bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of different medium‐chain fatty acids on intestinal absorption of structured triacylglycerols
Authors: Mu Huiling , Høy Carl‐Erik 
Published: November 2006

AbstractTo study the effect of the chain length of medium‐chain fatty acids on the intestinal absorption of long‐chain fatty acids, we examined the lymphatic transport of fat following administration of five purified structured triacylglycerols (STAG) containing different medium‐chain fatty acids in the sn‐1, 3 positions and long‐chain fatty acids in the sn‐2 position in a rat model. Significant amounts of medium‐chain fatty acids were found in lymph samples after intragastric administration of 1,3‐dioctanoyl‐2‐linoleyl‐sn‐glycerol (8∶0/18∶2/8∶0), 1,3‐didecanoyl‐2‐linoleyl‐sn‐glycerol, and 1,3‐didodecanoyl‐2‐linoleyl‐sn‐glycerol. The accumulated lymphatic transport of medium‐chain fatty acids increased with increasing carbon chain length. The recoveries of caprylic acid (8∶0), capric acid (10∶0), and lauric acid (12∶0) were 7.3±0.9, 26.3±2.4, and 81.7±6.9%, respectively. No significant differences were observed for the maximal intestinal absorption of linoleic acid (18∶2n−6) when the chain length of medium‐chain fatty acids at the primary positions was varied, and the absorption of 18∶2 and oleic acid (18∶1) from 8∶0/18∶2/8∶0 and 1,3‐dioctanoyl‐2‐oleyl‐sn‐glycerol was similar. We conclude that the chain length of the medium‐chain fatty acids in the primary positions of STAG does not affect the maximal intestinal absorption of long‐chain fatty acids in the sn‐2 position in the applied rat model, whereas the distribution of fatty acids between the lymphatics and the portal vein reflects the chain length of the fatty acids.
Breast‐fed infants achieve a higher rate of brain and whole body docosahexaenoate accumulation than formula‐fed infants not consuming dietary docosahexaenoate
Authors: Cunnane Stephen C. , Francescutti Valerie , Brenna J. Thomas , Crawford Michael A. 
Published: November 2006

AbstractDocosahexaenoate (DHA) has been increasingly recognized as an important fatty acid for neural and visual development during the first 6 mon of life. One important point of controversy that remains is the degree to which adequate levels of DHA can be acquired from endogenous synthesis in infants vs. what should be provided as dietary DHA. We have approached this problem by a retrospective analysis of published body composition data to estimate the actual accumulation of DHA in the human infant brain, liver, adipose tissue, remaining lean tissue, and whole body. Estimating whether infants can synthesize sufficient DHA required comparison to and extrapolation from animal data. Over the first 6 mon of life, DHA accumulates at about 10 mg/d in the whole body of breast‐fed infants, with 48% of that amount appearing in the brain. To achieve that rate of accumulation, breast‐fed infants need to consume a minimum of 20 mg DHA/d. Virtually all breast milk provides a DHA intake of at least 60 mg/d. Despite a store of about 1,050 mg of DHA in body fat at term birth and an intake of about 390 mg/d α‐linolenate (α‐LnA), the brain of formula‐fed infants not consuming DHA accumulates half the DHA of the brain of breast‐fed infants while the rest of the body actually loses DHA over the first 6 mon of life. No experimental data indicate that formula‐fed infants not consuming DHA are able to convert the necessary 5.2% of α‐LnA intake to DHA to match the DHA accumulation of breast‐fed infants. We conclude that dietary DHA should likely be provided during at least the first 6 mon of life.
Biochemical modifications and transcriptional alterations attendant to sterol feeding in Phytophthora parasitica
Authors: Dotson W. David , Tove Shirley R. , Parks Leo W. 
Published: November 2006

AbstractPhytophthora species are eukaryotic sterol auxotrophs that possess the ability to grow, albeit poorly, in the complete absence of sterols. Growth of Phytophthora is often improved substantially when an exogenous source of sterol is provided. Additionally, sterols may be required for sexual and asexual sporulation in Phytophthora. Our research has been focused on identifying and characterizing the immediate physiological effects following sterol addition to cultures of P. parasitica. Through gas chromatographic analysis of extracts from P. parasitica cultures that were fed various sterols, we have ob‐tained evidence for sterol C5 desaturase and Δ7 reductase activities in this organism. Zoo blots were probed with DNA sequences encoding these enzymes, from Saccharomyces cerevisiae and Arabidopsis thaliana. Hybridization of a S. cerevisiae ERG3 probe to P. parasitica DNA was observed, implicating sequence similarity between the sterol C5 desaturase encoding genes. Differential display experiments, using RNA from P. parasitica, have demonstrated a pattern of altered gene expression between cultures grown in the presence and absence of sitosterol. Characterization of sterol‐related metabolic effects and sterol functions in Phytophthora should lead to improved measures for control of this important group of plant pathogens.
Design and synthesis of new steroidal inhibitors of estrogen synthase (aromatase)
Authors: Parish Edward J. , Li Shengrong , Rao Zhigang 
Published: November 2006

