Hidden scars in depression? Implicit and explicit self-associations following recurrent depressive episodes

To help explain the recurrent nature of major depressive disorder, we tested the hypothesis that depressive episodes and/or the duration of depressive symptoms may give rise to persistent dysfunctional implicit and/or more explicit self-associations, which in turn may place people at risk for the recurrence of symptoms. We therefore examined, in the context of the Netherlands Study of Depression and Anxiety, whether the strength of self-depressed associations at baseline was related to the number of past episodes (retrospective analysis; n = 666), and whether the duration of symptoms between baseline and follow-up predicted self-depressed associations at 2-year follow-up (prospective analysis; n = 726). The lifetime Composite International Diagnostic Interviews and Life Chart Interview were used to index the number of depressive episodes; the Implicit Association Test and its explicit equivalent were used to index self-associations. Consistent with the hypothesis that self-depressed associations strengthen following prolonged activation of negative self-associations during depressive episodes, individuals' implicit and explicit self-depressed associations correlated positively both with the number of prior depressive episodes at baseline and with the duration of depressive symptoms between baseline and 2-year follow-up. There was evidence that these relationships held, particularly in the prospective study, even when controlling for neuroticism and current depressive symptoms, whereas the retrospective relationship between number of episodes and implicit self-associations fell just short of significance

Changes in cholesterol kinetics following sugar cane policosanol supplementation: a randomized control trial

<p>Abstract</p> <p>Background</p> <p>Sugar cane policosanols (SCP) have been shown to exert cholesterol-modulating properties in various studies conducted in Cuba by substantially reducing cholesterol synthesis. Independent research examining changes in cholesterol kinetics in response to SCP is limited to few studies, none of which was able to replicate findings of the original research. Moreover, no data are available on the effect of SCP on cholesterol absorption to date. The present study was undertaken to determine effects on cholesterol kinetics, namely synthesis and absorption, within hypercholesterolemic individuals consuming a SCP treatment. Twenty-one otherwise healthy hypercholesterolemic subjects participated in a randomized double-blind crossover study where they received 10 mg/day of policosanols or a placebo incorporated in margarine as an evening snack for a period of 28 days. The last week of the study phase, subjects were given ¹³C labelled cholesterol and deuterated water for the measurement of cholesterol absorption and synthesis respectively. Blood was collected on the first two and last five days of the trial. Cholesterol absorption and synthesis were determined by measuring red cell cholesterol ¹³C and deuterium enrichment, respectively.</p> <p>Results</p> <p>There was no significant change in LDL cholesterol levels as compared to control. In addition, the area under the curve for red cell cholesterol ¹³C enrichment across 96 hours was not significantly different in the SCP group as compared to control. Similarly, no difference was observed in the fractional rate of cholesterol synthesis over the period of 24 hours between the two treatment groups.</p> <p>Conclusion</p> <p>The findings of the present study fail to support previous research concerning efficacy and mechanism of action for policosanols.</p

Plant sterols, marine-derived omega-3 fatty acids and other functional ingredients: a new frontier for treating hyperlipidemia

As hyperlipidemia, including hypercholesterolemia (HC) and hypertriglyceridemia (HTN), continue to challenge North America's healthcare systems, patients continue to seek efficacious and safe natural therapies that complement pharmaceutical interventions. However, despite the ever-growing body of research supporting the use of functional foods and nutraceuticals (FFN) for the prevention and treatment of hyperlipidemia, reception amongst the medical community regarding the implementation of FFN into clinical guidelines continues to lag. Research demonstrates that specific FFN target and modulate molecular processes that perpetuate hyperlipidemia. In addition, studies consistently demonstrate that combining certain FFN such as marine-derived omega-3 fatty acids or plant sterols/stanols with statins enhances triglyceride and cholesterol-lowering efficacy, respectively. Thus, the purpose of this commentary is to contend that efficacious FFN not only reduce HC and HTG but also boost the lipid-lowering effects of pharmaceutical hypolipidemic medications. Finally, this editorial aims to challenge current medical guidelines to emphasize efficacious FFN during all stages of treatment of hyperlipidemias as adjuncts to pharmacotherapy

Plant sterols: factors affecting their efficacy and safety as functional food ingredients

