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Retrograde amnesia in patients with Alzheimer's disease or Huntington's disease.

Retrograde amnesia (RA) was studied in patients with Huntington's disease (HD) or Alzheimer's disease (AD) using an updated version of the remote memory battery originally developed by Albert, Butters and Levin. Regardless of whether remote memory was measured by unaided recall or cued recall, HD patients exhibited deficits that were equally severe across decades. RA was more severe in AD than in HD patients and the AD patients recalled significantly more items from the 1940s and 50s than from the 60s, 70s or 80s. The AD patients also displayed dysnomia, while the HD patients did not. Naming difficulties appeared to contribute to the poor overall performance of the AD patients, but did not account for the temporal gradient of their RA. These findings, like recent reports focusing on these patients' ability to learn new information and to search semantic memory, indicate that the processes underlying AD and HD patients' memory failures are distinct.

Adult↗

Elaidic and trans-vaccenic acids in plasma phospholipids as indicators of dietary intake of 18:1 trans-fatty acids.

Octadecenoic (18:1) trans-fatty acid fractions from margarine, butter and plasma phospholipids (PL) were isolated by silver ion TLC, and nine positional isomers (n-11-n-3) were identified by GC-MS based on their ozonolysis products. The GC analysis of the isolated fractions gave similar peak profiles and separated seven trans-isomers (n-11-n-6 and n-3). Without a preceding isolation step, the reproducibility of the GC method for plasma PL elaidic (18:1 n 9 trans) and trans-vaccenic acids (n-7) was 3.4 and 2.7% (R.S.D.), respectively. These trans-isomers were rapidly incorporated and cleared in plasma PL and they closely reflected both increased and decreased intake of 18:1 trans-fatty acids during moderate fat substitutions. Significant associations between high-density lipoprotein cholesterol (HDL-C) and PL elaidic and trans-vaccenic acids appeared in habitual margarine users only.

Adult↗

Hydrogel network entrapping cholesterol oxidase and octadecylsilica for optical biosensing in hydrophobic organic or aqueous micelle solvents.

Two optical cholesterol biosensors have been fabricated by immobilizing cholesterol oxidase (ChOx) and octadecylsilica (ODS) particles in hydrogel network matrixes of copolymer of poly(vinyl alcohol) (PVA)/hydroxyethyl carboxymethyl cellulose (HECMC), and sol-gel, respectively. In conjunction with an optical oxygen transducer, the immobilized ChOx in the sol-gel/ODS matrix was assembled as an optical cholesterol biosensor to continuously detect free cholesterol in aqueous micelle solution, while the immobilized ChOx in the PVA/HECMC/ODS matrix was constructed as an organic-phase optical cholesterol biosensor for the continuous analysis of free cholesterol in hydrophobic organic solvent. The compositions and properties of the immobilization matrixes, the effects of solvents and the analytical features were studied in detail. Both biosensors showed stable and reliable responses toward free cholesterol. For the aqueous micelle cholesterol biosensor, the analytical working range was from 0.05 to 8.0 mM cholesterol, the response time was 7-12 min, the operation life was more than 35 assays, and the shelf life was approximately 4 months. For the organic-phase cholesterol biosensor, the analytical working range was from 0.07 to 18.0 mM cholesterol, the response time was 4-8 min, the operation life was more than 120 assays, and the shelf life was longer than 5 months. The organic-phase cholesterol biosensor has been successfully applied to determine the free cholesterol content in commercial butter samples.

Biosensing Techniques↗

Differential pulse polarographic determination of alpha-dicarbonyl compounds in foodstuffs after derivatization with o-phenylenediamine.

A differential pulse polarographic method has been developed for the indirect determination of diacetyl and other vicinal diketones in foodstuffs, based on the quantitative derivatization of the diketones with o-phenylenediamine to give quinoxalines. The method allows the identification of diacetyl and methylglyoxal in brandy, vinegar, wine, and butter samples. The polarographic reduction peaks of the quinoxalines formed are sufficiently separate, in some cases, to allow the simultaneous determination of these two compounds. The polarographic method is not affected by the presence of sulfite ion, probably because the o-phenylenediamine is capable of dislodging the alpha-diketones from their sulfite complexes.

Acetic Acid↗

Breast cancer anomalies.

The death rate from breast cancer among females in England and Wales which had been falling during 1951-59 at ages before 45 increased from 1960 to 1967; and at ages 45-64 there has been a progressive increase ever since 1955. Regional rates at the early ages were considerably higher in Greater London than in the north until 1961, but the difference then gradually disappeared; and at higher ages an excess in the south over that in the north and Wales has persisted at ages 45-64.Whilst the total mortality from breast and uterine cancers combined has shown little regional variation, the proportion of breast cancer in the total has been consistently higher in the south than in the north, and possible implications of this are discussed. Breast cancer rates in the regions are positively associated with the dietary intake per person of butter, cheese, liquid milk and green vegetables but this in itself does not prove a causative connection.

