Published Science

The role of diet in cancer is a major public health issue. Foods associated with a low risk of cancer are those typically included in the so-called Mediterranean diet, which is also associated with low mortality rates from cardiovascular disease. Implementing such a diet would involve increasing the consumption of fruits, vegetables, cereals, whole-grain foods and fish, while reducing the intake of refined carbohydrates and red meat. In addition, olive oil should replace saturated fats. Omega-3 fatty acids found in fish inhibit the growth in vitro of colon, breast and prostate cancers. Fibre can bind bile acids, which produce carcinogenic metabolites, and fermented fibre produces volatile fatty acids that can protect against colon cancer. It has been hypothesized that the anti-cancer actions of olive oil may relate to the ability of its mono-unsaturated fatty acid, oleic acid, to regulate oncogenes.

Meat and meat products are essential components of diets in developed countries and despite the convincing evidence that relate them to an increased risk for CVD, a growing consumption of meat products is foreseen. Epidemiological studies show that regular consumption of nuts, in general, and walnuts in particular, correlates inversely with myocardial infarction and ischaemic vascular disease. We assess the nutritional basis for and technological approach to the development of functional meat-based products potentially relevant in cardiovascular disease (CVD) risk reduction. Using the available strategies in the meat industry (reformulation processes) and a food-based approach, we address the design and development of restructured beef steak with added walnuts, potentially functional for CVD risk reduction. Its adequacy as a vehicle for active nutrients is confirmed by a pharmacokinetic pilot study in humans using γ-tocopherol as an exposure biomarker in chylomicrons during the post-prandial state. Effect and potential "functionality is being assessed by a dietary intervention study in subjects at risk and markers and indicators related to CVD are being evaluated. Within the conceptual framework of evidence-based medicine, development of meat-based functional products may become a useful approach for specific applications, with a potential market and health benefits of great importance at a population level. Copyright © Taylor and Francis Group, LLC.

Obesity and attention-deficit hyperactivity disorder (ADHD) are both increasing in prevalence. Childhood exposure to television has shown linkage to both ADHD and obesity with the former ascribed to dysfunctional cognitive hyperstimulation and the latter to altered patterns of diet and exercise. Empirical evidence has contradicted prior presumptions that the hyperactivity of ADHD would decrease the risk of obesity. Instead, obesity and ADHD demonstrate significant comorbidity. We propose that obesity and ADHD represent different manifestations of the same underlying dysfunction, a phenomenon we term environmental oversampling syndrome. Oversupply of information in the form of nutritional content and sensory content may independently predispose to both obesity and ADHD. Moreover, the pathogenic mechanisms of these conditions may overlap such that nutritional excess contributes to ADHD and cognitive hyperstimulation contributes to obesity. The overlapping effects of medications provide further evidence towards the existence of shared etiologic pathways. Metabolism and cognition may represent parallel systems of intelligence, and oversampling of content may constitute the source of parallel dysfunctions. The emerging association between psychiatric and metabolic disorders suggests a fundamental biologic link between these two systems. In addition, the immune system may represent yet another form of intelligence. The designation of syndrome X subsumes seemingly unrelated metabolic and inflammatory entities. Environmental oversampling syndrome may represent an even more inclusive concept that encompasses various metabolic, inflammatory, and behavioral conditions. Apparently disparate conditions such as insulin resistance, diabetes, hypertension, syndrome X, obesity, ADHD, depression, psychosis, sleep apnea, inflammation, autism, and schizophrenia may operate through common pathways, and treatments used exclusively for one of these conditions may prove beneficial for the others.

Mitochondrial disease in adults: A scale to monitor progression and treatment

Endurance running may be a derived capability of the genus Homo and may have been instrumental in the evolution of the human body form. Two hypotheses have been presented to explain why early Homo would have needed to run long distances: scavenging and persistence hunting. Persistence hunting takes place during the hottest time of the day and involves chasing an animal until it is run to exhaustion. A critical factor is the fact that humans can keep their bodies cool by sweating while running. Another critical factor is the ability to track down an animal. Endurance running may have had adaptive value not only in scavenging but also in persistence hunting. Before the domestication of dogs, persistence hunting may have been one of the most efficient forms of hunting and may therefore have been crucial in the evolution of humans.

