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Title:
Effects of a prolonged standardized diet on normalizing the human metabolome
Authors:
Winnike JH; Busby MG; Watkins PB; O'Connell TM
Abstract:
BACKGROUND: Although the effects of acute dietary interventions on the human metabolome have been studied, the extent to which the metabolome can be normalized by extended dietary standardization has not yet been examined. OBJECTIVE: We examined the metabolic profiles of healthy human subjects after extended dietary standardization to see whether the inherent variation in the human metabolome could be decreased. DESIGN: A cohort of 10 healthy volunteers was admitted to a clinical research center for 2 wk of dietary standardization. Daily serum and urine samples and serum samples at a 2-wk follow-up visit were collected. The samples were analyzed by (1)H nuclear magnetic resonance (NMR) spectroscopy and multivariate statistical analyses. RESULTS: NMR spectra were collected to globally profile the higher-concentration metabolites (>micromol/L concentrations). Metabolic changes were observed in some serum samples after day 1 or the 2-wk follow-up visit. For each subject, the samples from all other days had similar profiles. The urinary metabolome reflected no effects from dietary standardization. Pooled 24-h urine samples were studied, which indicated that any normalization that does occur would do so in
Published:
2009-12
Title:
Four selenoproteins, protein biosynthesis, and Wnt signalling are particularly sensitive to limited selenium intake in mouse colon
Authors:
Kipp, Anna; Banning, Antje; van Schothorst, Evert M.; Méplan, Catherine; Schomburg, Lutz; Evelo, Chris; Coort, Susan; Gaj, Stan; Keijer, Jaap; Hesketh, John; Brigelius-Flohé, Regina
Abstract:
Selenium is an essential micronutrient. Its recommended daily allowance is not attained by a significant proportion of the population in many countries and its intake has been suggested to affect colorectal carcinogenesis. Therefore, microarrays were used to determine how both selenoprotein and global gene expression patterns in the mouse colon were affected by marginal selenium deficiency comparable to variations in human dietary intakes. Two groups of 12 mice each were fed a selenium-deficient (0.086 mg Se/kg) or a selenium-adequate (0.15 mg Se/kg) diet. After 6 wk, plasma selenium level, liver, and colon glutathione peroxidase (GPx) activity in the deficient group was 12, 34, and 50%, respectively, of that of the adequate group. Differential gene expression was analysed with mouse 44K whole genome microarrays. Pathway analysis by GenMAPP identified the protein biosynthesis pathway as most significantly affected, followed by inflammation, Delta-Notch and Wnt pathways. Selected gene expression changes were confirmed by quantitative real-time PCR. GPx1 and the selenoproteins W, H, and M, responded significantly to selenium intake making them candidates as biomarkers for selenium status. Thus, feeding a marginal selenium-deficient diet resulted in distinct changes in global gene expression in the mouse colon. Modulation of cancer-related pathways may contribute to the higher susceptibility to colon carcinogenesis in low selenium status.
Published:
2009-12
Title:
Mass-spectrometry-based metabolomics: limitations and recommendations for future progress with particular focus on nutrition research
Authors:
Scalbert, Augustin; Brennan, Lorraine; Fiehn, Oliver; Hankemeier, Thomas; Kristal, Bruce S.; van Ommen, Ben; Pujos-Guillot, Estelle; Verheij, Elwin; Wishart, David; Wopereis, Suzan
Abstract:
Mass spectrometry (MS) techniques, because of their sensitivity and selectivity, have become methods of choice to characterize the human metabolome and MS-based metabolomics is increasingly used to characterize the complex metabolic effects of nutrients or foods. However progress is still hampered by many unsolved problems and most notably the lack of well established and standardized methods or procedures, and the difficulties still met in the identification of the metabolites influenced by a given nutritional intervention. The purpose of this paper is to review the main obstacles limiting progress and to make recommendations to overcome them. Propositions are made to improve the mode of collection and preparation of biological samples, the coverage and quality of mass spectrometry analyses, the extraction and exploitation of the raw data, the identification of the metabolites and the biological interpretation of the results.
Published:
2009-12
Title:
Therapeutic role of low-carbohydrate ketogenic diet in diabetes
Authors:
Al-Khalifa, Alaa; Mathew, Thazhumpal Chacko; Al-Zaid, Naji S.; Mathew, Elizabeth; Dashti, Hussein M.
Abstract:
INTRODUCTION: Changes in dietary habits influence the glycemic level. Preliminary studies using the low-carbohydrate ketogenic diet (LCKD) were found to be quite promising in controlling diabetes mellitus. Therefore, the objectives of this study are to investigate the therapeutic effects of LCKD in experimental diabetic rats following the administration of streptozotocin (STZ). MATERIALS AND METHODS: Adult rats were divided into three groups: normal diet, LCKD, and high-carbohydrate diet. Each group was subdivided into normal, sham, and diabetic groups. Diabetes was induced by a single intraperitoneal injection of STZ (55mg/kg). Specific diets were given to each group of animals for a period of 8 wk and then the animals were sacrificed. The rats were monitored daily for food and water intake, whereas body weight, urine output, and blood glucose levels were monitored weekly. The histology of the islets of Langerhans was studied by histochemical methods. RESULTS: The results showed that LCKD was effective in bringing blood glucose level close to normal (P<0.01). Food and water intake and urine output were increased in all groups except the LCKD group (P<0.01). The body weight was significantly reduced in all diabetic animals except in the LCKD group (P
Published:
2009-12
Title:
Treatment of familial male-limited precocious puberty (testotoxicosis) with anastrozole and bicalutamide in a boy with a novel mutation in the luteinizing hormone receptor
Authors:
Mitre, Naim; Lteif, Aida
Abstract:
We report the use of anastrozole and bicalutamide in a 5 year-old boy with familial male-limited precocious puberty. Clinical response showed decreased advancement of skeletal maturation, secondary sexual characteristics and aggressiveness with no short-term side effects. The combination seems a better option until long-term data are available.
Published:
2009-12
Title:
Veganism, bone mineral density, and body composition: a study in Buddhist nuns
Authors:
Ho-Pham, L. T.; Nguyen, P. L. T.; Le, T. T. T.; Doan, T. a. T.; Tran, N. T.; Le, T. A.; Nguyen, T. V.
