plasmid DNA can be efficiently encapsulated in well-defined "stabilized plasmid-lipid particles" (SPLP) that have potential as systemic gene therapy vehicles [Gene Ther. 6 (1999) 271]. In this work, we examine the influence of ligands that enhance cellular uptake on the transfection potency of SPLP. The ligand employed is a cationic poly(ethylene glycol) (PEG) lipid (CPL) consisting of a lipid anchor and a PEG(3400) spacer chain with four positive charges at the end of the PEG (CPL(4)). It is shown that up to 4 mol% CPL(4) can be inserted into preformed SPLP, resulting in up to 50-fold enhancements in uptake into baby hamster kidney (BHK) cells. The addition of Ca(2+) to SPLP-CPL(4) (CPL(4)-incorporated SPLP) results in up to 10(6)-fold enhancements in transgene expression, as compared to SPLP in the absence of either CPL(4) or Ca(2+). These transfection levels are comparable to those observed for plasmid DNA-cationic lipid complexes (lipoplexes) but without the cytotoxic effects noted for lipoplex systems. It is concluded that in the presence of Ca(2+) and appropriate ligands to stimulate uptake, SPLP are highly potent transfection agents.

Animals↗
PubMed2003

Binding of a fluorescent lipid amphiphile to albumin and its transfer to lipid bilayer membranes.

Kinetics and thermodynamics of the binding of a fluorescent lipid amphiphile, Rhodamine Green(TM)-tetradecylamide (RG-C(14:0)), to bovine serum albumin were characterized in an equilibrium titration and by stopped-flow fluorimetry. The binding equilibrium of RG-C(14:0) to albumin was then used to reduce its concentration in the aqueous phase to a value below its critical micelle concentration. Under these conditions, the only two species of RG-C(14:0) in the system were the monomer in aqueous solution in equilibrium with the protein-bound species. After previous determination of the kinetic and thermodynamic parameters for association of RG-C(14:0) with albumin, the kinetics of insertion of the amphiphile into and desorption off lipid bilayer membranes in different phases (solid, liquid-ordered, and liquid-disordered phases, presented as large unilamellar vesicles) were studied by stopped-flow fluorimetry at 30 degrees C. Insertion and desorption rate constants for association of the RG-C(14:0) monomer with the lipid bilayers were used to obtain lipid/water equilibrium partition coefficients for this fluorescent amphiphile. The direct measurement of these partition coefficients is shown to provide a new method for the indirect determination of the equilibrium partition coefficient of similar molecules between two defined lipid phases if they coexist in the same membrane.

Animals↗
PubMed1994

Lipid mono- and bilayer supported on polymer films: composite polymer-lipid films on solid substrates.

We report the deposition of lipid monolayers and bilayers on polyacrylamide films deposited by radical chain reaction onto solid substrates in aqueous solutions. Polymer films of various degrees of monomer density and cross-linking are prepared. Lateral diffusion and fluorescent probe permeation measurements yield insight into the continuity of the lipid layers and show that monolayers exposed to air are much less sensitive towards polymer heterogeneities than bilayers below water, which is explained in terms of the wetting laws. The diffusion studies of lipid and lipopeptide probes yield absolute values of the frictional coefficients between the lipid layer and the polymer films and allow one to estimate the surface viscosity of the polymer film. The potential applications of supported membranes on soft thin polymer films for the preparation of biofunctionalized surfaces or biocompatible receptive surfaces for biosensors are discussed.

Acrylic Resins↗
PubMed1994

Reorganization of lipid domain structure in membranes by a transmembrane peptide: an ESR spin label study on the effect of the Escherichia coli outer membrane protein A signal peptide on the fluid lipid domain connectivity in binary mixtures of dimyristoyl phosphatidylcholine and distearoyl phosphatidylcholine.