Endothelial dysfunction contributes to cardiovascular diseases that are also characterized by insulin resistance. Insulin resistance is a hallmark of metabolic disorders including Type 2 diabetes, obesity, and the metabolic syndrome that are also characterized by endothelial dysfunction. Metabolic actions of insulin to promote glucose disposal are augmented by vascular actions of insulin in endothelium to stimulate production of the vasodilator nitric oxide (NO). Indeed, NO-dependent increases in blood flow to skeletal muscle account for 25% to 40% of the increase in glucose uptake in response to insulin stimulation. PI 3-kinase-dependent insulin signaling pathways in endothelium related to production of NO share striking similarities with metabolic pathways in skeletal muscle that promote glucose uptake. Other distinct non-metabolic branches of insulin signaling pathways regulate secretion of the vasoconstrictor endothelin-1 (ET-1) in endothelium. Metabolic insulin resistance is characterized by pathway-specific impairment in PI 3-kinase-dependent signaling that in endothelium may cause imbalance between production of NO and secretion of ET-1 leading to decreased blood flow that worsens insulin resistance. Therapeutic interventions in both animal models and human studies demonstrate that improving endothelial function ameliorates insulin resistance while improving insulin sensitivity ameliorates endothelial dysfunction. Taken together, cellular, physiological, clinical, and epidemiological studies strongly support a reciprocal relationship between endothelial dysfunction and insulin resistance that helps to link cardiovascular and metabolic diseases. In this review, pathophysiological mechanisms that couple endothelial dysfunction with insulin resistance will be discussed with an emphasis on important therapeutic implications for the metabolic syndrome.

PURPOSE: The results of several studies point to the positive role of vegetarian diets in reducing the risk of diabetes, some cancers and cardiovascular diseases. However, exclusion of animal products in vegetarian diets may affect the cobalamin status and cause an elevation of the plasma homocysteine level. The aim of this study was to assess the effect of vegetarian diets on serum concentrations of homocysteine, folate, vitamin B12 and total antioxidant status (TAS) in children. MATERIAL AND METHODS: The study included 32 vegetarians (including 5 vegans), age 2-10 years. Dietary constituents were analyzed using a local nutritional programme. Serum homocysteine, folate and vitamin B12 were determined with fluorescence and chemiluminescence immunoassays. The concentration of TAS was measured by a colorimetric method. RESULTS: Average daily energy intake and the percentage of energy from protein, fat and carbohydrates in the diets of the studied children were just above or similar to the recommended amounts. It could be shown that vegetarian diets contain high concentrations of folate. In vegan diets it even exceeds the recommended dietary allowance. Mean daily intake of vitamin B12 in the studied diets was adequate but in vegans was below the recommended range. The serum concentrations of homocysteine, folate, vitamin B12 and TAS in vegetarian children remained within the physiological range. CONCLUSIONS: The presented data indicate that vegetarian children, contrary to adults, have enough vitamin B12 in their diet (excluding vegans) and normal serum concentrations of homocysteine, folate and vitamin B12. Therefore, in order to prevent deficiencies in the future, close monitoring of vegetarian children (especially on a vegan diet) is important to make sure that they receive adequate quantities of nutrients needed for healthy growth.

Nandrolone and other 19-norsteroid potent anabolic steroids have been prohibited in sports for 30 years. The detection of the main urinary metabolite- 19-norandrosterone- in amounts greater than 2 ng/ml constitutes an adverse analytical finding. The presence in nutritional sport supplements of steroids not listed on the label has undoubtedly resulted in positive tests, but inadvertent consumption of meat containing residues of hormonal treatment should not realistically cause apprehension. Although highly improbable, athletes should prudently avoid meals composed of pig offal in the hours preceding the test since the consumption of edible parts of a non-castrated pig, containing 19-nortestosterone, has been shown to results in the excretion of 19-norandrosterone in the following hours. Norsteroid metabolites are formed during pregnancy and excreted as minor metabolites of norethisterone, and minute amounts have been identified in some male and female samples when using more sensitive techniques of detection. Whereas exercise does not seem to be a significant factor in 19-norandrosterone excretion, some rare urine samples were found to be a suitable medium for in situ 19-demethylation of urinary metabolites.