Plant sterols are naturally occurring molecules that humanity has evolved with. Herein, we have critically evaluated recent literature pertaining to the myriad of factors affecting efficacy and safety of plant sterols in free and esterified forms. We conclude that properly solubilized 4-desmetyl plant sterols, in ester or free form, in reasonable doses (0.8–1.0 g of equivalents per day) and in various vehicles including natural sources, and as part of a healthy diet and lifestyle, are important dietary components for lowering low density lipoprotein (LDL) cholesterol and maintaining good heart health. In addition to their cholesterol lowering properties, plant sterols possess anti-cancer, anti-inflammatory, anti-atherogenicity, and anti-oxidation activities, and should thus be of clinical importance, even for those individuals without elevated LDL cholesterol. The carotenoid lowering effect of plant sterols should be corrected by increasing intake of food that is rich in carotenoids. In pregnant and lactating women and children, further study is needed to verify the dose required to decrease blood cholesterol without affecting fat-soluble vitamins and carotenoid status

In planta transient expression as a system for genetic and biochemical analyses of chlorophyll biosynthesis

BACKGROUND: Mg chelatase is a multi-subunit enzyme that catalyses the first committed step of chlorophyll biosynthesis. Studies in higher plants and algae indicate that the Mg chelatase reaction product, Mg-protoporphyrin IX plays an essential role in nuclear-plastid interactions. A number of Mg chelatase mutants have been isolated from higher plants, including semi-dominant alleles of ChlI, the gene encoding the I subunit of the enzyme. To investigate the function of higher plant CHLI, bacterial orthologues have been engineered to carry analogous amino acid substitutions to the higher plant mutations and the phenotypes examined through in vitro characterization of heterologously produced proteins. Here, we demonstrate the utility of a transient expression system in Nicotiana benthamiana for rapidly assaying mutant variants of the maize CHLI protein in vivo. RESULTS: Transient expression of mutant maize ChlI alleles in N. benthamiana resulted in the formation of chlorotic lesions within 4 d of inoculation. Immunoblot analyses confirmed the accumulation of maize CHLI protein suggesting that the chlorosis observed resulted from an interaction between maize CHLI and endogenous components of the N. benthamiana chlorophyll biosynthetic pathway. On the basis of this assay, PCR-based cloning techniques were used to rapidly recombine polymorphisms present in the alleles studied allowing confirmation of causative lesions. A PCR-based mutagenesis was conducted and clones assayed by transient expression. A number of novel allelic variants of maize ZmChlI were generated and analyzed using this assay, demonstrating the utility of this technique for fine mapping. CONCLUSION: Transient expression provides a convenient, high-throughput, qualitative assay for functional variation in the CHLI protein. Furthermore, we suggest that the approach used here would be applicable to the analysis of other plastid-localized proteins where gain-of-function mutations will result in readily observable mutant phenotypes

Guar gum and similar soluble fibers in the regulation of cholesterol metabolism: Current understandings and future research priorities

The hypocholesterolemic effects associated with soluble fiber consumption are clear from animal model and human clinical investigations. Moreover, the modulation of whole-body cholesterol metabolism in response to dietary fiber consumption, including intestinal cholesterol absorption and fecal sterol and bile acid loss, has been the subject of many published reports. However, our understanding of how dietary fibers regulate molecular events at the gene/protein level and alter cellular cholesterol metabolism is limited. The modern emphasis on molecular nutrition and rapid progress in ‘high-dimensional’ biological techniques will permit further explorations of the role of genetic polymorphisms in determining the variable interindividual responses to soluble fibers. Furthermore, with traditional molecular biology tools and the application of ‘omic’ technology, specific insight into how fibers modulate the expression of genes and proteins that regulate intestinal cholesterol absorption and alter hepatic sterol balance will be gained. Detailed knowledge of the molecular mechanisms by which soluble fibers reduce plasma cholesterol concentrations is paramount to developing novel fiber-based “cocktails” that target specific metabolic pathways to gain maximal cholesterol reductions

Fish-oil esters of plant sterols differ from vegetable-oil sterol esters in triglycerides lowering, carotenoid bioavailability and impact on plasminogen activator inhibitor-1 (PAI-1) concentrations in hypercholesterolemic subjects