Adult↗

Spreads enriched with three different levels of vegetable oil sterols and the degree of cholesterol lowering in normocholesterolaemic and mildly hypercholesterolaemic subjects.

OBJECTIVE: To investigate the dose-response relationship between cholesterol lowering and three different, relatively low intake levels of plant sterols (0.83, 1.61, 3.24 g/d) from spreads. To investigate the effects on lipid-soluble (pro)vitamins. DESIGN: A randomized double-blind placebo controlled balanced incomplete Latin square design using five spreads and four periods. The five study spreads included butter, a commercially available spread and three experimental spreads fortified with three different concentrations of plant sterols. SUBJECTS: One hundred apparently healthy normocholesterolaemic and mildly hypercholesterolaemic volunteers participated. INTERVENTIONS: Each subject consumed four spreads, each for a period of 3.5 week. RESULTS: Compared to the control spread, total cholesterol decreased by 0.26 (CI: 0.15-0.36), 0.31 (CI: 0.20-0.41) and 0.35 (CI: 0.25-0.46) mmol/L, for daily consumption of 0.83, 1.61 and 3.24 g plant sterols, respectively. For LDL-cholesterol these decreases were 0.20 (CI: 0.10-0.31), 0.26 (CI: 0.15-0.36) and 0.30 (CI: 0.20-0.41). Decreases in the LDL/HDL ratio were 0.13 (CI: 0.04-0.22), 0.16 (CI: 0.07-0.24) and 0.16 (CI: 0.07-0.24) units, respectively. Differences in cholesterol reductions between the plant sterol doses consumed were not statistically significant. Plasma vitamin K1 and 25-OH-vitamin D and lipid standardized plasma lycopene and alpha-tocopherol were not affected by consumption of plant sterol enriched spreads, but lipid standardized plasma (alpha + beta)-carotene concentrations were decreased by about 11 and 19% by daily consumption of 0.83 and 3.24 g plant sterols in spread, respectively. CONCLUSIONS: The three relatively low dosages of plant sterols had a significant cholesterol lowering effect ranging from 4.9-6.8%, 6.7-9.9% and 6.5-7.9%, for total, LDL-cholesterol and the LDL/HDL cholesterol ratio, respectively, without substantially affecting lipid soluble (pro)vitamins. No significant differences in cholesterol lowering effect between the three dosages of plant sterols could be detected. This study would support that consumption of about 1.6 g of plant sterols per day will beneficially affect plasma cholesterol concentrations without seriously affecting plasma carotenoid concentrations.

Adult↗

The occurrence of trans-18:1 isomers in plasma lipids classes in humans.

OBJECTIVE: The aim of this study was to examine the distribution of trans fatty acids (TFA) in plasma lipid classes and the relationship with dietary intake of TFA. DESIGN: After a 2 week baseline (habitual) diet, all subjects consumed a moderate fat (MF) diet for 3 weeks with the fat being derived mainly from margarine and the rest from lean beef, and then a very low fat (VLF) diet for 3 weeks with the TFA being derived only from the lean beef. Blood samples were collected 2 days prior to the end and also on the last day of each dietary period. SETTING: Deakin Institute of Human Nutrition, Deakin University, Geelong, Australia. SUBJECTS: Ten free-living mildly hypercholesterolaemic subjects aged 22-66 were recruited in Geelong. OUTCOME MEASURES: TFA intake was calculated from analyses of Australian margarines, butter, lean meat and animal fat. The TFA in plasma lipid fractions were separated by AgNO3 thin-layer chromatography and quantitated by capillary gas-liquid chromatography using internal standards. RESULTS: The phospholipid (PL) fraction contained more than 60% of the trans-18:1 isomers in the plasma lipids in all subjects. On the baseline diet, the predominant positional isomer of trans-18:1 in PL was delta11, whereas in the other lipid classes it was the delta9 isomer. The concentration of the delta9 isomer increased on the MF diet, particularly in the PL fraction, while the concentration of the delta11 isomer decreased in all fractions. On the VLF diet, the total TFA level decreased by approximately 50%, mainly due to decreases in the TFA isomers in the PL and TG fractions. Changes in plasma total and PL TFA, PL delta9, delta10 and delta11 were strongly correlated with dietary TFA intake (P < 0.0001). There were also significant association between dietary TFA intake and PL delta12 (P = 0.003), triacylglycerol delta9 (P=0.009), delta11 (P=0.0005), total triacylglycerol (P=0.023) and free fatty acid TFA (P = 0.042). CONCLUSIONS: The results suggest that the measurement of trans-18:1 in plasma PL and TAG, and plasma total TFA could be used to estimate the intake of TFA.