Dietary composition has been shown to influence metabolism and to impact on the prevalence and risk for certain diseases, but hitherto, there have been no systematic studies on the effects of dietary modulation of human metabolic phenotype (metabotype). Here, we have applied 1H NMR spectroscopy in combination with multivariate statistical analysis to characterize the effects of three diets: "vegetarian", "low meat", and "high meat" on the metabotype signature of human participants. Twelve healthy male participants (age range of 25-74 years) consumed each of these diets, in a randomized order, for continuous 15-day-periods with an intervening washout period between each diet of 7 days duration. Each participant provided three consecutive 24-hour urine collections on days 13, 14, and 15 of each dietary period, and 1H NMR spectra were acquired on all samples. Pattern recognition analysis allowed differentiation of the characteristic metabolic signatures of the diets with creatine, carnitine, acetylcarnitine, and trimethylamine-N-oxide (TMAO) being elevated in the high-meat consumption period. Application of orthogonal projection to latent structure discriminant analysis (O-PLS-DA) allowed the low-meat diet and vegetarian diet signatures to be characterized, and p-hydroxyphenylacetate (a microbial mammalian cometabolite) was higher in the vegetarian than meat diet samples, signaling an alteration of the bacterial composition or metabolism in response to diet. This work shows the potential for the routine use of metabonomics in nutritional and epidemiological studies, in characterizing and predicting the metabolic effects and the influence of diet on human metabotypes. © 2006 American Chemical Society.

This thesis is primarily concerned with human-environment interactions on the tropical coast of northern Australia during the late Holocene. Based on the suggestion that significant change can occur within short time-frames as a direct result of interactive processes, the archaeological evidence from the Point Blane peninsula, Blue Mud Bay, is used to address the issue of how much change and variability occurred in hunter-gatherer economic and social structures during the late Holocene in coastal northeastern Arnhem Land. The suggestion proposed in this thesis is that processes of environmental and climatic change resulted in changes in resource distribution and abundance, which in turn affected patterns of settlement and resource exploitation strategies, levels of mobility and, potentially, the size of foraging groups on the coast. Whereas previous archaeological models for coastal northern Australia have used ethnographies as interpretive tools, it is demonstrated that using ethnographies to aid interpretations of the archaeological record is a problematic approach for this specific region. In particular, such an approach has most likely underestimated the nature and extent of variability that may have existed in the late Holocene. Therefore, the focus here is on what the archaeological and ecological evidence can tell us about human behaviour in the late Holocene. The question of human behavioural variability relative to the climatic and ecological parameters of the last 3000 years in Blue Mud Bay has been addressed by examining issues of scale and resolution in archaeological interpretation. Specifically, the differential chronological and spatial patterning of shell midden and mound sites on the peninsula in conjunction with variability in molluscan resource exploitation. To this end, the biological and ecological characteristics of Anadara granosa, the dominant molluscan species for much of the known period of occupation in the region, are considered in detail, in combination with assessing the potential for human impact through predation. In explaining long-term economic change, the focus has been placed on the analysis of relative changes and trends through time in prehistoric resource exploitation, and their relationship to environmental factors. This thesis therefore makes a contribution to our knowledge of pre-contact coastal foragers by viewing the archaeological record as a reflection of the process of the interaction of humans with their environment. In doing so, an opportunity is provided in which change can be recognised in a number of ways. For example, differential focus on resources, variations in group size and levels of mobility can all be identified. It has also been shown that human-environment interactions are non-linear or progressive, and that human behaviour during the late Holocene was both flexible and dynamic.