Abstract:
SUMMARY: This cross-sectional study showed that, although vegans had lower dietary calcium and protein intakes than omnivores, veganism did not have adverse effect on bone mineral density and did not alter body composition. INTRODUCTION: Whether a lifelong vegetarian diet has any negative effect on bone health is a contentious issue. We undertook this study to examine the association between lifelong vegetarian diet and bone mineral density and body composition in a group of postmenopausal women. METHODS: One hundred and five Mahayana Buddhist nuns and 105 omnivorous women (average age = 62, range = 50-85) were randomly sampled from monasteries in Ho Chi Minh City and invited to participate in the study. By religious rule, the nuns do not eat meat or seafood (i.e., vegans). Bone mineral density (BMD) at the lumbar spine (LS), femoral neck (FN), and whole body (WB) was measured by DXA (Hologic QDR 4500). Lean mass, fat mass, and percent fat mass were also obtained from the DXA whole body scan. Dietary calcium and protein intakes were estimated from a validated food frequency questionnaire. RESULTS: There was no significant difference between vegans and omnivores in LSBMD (0.74 +/- 0.14 vs. 0.77 +/- 0.14 g/cm(2); mean +/- SD; P = 0.18), FNBMD (0.62 +/- 0.11 vs. 0.63 +/- 0.11 g/cm(2); P = 0.35), WBBMD (0.88 +/- 0.11 vs. 0.90 +/- 0.12 g/cm(2); P = 0.31), lean mass (32 +/- 5 vs. 33 +/- 4 kg; P = 0.47), and fat mass (19 +/- 5 vs. 19 +/- 5 kg; P = 0.77) either before or after adjusting for age. The prevalence of osteoporosis (T scores < or = -2.5) at the femoral neck in vegans and omnivores was 17.1% and 14.3% (P = 0.57), respectively. The median intake of dietary calcium was lower in vegans compared to omnivores (330 +/- 205 vs. 682 +/- 417 mg/day, P
Published:
2009-12
Title:
A very low carbohydrate ketogenic diet improves glucose tolerance in ob/ob mice independently of weight loss
Authors:
Badman, Michael K.; Kennedy, Adam R.; Adams, Andrew C.; Pissios, Pavlos; Maratos-Flier, Eleftheria
Abstract:
In mice of normal weight and with diet-induced obesity, a high-fat, low-carbohydrate ketogenic diet (KD) causes weight loss, reduced circulating glucose and lipids, and dramatic changes in hepatic gene expression. Many of the effects of KD are mediated by fibroblast growth factor 21 (FGF21). We tested the effects of KD feeding on ob/ob mice to determine if metabolic effects would occur in obesity secondarily to leptin deficiency. We evaluated the effect of prolonged KD feeding on weight, energy homeostasis, circulating metabolites, glucose homeostasis, and gene expression. Subsequently, we evaluated the effects of leptin and fasting on FGF21 expression in ob/ob mice. KD feeding of ob/ob mice normalized fasting glycemia and substantially reduced insulin and lipid levels in the absence of weight loss. KD feeding was associated with significant increases in lipid oxidative genes and reduced expression of lipid synthetic genes, including stearoyl-coenzyme A desaturase 1, but no change in expression of inflammatory markers. In chow-fed ob/ob mice, FGF21 mRNA was elevated 10-fold compared with wild-type animals, and no increase from this elevated baseline was seen with KD feeding. Administration of leptin to chow-fed ob/ob mice led to a 24-fold induction of FGF21. Fasting also induced hepatic FGF21 in ob/ob mice. Thus, KD feeding improved ob/ob mouse glucose homeostasis without weight loss or altered caloric intake. These data demonstrate that manipulation of dietary macronutrient composition can lead to marked improvements in metabolic profile of leptin-deficient obese mice in the absence of weight loss.
Published:
2009-11
Title:
Body fat and animal protein intakes are associated with adrenal androgen secretion in children
Authors:
Shi L; Wudy SA; Buyken AE; Hartmann MF; Remer T
Abstract:
BACKGROUND: Adrenarche is the increase in adrenal androgen (AA) production starting in childhood. Until now, it has been unknown whether or not nutritional factors modulate adrenarche. OBJECTIVE: The objective was to examine whether body composition and certain dietary intakes are associated with AA production in children after accounting for urinary indicators of major adrenarche-related steroidogenic enzymes. DESIGN: Androgen and glucocorticoid metabolites were profiled by gas chromatography-mass spectrometry in 24-h urine samples of 137 healthy prepubertal children aged 3-12 y, for whom birth characteristics, growth velocity data, and 3-d weighed-diet record information were available. Associations of the sum of C19 metabolites (reflecting daily AA secretion) with nutritional factors [fat mass (FM), fat-free mass (FFM), nutrient intakes, glycemic index, and glycemic load] and AA-relevant estimates of steroidogenic enzyme were examined in stepwise multiple regression models adjusted for age, sex, urine volume, and total energy intake. Enzyme activity estimates were calculated by using specific urinary steroid metabolite ratios. RESULTS: Of the nutrition-relevant predictors, FM (P < 0.0001) explained most of the variation of AA secretion (R(2) = 5%). Animal protein intake was also positively associated with AA secretion (P
Published:
2009-11
Title:
Effects of meals high in carbohydrate, protein, and fat on ghrelin and peptide YY secretion in prepubertal children
Authors:
Lomenick, Jefferson P.; Melguizo, Maria S.; Mitchell, Sabrina L.; Summar, Marshall L.; Anderson, James W.
Abstract:
CONTEXT: Ghrelin and peptide YY (PYY) are two hormones produced by the gastrointestinal tract that have effects on appetite. However, little is known about their secretion in response to meals high in individual macronutrients in prepubertal children. OBJECTIVE: We sought to understand how meals high in carbohydrate, protein, and fat affect serum concentrations of total ghrelin and total PYY, hypothesizing that these macronutrients would exert differential effects on their secretion. DESIGN AND SETTING: This was a cross-sectional study at one tertiary care center. SUBJECTS: Subjects were 7- to 11-yr-old healthy normal-weight (NW) and obese (OB) volunteers recruited from local advertisements. INTERVENTIONS: After an overnight fast, the subjects were given a breakfast high in carbohydrate, protein, or fat at 0800 h. Blood samples for total ghrelin and total PYY were taken at baseline, 30 min, and hourly from 0900 to 1200 h. MAIN OUTCOME MEASURE: We assessed postprandial ghrelin suppression and PYY elevation, as well as changes in reported hunger and satiety, after the three test meals. RESULTS: After the high-protein meal, ghrelin declined gradually in both groups over the study period without subsequent increase, whereas ghrelin suppressed more rapidly to a nadir at 60 min after the high-carbohydrate meal in both NW and OB children, followed by rebound in ghrelin levels. Similarly, after the high-protein meal, PYY concentrations increased steadily over the course of the morning in both groups without decline, whereas PYY levels peaked 30 min after the high-carbohydrate meal in both NW and OB subjects with significant decline thereafter. Ghrelin and PYY responses to the high-fat meal were somewhat intermediate between that observed with high carbohydrate and high protein. The OB children reported higher hunger and lower satiety after the high-carbohydrate meal compared to the NW subjects, whereas appetite ratings were similar between the groups after the high-protein and high-fat meals. Additionally, within the OB group, area under the curve (AUC) analysis revealed significantly greater PYY response, as well as lower AUC hunger and higher AUC satiety, to the high-protein meal than the high-carbohydrate and high-fat meals. CONCLUSIONS: The patterns of secretion of ghrelin and PYY in our study of prepubertal children suggest that they may play a role in the effectiveness of high-protein/low-carbohydrate diets in promoting weight loss.
Published:
2009-11
Title:
Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer
Authors:
Cooper, David S; Doherty, Gerard M; Haugen, Bryan R; Hauger, Bryan R; Kloos, Richard T; Lee, Stephanie L; Mandel, Susan J; Mazzaferri, Ernest L; McIver, Bryan; Pacini, Furio; Schlumberger, Martin; Sherman, Steven I; Steward, David L; Tuttle, R Michael
Abstract:
BACKGROUND: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the publication of the American Thyroid Association's guidelines for the management of these disorders was published in 2006, a large amount of new information has become available, prompting a revision of the guidelines. METHODS: Relevant articles through December 2008 were reviewed by the task force and categorized by topic and level of evidence according to a modified schema used by the United States Preventative Services Task Force. RESULTS: The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to optimal surgical management, radioiodine remnant ablation, and suppression therapy using levothyroxine. Recommendations related to long-term management of differentiated thyroid cancer include those related to surveillance for recurrent disease using ultrasound and serum thyroglobulin as well as those related to management of recurrent and metastatic disease. CONCLUSIONS: We created evidence-based recommendations in response to our appointment as an independent task force by the American Thyroid Association to assist in the clinical management of patients with thyroid nodules and differentiated thyroid cancer. They represent, in our opinion, contemporary optimal care for patients with these disorders.
