Nutrient, fibre, sorbitol and chlorogenic acid content of prunes (Prunus domestica): an updated analysis and comparison of different countries of origin and database values.

Current prune composition data are outdated and require a comprehensive and comparative re-analysis. This novel study aimed to: (i) analyse and compare prune composition from major countries of origin; and (ii) provide a comprehensive compositional analysis of prunes of USA origin and compare this with UK and USA database data. Prune samples were analysed for major nutrients and bioactive compounds and compared between countries of origin. Total fibre was higher in prunes from the USA (12.0 g/100 g) and Chile (11.5 g/100 g) compared with France (8.4 g/100 g) and Argentina (8.9 g/100 g), while prunes from all countries contained high levels of sorbitol (11.2-15.5 g/100 g). Differences in energy and starch values compared with national databases reflected different approaches to sampling and analysis. In conclusion, prunes contain high levels of fibre and other bioactive compounds. Variations between country of origin and database values highlight the importance of transparency in documenting sampling and analysis methods.

Risk of Malnutrition Is an Independent Predictor of Mortality, Length of Hospital Stay, and Hospitalization Costs in Stroke Patients.

BACKGROUND: Malnutrition is associated with poor outcomes after stroke. Nutrition screening tools (NSTs) are used to identify patients at risk of malnutrition, but so far no NST has been validated for use with patients who have had a stroke. This study aimed to determine the ability of the Malnutrition Universal Screening Tool (MUST) to predict poor outcomes in stroke patients, including mortality, cumulative length of hospital stay (LOS), and hospitalization costs. METHODS: Patients were recruited from consecutive admissions at 2 hyperacute stroke units in London and were screened for risk of malnutrition (low, medium, and high) according to MUST. Six-month outcomes were obtained for each patient through a national database. RESULTS: Of 543 recruited patients, 51% were males, the mean age was 75 years, and 87% had an ischemic stroke. Results showed a highly significant increase in mortality with increasing risk of malnutrition (P < .001). This association remained significant after adjusting for age, severity of stroke, and a range of stroke risk factors (P < .001). For those patients who survived, the LOS and hospitalization costs increased with increasing risk of malnutrition (P < .001 and P = .049, respectively). This association remained significant in the adjusted model (P < .001 and P = .001, respectively). CONCLUSIONS: Risk of malnutrition is an independent predictor of mortality, LOS, and hospitalization costs at 6 months post stroke. Research is needed to determine if nutritional support for medium- or high-risk patients results in better outcomes. Routine screening of stroke patients for risk of malnutrition is recommended.

Quality of the Evidence Supporting the Role of Oral Nutritional Supplements in the Management of Malnutrition: An Overview of Systematic Reviews and Meta-Analyses.

There is considerable heterogeneity across the findings of systematic reviews of oral nutritional supplement (ONS) interventions, presenting difficulties for healthcare decision-makers and patients alike. It is not known whether heterogeneity arises from differences in patient populations or relates to methodological rigor. This overview aimed to collate and compare findings from systematic reviews of ONSs compared with routine care in adult patients who were malnourished or at risk of malnutrition with any clinical condition and to examine their methodological quality. Three electronic databases were searched to July 2019, supplemented with hand-searching. Data on all outcomes were extracted and review methodological quality assessed using A MeaSurement Tool for Assessment of systematic Reviews (AMSTAR). Twenty-two reviews were included, 11 in groups from mixed clinical backgrounds and 11 in specific clinical conditions. Ninety-one meta-analyses were identified for 12 different outcomes but there was discordance between results. Significant benefits of ONSs were reported in 4 of 4 analyses of energy intake, 7 of 11 analyses of body weight, 7 of 22 analyses of mortality, 10 of 17 analyses of complications (total and infectious), 1 of 3 analyses of muscle strength, 4 of 9 analyses of body composition/nutritional status, 2 of 14 analyses of length of stay, and 2 of 5 analyses of hospital readmissions. Ten reviews were high quality (AMSTAR scores 8-11), 9 moderate (AMSTAR scores 3-8), and 3 poor (AMSTAR scores 0-3). Methodological deficiencies were limitations to searches, poor reporting of heterogeneity, and failure to incorporate quality of evidence into any recommendations. Discordance between reviews was not markedly reduced when only high-quality reviews were considered. Evidence for the effects of ONS in malnourished patients or those who are at risk of malnutrition is uncertain, and discordance in results can arise from differences in clinical background of patients or the etiological basis of malnutrition.