The effect of a transmembrane peptide on the domain structure of a two-component, two-phase lipid bilayer composed of dimyristoyl phosphatidylcholine (DMPC) and distearoyl phosphatidylcholine (DSPC) was examined by spin label electron spin resonance (ESR) spectroscopy. The peptide, pOmpA, is the hydrophobic, 25-residue signal sequence of the outer membrane protein A from Escherichia coli. Nitroxide derivatives of the phospholipid DSPC, 16-DSPCSL, and of the pOmpA signal peptide, pOmpA-IASL, were used as probes. The first-derivative lineshapes of the ESR spectra were analyzed using a normalized intensity ratio, R, that gives information on the average sizes of the disconnected fluid domains and their point of connectivity (Sankaram, M.B., D. Marsh, and T.E. Thompson. 1992. Biophys. J. 63:340-349). In the absence of the peptide, the number of fluid lipid domains does not vary with the fraction of lipid that is in the fluid phase, and phase conversion is accomplished solely by changes in the domain size. The phase boundaries of the lipid mixture remain largely unchanged by the presence of the peptide at mole fractions up to 0.02, but both the size and number of the fluid domains is changed, and the point at which they become connected is shifted to lower fractions of the fluid phase. In addition, the number of domains in the presence of the peptide no longer remains constant but increases from a domain density at low fractions of the fluid phase that is much lower than that in the absence of peptide to one that is comparable to the natural state in the absence of peptide at the point of domain connectivity. A simple model is presented for the process of domain fission, where the latter is determined by a balance between the effects of peptide concentration in the fluid domains, the line tension at the domain boundaries, and the distributional entropy of the domains.

Amino Acid Sequence↗
PubMed1984

Effect of carnitine on lipid metabolism in the neonate. II. Carnitine addition to lipid infusion during prolonged total parenteral nutrition.

The effect of carnitine administration on lipid metabolism and carnitine and acylcarnitine plasma values of newborn infants, given total parenteral nutrition for the first 7 days of life, was studied during a 4-hour infusion of Intralipid. An increase in plasma concentrations of total carnitine, free carnitine, and short-chain and long-chain acylcarnitine was found, but no significant change in triglycerides, free fatty acids, glycerol, or beta-hydroxybutyrate plasma values was noted, as compared with values obtained without carnitine administration. Moreover, the low free carnitine and short-chain and long-chain acylcarnitine plasma levels found in newborn infants after 7 days of total parenteral nutrition did not seem to impair the utilization of infused lipids. The results support the concept that the relation between the carnitine pool and lipid metabolism can be influenced by intravenous glucose infusion. Low carnitine plasma concentrations do not necessarily signify a depletion of body carnitine, and sufficient tissue carnitine concentrations can probably maintain good lipid utilization for an extended period.

3-Hydroxybutyric Acid↗
PubMed1989

Plasma lipid and plasma lipoprotein concentrations in low birth weight infants given parenteral nutrition with twenty or ten percent lipid emulsion.

Because 10% and 20% intravenously administered lipid emulsions (intralipid preparations) differ in their phospholipid/triglyceride ratio (0.12 and 0.06, respectively), 28 low birth weight infants requiring parenteral nutrition for at least 1 week were selected at random to receive either emulsion to determine the effects on plasma lipids and lipoproteins. Triglyceride intake was progressively increased to reach 2 gm/kg per day between days 4 and 7. During that period, all plasma lipids in samples taken 6 hours after infusion were higher in the 10% intralipid group. In comparison with day 0 values, triglyceride concentrations decreased (63 +/- 7 to 45 +/- 4 mg/dl; p less than 0.05) in the 20% group. Cholesterol levels increased in both groups, but the rise was more than twofold higher in the 10% group. Phospholipid increase was approximately 25% in the 20% group but more than 125% in patients receiving the 10% emulsion (p less than 0.005). The changes in plasma cholesterol and phospholipid levels were almost entirely in low-density lipoproteins. After 7 days, eight infants from each group were given the alternate emulsion, which resulted in a reversal of lipid patterns in each patient. We conclude that the higher phospholipid intake in 10% than in 20% intralipid is associated with higher plasma triglyceride concentrations and leads to accumulation of cholesterol and phospholipids in low-density lipoproteins. Emulsions with lower phospholipid content may be preferable for low birth weight infants and perhaps other patient populations with impaired removal of parenteral fat emulsions.

Cholesterol, HDL↗
PubMed1999

Lipid transfer reactions and lipid composition of low-density lipoprotein particles in postmenopausal women receiving estrogen.

