Abstract：
:The polyene antibiotic amphotericin B (AMB) is an effective antifungal agent whose therapeutic potential is limited by poor aqueous solubility and toxicity toward host tissues. Addition of apolipoprotein A-I to a multilamellar phospholipid vesicle dispersion containing 20% (w/w) AMB induces the formation of reconstituted high density lipoprotein (rHDL), with solubilization of the antibiotic. Density gradient ultracentrifugation resulted in flotation of the complexes to a density of 1.16 g/ml, and negative stain electron microscopy revealed a population of disk-shaped particles. Native gradient polyacrylamide gel electrophoresis indicated a particle diameter of approximately 8.5 nm. Absorbance spectroscopy provided evidence for AMB integration into the lipid milieu. AMB-rHDLs were potent inhibitors of Saccharomyces cerevisiae growth, yielding 90% growth inhibition at <1 microg/ml yeast culture. In studies with pathogenic fungal species, similar growth inhibition characteristics were observed. Compared with AMB-deoxycholate micelles, AMB-rHDL displayed greatly attenuated red blood cell hemolytic activity and decreased toxicity toward cultured hepatoma cells. In in vivo studies in immunocompetent mice, AMB-rHDLs were nontoxic at 10 mg/kg, and they showed efficacy in a mouse model of candidiasis at concentrations as low as 0.25 mg/kg. These results indicate that AMB-rHDLs constitute a novel formulation that effectively solubilizes the antibiotic and elicits strong in vitro and in vivo antifungal activity with no observed toxicity at therapeutic doses.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Oda MN,Hargreaves PL,Beckstead JA,Redmond KA,van Antwerpen R,Ryan ROdoi
10.1194/jlr.D500033-JLR200keywords:
subject
Has Abstractpub_date
2006-02-01 00:00:00pages
260-7issue
2eissn
0022-2275issn
1539-7262pii
D500033-JLR200journal_volume
47pub_type
杂志文章abstract：:The factors involved in shuttling cholesterol among cellular membranes have not been defined. Using amphotericin B selection, we previously isolated Chinese hamster ovary cell mutants expressing defects in intracellular cholesterol transport. Complementation analysis among seven mutants identified one cell line, mutan...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-10-01 00:00:00
abstract：:N-arachidonylethanolamine (AEA) accumulates during brain injury and postmortem. Because fatty acid amide hydrolase (FAAH) regulates brain AEA content, the purpose of this study was to determine its role in the postmortal accumulation of AEA using FAAH null mice. As expected, AEA content in immediately frozen brain tis...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400377-JLR200
更新日期：2005-02-01 00:00:00
abstract：:Spontaneously transformed mouse fibroblasts (Balb/c 3T12-3 cells) displayed an increased adhesion when cultured in the presence of 10(-6) M all-trans retinol and acquired morphological characteristics of the normal phenotype. Thus it was of interest to investigate the metabolism of [15-(14)C]retinol in this system. Wi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1979-03-01 00:00:00
abstract：:We used a mouse C57BL/6J×CASA/Rk intercross to map a locus on chromosome 14 that displayed a gender-dependent effect on cholesterol absorption from the intestine. Studies in congenic animals revealed a complex locus with multiple operating genetic determinants resulting in alternating gender-dependent phenotypic effec...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M034579
更新日期：2013-03-01 00:00:00
abstract：:Six African green monkeys were labeled intravenously with [1,2-(3)H]cholesterol while consuming a cholesterol-free liquid formula diet. The plasma cholesterol specific activity was compared with the specific activity of the biliary cholesterol and bile acids and with the fecal neutral steroids in order to determine wh...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1980-09-01 00:00:00
abstract：:Epoxyeicosatrienoic acids were isolated and purified from female rabbit kidneys. They were identified as a group, prior to resolution, by packed column gas-liquid chromatography-mass spectroscopic techniques as their methyl esters as well as their trimethylsilyl bromohydrin methyl esters. Initial capillary gas-liquid ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1987-07-01 00:00:00
abstract：:Phospholipids serve as central structural components in cellular membranes and as potent mediators in numerous signaling pathways. There are six main classes of naturally occurring phospholipids distinguished by their distinct polar head groups that contain many unique molecular species with distinct fatty acid compos...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D051581