The effect of prunes on stool output, gut transit time and gastrointestinal microbiota: A randomised controlled trial.

BACKGROUND & AIM: Prunes (dried plums) are perceived to maintain healthy bowel function, however their effects on gastrointestinal (GI) function are poorly researched and potential mechanisms of action are not clear. We aimed to investigate the effect of prunes on stool output, whole gut transit time (WGTT), gut microbiota and short-chain fatty acids (SCFA) in healthy adults METHODS: We conducted a parallel group, randomised controlled trial with three treatment arms in 120 healthy adults with low fibre intakes and stool frequency of 3-6 stools/wk. Subjects were randomised to 80 g/d prunes (plus 300 ml/d water); 120 g/d prunes (plus 300 ml/d water) or control (300 ml/d water) for 4 weeks. Stool weight was the primary outcome and determined by 7-day stool collection. Secondary outcomes included stool frequency and consistency (stool diary), WGTT (radio-opaque markers), GI symptoms (diary), microbiota (quantitative PCR) and SCFA (gas liquid chromatography). Group assignment was concealed from the outcome assessors. RESULTS: There were significantly greater increases in stool weight in both the 80 g/d (mean + 22.2 g/d, 95% CI -1-45.3) and 120 g/d (+32.8 g/d, 95% CI 13.9-51.7) prune groups compared with control (-0.8 g/d, 95% CI -17.2 to 15.6, P = 0.026). Stool frequency was significantly greater following 80 g/d (mean 6.8 bowel movements/wk, SD 3.8) and 120 g/d (5.6, SD 1.9) prune consumption compared with control (5.4, SD 2.1) (P = 0.023), but WGTT was unchanged. The incidence of flatulence was significantly higher after prune consumption. There were no significant differences in any of the bacteria measured, except for a greater increase in Bifidobacteria across the groups (P = 0.046). Prunes had no effect on SCFA or stool pH. CONCLUSIONS: In healthy individuals with infrequent stool habits and low fibre intake, prunes significantly increased stool weight and frequency and were well tolerated. Prunes may have health benefits in populations with low stool weight. CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE: ISRCTN42793297 http://www.isrctn.com/ISRCTN42793297.

Alcoholic myopathy and acetaldehyde.

Alcoholic myopathy is characterized by biochemical and morphological lesions within muscle, ranging from impairment of muscle strength and loss of lean tissue to cellular disturbances and altered gene expression. The chronic form of the disease is five times more common than cirrhosis and is characterized by selective atrophy of type 11 (anaerobic) fibres: type I (aerobic) fibres are relatively protected. Although the causative agent is known (i.e. ethanol), the intervening steps between alcohol ingestion and the development of symptoms and lesions are poorly understood. However, acetaldehyde appears to have an important role in the aetiology of the disease. For example, alcohol is a potent perturbant of muscle protein synthesis in vivo, and this effect is exacerbated by cyanamide pre-dosage, which raises acetaldehyde concentrations. Acetaldehyde alone also reduces muscle protein synthesis in vivo and proteolytic activity in vitro. The formation of acetaldehyde protein adducts is another mechanism of putative importance in alcoholic myopathy. These adducts are formed within muscle in response to either acute or chronic alcohol exposure and the adducts are located preferentially within the sarcolemmal and sub-sarcolemmal regions. However, the significance of protein adduct formation is unclear since we do not currently know the identity of the adducted muscle proteins nor whether adduction alters the biochemical or functional properties of skeletal muscle proteins.

The effect of glutamine and dihydroxyacetone supplementation on food intake, weight gain, and postprandial glycogen synthesis in female Zucker rats.