INTRODUCTION: Low-carbohydrate diets have become popular as weight loss techniques. These diets are high in protein, saturated fats, and omega-6 fatty acids. They also lead to a ketogenic state. These factors could lead to increased bone turnover. This study was designed to see whether a low-carbohydrate diet would lead to increased bone turnover in humans. METHODS: Thirty patients (15 study subjects and 15 controls) were recruited for this 3-month study. The 15 patients on the diet were instructed to consume less than 20 g of carbohydrates per day for the 1st month and then less than 40 g per day for months 2 and 3. Control subjects had no restrictions on their diet. The primary end point was urinary N-telopeptide (UNTx) at 3 months. Secondary end points included UNTx at 1 month, bone-specific alkaline phosphatase (BSAP) at 1 month, bone turnover ratio (BSAP/UNTx) at 1 month, and weight loss. RESULTS: The mean UNTx in the study subjects increased by 1.6 [95% confidence interval (CI) +/-22.8] compared with an increase of 1.9 (95% CI +/-17.6) in the controls at 3 months (p=0.86). The mean UNTx decreased by 2.2 (95% CI +/-27.2) and 3.1 (95% CI +/-17.6) at 1 month in the dieters and controls, respectively (p=0.36). The mean BSAP decreased by 0.53 (95% CI +/-2.96) in the dieters and increased by 0.34 (95% CI +/-2.92) in the controls at 1 month (p=0.27). The bone turnover ratio increased by 0.08 (95% CI +/-0.81) in the dieters and by 0.05 (95% CI +/- 0.27) in the controls at 1 month (p=0.78). The dieters lost 6.39 kg versus 1.05 kg for the controls at 3 months (p=0.0008). CONCLUSIONS: Although the patients on the low-carbohydrate diet did lose significantly more weight than the controls did, the diet did not increase bone turnover markers compared with controls at any time point. Further, there was no significant change in the bone turnover ratio compared with controls.

Attention deficit hyperactivity disorder (ADHD) belongs to the neurodevelopmental disorders characterized by impulsivity, distractibility and hyperactivity. In the pathogenesis of ADHD genetic and non-genetic factors play an important role. It is assumed that one of non-genetic factors should be oxidative stress. Pycnogenol, an extract from the pine bark, consists of bioflavonoids, catechins, procyanidins and phenolic acids. Pycnogenol acts as powerful antioxidant, chelating agent; it stimulates the activities of some enzymes, like SOD, eNOS, and exhibits other biological activities. AIM: The aim of this randomized, double-blind, placebo-controlled trial was to investigate the influence of administered Pycnogenol or placebo on the level of reduced (GSH) and oxidized (GSSG) glutathione in children suffering from ADHD and on total antioxidant status (TAS). This is the first investigation of the redox glutathione state in relation to ADHD. RESULTS: One month of Pycnogenol administration (1 mg/kg body weight/day) caused a significant decrease in GSSG and a highly significant increase in GSH levels as well as improvement of GSH/GSSG ratio in comparison to a group of patients taking a placebo. TAS in children with ADHD was decreased in comparison with reference values. Pycnogenol administration normalizes TAS of ADHD children.

Holstein steer calves (n = 25) were used to evaluate the effects of treadmill exercise (TME) on blood metabolite status and formation of dark-cutting beef. Calves were blocked by BW (156 ± 33.2 kg) and assigned randomly within blocks to 1 of 5 TME treatments arranged in a 2 x 2 factorial design (4 or 8 km/ h for a duration of 10 or 15 min) with a nonexercised control. Venous blood was collected via indwelling jugular catheters at 10, 2, and 0 min before TME and at 2-min intervals during exercise. Nonexercised steers were placed on the treadmill but stood still for 15 min. Serum cortisol levels, as well as plasma concentrations of glucose, lactate, and NEFA, were similar (P > 0.05) before TME. Serum cortisol concentrations were unaffected (P > 0.05) during the first 6 min of TME, but between 8 and 15 min of TME, cortisol concentrations were greater (P < 0.05) in steers exercised at 8 km/h than those exercised at 4 km/h or controls (speed x time, P 0.05) plasma glucose levels, plasma lactate concentrations in steers exercised at 8 km/h increased (P < 0.05) sharply with the onset of the TME treatment and remained elevated compared with steers exercised at 4 km/h or unexercised controls (speed x time, P < 0.001). Exercised steers had the lowest (P < 0.05) plasma NEFA concentrations during the first 6 min of TME compared with unexercised steers; however, NEFA concentrations were similar after 10 and 12 min of TME, and by the end of TME, steers exercised at 8 km/h had greater (P < 0.05) NEFA levels than nonexercised controls or steers exercised at 4 km/h (speed x time, P < 0.001). Even though muscle glycogen levels and pH decreased (P < 0.001) and muscle lactate concentrations increased (P 0.05) differences in the color, water-holding capacity, shear force, or incidences of dark-cutting carcasses associated with preslaughter TME. It is apparent that preslaughter TME, at the speeds and durations employed in this study, failed to alter antemortem or postmortem muscle metabolism and would not be a suitable animal model for studying the formation of the dark-cutting condition in ruminants. ©2006 American Society of Animal Science. All rights reserved.