Adult↗

Interactions between forms of fat consumption and restaurant bread consumption.

How does fat consumption influence the consumption of companion foods such as bread? Adult restaurant goers who were randomly given olive oil for their bread used 26% more oil on each piece of bread compared to those who were given block butter, but they ended up eating 23% less bread in total. This finding illustrates one way in which fat intake can interact with the consumption of companion foods.

Adult↗

Two OPEEs (organic phase enzyme electrodes) used to check the percentage water content in hydrophobic foods and drugs.

The development and optimization of an analytical method using enzymatic biosensors able to operate in organic solvents [organic phase enzyme electrodes (OPEEs)] for the determination of the water content in food fats (butter, margarine) or pharmaceutical or cosmetic ointments is described. The method is based on the increase in enzymatic activity which is related to the increase in the percentage water content in the organic phase into which the biosensor is dipped. The enzymes used to assemble the biosensors were tyrosinase or catalase, the substrates were phenol or p-cresol and tert-butyl hydroperoxide, respectively, and the organic solvents were acetonitrile or dioxane. A gas diffusion amperometric electrode for oxygen measurement was used as electrochemical transducer. The results were compared with those obtained applying the Karl Fischer method to the same food or drug matrices. The correlations among the two methods proved satisfactory, as the difference in the computed values of water content was never higher than 7%. Also, the precision of measurements was acceptable (RSD < 6%) in all the analyses of real matrices.

Biosensing Techniques↗

Cellular effects of deoxynojirimycin analogues: inhibition of N-linked oligosaccharide processing and generation of free glucosylated oligosaccharides.

In the accompanying paper [Mellor, Neville, Harvey, Platt, Dwek and Butters (2004) Biochem. J. 381, 861-866] we treated HL60 cells with N-alk(en)yl-deoxynojirimycin (DNJ) compounds to inhibit glucosphingolipid (GSL) biosynthesis and identified a number of non-GSL-derived, small, free oligosaccharides (FOS) most likely produced due to inhibition of the oligosaccharide-processing enzymes a-glucosidases I and II. When HL60 cells were treated with concentrations of N-alk(en)ylated DNJ analogues that inhibited GSL biosynthesis completely, N-butyl- and N-nonyl-DNJ inhibited endoplasmic reticulum (ER) glucosidases I and II, but octadecyl-DNJ did not, probably due to the lack of ER lumen access for this novel, long-chain derivative. Glucosidase inhibition resulted in the appearance of free Glc1-3Man structures, which is evidence of Golgi glycoprotein endomannosidase processing of oligosaccharides with retained glucose residues. Additional large FOS was also detected in cells following a 16 h treatment with N-butyl- and N-nonyl-DNJ. When these FOS structures (>30, including >20 species not present in control cells) were characterized by enzyme digests and MALDI-TOF (matrix-assisted laser-desorption ionization-time-of-flight) MS, all were found to be polymannose-type oligosaccharides, of which the majority were glucosylated and had only one reducing terminal GlcNAc (N-acetylglucosamine) residue (FOS-GlcNAc1), demonstrating a cytosolic location. These results support the proposal that the increase in glucosylated FOS results from enzyme-mediated cytosolic cleavage of oligosaccharides from glycoproteins exported from the ER because of misfolding or excessive retention. Importantly, the present study characterizes the cellular properties of DNJs further and demonstrates that side-chain modifications allow selective inhibition of protein and lipid glycosylation pathways. This represents the most detailed characterization of the FOS structures arising from ER a-glucosidase inhibition to date.

1-Deoxynojirimycin↗

Characterization of response of gut GLI to fat ingestion in dogs.

Previous study from our laboratory demonstrated that an increased release of gut glucagon-like immunoreactivity (GLI) following triglyceride digestion was not observed in pancreatectomized dogs. Therefore, in order to clarify the response of gut GLI to triglyceride ingestion, experimental study was carried out in normal and pancreatectomized dogs. When butter was administered to pancreatectomized dogs in combination with pancreatic enzymes, plasma glucagon (IRG) measured by specific antiserum did not change significantly but plasma triglyceride as well as plasma total immunoreactive glucagon (total IRG) measured by nonspecific antiserum increased. Oral administration of glycerol induced no significant increase in plasma IRG but elicited a moderate increase of plasma total IRG. Gastric instillation of palmitic acid induced a remarkable rise of plasma total IRG in normal dogs, whereas plasma IRG did not reveal any changes. Oral administration of triglyceride of medium chain fatty acid, tricaprylin, did not promote any rise of plasma IRG but a slight increase of plasma total IRG. From the present experiment, it is concluded that hydrolysis of triglyceride and its metabolites are important in the release of gut GLI following fat ingestion. Among its metabolites, long chain fatty acid and glycerol promote the GLI secretion, whereas medium chain fatty acid does not.