OBJECTIVE: We sought to test the hypothesis that increasing postprandial hepatic glycogen synthesis rate would decrease food intake and growth rate in obese Zucker rats. DESIGN: Supplements of glutamine, with and without dihydroxyacetone (DHA), which have previously been shown to stimulate hepatic glycogen synthesis, were administered in the diet of obese Zucker rats for periods of 1 and 3 wk. MEASUREMENTS: Food intake and body weight were monitored throughout the experiments. At the end of the feeding period the rats were fed a test meal and injected with (3)H(2)O to measure in vivo rates of glycogen and lipid synthesis. Final plasma glucose and triacylglycerol and hepatic glycogen content were also determined. Carcass fat and water contents were also measured in the 3-wk study. RESULTS: Dietary glutamine had no effect on food intake, weight gain, or body composition. Addition of DHA caused a reduction in food intake and weight gain and a stimulation of in vivo hepatic glycogen synthesis after 1 wk, but these changes were abolished by the end of 3 wk. Hepatic lipogenesis in vivo was increased by DHA treatment for 1 and 3 wk. CONCLUSIONS: Stimulation of hepatic glycogen synthesis by DHA treatment was associated with a reduction in food intake. However, the effect of DHA on glycogen synthesis and food intake disappeared after 3 wk of supplementation.

Effect of diet supplementation with glutamine, dihydroxyacetone, and leucine on food intake, weight gain, and postprandial glycogen metabolism of rats.

OBJECTIVE: We tested the hypothesis that increasing the rate of postprandial hepatic glycogen synthesis would decrease food intake and growth rate in normal rats. METHODS: Diets supplemented with glutamine, glutamine plus dihydroxyacetone, and glutamine plus dihydroxyacetone plus leucine were administered to male Sprague-Dawley rats for 1 wk. These are combinations that have been shown to stimulate hepatic glycogen synthesis in vitro. Food intake and body weight were monitored throughout the experiment. At the end of the feeding period, rats were fed a test meal and injected with 3H2O to measure in vivo rates of glycogen and lipid synthesis. Positional analysis of the 3H incorporated into glycogen was used to determine the proportion of glycogen synthesized via pyruvate. Final levels of plasma glucose and triacylglycerol and hepatic glycogen were also measured. RESULTS: Dietary glutamine increased hepatic glycogen synthesis. Addition of dihydroxyacetone, with or without additional leucine, caused an additional increase in hepatic glycogen synthesis and increased the proportion of glycogen synthesized via pyruvate. Lipogenesis was not altered in the liver or adipose tissue. None of the dietary treatments had any effect on food intake, but the diets that contained dihydroxyacetone decreased the rate of weight gain. CONCLUSIONS: Increasing glycogen synthesis had no effect on food intake. Increasing the proportion of glycogen synthesized by the indirect pathway through pyruvate was associated with a decrease in weight gain.

The development, validation and reliability of a nutrition screening tool based on the recommendations of the British Association for Parenteral and Enteral Nutrition (BAPEN).

BACKGROUND & AIMS: Nutrition screening tools (NST) identify individuals who are malnourished or at risk of becoming malnourished and who may benefit from nutritional support. The aims of this study were to design, pilot and evaluate a NST based on four nutritional parameters (weight, height, recent unintentional weight loss and appetite) recommended by the British Association for Parenteral and Enteral Nutrition as the minimum required to identify patients with nutritional problems. METHODS: A dietitian assessed the nutritional status of 100 patients admitted to the general medical wards. Results from the study were used to design a NST. The concurrent validity of the screening tool was then assessed, by comparing it with a nutritional assessment by an experienced dietitian in 100 patients admitted to acute medical and elderly care wards. The inter-rater reliability of the screening tool was also assessed using three nurses and 26 acute medical patients. RESULTS: All four nutritional parameters were required to identify all at-risk patients. There was good agreement between the screening tool and the dietitian's assessment (kappa = 0.717) and inter-rater reliability was reasonable (mean kappa = 0.66). CONCLUSION: The screening tool was valid and reliable in identifying medical patients at risk of malnutrition and was quick and simple to use.

Additional oligofructose/inulin does not increase faecal bifidobacteria in critically ill patients receiving enteral nutrition: a randomised controlled trial.