更新日期：2014-11-01 00:00:00
abstract：:There is growing evidence of the capacity of vitamin A to regulate the expression of the genetic region that encodes apolipoproteins (apo) A-I, C-III, and A-IV. This region in turn has been proposed to modulate the expression of hyperlipidemia in the commonest genetic form of dyslipidemia, familial combined hyperlipid...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1999-03-01 00:00:00
abstract：:A qualitative iodometric test for lipoxygenase activity is described. The sensitive method is useful for rapidly screening large numbers of samples, as from a chromatography column or after enzyme inactivation treatment in food processing. ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1972-03-01 00:00:00
abstract：:Enzymes associated with glycerolipid biosynthesis were examined in microsomal fractions of liver and adipose tissue obtained from swine of various ages. Generally, liver glycerophosphate acyltransferase, phosphatidate phosphohydrolase, diglyceride acyltransferase, and choline phosphotransferase activities were substan...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1979-02-01 00:00:00
abstract：:In vitro experiments have demonstrated that exogenous phospholipid transfer protein (PLTP), i.e. purified PLTP added to macrophage cultures, influences ABCA1-mediated cholesterol efflux from macrophages to HDL. To investigate whether PLTP produced by the macrophages (i.e., endogenous PLTP) is also part of this process...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600051-JLR200
更新日期：2006-08-01 00:00:00
abstract：:Although the synthesis pathways of intracellular triacylglycerol (TAG) species have been well elucidated, assessment of the contribution of an individual pathway to TAG pools in different mammalian organs, particularly under pathophysiological conditions, is difficult, although not impossible. Herein, we developed and...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M033837
更新日期：2013-04-01 00:00:00
abstract：:Remnant-like emulsions were prepared with lipid compositions similar to remnants derived from triacylglycerol-rich lipoproteins. When injected into the bloodstream of conscious mice the remnant-like emulsions labeled with cholesteryl[13C]oleate were metabolized in the liver and the appearance of 13CO2 in the breath wa...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-03-01 00:00:00
abstract：:A deficiency of lysosomal phospholipase A2 (LPLA2) causes macrophage-associated phospholipidosis, suggesting that the enzyme is important in the lipid catabolism. Because LPLA2 is secreted by macrophages, extracellular LPLA2 activity may potentially reflect a change in macrophage activation. In this report, the detect...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D007146
更新日期：2010-08-01 00:00:00
abstract：:Human endothelial lipase (EL), a member of the triglyceride lipase gene family, has five potential N-linked glycosylation sites, two of which are conserved in both lipoprotein lipase and hepatic lipase. Reduction in molecular mass of EL after treatment with glycosidases and after treatment of EL-expressing cells with ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400162-JLR200
更新日期：2004-11-01 00:00:00
abstract：:Dysbetalipoproteinemia, an uncommon but highly atherogenic mixed hyperlipidemia due to the accumulation of remnants of triglyceride-rich lipoproteins, is characterized by cholesterol-enriched VLDL that migrates in the beta-position on agarose gels. The demonstration of a broad beta-band on agarose gel electrophoresis ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.d200013-jlr200
更新日期：2003-01-01 00:00:00
abstract：:The inverse relationship between plasma levels of high density lipoprotein (HDL) and coronary heart disease rates has suggested that HDL might influence body stores of cholesterol. Therefore, we have investigated potential relationships between the parameters of body cholesterol metabolism and the plasma levels of HDL...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1985-09-01 00:00:00
abstract：:Lipid lamellae present in the outermost layer of the skin, the stratum corneum, form the main barrier for the diffusion of molecules through the skin. The presence of a unique 13 nm lamellar phase and its high crystallinity are characteristic for the stratum corneum lipid phase behavior. In the present study, small-an...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M500221-JLR200
更新日期：2005-12-01 00:00:00
abstract：:Ketone bodies (KBs), acetoacetate and β-hydroxybutyrate (βHB), were considered harmful metabolic by-products when discovered in the mid-19th century in the urine of patients with diabetic ketoacidosis. It took physicians many years to realize that KBs are normal metabolites synthesized by the liver and exported into t...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R046599