Published:
2009-11
Title:
Variation in the human lipidome associated with coffee consumption as revealed by quantitative targeted metabolomics
Authors:
Altmaier, Elisabeth; Kastenmüller, Gabi; Römisch-Margl, Werner; Thorand, Barbara; Weinberger, Klaus M.; Adamski, Jerzy; Illig, Thomas; Döring, Angela; Suhre, Karsten
Abstract:
The effect of coffee consumption on human health is still discussed controversially. Here, we report results from a metabolomics study of coffee consumption, where we measured 363 metabolites in blood serum of 284 male participants of the Cooperative Health Research in the Region of Augsburg study population, aged between 55 and 79 years. A statistical analysis of the association of metabolite concentrations and the number of cups of coffee consumed per day showed that coffee intake is positively associated with two classes of sphingomyelins, one containing a hydroxy-group (SM(OH)) and the other having an additional carboxy-group (SM(OH,COOH)). In contrast, long- and medium-chain acylcarnitines were found to decrease with increasing coffee consumption. It is noteworthy that the concentration of total cholesterol also rises with an increased coffee intake in this study group. The association observed here between these hydroxylated and carboxylated sphingolipid species and coffee intake may be induced by changes in the cholesterol levels. Alternatively, these molecules may act as scavengers of oxidative species, which decrease with higher coffee intake. In summary, we demonstrate strong positive associations between coffee consumption and two classes of sphingomyelins and a negative association between coffee consumption and long- and medium-chain acylcarnitines.
Published:
2009-11
Title:
[Consequences of exclusive breast-feeding in vegan mother newborn--case report]
Authors:
Mariani, A.; Chalies, S.; Jeziorski, E.; Ludwig, C.; Lalande, M.; Rodière, M.
Abstract:
We report on the case of an infant who was hospitalized because of failure to thrive, megaloblastic anemia, and delayed psychomotor development. He was 10 months old and had been exclusively breast-fed by his vegan mother. Investigations showed vitamin B(12) deficiency with hematocytopenia and pervasive developmental disorders as well as vitamin K and vitamin D deficiencies. The infant's mother presented the same deficiencies. Introduction of vitamin supplementation normalized the biological disorders, and the infant showed weight gain and neurological improvement. This case highlights that a vegan diet during pregnancy followed by exclusive breast-feeding can induce nutritional deficiencies in the newborn, with clinical consequences. Detecting mother and child vitamin deficiencies and preventing them is essential.
Published:
2009-11
Title:
A naturalistic study of predictors and risks of atypical antipsychotic use in an attention-deficit/hyperactivity disorder clinic
Authors:
Weiss, Margaret; Panagiotopoulos, Constadina; Giles, Lauren; Gibbins, Christopher; Kuzeljevic, Boris; Davidson, Jana; Harrison, Rebecca
Abstract:
OBJECTIVE: This was an exploratory study to examine the use of atypical antipsychotics in an attention-deficit/hyperactivity disorder (ADHD) clinic. METHOD: A total of 194 patients was examined to compare those receiving atypical or second-generation antipsychotics (atypicals) from those who were not. A sample of 27 children on atypicals received laboratory investigation for indicators of possible metabolic effects. RESULTS: In all, 19.1% of the patients in the clinic were receiving atypicals with a mean duration of 313 days; 36 of 37 patients on atypicals had received risperidone, with a mean dose of 0.62 mg. Children receiving atypicals were statistically more likely to have a severe co-morbid disorder, a lower Children's Global Assessment Scale score, a greater total score on the teacher Strengths and Difficulties Questionnaire, and greater difficulty with parent-rated symptoms of being touchy, worried, rages, and explosive outbursts. There were no differences found in measures of functioning, adaptive skills, quality of life, or ADHD symptoms. In the subset of children studied for potential metabolic effects, 68.0% had a waist circumference > or =90(th) percentile that was independent of weight gain, 18.5% had impaired fasting glucose, 12.5% had elevated blood pressure, 11.1% had elevated triglycerides, and 16.7% met full criteria for metabolic syndrome. CONCLUSION: Clinical implementation of the efficacy studies of risperidone for disruptive behavior disorders has led to a significant change in practice. Almost 1 in 5 patients are now receiving atypical neuroleptics, typically to treat severe co-morbid disorders and symptoms other than ADHD per se. Despite these children receiving low doses, concomitant stimulants, and low body mass index z-scores, a significant proportion of children demonstrated either one or more components or the full criteria for metabolic syndrome.
Published:
2009-10
Title:
A new glucagon and GLP-1 co-agonist eliminates obesity in rodents
Authors:
Day, Jonathan W; Ottaway, Nickki; Patterson, James T; Gelfanov, Vasily; Smiley, David; Gidda, Jas; Findeisen, Hannes; Bruemmer, Dennis; Drucker, Daniel J; Chaudhary, Nilika; Holland, Jenna; Hembree, Jazzminn; Abplanalp, William; Grant, Erin; Ruehl, Jennifer; Wilson, Hilary; Kirchner, Henriette; Lockie, Sarah Haas; Hofmann, Susanna; Woods, Stephen C; Nogueiras, Ruben; Pfluger, Paul T; Perez-Tilve, Diego; DiMarchi, Richard; Tschöp, Matthias H
Abstract:
Published:
2009-10
Title:
Adopting a plant-based diet minimally increased food costs in WHEL Study
Authors:
Hyder, Joseph A.; Thomson, Cynthia A.; Natarajan, Loki; Madlensky, Lisa; Pu, Minya; Emond, Jennifer; Kealey, Sheila; Rock, Cheryl L.; Flatt, Shirley W.; Pierce, John P.; WHEL Study Group
Abstract:
OBJECTIVE: To assess the cost of adopting a plant-based diet. METHODS: Breast cancer survivors randomized to dietary intervention (n=1109) or comparison (n=1145) group; baseline and 12-month data on diet and grocery costs. RESULTS: At baseline, both groups reported similar food costs and dietary intake. At 12 months, only the intervention group changed their diet (vegetable-fruit: 6.3 to 8.9 serv/d.; fiber: 21.6 to 29.8 g/d; fat: 28.2 to 22.3% of E). The intervention change was associated with a significant increase of $1.22/ person/week (multivariate model, P=0.027). CONCLUSIONS: A major change to a plant-based diet was associated with a minimal increase in grocery costs.
Published:
2009-10
Title:
Artificial food colouring and hyperactivity symptoms in children
Authors:
Abstract:
(1) A hypothesis has been proposed that artificial food colourings have a role in exacerbating hyperactive behavior in children; (2) A placebo-controlled, double-blind, crossover clinical study in 297 children representative of the general population showed higher hyperactivity scores during the periods when they were ingesting food colourings; (3) A meta-analysis of 15 double-blind clinical trials that evaluated artificial food colouring in children already considered to be hyperactive showed an increase in their hyperactive behavior; (4) In practice, even though the mechanism underlying this phenomenon has not be elucidated, these data suggest that it is best to avoid exposing children to artificial food coloring.
Published:
2009-10
Title:
Effect of vegetarian diets on bone mineral density: a Bayesian meta-analysis
Authors:
Ho-Pham, Lan T.; Nguyen, Nguyen D.; Nguyen, Tuan V.