BACKGROUND & AIMS: Patients with diarrhoea during enteral nutrition (EN) have been shown to have low faecal bifidobacteria concentrations. Oligofructose/inulin selectively stimulate the growth of bifidobacteria in healthy humans. This study investigates the effect of additional oligofructose/inulin on the gastrointestinal microbiota, short-chain fatty acids (SCFA) and faecal output in patients receiving EN. METHODS: Adult patients in the intensive care unit (ICU) who were starting EN with a formula containing fibre were randomised to receive 7 g/d of additional oligofructose/inulin or an identically packaged placebo (maltodextrin). A fresh faecal sample was collected at baseline and following at least 7 days of supplementation. Faecal microbiota were analysed using fluorescent in-situ hybridisation and faecal output was monitored daily. RESULTS: Twenty-two patients (mean age 71 years) completed at least 7 days of intervention (mean 12 days). At the end of the intervention, there were no significant differences in the concentrations of bifidobacteria between the groups, after adjusting for baseline values (oligofructose/inulin 6.9 + 1.4, placebo 7.8 + 1.3 log10 cells/g dry faeces, P > 0.05), but there were significantly lower concentrations of Faecalibacterium prausnitzii (7.0 + 1.0 vs. 8.4 + 1.3 log10 cells/g, P = 0.01) and Bacteroides-Prevotella (9.1 + 1.0 vs. 9.9 + 0.9 log10 cells/g, P = 0.05) in patients receiving additional oligofructose/inulin. There were no differences in faecal concentrations of any SCFA, secretory IgA, daily faecal score or incidence of diarrhoea between the two groups. CONCLUSIONS: Additional oligofructose/inulin did not increase faecal bifidobacteria in critically ill patients receiving EN, although it did result in lower concentrations of F. prausnitzii and Bacteroides-Prevotella. This trial is registered at http://controlled-trials.com. Identifier: ISRCTN06446184.

Increased collagen synthesis rate during wound healing in muscle.

Wound healing in muscle involves the deposition of collagen, but it is not known whether this is achieved by changes in the synthesis or the degradation of collagen. We have used a reliable flooding dose method to measure collagen synthesis rate in vivo in rat abdominal muscle following a surgical incision. Collagen synthesis rate was increased by 480% and 860% on days 2 and 7 respectively after surgery in the wounded muscle compared with an undamaged area of the same muscle. Collagen content was increased by approximately 100% at both day 2 and day 7. These results demonstrate that collagen deposition during wound healing in muscle is achieved entirely by an increase in the rate of collagen synthesis.

Designing a national clinical audit of nutritional care in health and social care settings: consideration and future directions.

The aim of this review paper is to consider how the principles of clinical audit could be applied to the development of an audit of nutritional care in hospitals and care homes, based on criteria derived from the Essence of Care: Food and Drink. A literature review identified fifteen key papers that included guidance or standards for nutritional care in hospitals or care homes. These were used to supplement the ten factors suggested by the Essence of Care to develop a set of potential audit criteria covering all aspects of the nutritional care pathway including the identification of risk of malnutrition, implementation of nutritional care plans, referral to healthcare professionals for further nutritional assessment and nutritional support strategies. A series of audit tools have been developed, including an organisational level audit tool, a staff questionnaire, a patients' and residents' records audit tool and a patients' and residents' experiences questionnaire. Further issues to consider in designing a national nutritional audit include the potential role of direct observation of care, the use of trained auditors and the scope for including the results of pre-existing local audits. In conclusion, a national audit would need to encompass a very large number of health and care organisations of widely varying sizes and types and a diverse range of people.

Definitions, attitudes, and management practices in relation to diarrhea during enteral nutrition: a survey of patients, nurses, and dietitians.