更新日期：2014-09-01 00:00:00
abstract：:Taurocholate, a relatively hydrophobic bile salt, is a potent down-regulator of HMG-CoA reductase and cholesterol 7 alpha-hydroxylase (C7 alpha H), the rate-determining enzymes of the cholesterol and bile acid biosynthetic pathways, respectively. Inhibition of cholesterol synthesis with a bolus dose of mevinolin (lova...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1992-05-01 00:00:00
abstract：:Peroxisome proliferator-activated receptor alpha (PPAR alpha) is a transcriptional regulator of the expression of mitochondrial thioesterase I (MTE-I) and uncoupling protein 3 (UCP3), which are induced in the heart at the mRNA level in response to diabetes. Little is known about the regulation of protein expression of...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600364-JLR200
更新日期：2007-07-01 00:00:00
abstract：:Apolipoprotein E2 (apoE2)-associated hyperlipidemia is characterized by a disturbed clearance of apoE2-enriched VLDL remnants. Because excess apoE2 inhibits LPL-mediated triglyceride (TG) hydrolysis in vitro, we investigated whether direct or indirect stimulation of LPL activity in vivo reduces the apoE2-associated hy...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M800009-JLR200
更新日期：2008-05-01 00:00:00
abstract：:The activity of rat liver microsomal squalene epoxidase is inhibited effectively by digitonin. Concentrations of 0.8 to 1.2 mg/ml of digitonin cause total inhibition of microsomal (0.75 mg protein/ml) squalene epoxidase either in microsomes that were pretreated with digitonin and subsequently washed and subjected to e...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1989-08-01 00:00:00
abstract：:apoE is a multi-functional protein expressed in several cell types and in several organs. It is highly expressed in adipose tissue, where it is important for modulating adipocyte lipid flux and gene expression in isolated adipocytes. In order to investigate a potential systemic role for apoE that is produced in adipos...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M050567
更新日期：2015-02-01 00:00:00
abstract：:An enzyme-coupled, colorimetric method for the assay of acyl-CoA synthetase is described. Acyl-CoA formed from fatty acid and CoA by acyl-CoA synthetase was dehydrogenated by acyl-CoA oxidase. Hydrogen peroxide produced was then converted into formaldehyde in the presence of methanol by catalase. The formaldehyde reac...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-10-01 00:00:00
abstract：:The 3-methyl-branched fatty acid phytanic acid is degraded by the peroxisomal alpha-oxidation route because the 3-methyl group blocks beta-oxidation. In adult Refsum disease (ARD), peroxisomal alpha-oxidation is defective, which is caused by mutations in the gene coding for phytanoyl-CoA hydroxylase in the majority of...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400064-JLR200
更新日期：2004-07-01 00:00:00
abstract：:The differentiation of macrophages into lipid-filled foam cells is a hallmark of the lung granuloma that forms in patients with active tuberculosis (TB). Mycolic acids (MAs), the abundant lipid virulence factors in the cell wall of Mycobacterium tuberculosis (Mtb), can induce this foam phenotype possibly as a way to p...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M073171
更新日期：2017-04-01 00:00:00
abstract：:The proton NMR spectra of the N-methyl choline region of normal and lecithin:cholesterol acyltransferase (LCAT)-deficient lipoproteins and of egg yolk phosphatidylcholine-cholesterol 55:45 (mol %) vesicle mixtures have been examined in the presence and absence of manganous sulfate as a line-broadening reagent. Mangano...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1989-05-01 00:00:00
abstract：:Using [13C]-tracers and direct fetal doses, we show for the first time that the fetal primate converts alpha-linolenic acid (18:3) to docosahexaenoic acid (22:6) in vivo, and we estimate the relative bioefficacy of the two substrates for brain 22:6 accretion. Pregnant female baboons consumed a diet free of long chain ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2001-04-01 00:00:00
abstract：:A modification of the semiautomated assay method of Antonis (1965. J. Lipid Res. 6:307-312) for free fatty acid is presented. Free fatty acids are extracted from serum or plasma into di-n-butyl ether-2-methoxyethanol; the extract is almost free from phospholipids. The acids are analyzed in a portion of extract by a co...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1978-02-01 00:00:00