Animals↗

Comparison of two statistical approaches to predict all-cause mortality by dietary patterns in German elderly subjects.

Dietary patterns are comprehensive variables of dietary intake appropriate to model the complex exposure in nutritional research. The objectives of this study were to identify dietary patterns by applying two statistical methods, principal component analysis (PCA) and reduced rank regression (RRR), and to assess their ability to predict all-cause mortality. Motivated by previous studies we chose percentages of energy from different macronutrients as response variables in the RRR analysis. We used data from 9356 German elderly subject enrolled in the European Prospective Investigation into Cancer and Nutrition study. The first RRR pattern, subjects which explained 30.8 % of variation in energy sources and especially much variation in intake of saturated fat, monounsaturated fat and carbohydrates was a significant predictor of all-cause mortality. The pattern score had high positive loadings in all types of meat, butter, sauces and eggs, and was inversely associated with bread and fruits. After adjustment for other known risk factors, the relative risks from the lowest to highest quintiles of the first RRR pattern score were 1.0, 1.01, 0.96, 1.32, 1.61 (P for trend: 0.0004). In contrast, the first two PCA patterns explaining 19.7 % of food intake variation but only 7.0 % of variation in energy sources were not related to mortality. These results suggest that variation in macronutrients is meaningful for mortality and that the RRR method is more appropriate than the classic PCA method to identify dietary patterns relevant to mortality.

Aged↗

Persistent organochlorine pesticide residues in milk and dairy products in India.

Monitoring of milk and dairy product samples of various brands from different cities in Maharashtra, India, was carried out to determine if there is any contamination due to organochlorine pesticide residues. The measurements were made using a gas chromatograph-electron capture detector system. Trace levels of DDT and HCH were detected in the samples. Total HCH levels in milk and milk product samples were lower than total DDT levels, which could be attributed to earlier extensive antimalaria sanitary activities. Butter had higher levels of DDT than cheese and milk powder. All levels of organochlorine pesticide residues in milk and milk products were well below the maximum permissible limits given by the FAO/ WHO. More importantly, as compared with an earlier report, present levels of the contaminants are substantially lower, which indicate the gradual phase out of these compounds.

Animals↗

Prevention of hypercholesterolemia in monkeys (Macaca fascicularis) by digitonin.

Digitonin mixed in the diet was well tolerated by rats and cynomolgus monkeys (Macaca fascicularis), and prevented the expected rise in plasma cholesterol in monkeys fed a diet containing butter and cholesterol. Both digitonin and mildly hydrolyzed digitonin precipitated cholesterol dispersed in micellar suspensions and decreased intestinal absorption of cholesterol in rats, but only digitonin bound cholesterol in vitro. The hypocholesterolemic effect of digitonin may be secondary to decreased intestinal absorption of cholesterol associated with a disturbance in the micellar suspension of cholesterol in the intestinal content. Modification of other mechanisms that may be involved in membrane transport of cholesterol through the intestinal epithelium is not ruled out by the present findings.

Animals↗

Intake of conjugated linoleic acid, fat, and other fatty acids in relation to postmenopausal breast cancer: the Netherlands Cohort Study on Diet and Cancer.

BACKGROUND: Conjugated linoleic acid (CLA), which is present in milk products and meat from ruminants, appears to have anticarcinogenic activity against breast cancer in animal and in vitro experiments. To date, few epidemiologic data are available in humans. OBJECTIVE: This study evaluated the relation between intakes of CLA and other fatty acids and breast cancer incidence in the Netherlands Cohort Study. DESIGN: Intake data derived from a validated 150-item food-frequency questionnaire were linked to an existing database with analytic data on specific fatty acids in European foods (the TRANSFAIR study). With 6.3 y of follow-up and 941 incident cases of breast cancer, multivariate rate ratios and 95% CIs were calculated for energy-adjusted intakes of fatty acids and CLA-containing food groups (eg, butter, cheese, milk, other milk products, and meat). RESULTS: CLA intake showed a weak, positive relation with breast cancer incidence (rate ratio for highest compared with lowest quintile: 1.24, 95% CI: 0.91, 1.69; P for trend = 0.02). Statistically significant positive associations were found with total trans fatty acids and (borderline) with saturated fatty acids. Significant inverse associations were found with monounsaturated and cis unsaturated fatty acids, whereas total fat and energy intake of CLA-containing food groups were not related to breast cancer incidence. CONCLUSION: The suggested anticarcinogenic property of CLA in animal and tissue culture models could not be confirmed in this epidemiologic study in humans.