BACKGROUND: Diarrhea is a common complication in patients receiving enteral nutrition (EN), and understanding this problem among patients and healthcare professionals is required. The aim of the study was to investigate patients', nurses', and dietitians' definitions of diarrhea during EN, the attitudes of nurses and patients toward it, and the management practices of nurses and dietitians in response to diarrhea during EN. METHODS: Twenty-two patients receiving EN, 57 nurses, and 33 dietitians were recruited and interviewed in a cross-sectional study, using a questionnaire that had been developed following an extensive literature review and pretested for clarity. RESULTS: The ratings assigned by the 3 groups differed significantly for all the characteristics used to define diarrhea: frequency (P = .006), quantity (P < .001), consistency (P = .003), color (P < .001), odor (P < .001), and incontinence (P < .001). Patients gave incontinence the highest rank when defining diarrhea, whereas the healthcare professionals gave fecal consistency and frequency the highest ranks. Patients and nurses rated the unpleasantness of each characteristic of diarrhea during EN differently, with patients rating incontinence and fecal frequency and nurses rating odor and changing the patients' underwear as the most unpleasant characteristics. Nurses and dietitians differed in the frequency with which they adopted various strategies to manage patients who developed diarrhea during EN. CONCLUSIONS: Patients have different definitions and attitudes toward diarrhea during EN from those of nurses and dietitians. Patients' perceptions need to be understood and respected by healthcare professionals to improve patient-centered care.

Oral nutritional interventions in malnourished patients with cancer: a systematic review and meta-analysis.

BACKGROUND: International guidelines on the nutritional management of patients with cancer recommend intervention with dietary advice and/or oral nutritional supplements in patients who are malnourished or those judged to be at nutritional risk, but the evidence base for these recommendations is lacking. We examined the effect of oral nutritional interventions in this population on nutritional and clinical outcomes and quality of life (QOL). METHODS: Electronic searches of several databases including MEDLINE, EMBASE, and CINAHL (from the first record to February 2010) were searched to identify randomized controlled trials of patients with cancer who were malnourished or considered to be at risk of malnutrition and receiving oral nutritional support compared with routine care. We performed a meta-analysis using a fixed effect model, or random effects models when statistically significant heterogeneity was present, to calculate relative risk (mortality) or mean difference (weight, energy intake, and QOL) with 95% confidence intervals (CIs). Heterogeneity was determined by using the χ(2) test and the I(2) statistic. All statistical tests were two-sided. RESULTS: Thirteen studies were identified and included 1414 participants. The quality of the studies varied, and there was considerable clinical and statistical heterogeneity. Nutritional intervention was associated with statistically significant improvements in weight and energy intake compared with routine care (mean difference in weight = 1.86 kg, 95% CI = 0.25 to 3.47, P = .02; and mean difference in energy intake = 432 kcal/d, 95% CI = 172 to 693, P = .001). However, after removing the main sources of heterogeneity, there was no statistically significant difference in weight gain or energy intake. Nutritional intervention had a beneficial effect on some aspects of QOL (emotional functioning, dyspnea, loss of appetite, and global QOL) but had no effect on mortality (relative risk = 1.06, 95% CI = 0.92 to 1.22, P = .43; I(2) = 0%; P(heterogeneity) = .56). CONCLUSION: Oral nutritional interventions are effective at increasing nutritional intake and improving some aspects of QOL in patients with cancer who are malnourished or are at nutritional risk but do not appear to improve mortality.

Measurement of specific radioactivity in proteins separated by two-dimensional gel electrophoresis.

We report a method to quantify the specific radioactivity of proteins that have been separated by 2-DE. Gels are stained with SyproRuby, and protein spots are excised. The SyproRuby dye is extracted from each spot using DMSO, and the fluorescence is quantified automatically using a plate reader. The extracted gel piece is then dissolved in hydrogen peroxide and radioactivity is quantified by liquid scintillation counting. Gentle agitation with DMSO for 24 h was found to extract all the SyproRuby dye from gel fragments. The fluorescence of the extract was linearly related to the amount of BSA loaded onto a series of 1-D gels. When rat muscle samples were run on 2-DE gels, the fluorescence extracted from 54 protein spots showed a good correlation (r = 0.79, p < 0.001) with the corresponding spot intensity measured by conventional scanning and image analysis. DMSO extraction was found not to affect the amount of radioactive protein left in the gel. When a series of BSA solutions of known specific radioactivity were run on 2-DE gels, the specific radioactivity measured by the new method showed a good correlation (r = 0.98, p < 0.01, n = 5) with the specific radioactivity measured directly before loading. Reproducibility of the method was measured in a series of 2-DE gels containing proteins from the livers of rats and mice that had been injected with [35S]methionine. Variability tended to increase when the amount of radioactivity in the protein spot was low, but for samples containing at least 10 dpm above background the CV was around 30%, which is comparable to that obtained when measuring protein expression by conventional image analysis of SyproRuby-stained 2-DE gels. Similar results were obtained whether spots were excised manually or using a spot excision robot. This method offers a high-throughput, cost-effective and reliable method of quantifying the specific radioactivity of proteins from metabolic labelling experiments carried out in vivo, so long as sufficient quantities of radioactive tracer are used.