OBJECTIVE: To investigate the effects of estrogen on lipid transfer reactions and lipid composition of low-density lipoprotein (LDL) particles in postmenopausal women. METHODS: Twelve postmenopausal women were treated with conjugated equine estrogen, 0.625 mg daily, for 3 months. Plasma concentrations of total cholesterol, triglyceride, and high-density lipoprotein (HDL) cholesterol were measured before and after therapy. We also determined the amount of total, free, and esterified cholesterol, triglyceride, and apolipoprotein B in LDL. To evaluate lipid transfer reactions, plasma samples were incubated at 37C for 24 hours, and replacement of cholesteryl ester by triglyceride in LDL particles was analyzed. Cholesterol and triglyceride concentrations were measured enzymatically. Apolipoprotein B concentrations were determined by an immunoturbidimetric assay. RESULTS: Estrogen significantly reduced the plasma levels of total cholesterol and significantly increased those of triglyceride and HDL cholesterol. The ratio of cholesteryl ester to apolipoprotein B was reduced significantly, whereas the ratio of triglyceride to apolipoprotein B increased significantly after estrogen treatment. Both before and after estrogen treatment, incubation of plasma induced a significant increase in the ratio of LDL-triglyceride to apolipoprotein B with a concomitant decrease in the ratio of LDL-cholesteryl ester to apolipoprotein B. Incubation-induced changes in these ratios were significantly enhanced by estrogen therapy. The plasma concentration of triglyceride was correlated positively with incubation-induced changes in the ratio of LDL-triglyceride to apolipoprotein B (r = .83, P < .001) and correlated negatively with changes in the ratio of LDL-cholesteryl ester to apolipoprotein B (r = -.61, P < .01). CONCLUSION: Estrogen-induced increase in the plasma level of triglyceride may enhance lipid transfer reactions, resulting in triglyceride-rich and cholesteryl ester-poor LDL particles.

Estrogen Replacement Therapy↗
PubMedDate not supplied

Treatment strategies for management of serum lipids: lessons learned from lipid metabolism, recent clinical trials, and experience with the HMG CoA reductase inhibitors.

The Adult Treatment Panel (ATP) guidelines, published initially in 1988 and revised in 1993, are based on sentinel observations and early clinical trials in support of treating and preventing coronary artery disease by cholesterol lowering. With the conclusion of several large long-term trials using HMG CoA reductase inhibitors for primary and secondary coronary prevention, the ATP II recommendations, which remain remarkably accurate, can be supplemented with more evidence-based strategies. Increasing evidence suggests that thoughtful lipid management for coronary prevention should include a more complete assessment of lipoproteins with an emphasis on apolipoproteins, triglycerides, and very low-density (VLDL) remnant particles, LDL particle size, and lipoprotein(a). This review summarizes clinically relevant lipid metabolism with an emphasis on the concept of atherogenic plasma lipids, discusses the clinical benefits and specific uses of each of the lipid-lowering drug classes, and provides an analysis of recent cholesterol-lowering primary and secondary coronary prevention trials from which a new treatment strategy can be derived.

Clinical Trials as Topic↗
PubMed1993

The antibody reactivity of monoclonal lipid A antibodies is influenced by the acylation pattern of lipid A and the assay system employed.

The influence of the acylation pattern of lipid A on the reactivity of murine monoclonal antibodies (mAb) was tested in different assay systems with synthetic lipid A antigens. Both the number and type of fatty acids had an impact on the antigen amounts needed for optimal sensitization of sheep red blood cells, on the inhibition capacity of compounds and on the reactive antigen amounts in enzyme immunoassay and dot blot assay. Results obtained with two pentaacyl isomers indicated that the location of fatty acids is of no importance. Although all mAbs used recognized epitopes residing in the hydrophilic backbone of lipid A, their reactivities were greatly influenced by the number as well as the type of acyl chains present. In the various assays, the mAbs reacted either similarly or discrepantly suggesting that epitopes are exposed differently in the test systems. We conclude that for the determination of the reactivity of lipid A mAbs it is useful and sometimes necessary to run various assays in parallel and to compare mAbs on the basis of reaction patterns.

Acylation↗
PubMed1998

Coenzyme Q10 in vesicles composed of archaeal ether lipids or conventional lipids enhances the immuno-adjuvanticity to encapsulated protein.