AbstractThe estrogen synthase (aromatase) enzyme system is responsible for the biosynthesis of estrogen hormones in human females. Estrogens are vital for normal growth and development, but will promote the growth of certain breast cancers. Appromaximately 30–50% of breast cancers are considered to be hormone‐dependent. Consequently regulation of estrogen biosynthesis has advanced as a potential therapeutic strategy. This has led to the development of active‐site inhibitors, which may have potential for the control of breast cancer. We have recently prepared a number of new steroidal inhibitors that have been evaluated as aromatase inhibitors. These include steroidal A/B‐ring isoxazoles and a series of A/B‐ring pyrazoles with alkyl‐ and aryl‐substituted nitrogen. In addition, we have developed new chemical procedures for the synthesis of 6β‐hydroxy steroids, which could be key intermediates in the preparation of C‐19 inhibitors of aromatase activity.
Cholesterol synthesis in the vertebrate retina: Effects of U18666A on rat retinal structure, photoreceptor membrane assembly, and sterol metabolism and composition
Authors: Fliesler S. J. , Richards M. J. , Miller C. ‐Y. , Cenedella R. J. 
Published: November 2006

AbstractTreatment of neonatal rats with U18666A, an inhibitor of desmosterol Δ24‐reductase, results in accumulation of desmosterol (Δ5,24) and depletion of cholesterol (Δ5) in various bodily tissues and also causes cataracts. We evaluated the effects of U18666A on the sterol composition, de novo sterol synthesis, and histological structure of the retina. Neonatal Sprague‐Dawley rats were injected subcutaneously with U18666A (15 mg/kg, in olive oil) every other day from birth through 3 wk of age; in parallel, control rats received olive oil alone. At 21 d, treated and control groups each were subdivided into two groups: one group of each was injected intravitreally with [3H]acetate; retinas were removed 20 h later and non‐saponifiable lipids (NSL) were analyzed by radio‐high‐performance liquid chromatography. The other group was injected intravitreally with [3H]leucine; 4 d later, one eye of each animal was evaluated by light and electron microscopy and light microscopic autoradiography, while contralateral retinas and rod outer segment (ROS) membranes prepared thereform were analyzed by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis/fluorography. In the treated group, the Δ5/Δ5,24 mole ratio of retinas was ca. 1.0, and >88% of the NSL radioactivity was in Δ5,24; in contrast, control retinas had Δ5/Δ5,24 >170, with >80% of the NSL radioactivity in Δ5. Retinal histology, ultrastructure, ROS renewal rates, and rhodopsin synthesis and intracellular trafficking were comparable in both treated and control animals. These results suggest that desmosterol can either substitute functionally for cholesterol in the retina or it can complement subthreshold levels of cholesterol by sterol synergism.
Rationally designed inhibitors as tools for comparing the mechanism of squalene‐hopene cyclase with oxidosqualene cyclase
Authors: Viola Franca , Ceruti Maurizio , Cattel Luigi , Milla Paola , Poralla Karl , Balliano Gianni 
Published: November 2006