The quality of vegetarian diets to meet nutritional needs and support peak performance among athletes continues to be questioned. Appropriately planned vegetarian diets can provide sufficient energy and an appropriate range of carbohydrate, fat and protein intakes to support performance and health. The acceptable macronutrient distribution ranges for carbohydrate, fat and protein of 45-65%, 20-35% and 10-35%, respectively, are appropriate for vegetarian and non-vegetarian athletes alike, especially those who perform endurance events. Vegetarian athletes can meet their protein needs from predominantly or exclusively plant-based sources when a variety of these foods are consumed daily and energy intake is adequate. Muscle creatine stores are lower in vegetarians than non-vegetarians. Creatine supplementation provides ergogenic responses in both vegetarian and non-vegetarian athletes, with limited data supporting greater ergogenic effects on lean body mass accretion and work performance for vegetarians. The potential adverse effect of a vegetarian diet on iron status is based on the bioavailability of iron from plant foods rather than the amount of total iron present in the diet. Vegetarian and non-vegetarian athletes alike must consume sufficient iron to prevent deficiency, which will adversely affect performance. Other nutrients of concern for vegetarian athletes include zinc, vitamin B12 (cyanocobalamin), vitamin D (cholecalciferol) and calcium. The main sources of these nutrients are animal products; however, they can be found in many food sources suitable for vegetarians, including fortified soy milk and whole grain cereals. Vegetarians have higher antioxidant status for vitamin C (ascorbic acid), vitamin E (tocopherol), and beta-carotene than omnivores, which might help reduce exercise-induced oxidative stress. Research is needed comparing antioxidant defences in vegetarian and non-vegetarian athletes.

Objective: To determine the acute and chronic effects of low doses of long chain (LC) n-3 polyunsaturated fatty acids (PUFA) on plasma LC n-3 PUFA levels.Design: In the acute study, six healthy omnivores, avoiding fish meals on the day prior to the study, provided a fasting blood sample initially and post prandially at four hours. In the chronic study, 12 healthy subjects provided a fasting blood sample at baseline and three weeks after daily consumption of the test food.Main outcome measures: Plasma non-esterified fatty acid and phospholipid LC n-3 PUFA composition.Statistical analysis: Differences in plasma non-esterified fatty acids and phospholipid LC n-3 PUFA. A pre- and post-consumption of the test food were assessed using paired t-tests (spss).Results: The acute study demonstrated that a low dose of LC n-3 PUFA (25% eicosapentaenoic acid and 75% docosahexaenoic acid) significantly increased eicosapentaenoic acid levels in plasma of human subjects postprandially from 0.30% to 0.42% of total non-esterified fatty acids, a per cent change of 39% (P

The National Kidney Foundation developed and oversees the Kidney Disease Outcomes Quality Initiative, a process that develops clinical practice guidelines in nephrology. Recent guidelines address the aberrations in bone metabolism and disease that occur as a complication of chronic kidney disease. These guidelines provide, for the first time, a standard approach to the detection and management of alterations in calcium, phosphorus, and parathyroid hormone metabolism. The problems and sequelae of soft-tissue calcification are discussed, and recommendations are provided for reducing the associated morbidity and mortality.

Every year, more young people start the slow progressive injury that eventually becomes cardiovascular disease and death. It could be prevented with nutrition education, but medical efforts focus more on treatments for older people than on preventing primary causes of disease in young people. Two avoidable risks are prevented by simple dietary interventions: (1) Eat more omega-3 and less omega-6 fats, so tissues have less intense n-6 eicosanoid action, and (2) eat less food per meal to lower vascular postprandial oxidant stress. An empirical diet-tissue relationship was developed and put into an interactive personalized software program to aid informed food choices.