Abstract:
BACKGROUND: The association between vegetarian diets and bone mineral density (BMD) is controversial because of conflicting findings from previous studies. OBJECTIVE: The aim of this study was to estimate the effect of vegetarian diets on BMD by using a meta-analytic approach. DESIGN: A systematic electronic literature search was conducted to identify all relevant articles on the association between vegetarian diet and BMD. Nine studies of 2749 subjects (1880 women and 869 men) were included in the analysis. Traditional and Bayesian methods of meta-analysis were applied to synthesize the data. RESULTS: Overall, BMD was approximately 4% lower in vegetarians than in omnivores (95% CI: 2%, 7%) at both the femoral neck and the lumbar spine. Compared with omnivores, vegans had a significantly lower lumbar spine BMD (6% lower; 95% CI: 2%, 9%), which was more pronounced than in lactoovovegetarians (2% lower; 95% CI: 1%, 4%). The probability that BMD was > or =5% lower in vegetarians than in omnivores (or approximately 0.3 SD) was 42% for the femoral neck and 32% for the lumbar spine. There was no evidence of publication bias. There was a moderate degree of between-study heterogeneity; the coefficient of heterogeneity varied between 46% and 51%. CONCLUSION: The results suggest that vegetarian diets, particularly vegan diets, are associated with lower BMD, but the magnitude of the association is clinically insignificant.
Published:
2009-10
Title:
Effects of a low carbohydrate weight loss diet on exercise capacity and tolerance in obese subjects
Authors:
Brinkworth, Grant D.; Noakes, Manny; Clifton, Peter M.; Buckley, Jonathan D.
Abstract:
Dietary restriction and increased physical activity are recommended for obesity treatment. Very low carbohydrate diets are used to promote weight loss, but their effects on physical function and exercise tolerance in overweight and obese individuals are largely unknown. The aim of this study was to compare the effects of a very low carbohydrate, high fat (LC) diet with a conventional high carbohydrate, low fat (HC) diet on aerobic capacity, fuel utilization during submaximal exercise, perceived exercise effort (RPE) and muscle strength. Sixty subjects (age: 49.2+/-1.2 years; BMI: 33.6+/-0.5 kg/m2) were randomly assigned to an energy restricted (approximately 6-7 MJ, 30% deficit), planned isocaloric LC or HC for 8 weeks. At baseline and week 8, subjects performed incremental treadmill exercise to exhaustion and handgrip and isometric knee extensor strength were assessed. Weight loss was greater in LC compared with HC (8.4+/-0.4% and 6.7+/-0.5%, respectively; P=0.01 time x diet). Peak oxygen uptake and heart rate were unchanged in both groups (P>0.17). Fat oxidation increased during submaximal exercise in LC but not HC (P<0.001 time x diet effect). On both diets, perception of effort during submaximal exercise and handgrip strength decreased (P0.25). An LC weight loss diet shifted fuel utilization toward greater fat oxidation during exercise, but had no detrimental effect on maximal or submaximal markers of aerobic exercise performance or muscle strength compared with an HC diet. Further studies are required to determine the interaction of LC diets with regular exercise training and the long-term health effects.
Published:
2009-10
Title:
Impact of food consumption habits on the pesticide dietary intake: comparison between a French vegetarian and the general population
Authors:
Van Audenhaege, Marieke; Heraud, Fanny; Menard, Celine; Bouyrie, Juliette; Morois, Sophie; Calamassi-Tran, Gloria; Lesterle, Sebastien; Volatier, Jean-Luc; Leblanc, Jean-Charles
Abstract:
This study aims to compare the pesticide residue dietary intake of the French general population and the vegetarian population, separated into five specific diets: omnivorous (OMN), lacto-vegetarian (LV), ovo-lacto-vegetarian (OLV), pesco-lacto-vegetarian (PLV) and vegan (VG). Theoretical Maximum Daily Intakes (TMDIs) based on Maximum Residue Levels (MRLs) were calculated as a percentage of the Acceptable Daily Intake (ADI). Among the 421 pesticides studied, only 48 had TMDI above ADI for at least one population subgroup. An excessive exposure was noticed for 44, 43, 42, 41 and 30 pesticides in the OLV, VG, OMN, LV and PLV groups, respectively, versus 29 in the general population. Meat and egg products consumption was responsible for higher intakes of organochlorine pesticides in the general population than in the vegetarian population (TMDI = 348% versus 146-183% ADI for aldrin). However, as the limited consumption of animal-origin commodities was largely offset by a higher fruit, vegetable and cereal intake in the vegetarian diets, vegetarians appear to be preferentially exposed to pesticides, for which fruit, vegetables and cereals are the main contributors, such as tri-allate, chlorpyrifos-methyl and diazinon. This study illustrates that consumption habits have a real impact on pesticide exposure in terms of intake levels, number and type of pesticides, representing a potential risk of dietary exposure. Except for organochlorine compounds, the vegetarian population may be more exposed to pesticide residues than the general population due to specific dietary habits. Thus, this population should be considered for risk assessment of pesticide residues.
Published:
2009-10
Title:
Mechanisms of Obesity and Related Pathologies: The Macro- and Microcirculation of Adipose Tissue
Authors:
Rutkowski, Joseph M.; Davis, Kathryn E.; Scherer, Philipp E.
Abstract:
Adipose tissue is an endocrine organ made up of adipocytes, various stromal cells including many immune cells, and an endothelial network. Adipose secretory products, collectively referred to as adipokines, have been identified as contributors to the negative consequences of adipose tissue expansion including cardiovascular disease, diabetes, and cancer. Systemic circulation provides transport capabilities for adipokines and fuels for proper adipose tissue function. The adipose tissue microcirculation is heavily impacted by adipose tissue expansion. A subset of adipokines can induce endothelial dysfunction. Furthermore, angiogenesis is necessary to counter hypoxia arising as a result of tissue expansion. Tumors, such as invasive lesions in the mammary gland, co-opt the adipose tissue microvasculature for local growth and metastatic growth and lymphatic circulation provides an important route for lipid transport. Here, we review this area that has not received a lot of attention and focus on the established and potential interplay between adipose tissue and the microvascular endothelium.
Published:
2009-10
Title:
Pasture-feeding of Charolais steers influences skeletal muscle metabolism and gene expression
Authors:
Cassar-Malek, I.; Jurie, C.; Bernard, C.; Barnola, I.; Micol, D.; Hocquette, J.-F.
Abstract:
Extensive beef production systems on pasture are promoted to improve animal welfare and beef quality. This study aimed to compare the influence on muscle characteristics of two management approaches representative of intensive and extensive production systems. One group of 6 Charolais steers was fed maize-silage indoors and another group of 6 Charolais steers grazed on pasture. Activities of enzymes representative of glycolytic and oxidative (Isocitrate dehydrogenase [ICDH], citrate synthase [CS], hydroxyacyl-CoA dehydrogenase [HAD]) muscle metabolism were assessed in Rectus abdominis (RA) and Semitendinosus (ST) muscles. Activities of oxidative enzymes ICDH, CS and HAD were higher in muscles from grazing animals demonstrating a plasticity of muscle metabolism according to the production and feeding system. Gene expression profiling in RA and ST muscles was performed on both production groups using a multi-tissue bovine cDNA repertoire. Variance analysis showed an effect of the muscle type and of the production system on gene expression (P
Published:
2009-10
Title:
The Expensive Brain: a framework for explaining evolutionary changes in brain size
Authors:
Isler, Karin; van Schaik, Carel P.