AbstractThe inhibition of squalene‐hopene cyclase (SHC) (E.C. 5.4.99.‐), an enzyme of bacterial membranes catalyzing the formation of pentacyclic sterol‐like triterpenes, was studied by using different classes of compounds originally developed as inhibitors of oxidosqualene cyclase (OCS) (E.C. 5.4.99.7), the enzyme of eukaryotes responsible for the formation of tetracyclic precursors of sterols. The mechanism of cyclization of squalene by SHC, beginning with a protonation of the 2,3 double bond by an acidic residue of the enzyme, followed by a series of electrophilic additions of the carbocationic intermediates to the double bonds, is similar to the mechanism of cyclization of 2,3‐oxidosqualene by OSC. The inhibitors studied included: (i) analogs of the carbocationic intermediates formed during cyclization, such as aza‐analogs of squalene and 2,3‐oxidosqualene; (ii) affinity‐labeling inhibitors bearing a methylidene reactive group; and (iii) vinyldioxidosqualenes and vinylsulfide derivatives of the substrates. Comparison of the results obtained with the two enzymes, SHC and OSC, showed that many of the most effective inhibitors of OSC were also able to inhibit SHC, while some derivatives acted as specific inhibitors. Differences could be easily explained on the basis of the different substrate specificity of the two enzymes.
Structure‐apoptotic potency evaluations of novel sterols using human leukemic cells
Authors: Johnson Betty H. , Russell Michael J. , Krylov Alexander S. , Medh Rheem D. , Ayala‐Torres Sylvette , Regner Justin Lee , Thompson E. Brad 
Published: November 2006

AbstractThree oxidized analogs of cholesterol have been characterized for their ability to cause apoptotic cell death in CEM‐C7‐14 human leukemic cells. In addition to testing 15‐ketocholestenol (K15), 15‐ketocholestenol hydroxyethyl ether (CK15), and 7‐ketocholesterol hydroxyethyl ether (CK7), an oxysterol of known apoptotic response, 25‐hydroxycholesterol (25OHC), served as a standard for comparison. Growth studies based on dye exclusion by viable cells while using a sublethal concentration of oxysterols ranked their potency for cell kill as 25OHC>K15>CK15>CK7. Both the TUNEL assay (terminal deoxynucleotidyl transferase‐mediated dUTP‐X nick end labeling), which quantifies the amount of DNA nicks caused by a toxic agent, and the MTT assay, which measures cell metabolism and thus reflects cell viability, substantiated the same rank order. An ELISA assay for evaluating release of DNA fragments into the cytosol after treatment gave a similar potency order. The oncogene c‐myc mRNA was suppressed by all three oxysterols. with 25OHC and K15 being the most potent suppressors. Hoechst and Annexin V staining documented that these oxysterols kill cells by an apoptotic pathway as evidenced by condensation of nuclear chromatin and plasma membrane inversion, respectively. From these in vitro studies, we believe that 25OHC, K15, and possibly CK15 have the potential to be chemotherapeutic agents.
C27 to C32 sterols found in Pneumocystis, and opportunistic pathogen of immunocompromised mammals
Authors: Kaneshiro Edna S. , Wyder Michael A. 
Published: November 2006

AbstractPneumocystis carinii is the paradigm of opportunistic infections in immunocompromised mammals. Prior to the acquired immunodeficiency syndrome (AIDS) pandemic and the use of immunosuppressive therapy in organ transplant and cancer patients, P. carinii was regarded as a curiosity, rarely observed clinically. Interest in this organism exploded when it was identified as the agent of P. carinii pneumonia (PcP), the direct cause of death among many AIDS patients. Aggressive prophylaxis has decreased the number of acute PcP cases, but it remains among the most prevalent opportunistic infections found within this patient population. The taxonomic assignment of P. carinii has long been argued; molecular genetics data now demonstrate that it is a fungus. Several antimycotic drugs are targeted against ergosterol or its biosynthesis, but these are not as effective against PcP as they are against other fungal infections. This can now be explained in part by the identification of the sterols of P. carinii. The organism lacks ergosterol but contains distinct C28 and C29 Δ7 24‐alkylsterols. Also, 24‐methylenelanost‐8‐en‐3β‐ol (C31) and pneumocysterol, (24Z)‐ethylidenelanost‐8‐en‐3β‐ol (C32) were recently identified in organisms infecting humans. Together, the Δ7 24‐alkylsterols and pneumocysterol are regarded as signature lipids of the pathogen that can be useful for the diagnosis of PcP, since no other lung pathogen is known to contain them. Cholesterol (C27), the dominant sterol component in P. carinii, is probably totally scavenged from the host. De novo synthesis of sterols has been demonstrated by the presence of lovastatin‐sensitive 3‐hydroxy‐3‐methylglutaryl‐CoA reductase activity, the incorporation of radiolabeled mevalonate and squalene into P. carinii sterols, and the reduction in cellular ATP in cells treated with inhibitors of enzymes in sterol biosynthesis.
Plasma oxysterols and tocopherol in patients with diabetes mellitus and hyperlipidemia
Authors: Murakami Hiroshi , Tamasawa Naoki , Matsui Jun , Yasujima Minoru , Suda Toshihiro 
Published: November 2006