Cellular accumulation, tissue distribution, and immuno-adjuvanticity were evaluated for liposomal CoQ10 prepared from either distearoylphosphatidylcholine:dicetylphosphate:cholesterol (4:1:5, mol. ratio) (conventional liposomes) or from the total polar lipids of the archaeon Methanosarcina mazei (archaeosomes). Liposomal CoQ10 vesicles of approximately 100 nm diameter, containing up to 179 mumol of CoQ10 per mg of lipid have been evaluated using J774A.1 macrophages and Balb/c mice. Archaeosomes uptake by J774A.1 macrophages was better than with the conventional liposome, and the incorporation of CoQ10 enhanced the uptake of both lipid vesicle types. All vesicle types were detected in the liver and spleen of mice (4-27% of injected dose) within 3 h of intraperitoneal injection. Moreover, incorporation of CoQ10 into lipid vesicles enhanced the immuno-adjuvanticity of both conventional liposomes and archaeosomes, to achieve approximately a doubling in the titres of BSA-specific antibody in sera to 169 and 430 micrograms ml-1, respectively. Increases in IgG1 and IgG2a/2b accounted for most of the CoQ10-induced increases in anti-BSA titres. These results are rationalized on the basis of surface hydrophobicity and opsonization changes induced by the presence of CoQ10 in vesicles. We suggest that liposomal CoQ10 has potential as a new generation of vaccine delivery system to enhance the immune response. Its use as a novel delivery system may be particularly effective under pathological conditions where the occurrence of an oxidative stress condition significantly impairs the immune system functions.

Adjuvants, Immunologic↗
PubMed2000

Lipid clearance and total parenteral nutrition: the importance of monitoring plasma lipids.

Lipid provides two major advantages for total parenteral nutrition (TPN). First, it provides essential fatty acids, thus avoiding essential fatty acid deficiency, and secondly, it is a useful energy source, providing 9 kcal/g. However, we describe a patient who had TPN containing Intralipid, where problems of lipid clearance developed. We also review the literature of lipid clearance problems in TPN patients and suggest ways by which such problems can be managed. We suggest that patients taking TPN should have their plasma lipids (triacylglycerols) measured before and during TPN initiation. This is particularly important in patients who are at high risk of impaired fat clearance, such as those who are hyperlipidemic, diabetic, septic, or with impaired renal or hepatic function, or those who are critically ill.

Aged↗
PubMed1998

Lipids and lipid-activated vitamins in chronic cholestatic diseases.

Primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune cholangiopathy are cholestatic liver diseases of unknown cause. Destruction of small to medium bile ducts (in primary biliary cirrhosis and autoimmune cholangiopathy) and large bile ducts (in primary sclerosing cholangitis) leads to progressive cholestasis, liver failure and end-stage liver disease. A variety of abnormalities in lipid metabolism have been described in primary biliary cirrhosis, and range from alterations in serum lipid levels and lipoprotein subsets to deranged metabolism of cholesterol. Progressive cholestasis and, consequently, decreased small intestinal bile acid concentrations in these cholestatic liver disease can also lead to impaired absorption of fats and fat-soluble vitamins, resulting in steatorrhea and deficiencies in vitamins A, D, E, and K. This article focuses on abnormalities in lipid metabolism in primary biliary cirrhosis and primary sclerosing cholangitis, and on lipid-activated vitamin deficiencies in these disorders.

Avitaminosis↗
PubMed2002

Specific natural DNA-bound lipids in post-genome era. The lipid conception of chromatin organization.

Two pools of DNA-bound lipids were isolated from DNA supramolecular complex (SC-DNA): loosely bound (extracted with 35% ethanol) and tightly bound lipids (extracted after additional treatment DNase I). The compositions of the two lipid pools from different sources (rat thymus, liver, loach sperm, pigeon erythrocytes, Zajdel ascites hepatoma, Ehrlich ascites carcinoma, sarcoma 37, Escherichia coli B and T2 phage) were studied. The possible functions of DNA-bound lipids, especially of cardiolipin and cholesterol, at the attachment of DNA loops to the nuclear matrix, in DNA replicon organization, replication and transcription are discussed.

Animals↗
PubMedDate not supplied

Facile functionalization of lipid bilayer vesicles by titania: the use of cerasome-forming lipids for surface and core modification.

Two kinds of functionalization of a lipid bilayer vesicle by titania were achieved by utilizing a cerasome-forming lipid, which is the starting material to prepare a cerasome, a morphologically stable lipid bilayer vesicle having an atomic layer of siloxane networks on its surface. One system is the preparation of the titania-coated cerasomes by immobilizing nanaometer-sizes of titania onto the surface siloxane network of cerasomes. The other is the creation of an asymmetric lipid bilayer structure on the surface of the colloidal titania particles. The characteristics of these surface- and core-functionalized vesicles were investigated, and it was found that these conjugates showed photocatalytic activity as evaluated by photolysis experiments of the cationic dye methylene blue.