<p>Abstract</p> <p>Background</p> <p>Consumption of plant sterol (PS) esters lower low-density lipoprotein (LDL)-cholesterol levels by suppressing intestinal absorption of cholesterol. Commercially available PS are mainly esterified to omega-6 fatty acid (FA), such as sunflower oil (SO) FA. Emerging trends include using other sources such as olive oil (OO) or omega-3 FA from fish oil (FO), known to exert potent hypotriglyceridemic effects. Our objective was to compare the actions of different FA esterified to PS on blood lipids, carotenoid bioavailability as well as inflammatory and coagulation markers.</p> <p>Methods</p> <p>Twenty-one moderately overweight, hypercholesterolemic subjects consumed experimental isoenergetic diets enriched with OO (70% of fat), each lasting 28-day and separated by 4-week washout periods, using a randomized crossover design. Diets were supplemented with three PS esters preparations, PS-FO, PS-SO, or PS-OO. All PS treatments contained an equivalent of 1.7 PS g/d, and the PS-FO provided a total of 5.4 g/d FO FA (eicosapentaenoic and docosahexaenoic acids).</p> <p>Results</p> <p>There were no differences between PS-containing diet effects on total cholesterol, LDL-cholesterol, or high-density lipoprotein (HDL)-cholesterol levels. However, PS-FO consumption resulted in markedly lower (P < 0.0001) fasting and postprandial triglyceride concentrations compared with PS-SO and PS-OO. These treatments affected plasma β-carotene (P = 0.0169) and retinol (P = 0.0244), but not tocopherol (P = 0.2108) concentrations. Consumption of PS-FO resulted in higher β-carotene (P = 0.0139) and retinol (P = 0.0425) levels than PS-SO and PS-OO, respectively. Plasma TNF-α, IL-6, C-reactive protein, prostate specific antigen, and fibrinogen concentrations were unaffected by the PS-interventions. In contrast, plasminogen activator inhibitor 1 (PAI-1) concentrations were lower (P = 0.0282) in the PS-FO-fed than the PS-SO, but not the PS-OO (P = 0.7487) groups.</p> <p>Conclusion</p> <p>Our findings suggest that, in hypercholesterolemic subjects consuming an OO-based diet, PS-FO results in lowered blood triglyceride and PAI-1 concentrations, and higher fat-soluble vitamin levels in comparison to the vegetable oil FA esters of PS (PS-SO and PS-OO). Thus, PS-FO may offer hyperlipidemic subjects a more comprehensive lipid lowering approach while reducing the potential risk of decreased plasma carotenoid concentrations.</p

Carboxyhaemoglobin levels and their determinants in older British men

Background: Although there has been concern about the levels of carbon monoxide exposure, particularly among older people, little is known about COHb levels and their determinants in the general population. We examined these issues in a study of older British men.Methods: Cross-sectional study of 4252 men aged 60-79 years selected from one socially representative general practice in each of 24 British towns and who attended for examination between 1998 and 2000. Blood samples were measured for COHb and information on social, household and individual factors assessed by questionnaire. Analyses were based on 3603 men measured in or close to (< 10 miles) their place of residence.Results: The COHb distribution was positively skewed. Geometric mean COHb level was 0.46% and the median 0.50%; 9.2% of men had a COHb level of 2.5% or more and 0.1% of subjects had a level of 7.5% or more. Factors which were independently related to mean COHb level included season (highest in autumn and winter), region (highest in Northern England), gas cooking (slight increase) and central heating (slight decrease) and active smoking, the strongest determinant. Mean COHb levels were more than ten times greater in men smoking more than 20 cigarettes a day (3.29%) compared with non-smokers (0.32%); almost all subjects with COHb levels of 2.5% and above were smokers (93%). Pipe and cigar smoking was associated with more modest increases in COHb level. Passive cigarette smoking exposure had no independent association with COHb after adjustment for other factors. Active smoking accounted for 41% of variance in COHb level and all factors together for 47%.Conclusion: An appreciable proportion of men have COHb levels of 2.5% or more at which symptomatic effects may occur, though very high levels are uncommon. The results confirm that smoking (particularly cigarette smoking) is the dominant influence on COHb levels