Aged↗

Unesterified plant sterols and stanols lower LDL-cholesterol concentrations equivalently in hypercholesterolemic persons.

BACKGROUND: Plant sterols, in various forms, have been shown to reduce total and LDL-cholesterol concentrations. Particularly controversial at present is the effect of the degree of hydrogenation of the plant sterols on cholesterol-lowering efficacy and the responsible mechanisms. OBJECTIVE: Our goal was to examine the effect of supplementation with unesterified plant sterols and stanols on plasma lipid and phytosterol concentrations and cholesterol absorption, synthesis, and turnover. DESIGN: Fifteen otherwise healthy hypercholesterolemic subjects consumed each of 4 dietary treatments in a randomized crossover design. Unesterified sterols and stanols were blended into the butter component of the diet at a dosage of 1.8 g/d. The diets contained plant sterols (NS), plant stanols (SS), a 50:50 mixture of sterols and stanols (NSS), or cornstarch (control). RESULTS: Plasma total cholesterol concentrations were 7.8%, 11.9%, and 13.1% lower (P < 0.01) in the NS, SS, and NSS groups, respectively, than in the control group. LDL-cholesterol concentrations were 11.3%, 13.4%, and 16.0% lower (P < 0.03) in the NS, SS, and NSS groups, respectively, than in the control group. Plasma triacylglycerols and HDL-cholesterol concentrations did not differ significantly across diets. Cholesterol absorption efficiency was 56.0%, 34.4%, and 48.9% lower (P < 0.001) in the NS, SS, and NSS groups, respectively, than in the control group. The fractional synthesis rate was higher by 45.5% (P < 0.003) in the NSS group than in the control group. Plasma campesterol and sitosterol concentrations were higher (P < 0.01) in the NS group and sitosterol concentrations were lower (P < 0.01) in the SS group than in the control group. CONCLUSION: These data indicate that, in their free unesterified form, sterols and stanols lower plasma LDL cholesterol equivalently in hypercholesterolemic persons by suppressing cholesterol absorption.

Adult↗

Effects of three fat-enriched diets on the arterial pressure of rabbits.

Rabbits were fed diets enriched with proprietary edible fats for 5 weeks, raising the fat content of their diet from 4% to 23%. The diet enriched with animal fat caused a 13.5% rise in arterial pressure. The diet enriched with vegetable oil caused an 8.5% rise in arterial pressure. The diet enriched with butter caused an initial rise of 10% decreasing to 6% by the fifth week. Histological examination of the carotid and renal arteries, and aorta revealed no changes in connective tissue or lipid content as compared with those of control animals. It is concluded that changes in arterial pressure can occur after ingestion of excess dietary lipid, and that these changes are not confined to any class of lipid, or related to its properties as an atherosclerotic agent.

Animals↗

Further observations on ghee as a risk factor for neonatal tetanus.

BACKGROUND: Previous case-control studies of neonatal tetanus (NNT) in the North West Frontier Province of Pakistan indicated that clarified butter (ghee) applied to the umbilical wound of newborns was a significant risk factor for NNT. However, the mechanisms underlying the risk remained undisclosed. METHODS: A hospital-based case-control study was undertaken to evaluate further ghee and other factors possibly associated with risk of NNT. Mothers of several recent ghee-associated cases were visited in their homes, asked to simulate the procedures used in preparing the ghee, and samples of ghee were collected for culture. RESULTS: Topical application of ghee to the umbilical wound was again shown to pose a significant risk for NNT. In-use contamination of ghee was documented as mothers repeatedly heated and manipulated samples of ghee set aside in special containers for this purpose. Ghee was usually applied to the umbilical wound of the baby several times each day for the first few days of life. Mothers of cases were again confirmed to be substantially more likely to report prior NNT cases than mothers of controls. CONCLUSIONS: Educational interventions to reduce umbilical ghee use or to wash hands before each manipulation might reduce the risk of NNT in babies exposed to ghee who are born to non-immunized mothers. Increased efforts to immunize women of childbearing age with tetanus toxoid are also needed, with special priority for mothers known to have been associated with a previous NNT case. Topical antibiotics should be further evaluated for protective effects in non-immunized mothers.

Administration, Topical↗