Protein adduct species in muscle and liver of rats following acute ethanol administration.

AIMS: Previous immunohistochemical studies have shown that the post-translational formation of aldehyde-protein adducts may be an important process in the aetiology of alcohol-induced muscle disease. However, other studies have shown that in a variety of tissues, alcohol induces the formation of various other adduct species, including hybrid acetaldehyde-malondialdehyde-protein adducts and adducts with free radicals themselves, e.g. hydroxyethyl radical (HER)-protein adducts. Furthermore, acetaldehyde-protein adducts may be formed in reducing or non-reducing environments resulting in distinct molecular entities, each with unique features of stability and immunogenicity. Some in vitro studies have also suggested that unreduced adducts may be converted to reduced adducts in situ. Our objective was to test the hypothesis that in muscle a variety of different adduct species are formed after acute alcohol exposure and that unreduced adducts predominate. METHODS: Rabbit polyclonal antibodies were raised against unreduced and reduced aldehydes and the HER-protein adducts. These were used to assay different adduct species in soleus (type I fibre-predominant) and plantaris (type II fibre-predominant) muscles and liver in four groups of rats administered acutely with either [A] saline (control); [B] cyanamide (an aldehyde dehydrogenase inhibitor); [C] ethanol; [D] cyanamide+ethanol. RESULTS: Amounts of unreduced acetaldehyde and malondialdehyde adducts were increased in both muscles of alcohol-dosed rats. However there was no increase in the amounts of reduced acetaldehyde adducts, as detected by both the rabbit polyclonal antibody and the RT1.1 mouse monoclonal antibody. Furthermore, there was no detectable increase in malondialdehyde-acetaldehyde and HER-protein adducts. Similar results were obtained in the liver. CONCLUSIONS: Adducts formed in skeletal muscle and liver of rats exposed acutely to ethanol are mainly unreduced acetaldehyde and malondialdehyde species.

A quantitative investigation into the losses of proteins at different stages of a two-dimensional gel electrophoresis procedure.

We report the results of a systematic investigation to quantify the losses of protein during a well-established two-dimensional polyacrylamide gel electrophoresis (2-DE) procedure. Radioactively labelled proteins ([(14)C]bovine serum albumin and a homogenate prepared from the liver of a rat that had been injected with [(35)S]methionine) were used, and recovery was quantified by digesting pieces of gel in H(2)O(2) and subjecting the digests to liquid scintillation counting. When samples were loaded onto the first dimension immobilised pH gradient strips by in-gel rehydration, recovery of protein from the strips was 44-80% of the amount of protein loaded, depending on the amount of protein in the sample. Most of the unrecovered protein appeared to have adhered to the reswelling tray. Losses during isoelectric focusing (IEF) were much smaller (7-14%), although approximately 2% of the protein appeared to migrate from sample strips to adjacent blank strips in the focussing apparatus. A further 17-24% of the proteins were lost into the buffers during equilibration prior to running in the second dimension. Losses during the second dimension run and subsequent staining with SYPRO Ruby amounted to less than 10%. The overall loss during 2-DE was reduced by approximately 25% when proteins were loaded onto the IEF strips using sample cups instead of by in-gel rehydration. These extensive and variable losses during the 2-DE procedure mean that spot intensities on 2-DE gels cannot be used to derive reliable, quantitative information on the amounts of proteins present in the original sample.

Folate, DNA methylation and colo-rectal cancer.