AbstractThe plasma levels of free oxysterols (7‐ketocholesterol: 7α‐hydroxy‐, 7β‐hydroxy‐, 25‐hydroxy‐, and 27‐hydroxycholesterol; and 5α,6α‐epoxycholestanol) in patients with diabetes mellitus and hypercholesterolemia were determined using gas chromatography‐mass spectrometry with selective ion monitoring. We studied 39 patients with diabetes mellitus, 20 nondiabetic patients with hypercholesterolemia, and 37 normal controls. Plasma cholesterol levels in diabetic and hypercholesterolemic patients showed no statistical difference. Plasma 7‐ketocholesterol was significantly higher in patients with diabetes (31.6±2.8 ng/mL) or hypercholesterolemia (52.3±5.9) than in the control group (22.4±1.2). The increased plasma cholesterol can be regarded as an oxidation substrate for the oxidant stress and the higher absolute levels of oxysterols in hypercholesterolemic plasma compared with the control plasma. This difference disappeared when 7‐ketocholesterol was expressed in proportion to total cholesterol. The oxidizability of plasma cholesterol was evaluated by comparing the increased ratio of 7‐ketocholesterol after CuSO4 oxidation to the ratio before. We demonstrated that the patients with diabetes showed increased oxidizability (77.5%) compared with the control (36.6%) or hyperlipemic group (45.3%), which is likely due to the lower amounts of α‐tocopherol in the diabetics. Measurement of oxysterols may serve as a marker for in vivo oxidized lipoproteins in diabetes and hyperlipemia.
Use of a 13C tracer to quantify the plasma appearance of a physiological dose of lutein in humans
Authors: Yao Lihang , Liang Yuexia , Trahanovsky Walter S. , Serfass Robert E. , White Wendy S. 
Published: November 2006

AbstractIncreased intake of lutein from vegetables promotes increased density of the macular pigment and therefore may protect against age‐related macular degeneration. Our objective was to use a 13C tracer and high‐precision gas chromatography‐combustion interfaced‐isotope ratio mass spectrometry (GC‐C‐IRMS) to investigate metabolism of a lutein dose equivalent to that absorbed from vegetables. Biosynthetic per‐labeled (>99% 13C) lutein was purified from a commercially available extract of algal biomass. Subjects (n=4) ingested 3 mg of [13C]lutein with a standardized low‐carotenoid breakfast. Blood samples were collected at baseline and then hourly for 12 h; additional blood samples were drawn at 16, 24, 48, 72, 96, 192, 360, and 528 h. To produce perhydro‐β‐carotene suitable for analysis by GC‐C‐IRMS, the plasma lutein fraction was hydrogenated on palladium‐on‐carbon catalyst with acid‐catalyzed hydrogenolysis. The stable carbon isotope (13C/12C) ratio measured by GC‐C‐IRMS was used to calculate the plasma concentration of [13C]lutein. There was a rapid increase in [13C]lutein in plasma until peak enrichment at 16 h followed by a decline to the next measurement at 24 h. At 528 h, small changes in 13C enrichment from baseline could still be measured in plasma lutein. High‐precision GC‐C‐IRMS enables complete definition of the appearance and disappearance of [13C]lutein in plasma after ingestion of a dose similar to that absorbed from foods.
Membrane physical properties do not explain increased cyclic AMP production in hepatocytes from rats fed menhaden oil
Authors: Bizeau Michael E. , Hazel Jeffrey R. 
Published: November 2006