Abstract:
To explain variation in relative brain size among homoiothermic vertebrates, we propose the Expensive Brain hypothesis as a unifying explanatory framework. It claims that the costs of a relatively large brain must be met by any combination of increased total energy turnover or reduced energy allocation to another expensive function such as digestion, locomotion, or production (growth and reproduction). Focusing on the energetic costs of brain enlargement, a comparative analysis of the largest mammalian sample assembled to date shows that an increase in brain size leads to larger neonates among all mammals and a longer period of immaturity among monotokous precocial species, but not among the polytokous altricial ones, who instead reduce their litter size. Relatively large brained mammals, altricial and precocial, also show reduced annual fertility rates as compared to their smaller brained relatives, but allomaternal energy inputs allow some cooperatively breeding altricial carnivores to produce even more offspring in a shorter time despite having a relatively large brain. Thus, the Expensive Brain framework explains why brain size is linked to life history pace in some, but not all mammalian lineages. This framework encompasses other hypotheses of energetic constraints on brain size variation and is also compatible with the Brain Malnutrition Risk hypothesis, but the absence of a mammal-wide correlation between brain size and immature period argues against the Needing-to-Learn explanation for slower development among large brained mammals.
Published:
2009-10
Title:
The effects of a low-sodium base-producing diet including red meat compared with a high-carbohydrate, low-fat diet on bone turnover markers in women aged 45-75 years
Authors:
Nowson, Caryl A.; Patchett, Annabelle; Wattanapenpaiboon, Naiyana
Abstract:
A randomised, parallel-design dietary intervention study was conducted in women (aged 45-75 years) with prehypertension or stage 1 hypertension. The aim was to compare the effects on bone turnover of a low-Na base-producing (LNAB) Dietary Approaches to Stop Hypertension (DASH)-type diet (including six serves lean red meat/week) with a high-carbohydrate low-fat (HCLF) diet with a higher acid load (both >800 mg dietary Ca/d). Fasting serum bone markers (baseline and week 14) and 24 h urinary electrolyte excretion (baseline, weeks 4, 8, 12 and 14) were measured. After the intervention period, the LNAB group (n 46) had a fall of 26 (sem 6) % (P < 0.0001) in urinary Na, an increase in K excretion (6.8 (sem 3.6) mmol/d; P = 0.07) and, compared with the HCLF group (n 49), a greater reduction in urinary Ca excretion by 0.7 (sem 0.3) mmol/d. Serum 25-hydroxyvitamin D, intact parathyroid hormone and osteocalcin did not change, and both groups had a similar increase of 23 (sem 5) % (P
Published:
2009-10
Title:
The genetics of attention-deficit/hyperactivity disorder
Authors:
Coghill, David; Banaschewski, Tobias
Abstract:
Attention-deficit/hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder that almost certainly represents the common outcome of multiple causal pathways and it is now generally accepted that genetic factors make a significant contribution to these pathways. Behavioral studies suggest a heritability of approximately 0.76. While molecular genetic approaches have identified a range of potential candidate genes, it is now clear that the genetics of ADHD are characterized by a number of genes each of which makes a small but significant contribution to the overall risk. Several genome-wide linkage studies have been conducted and, although there are considerable differences in findings between studies, several regions have been supported across several studies (bin 16.4, 5p13, 11q22-25, 17p11). The contribution of several candidate genes has been supported by meta-analyses (DRD4, DRD5, DAT1, HTR1B and SNAP25). Genome-wide association scans are starting to appear but have not yet had sufficient power to produce conclusive results. Gene-environment interactions, which are as yet relatively understudied, are likely to be of importance in fully understanding the role of genes in ADHD and will be discussed.
Published:
2009-10
Title:
The mainstream hypothesis that LDL cholesterol drives atherosclerosis may have been falsified by non-invasive imaging of coronary artery plaque burden and progression
Authors:
Ware, William R.
Abstract:
That LDL cholesterol drives atherosclerosis is a widely if not almost universally held belief, and this belief strongly influences the mainstream approach to coronary heart disease. However heart disease has a number of stages, and in terms of primary prevention, the initiation and progression of silent or sub-clinical atherosclerosis is clearly fundamental. However, studies that address the efficacy of interventions and practices aimed at the primary prevention of heart disease almost always use event-based endpoints such as fatal or non-fatal myocardial infarction or unstable angina. These endpoints do not directly relate to the primary prevention of silent atherosclerosis and to apply these results to asymptomatic individuals in this context involves an extrapolation. The advent of non-invasive imaging techniques which allow the determination of coronary artery plaque burden and progression of plaque has provided a unique opportunity to examine the relationship between both traditional and emerging risk factors and the extent of sub-clinical coronary artery disease and in particular allow the testing of the hypothesis that LDL cholesterol drives coronary atherosclerosis. Consistent with earlier autopsy studies, the use of electron beam tomography and contrast enhanced CT angiography techniques have created a large body of evidence which appears to falsify this hypothesis. The large number of null results for the association between serum LDL cholesterol levels and the prevalence or progression of both calcified and non-calcified plaque in the appropriate vascular bed and involving large numbers of men and women over a wide range of age, ethnic background, plaque burden and cholesterol levels cannot be easily dismissed. If the hypothesis is false, this has a significant impact on currently held views regarding risk factors and therapeutic interventions in the case of individuals who are asymptomatic, that is, issues associated with primary prevention. Also, if the hypothesis is false, then the use of changes in LDL as a surrogate marker for judging the importance of various risk factors for silent atherosclerosis and thus coronary artery disease can be called into question.
Published:
2009-10
Title:
What can mitochondrial heterogeneity tell us about mitochondrial dynamics and autophagy?
Authors:
Wikstrom, Jakob D.; Twig, Gilad; Shirihai, Orian S.
Abstract:
A growing body of evidence shows that mitochondria are heterogeneous in terms of structure and function. Increased heterogeneity has been demonstrated in a number of disease models including ischemia-reperfusion and nutrient-induced beta cell dysfunction and diabetes. Subcellular location and proximity to other organelles, as well as uneven distribution of respiratory components have been considered as the main contributors to the basal level of heterogeneity. Recent studies point to mitochondrial dynamics and autophagy as major regulators of mitochondrial heterogeneity. While mitochondrial fusion mixes the content of the mitochondrial network, fission dissects the mitochondrial network and generates depolarized segments. These depolarized mitochondria are segregated from the networking population, forming a pre-autophagic pool contributing to heterogeneity. The capacity of a network to yield a depolarized daughter mitochondrion by a fission event is fundamental to the generation of heterogeneity. Several studies and data presented here provide a potential explanation, suggesting that protein and membranous structures are unevenly distributed within the individual mitochondrion and that inner membrane components do not mix during a fusion event to the same extent as the matrix components do. In conclusion, mitochondrial subcellular heterogeneity is a reflection of the mitochondrial lifecycle that involves frequent fusion events in which components may be unevenly mixed and followed by fission events generating disparate daughter mitochondria, some of which may fuse again, others will remain solitary and join a pre-autophagic pool. © 2009 Elsevier Ltd. All rights reserved.