Prospective cohort and case-control studies suggest an association between low folate intake and increased risk of colo-rectal adenoma and cancer. Some, but not all, animal studies indicate that folate supplementation protects against the development of colo-rectal neoplasms, although supraphysiological folate doses have been shown to enhance tumour growth. Folate is a methyl donor for nucleotide synthesis and biological methylation reactions, including DNA methylation. A low dietary folate intake may increase the risk of colo-rectal neoplasia by inducing genomic DNA hypomethylation, which can affect the expression of proto-oncogenes and tumour suppressor genes associated with the development of cancer. Common polymorphisms in genes involved in the methylation pathway, such as methylenetetrahydrofolate reductase and methionine synthase, have been shown to influence risk of colo-rectal neoplasia, with interactions dependent on folate status and/or alcohol intake, which is known to antagonise methyl group availability. There is some evidence to show that DNA from normal-appearing colo-rectal mucosa in individuals with colo-rectal cancer is hypomethylated. In a case-control study DNA methylation in normal-appearing colo-rectal mucosa has been shown to be lower in individuals with colo-rectal cancer (P = 0.08) and colo-rectal adenoma (P = 0.009) than in controls free of colo-rectal abnormalities. Human intervention trials to date suggest that supraphysiological doses of folate can reverse DNA hypomethylation in colo-rectal mucosa of individuals with colo-rectal neoplasia. In a double-blind randomised placebo-controlled study folate supplementation at physiological doses has been shown to increase DNA methylation in leucocytes (P = 0.05) and colonic mucosa (P = 0.09). Further studies are required to confirm these findings in larger populations and to define abnormal ranges of DNA methylation.

Validation of a short food frequency questionnaire to assess folate intake.

A short quantitative food frequency questionnaire (FFQ) to assess folate intake was developed and validated against a 7-d weighed food intake record (7d-WR) and biochemical indices of folate status. Thirty-six men and women completed the self-administered FFQ on two occasions a month apart, kept a 7d-WR and gave two fasting blood samples at the beginning and end of the study for measuring serum and erythrocyte folate, respectively. Mean folate intakes were similar by repeat FFQ and correlated strongly (r 077 and r 072, P<0.001, for men and women, respectively). All other comparisons were done using the results of the FFQ administered on the first occasion. Men reported similar folate intakes on the FFQ and 7d-WR, but women reported greater intakes on the FFQ compared with the 7d-WR (P<0.05). There was a statistically significant correlation (partial, controlling for gender) between folate intakes reported by FFQ and 7d-WR (r 0.53, P<0.01). Folate intakes estimated by FFQ correlated significantly with serum (r 0.47, P<0.01), but not erythrocyte folate (r 0.25, P>0.05), the strength of the association was greater in men than in women. Validity coefficients estimated using the method of triads were higher for the FFQ than for the 7d-WR when serum folate was used as the biomarker. Overall, these results suggest that this short FFQ is a useful method for assessing folate intake, particularly in men.

Generation of aldehyde-derived protein modifications in ethanol-exposed heart.

BACKGROUND: Although excessive ethanol consumption is known to lead to a variety of adverse effects in the heart, the molecular mechanisms of such effects have remained poorly defined. We hypothesized that posttranslational covalent binding of reactive molecular species to proteins occurs in the heart in response to acute ethanol exposure. METHODS: The generation of protein adducts with several aldehydic species was examined by using monospecific antibodies against adducts with malondialdehyde (MDA), acetaldehyde (AA), MDA-AA hybrids, and hydroxyethyl radicals. Specimens of heart tissue were obtained from rats after intraperitoneal injections with alcohol (75 mmol/kg body weight) with or without pretreatment with cyanamide (0.05 mmol/kg body weight), an aldehyde dehydrogenase inhibitor. RESULTS: The amounts of MDA and unreduced AA adducts were found to be significantly increased in the heart of the rats treated with ethanol, cyanamide, or both, whereas no other adducts were detected in statistically significant quantities. Immunohistochemical studies for characterization of adduct distribution revealed sarcolemmal adducts of both MDA and AA in the rats treated with ethanol and cyanamide in addition to intracellular adducts, which were also present in the group treated with ethanol alone. CONCLUSIONS: These findings support the role of enhanced lipid peroxidation and the generation of protein-aldehyde condensates in vivo as a result of excessive ethanol intake. These findings may have implications in the molecular mechanisms of cardiac dysfunction in alcoholics.