AbstractTo study the effect of altering plasma membrane fatty acid composition on the glucagon signal transduction pathway, cAMP accumulation was measured in hepatocytes from rats fed diets containing either menhaden oil (MO) or coconut oil (CO). Hepatocytes from MO‐fed animals produced significantly more cAMP in response to glucagon and forskolin compared to CO‐fed animals. Glucagon receptor number and affinity were similar in MO‐ and CO‐fed rats. Liver plasma membranes from MO‐fed animals were enriched in long‐chain n‐3 fatty acids and contained significantly lower amounts of saturated C10−C16 and 18∶1n−9 than CO‐fed animals. Membrane physical properties were examined using both Fourier transform infrared spectroscopy (FTIR) and the fluorescent probe 1,6‐diphenyl‐1,3,5‐hexatriene (DPH). FTIR analysis revealed that below 34°C, CO membranes were more ordered than MO membranes. However, as assay temperature approached 37°C, MO and CO membranes became similarly ordered. DPH polarization values indicated no differences in membrane order at 37°C, whereas membrane order was decreased in CO‐fed animals at 25°C. These data indicate the importance of assay temperature in assessing the influence of membrane physical properties on the activity of signal transduction pathways. Whereas increased signal transduction activity has been correlated to reduced membrane order in MO‐fed animals, these data indicate that at physiological temperatures membrane order did not vary between groups. Enhanced cAMP accumulation in response to forskolin indicates that adenylate cyclase activity or content may be elevated in MO‐vs. CO‐fed rats. Enhanced adenylate cyclase activity may result, in part, from changes in specific fatty acids in hepatocyte plasma membranes without demonstrable changes in membrane physical properties.
Dietary cod liver oil decreases arachidonic acid in rat gastric mucosa and increases stress‐induced gastric erosions
Authors: Olafsson Sigurdur Oli , Hallgrimsson Jonas , Gudbjarnason Sigmundur 
Published: November 2006

AbstractThe purpose of this study was to examine the influence of long‐term feeding of dietary fat rich in either n−3 or n−6 fatty acids on the availability of arachidonic acid (20∶4n−6) in major phospholipids of gastric mucosa in rats. Three groups of male Wistar rats were fed either a standard diet, a cod liver oil‐enriched diet (10% by weight), or a corn oil‐enriched diet (10% by weight) for 8 mon. Dietary cod liver oil significantly reduced the level of 20∶4n−6 in phosphatidylcholine (PC) and in phosphatidylethanolamine (PE) of gastric mucosa. The loss of 20∶4n−6 was compensated for by eicosapentaenoic acid (20∶5n−3) in PC, whereas the decrease in 20∶4n−6 in PE corresponded to the increase in three n−3 fatty acids: 20∶5n−3, docosapentaenoic acid (22∶5n−3), and docosahexaenoic acid (22∶6n−3). The level of 20∶5n−3 was higher than the level of 22∶6n−3 both in PC and PE of mucosa in rats fed cod liver oil. Diets supplemented with corn oil increased the level of 18∶2n−6 but decreased the monoene fatty acids 16∶1 and 18∶1n−7 in PC but not in PE of gastric mucosa. The 20∶4n−6 levels of both PC and PE were markedly reduced by dietary cod liver oil, to about one‐third of control levels. Similar changes were also observed in the stomach wall. Gastric erosions were observed in all rats exposed to restriction stress, but this form of stress induced twice the number of erosions in rats fed fish oil compared to control rats or rats fed corn oil. We conclude that a diet rich in fish oil altered the balance between n−6 and n−3 fatty acids in major gastric mucosal phospholipids, markedly reduced the availability of 20∶4n−6, and increased the incidence of gastric erosions induced by restriction or emotional stress.
Low erucic acid canola oil does not induce heart triglyceride accumulation in neonatal pigs fed formula
Authors: Green Timothy J. , Innis Sheila M. 
Published: November 2006

AbstractCanola oil is not approved for use in infant formula largely because of concerns over possible accumulation of triglyceride in heart as a result of the small amounts of erucic acid (22∶1n−9) in the oil. Therefore, the concentration and composition of heart triglyceride were determined in piglets fed from birth for 10 (n=4–6) or 18 (n=6) d with formula containing about 50% energy fat as 100% canola oil (0.5% 22∶1n−9) or 100% soybean oil, or 26% canola oil or soy oil (blend) with palm, high‐oleic sunflower and coconut oil, providing amounts of 16∶0 and 18∶1 closer to milk, or a mix of soy, high‐oleic sunflower and flaxseed oils with C16 and C18 fatty acids similar to canola oil but without 22∶1. Biochemical analysis found no differences in heart triglyceride concentrations among the groups at 10 or 18 d. Assessment of heart triglycerides using Oil Red O staining in select treatments confirmed no differences between 10‐d‐old piglets fed formula with 100% canola oil (n=4), 100% soy oil (n=4), or the soy oil blend (n=2). Levels of 22∶1n−9 in heart triglyceride and phospholipid, however, were higher (P<0.01) in piglets fed 100% canola oil or the canola oil blend, with higher levels found in triglycerides compared with phospholipids. The modest accumulation of 22∶1n−9 associated with feeding canola oil was not associated with biochemical evidence of heart triglyceride accumulation at 10 and 18 d.