Published:
2009-10
Title:
[The role of zinc in the treatment of hyperactivity disorder in children]
Authors:
Dodig-Curković, Katarina; Dovhanj, Jasna; Curković, Mario; Dodig-Radić, Josipa; Degmecić, Dunja
Abstract:
Zinc is an essential cofactor of more than 100 enzymes, including metalloenzymes and metalloenzyme complexes, which are necessary in the metabolism of carbohydrates, fatty acids, proteins and nucleic acids. It is an important factor in the metabolism of neurotransmitters, prostaglandins, and for maintaining brain structure and function. Dopamine is one of the most important factors in the pathophysiology of hyperactivity disorder, and the hormone melatonin has an important role in the regulation of dopamine. Because zinc is necessary in the metabolism of melatonin, it can be assumed that zinc is a very important factor in the treatment of attention deficit and hyperactivity disorder (ADHD). It is known that deficit of some minerals and vitamins is connected with hyperkinetic disorder. Preliminary investigations in humans show that many children with ADHD have lower zinc concentration in relation to healthy children. Zinc sulfate as an adjunct to methylphenidate has favorable effects in the treatment of ADHD children, pointing to the possible association of zinc deficit and ADHD pathophysiology. Zinc concentration can only point to some other factors (malnutrition) that can lead to ADHD, but is not a factor that has a causative role in ADHD. Therefore, zinc supplementation to nutrition or to ADHD therapy may be of great benefit in ADHD children with zinc deficit or low plasma zinc concentration. ADHD occurs in different cultures, mostly before seven years of age. In children younger than five years it is difficult to make an accurate diagnosis because their behavior is more variable than in older children. Hyperactive disorder is mostly observed in younger age, i.e. in childhood and adolescence. The majority of the main characteristics are less pronounced or completely lost in adult age. In the 1960s, the disorder was named "minimal cerebral dysfunction" and was most often the consequence of head trauma or low birth weight. Later, the term was changed as hyperactive reaction in childhood. Recent studies estimate its prevalence to three of ten hyperactive children, and there are data that about 4% of children have the complete frame of the disorder. The condition is more common in boys than in girls. The reason probably lies in the fact that girls primarily develop attention disorder and cognitive problems (concentration, memory, thinking), and less often have symptoms of aggressive and impulsive behavior, thus boys being earlier referred for examination. There are many theories about the possible origin of hyperactive disorder, and one of the most widely studied is the theory of the role of dopamine, which is supported by the results of treatment in these children with dopamine agonists like methylphenidate and amphetamines. Recent studies do not neglect the influence of maternal intake of food and drink additives, alcohol consumption and smoking during pregnancy, soil contamination, and low birth weight. Zinc is a coenzyme of the enzyme delta-6 desaturase, which is important in the anabolism of polyunsaturated long chain fatty acids, linolic and linolenic acids that constitute neuronal membrane. Studies point to the possible association of zinc deficiency and ADHD pathophysiology. In ADHD children with zinc deficiency or low plasma zinc concentration, zinc dietary supplementation or during therapy for ADHD may be of great benefit. A study of ADHD treatment with zinc sulfate as a supplement to methylphenidate showed beneficial effects of zinc supplementation in the treatment of children with ADHD. The dose of zinc sulfate used was 55 mg/day, which is equivalent to 15 mg zinc. The improvement achieved in ADHD children with the use of zinc sulfate appears to confirm the role of zinc deficiency in the etiopathogenesis of ADHD. Additional studies are needed to identify the real and efficient dose of zinc.
Published:
2009-10
Title:
A maternal high-fat diet is accompanied by alterations in the fetal primate metabolome
Authors:
Cox J; Williams S; Grove K; Lane RH; Aagaard-Tillery KM; Cox, James; Williams, Sarah; Grove, Kevin; Lane, Robert H; Aagaard-Tillery, Kjersti M
Abstract:
Objective: To characterize the serum metabolome of a primate model of in utero high-fat exposure.Study Design: Serum from maternal and fetal (e130) macaque monkeys exposed to either a high-fat or control diet were analyzed by gas chromatography-mass spectrometry. Multivariate data analysis was performed to reduce the generated data set. Candidate metabolites were further analyzed for significance by using the analysis of variance and comparative t tests.Results: Approximately 1300 chromatographic features were detected. Through multivariate data analysis this number was reduced to 60 possible metabolites. With the use of comparative t tests, 22 metabolites had statistical significance (P < .05) over the entire study. By virtue of maternal high-fat diet alone, fetal phenotypic differences are accompanied by altered metabolite concentrations of 7 metabolites (P
Published:
2009-09
Title:
Antidepressant electroconvulsive therapy: Mechanism of action, recent advances and limitations
Authors:
Merkl, Angela; Heuser, Isabella; Bajbouj, Malek
Abstract:
A considerable number of depressive patients do not respond to or remit during pharmacotherapeutical or psychotherapeutical interventions resulting in an increasing interest in non-pharmacological strategies to treat affective disorders. Electroconvulsive therapy (ECT) dates back to the beginning of modern biologic psychiatry and ongoing research has successfully improved efficacy in addition to safety while reducing side effects. Double-blind, randomized, controlled trials have shown powerful interactions between electrode placement (right unilateral, bifrontal, bitemporal) and dosage (relative to seizure threshold) in the efficacy and side effects of ECT. This review aims to summarize current research data on the mechanism of action, efficacy, and recent advances in ECT technique.
Published:
2009-09
Title:
DHA status of vegetarians
Authors:
Sanders, Thomas A. B.
Abstract:
BACKGROUND: Docosahexaenoic acid (22:6n-3; DHA) is absent from vegan diets and present in limited amounts in vegetarian diets. OBJECTIVE: To review DHA status in vegetarians and vegans. DESIGN: To identify published studies and review their findings. RESULTS: Dietary analyses show that vegan diets are devoid of DHA and vegetarian diets that included dairy food and eggs only provide about 0.02 g DHA/d. Vegetarian and especially vegan diets supply more linoleic acid (18:2n-6) than omnivore diets. The intake of alpha-linolenic acid (18:3n-3) also tends to be similar or greater but depends on culinary oils used. The proportions of DHA in plasma, blood cells, breast milk, and tissues are substantially lower in vegans and vegetarians compared with omnivores. The lower proportions of DHA are accompanied by correspondingly higher proportions of the long-chain derivatives of linoleic acid, indicating that the capacity to synthesize long-chain polyunsaturated fatty acids is not limited. Short-term dietary supplementation with alpha-linolenic acid increases the proportion of eicosapentaenoic acid (20:5n-3) but does not increase the proportion of DHA in blood lipids. Small amounts of preformed DHA (as low as 200mg) result in a large increase in the proportion of DHA in blood lipids in vegetarians and vegans. There is no evidence of adverse effects on health or cognitive function with lower DHA intake in vegetarians. CONCLUSIONS: Preformed DHA in the diet of omnivores explains the relatively higher proportion of this fatty acid in blood and tissue lipids compared with vegetarians. The pathophysiological significance of this difference remains to be determined.
Published:
2009-09
Title:
Electroconvulsive Therapy: Part I. A Perspective on the Evolution and Current Practice of ECT:
Authors:
Payne, Nancy A.; Prudic, Joan
Abstract:
The concept of inducing convulsions, mainly through chemical means, to promote mental wellness has existed since the 16th century. In 1938, Italian scientists first applied electrically induced therapeutic seizures. Although electroconvulsive therapy (ECT) is employed in the treatment of several psychiatric disorders, it is most frequently used today to treat severe depressive episodes and remains the most effective treatment available for those disorders. Despite this, ECT continues to be the most stigmatized treatment available in psychiatry, resulting in restrictions on and reduced accessibility to a helpful and potentially life-saving treatment. The psychiatric and psychosocial ramifications of this stigmatization may include the exacerbation of the increasingly serious, global health problem of major depressive disorders as well as serious consequences for individual patients who may not be offered, or may refuse, a potentially beneficial treatment. The goal of this first article in this two-part series is to provide an overview of ECT's historical development and discuss the current state of knowledge about ECT, including technical aspects of delivery, patient selection, its side-effect profile, and factors that may contribute to underuse of ECT.