The intriguing concept of exercise training as therapy for mitochondrial disease is currently unsettled: in the unique setting of mitochondrial heteroplasmy, what are the effects of chronic exercise on skeletal muscle containing a mixture of mutated and wild-type mitochondrial DNA (mtDNA)? Furthermore, what are the consequences of habitual physical inactivity on mitochondrial heteroplasmy? In patients with mtDNA defects, deleterious effects of limited physical activity likely magnify the mitochondrial oxidative impairment contributing to varying degrees of exercise intolerance. Normal adaptive responses to endurance training offer the potential to increase levels of functional mitochondria, improving exercise tolerance. The few clinical studies assessing such training effects in patients with mtDNA defects have unequivocally demonstrated physiologic and biochemical adaptations that improve exercise tolerance and quality of life. Uncertain, however, is the training effect on mitochondrial heteroplasmy. To determine therapeutic advisability of endurance training, it remains imperative to establish whether: reported increases in mutant mtDNA levels can be offset by increases in absolute wild-type mtDNA levels: and chronic physical inactivity leads to a selective down-regulation of wild-type mtDNA. Resistance exercise training offers an alternate, innovative therapeutic approach in patients with sporadic mtDNA mutations; exercise-induced transfer of normal mtDNA templates from muscle satellite cells to mature myofibers, thereby lowering mutation load (increasing functional mitochondrial load). Efficacy and safety of this approach needs to be replicated in a larger group of patients. Currently, appropriate recommendation (either in support or against) exercise training in mitochondrial disease is lacking, which is frustrating for physicians and disheartening for patients. Although considerable progress has been made, an immediate urgency exists to resolve the effects of chronic exercise on skeletal muscle in patients with heteroplasmic mtDNA mutations. Copyright © 2005 by the American College of Sports Medicine.

Rapid progress in gastroenterological research, during past century, was initiated by the discovery by W. Prout in early 18th century of the presence of inorganic, hydrochloric acid in the stomach and by I.P. Pavlov at the end of 19th century of neuro-reflex stimulation of secretion of this acid that was awarded by Nobel prize in 1904. Then, J. W. Black, who followed L. Popielski's concept of histamine involvement in the stimulation of this secretion, was awarded second Nobel prize in gastrology within the same century for the identification of histamine H2-receptor (H2-R) antagonists, potent gastric acid inhibitors, accelerating ulcer healing. The concept of H2-R interaction with other receptors such as muscarinic receptors (M3-R), mediating the action of acetylocholine released from local cholinergic nerves, and those mediating the action of gastrin (CCK2-R) on parietal cells, has been confirmed both in vivo studies and in vitro isolated parietal cells. The discovery of H2-R antagonists by Black and their usefulness in control of gastric secretion and ulcer healing, were considered as real breakthrough both in elucidation of gastric secretory mechanisms and in ulcer therapy. Discovery of even more powerful gastric acid inhibitors, proton pump inhibitors (PPI), also highly effective in acceleration of ulcer healing was, however, not awarded Nobel prize. Unexpectedly, two Australian clinical researchers, R.J. Warren and B.J. Marshall, who discovered in the stomach spiral bacteria, named Helicobacter pylori, received the third in past century Nobel prize in gastrology for the finding that this bacterium, is related to the pathogenesis of gastritis and peptic ulcer. They documented that eradication of H. pylori from the stomach, using antibiotics and potent gastric inhibitors, not only accelerates healing of ulcer but also prevents its recurrence, the finding considered as greatest discovery in practical gastrology during last century. Thus, the outstanding achievements in gastroenterology during last century have been awarded by three Nobel prizes and appreciated by millions of ulcer patients all over the world.

BACKGROUND/AIM: Evaluation of cardiovascular risk profile in 154 German vegans. METHODS: Cross-sectional study, Germany. Study instruments: 2 FFQ, 2 questionnaires, analyses of fasting venous blood samples. RESULTS: The total study population had a low BMI (mean: 22.3 kg/m(2)), a moderate blood pressure (mean: 120/75 mm Hg), an extremely low consumption of alcohol (mean: 0.77 g/day) and 96.8% were nonsmokers. Moderate physical activity (PAL) was reported by nearly 50%, whereas 22.7% declared to have a high PAL (>3 h/week). Median triacylglycerol (TG) was 0.81 mmol/l, total cholesterol (TC) was 4.33 mmol/l, HDL was 1.34 mmol/l. The mean TC/HDL-ratio was 3.3. Lipoprotein(a) (Lp(a)) was 8.13 mg/dl, concentrations of >30 mg/dl were prevalent in 25% of the participants. In general, status of folate and pyridoxine were sufficient, while 49.7% showed cobalamin concentrations