Catalysis↗
PubMed1991

Cytochrome c-lipid interactions studied by resonance Raman and 31P NMR spectroscopy. Correlation between the conformational changes of the protein and the lipid bilayer.

The interaction of cytochrome c with negatively charged lipids has been studied by resonance Raman spectroscopy of the protein heme group and 31P NMR of the phospholipid headgroups. The gel-to-fluid-phase transition of dimyristoylphosphatidylglycerol induces shifts in the conformational and coordination equilibria of the bound cytochrome c, as recorded by the resonance Raman spectra in the fingerprint and marker band regions. Conformational and coordination shifts of the bound cytochrome are also induced on admixture of dioleoylglycerol or dioleoylphosphatidylcholine with dioleoylphosphatidylglycerol. In the case of dioleoylglycerol, significant changes take place even at levels as low as 5 mol %. Binding of cytochrome c induces or increases the content of near isotropically diffusing lipid registered by the 31P NMR spectra of the different lipids studied. Admixture of dioleoylglycerol also increases the bilayer curvature of dioleoylphosphatidylglycerol, inducing an inverted hexagonal phase at 50 mol % concentration; the tendency to spontaneous curvature in the lipid appears to relax the conformational change detected in the protein.

Cytochrome c Group↗
PubMed1994

Insertion of filamin into lipid membranes examined by calorimetry, the film balance technique, and lipid photolabeling.

The interaction of the actin-binding protein filamin with mixtures of zwitterionic and anionic phospholipids (DMPC, DMPG, PC, PS) was studied in reconstituted lipid monolayers and bilayers. Protein-lipid interactions were investigated by differential scanning calorimetry, the film balance technique, and hydrophobic photoradiolabeling. For calorimetric assays, multilamellar vesicles (MLVs) and large unilamellar vesicles produced by the extrusion technique (LUVETs) were used. With MLVs, filamin induced a pronounced drop in phase transition cooperativity. Mixed DMPC/DMPG LUVETs showed a linear decrease of the main phase transition enthalpy and a significant shift in temperature for the solidus and liquidus lines with increasing mole fractions of reconstituted filamin. The insertion of native filamin into uncharged and negatively charged lipid monolayers was measured in time/area diagrams with the film balance technique. Finally, we have newly synthesized a highly sensitive lipid analogue, [125]TID-PC/16, which selectively labels membrane-embedded hydrophobic domains of proteins, and which proved to label filamin, supporting evidence that this protein partially inserts into the hydrophobic domain of liposomes.

Calorimetry, Differential Scanning↗
PubMed1988

Effects of lipid composition and packing on the adsorption of apolipoprotein A-I to lipid monolayers.

To better understand the factors controlling the binding of apolipoprotein molecules at the surfaces of serum lipoprotein particles, the adsorption of human apolipoprotein A-I to phospholipid monolayers has been studied. The influence of lipid packing was investigated by spreading the monolayers at various initial surface pressures (pi i) and by using various types of lipid. The adsorption of 14C-methylated apolipoprotein A-I was monitored by simultaneously following the surface radioactivity (which could be converted to the surface concentration of protein, gamma) and the change in surface pressure (delta pi). In general, increasing the pi i of lipid monolayers reduces the adsorption of apolipoprotein A-I; for expanded egg phosphatidylcholine (PC) monolayers at pi i greater than or equal to 32 dyn/cm, gamma and delta pi are zero. The degree of adsorption of the apolipoprotein is also influenced by the physical state of the lipid monolayers. Thus, at a given pi i, apolipoprotein A-I adsorbs more to expanded monolayers than to condensed monolayers so that, at a given subphase concentration of protein, gamma of apolipoprotein A-I with various phospholipid monolayers decreases in the order egg PC greater than egg sphingomyelin greater than distearoyl-PC. The plot of gamma against pi i for adsorption of apolipoprotein A-I to dipalmitoylphosphatidylcholine (DPPC) monolayers shows an inflection at pi i = 8 dyn/cm; at this pi, the DPPC monolayer undergoes a phase transition from liquid (expanded) to solid (condensed) state. Addition of cholesterol generally decreases the adsorption of apolipoprotein A-I to egg PC monolayers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adsorption↗