Published:
2009-09
Title:
Electroconvulsive Therapy: Part II: A Biopsychosocial Perspective:
Authors:
Payne, Nancy A.; Prudic, Joan
Abstract:
The myths surrounding electroconvulsive therapy (ECT) and the misconceptions held by the general public, clinicians, and patients have interfered with acceptance of this treatment throughout its history. Misunderstandings surrounding ECT, and its consequent stigmatization, are reviewed, including negative depictions of ECT in film, print media, and on the Internet. Clinicians involved in the delivery of ECT benefit from gaining an understanding of how ECT may be perceived by patients and other mental health professionals; they can play a vital role in educating patients and helping ensure the delivery of a successful course of ECT. Guidance is provided for clinicians on how to support patients and families through the ECT process using a model team approach. Anxiety reduction, meeting individual needs, patient and family psychoeducation, assessment of psychosocial supports, and discharge planning are discussed.
Published:
2009-09
Title:
Fish, docosahexaenoic acid and Alzheimer's disease
Authors:
Cunnane, S. C.; Plourde, M.; Pifferi, F.; Bégin, M.; Féart, C.; Barberger-Gateau, P.
Abstract:
Cognitive decline in the elderly, particularly Alzheimer's disease (AD), is a major socio-economic and healthcare concern. We review here the literature on one specific aspect of diet affecting AD, that of the omega3 fatty acids, particularly the brain's principle omega3 fatty acid - docosahexaenoic acid (DHA). DHA has deservedly received wide attention as a nutrient supporting both optimal brain development and for cardiovascular health. Our aim here is to critically assess the quality of the present literature as well as the potential of omega3 fatty acids to treat or delay the onset of AD. We start with a brief description of cognitive decline in the elderly, followed by an overview of well recognized biological functions of DHA. We then turn to epidemiological studies, which are largely supportive of protective effects of fish and DHA against risk of AD. However, biological studies, including blood and brain DHA analyses need careful interpretation and further investigation, without which the success of clinical trials with DHA may continue to struggle. We draw attention to some of the methodological issues that need resolution as well as an emerging mechanism that may explain how DHA could be linked to protecting brain function in the elderly.
Published:
2009-09
Title:
Glucosinolates in Brassica vegetables: the influence of the food supply chain on intake, bioavailability and human health
Authors:
Verkerk, Ruud; Schreiner, Monika; Krumbein, Angelika; Ciska, Ewa; Holst, Birgit; Rowland, Ian; De Schrijver, Remi; Hansen, Magnor; Gerhäuser, Clarissa; Mithen, Richard; Dekker, Matthijs
Abstract:
Glucosinolates (GLSs) are found in Brassica vegetables. Examples of these sources include cabbage, Brussels sprouts, broccoli, cauliflower and various root vegetables (e.g. radish and turnip). A number of epidemiological studies have identified an inverse association between consumption of these vegetables and the risk of colon and rectal cancer. Animal studies have shown changes in enzyme activities and DNA damage resulting from consumption of Brassica vegetables or isothiocyanates, the breakdown products (BDP) of GLSs in the body. Mechanistic studies have begun to identify the ways in which the compounds may exert their protective action but the relevance of these studies to protective effects in the human alimentary tract is as yet unproven. In vitro studies with a number of specific isothiocyanates have suggested mechanisms that might be the basis of their chemoprotective effects. The concentration and composition of the GLSs in different plants, but also within a plant (e.g. in the seeds, roots or leaves), can vary greatly and also changes during plant development. Furthermore, the effects of various factors in the supply chain of Brassica vegetables including breeding, cultivation, storage and processing on intake and bioavailability of GLSs are extensively discussed in this paper.
Published:
2009-09
Title:
Inflammation Causes Mood Changes Through Alterations in Subgenual Cingulate Activity and Mesolimbic Connectivity
Authors:
Harrison, Neil A.; Brydon, Lena; Walker, Cicely; Gray, Marcus A.; Steptoe, Andrew; Critchley, Hugo D.
Abstract:
Background: Inflammatory cytokines are implicated in the pathophysiology of depression. In rodents, systemically administered inflammatory cytokines induce depression-like behavior. Similarly in humans, therapeutic interferon-␣ induces clinical depression in a third of patients. Conversely, patients with depression also show elevated pro-inflammatory cytokines. Objectives: To determine the neural mechanisms underlying inflammation-associated mood change and modulatory effects on circuits involved in mood homeostasis and affective processing. Methods: In a double-blind, randomized crossover study, 16 healthy male volunteers received typhoid vaccination or saline (placebo) injection in two experimental sessions. Mood questionnaires were completed at baseline and at 2 and 3 hours. Two hours after injection, participants performed an implicit emotional face perception task during functional magnetic resonance imaging. Analyses focused on neurobiological correlates of inflammation-associated mood change and affective processing within regions responsive to emotional expressions and implicated in the etiology of depression. Results: Typhoid but not placebo injection produced an inflammatory response indexed by increased circulating interleukin-6 and significant mood reduction at 3 hours. Inflammation-associated mood deterioration correlated with enhanced activity within subgenual anterior cingulate cortex (sACC) (a region implicated in the etiology of depression) during emotional face processing. Furthermore, inflammation-associated mood change reduced connectivity of sACC to amygdala, medial prefrontal cortex, nucleus accumbens, and superior temporal sulcus, which was modulated by peripheral interleukin-6. Conclusions: Inflammation-associated mood deterioration is reflected in changes in sACC activity and functional connectivity during evoked responses to emotional stimuli. Peripheral cytokines modulate this mood-dependent sACC connectivity, suggesting a common pathophysiological basis for major depressive disorder and sickness-associated mood change and depression.
Published:
2009-09
Title:
Targeting energy metabolism in brain cancer through calorie restriction and the ketogenic diet
Authors:
Seyfried, B. Thomas N.; Kiebish, Michael; Marsh, Jeremy; Mukherjee, Purna
Abstract:
Malignant brain tumors are a significant health problem in children and adults and are largely unmanageable. As a metabolic disorder involving the dysregulation of glycolysis and respiration (the Warburg effect), malignant brain cancer can be managed through changes in metabolic environment. In contrast to malignant brain tumors that are mostly dependent on glycolysis for energy, normal neurons and glia readily transition to ketone bodies (beta-hydroxybutyrate) for energy in vivo when glucose levels are reduced. The transition from glucose to ketone bodies as a major energy source is an evolutionary conserved adaptation to food deprivation that permits the survival of normal cells during extreme shifts in nutritional environment. Only those cells with a flexible genome, honed through millions of years of environmental forcing and variability selection, can transition from one energy state to another. We propose a different approach to brain cancer management that exploits the metabolic flexibility of normal cells at the expense of the genetically defective and less metabolically flexible tumor cells. This approach to brain cancer management is supported from recent studies in orthotopic mouse brain tumor models and in human pediatric astrocytoma treated with calorie restriction and the ketogenic diet. Issues of implementation and use protocols are discussed.
Published:
2009-09
Title:
Dietary beta-hydroxy-beta-methylbutyrate supplementation influences performance differently after immunization in broiler chickens
Authors:
Buyse, J.; Swennen, Q.; Vandemaele, F.; Klasing, K. C.; Niewold, T. A.; Baumgartner, M.; Goddeeris, B. M.
Abstract:
Dietary addition of the leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) promotes growth in various species. In addition, HMB is described to enhance immune responses which might be associated with metabolic costs. We elaborated further on the role of HMB in growth, metabolism and immunity of meat-type chickens using the following parameters: zootechnical performance, blood chemistry and a specific immune responses after immunization with a human serum albumin (HSA)/Freund's (in) complete adjuvant combination. The chickens received commercial feeds either unsupplemented or supplemented with 300 mg HMB/kg feed. beta-hydroxy-beta-methylbutyrate-supplemented chickens were significantly heavier at 2 weeks of age but this difference was attenuated at later ages. Compared with their unsupplemented controls, cumulative feed conversion was significantly lower in HMB-supplemented chickens. There were no differences in blood chemistry between both dietary treatments. After immunization, HMB significantly attenuated the acute phase protein response at day 1 of post-immunization compared with that of their unsupplemented counterparts. After day 7 post-immunization, body weight gain of the immuno-challenged HMB-supplemented chickens was significantly depressed, but their specific anti-HSA IgG response was significantly enhanced compared with that of their immuno-challenged unsupplemented counterparts. The underlying mechanisms and signalling pathways for these phenomena need to be elucidated. Nevertheless, we are able to conclude that HMB is beneficial for performance under normal circumstances. On the other hand, HMB stimulates the immune response after an immunological challenge, though at the cost of reduced growth.
Published:
2009-08
Title:
Dietary β-hydroxy-β-methylbutyrate supplementation influences performance differently after immunization in broiler chickens
Authors:
Buyse, J.; Swennen, Q.; Vandemaele, F.; Klasing, K. C.; Niewold, T. A.; Baumgartner, M.; Goddeeris, B. M.
Abstract:
Dietary addition of the leucine metabolite β-hydroxy-β-methylbutyrate (HMB) promotes growth in various species. In addition, HMB is described to enhance immune responses which might be associated with metabolic costs. We elaborated further on the role of HMB in growth, metabolism and immunity of meat-type chickens using the following parameters: zootechnical performance, blood chemistry and a specific immune responses after immunization with a human serum albumin (HSA)/Freund’s (in) complete adjuvant combination. The chickens received commercial feeds either unsupplemented or supplemented with 300 mg HMB/kg feed. β-hydroxy-β-methylbutyrate-supplemented chickens were significantly heavier at 2 weeks of age but this difference was attenuated at later ages. Compared with their unsupplemented controls, cumulative feed conversion was significantly lower in HMB-supplemented chickens. There were no differences in blood chemistry between both dietary treatments. After immunization, HMB significantly attenuated the acute phase protein response at day 1 of post-immunization compared with that of their unsupplemented counterparts. After day 7 post-immunization, body weight gain of the immuno-challenged HMB-supplemented chickens was significantly depressed, but their specific anti-HSA IgG response was significantly enhanced compared with that of their immuno-challenged unsupplemented counterparts. The underlying mechanisms and signalling pathways for these phenomena need to be elucidated. Nevertheless, we are able to conclude that HMB is beneficial for performance under normal circumstances. On the other hand, HMB stimulates the immune response after an immunological challenge, though at the cost of reduced growth.
Published:
2009-08
Title:
Epidemiology and Pathophysiology of Diverticular Disease
Authors:
Matrana, Marc R.; Margolin, David A.
Abstract:
Diverticular disease is common and thought to result from structural abnormalities of the colonic wall, disordered intestinal motility, or deficiencies of dietary fiber. Signs and symptoms of inflammation include fever, abdominal pain, and leukocytosis.
Published:
2009-08
Title:
Essential fatty acids and attention-deficit-hyperactivity disorder: a systematic review
Authors:
Raz, Raanan; Gabis, Lidia
Abstract:
AIM: Essential fatty acids (EFAs), also known as omega-3 and omega-6 fatty acids, have been claimed to have beneficial effects as a treatment for attention-deficit-hyperactivity disorder (ADHD). Animal experiments have provided information about the role of EFA in the brain, and several mechanisms of EFA activity are well known. The current review provides an updated, systematic overview of the theory and use of EFA in ADHD. METHOD: Clinical studies and review papers of EFA blood levels and EFA supplementation trials in children with ADHD were researched in the Medline PubMed database. Additional studies were found from the references of these reports. RESULTS: Children with ADHD present lower levels of blood EFAs, and open-label EFA supplementation trials in ADHD raise EFA blood levels and improve symptoms of ADHD. Randomized controlled trials, however, have generally been unsuccessful in demonstrating any behavioural treatment effects. INTERPRETATION: Current findings do not support the use of EFA supplements as a primary or supplementary treatment for children with ADHD.
Published:
2009-08
Title:
Fish consumption and markers of colorectal cancer risk: a multicenter randomized controlled trial
Authors:
Pot, Gerda K.; Majsak-Newman, Gosia; Geelen, Anouk; Harvey, Linda J.; Nagengast, Fokko M.; Witteman, Ben J. M.; van de Meeberg, Paul C.; Timmer, Robin; Tan, Adriaan; Wahab, Peter J.; Hart, Andrew R.; Williams, Matthew P.; Przybylska-Phillips, Kasia; Dainty, Jack R.; Schaafsma, Gertjan; Kampman, Ellen; Lund, Elizabeth K.; FISHGASTRO Study Group
Abstract:
BACKGROUND: Diet is a major factor in the etiology of colorectal cancer, with high fish consumption possibly decreasing colorectal cancer risk, as was shown in several observational studies. To date, no intervention trials have examined the possible beneficial effects of fish intake on colorectal cancer risk. OBJECTIVE: The objective was to investigate the effects of a 6-mo intervention with oil-rich or lean fish on apoptosis and mitosis within the colonic crypt. DESIGN: In a multicenter, randomized, controlled intervention trial, patients with colorectal polyps, inactive ulcerative colitis, or no macroscopic signs of disease were recruited (n = 242) and randomly allocated to receive dietary advice plus either 300 g oil-rich fish (salmon) per week (n = 82), 300 g lean fish (cod) per week (n = 78), or only dietary advice (DA) (n = 82). Apoptosis and mitosis were measured in colonic biopsy samples collected before and after intervention (n = 213). RESULTS: The total number of apoptotic cells per crypt did not increase in the salmon or cod group: -0.10 (95% CI: -0.36, 0.16) and -0.06 (95% CI: -0.32, 0.20), respectively, compared with the DA group. The total number of mitotic cells per crypt decreased nonsignificantly in the salmon group (-0.87; 95% CI: -2.41, 0.68) and in the cod group (-1.04; 95% CI: -2.62, 0.53) compared with the DA group. Furthermore, the distribution of mitosis within the crypt did not significantly change in either group. CONCLUSION: An increase in the consumption of either oil-rich or lean fish to 2 portions weekly over 6 mo does not markedly change apoptotic and mitotic rates in the colonic mucosa. This trial was registered at www.clinicaltrials.gov as NCT00145015.
Published:
2009-08
Title:
Ketogenic diets: an update for child neurologists
Authors:
Kossoff, Eric H.; Zupec-Kania, Beth A.; Rho, Jong M.
Abstract:
The ketogenic diet, modified Atkins diet, and low-glycemic-index treatment have all emerged over the past decade as important therapeutic options for children with intractable epilepsy. Whereas only a decade ago the ketogenic diet was seen as an "alternative'' treatment of last resort, it has become more frequently used throughout the world. The past year alone 2 randomized and controlled trials of the ketogenic diet were published, as well as the use of the ketogenic diet for new-onset epilepsy (infantile spasms), and a 26-member international consensus statement guiding optimal clinical management. There has been an equally dramatic increase of interest into mechanisms of action using various experimental models. Researchers are also highly interested in using diets for neurologic disorders other than epilepsy, including autism and brain tumors. This review will update child neurologists on the recent advances in the use of ketogenic diets.
Published:
2009-08
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