BACKGROUND/AIM: Evaluation of cardiovascular risk profile in 154 German vegans. METHODS: Cross-sectional study, Germany. Study instruments: 2 FFQ, 2 questionnaires, analyses of fasting venous blood samples. RESULTS: The total study population had a low BMI (mean: 22.3 kg/m(2)), a moderate blood pressure (mean: 120/75 mm Hg), an extremely low consumption of alcohol (mean: 0.77 g/day) and 96.8% were nonsmokers. Moderate physical activity (PAL) was reported by nearly 50%, whereas 22.7% declared to have a high PAL (>3 h/week). Median triacylglycerol (TG) was 0.81 mmol/l, total cholesterol (TC) was 4.33 mmol/l, HDL was 1.34 mmol/l. The mean TC/HDL-ratio was 3.3. Lipoprotein(a) (Lp(a)) was 8.13 mg/dl, concentrations of >30 mg/dl were prevalent in 25% of the participants. In general, status of folate and pyridoxine were sufficient, while 49.7% showed cobalamin concentrations

OBJECTIVE: To assess long-term cardiovascular effects of mixed amphetamine salts extended release (MAS XR) in adults with attention-deficit/hyperactivity disorder (ADHD) combined subtype. METHODS: 223 otherwise healthy adults (>or=18 years of age) with ADHD combined subtype were exposed to <or=24 months of MAS XR (20-60 mg/day). Resting sitting diastolic blood pressure (DBP) and systolic blood pressure (SBP) and pulse were measured at baseline and weekly, then monthly during long-term treatment. Twelve-lead electrocardiograms were obtained at screening/baseline, weekly, then at 3- and 6-month intervals up to 24 months. FINDINGS: With MAS XR 20-60 mg/day, mean changes in DBP (1.3+/-9.2 mm Hg; P=.042), SBP (2.3+/-12.5 mm Hg; P=.006), and pulse (2.1+/-13.4 bpm; P=.019) were small and not clinically significant. A clinically insignificant increase in QTcB (corrected by Bazett's formula) interval (7.2 msec; P480 msec (QTcF [corrected by Fridericia's formula] >454 msec). Seven subjects discontinued due to a cardiovascular adverse event (hypertension, n=5, palpitation/tachycardia, n=2); none of these events was reported as serious. Few subjects with normal baseline vital signs (using approved parameters at the time of study initiation) exhibited clinically significant abnormalities at end point; several subjects with borderline baseline values exhibited shifts to abnormal values during MAS XR therapy. CONCLUSION: Cardiovascular effects of long-term MAS XR (

OBJECTIVE: To test the hypotheses that among overweight and obese participants, a breakfast consisting of eggs, in comparison to an isocaloric equal-weight bagel-based breakfast, would induce greater satiety, reduce perceived cravings, and reduce subsequent short-term energy intake. SUBJECTS: Thirty women with BMI's of at least 25 kg/M2 between the ages of 25 to 60 y were recruited to participate in a randomized crossover design study in an outpatient clinic setting. DESIGN: Following an overnight fast, subjects consumed either an egg or bagel-based breakfast followed by lunch 3.5 h later, in random order two weeks apart. Food intake was weighed at breakfast and lunch and recorded via dietary recall up to 36 h post breakfast. Satiety was assessed using the Fullness Questionnaire and the State-Trait Food Cravings Questionnaire, state version. RESULTS: During the pre-lunch period, participants had greater feelings of satiety after the egg breakfast, and consumed significantly less energy (kJ; 2405.6 +/- 550.0 vs 3091.3 +/- 445.5, Egg vs Bagel breakfasts, p < 0.0001), grams of protein (16.8 +/- 4.2 vs 22.3 +/- 3.4, Egg vs Bagel breakfasts, p < 0.0001), carbohydrate 83.1 +/- 20.2 vs 110.9 +/- 18.7, Egg vs Bagel breakfasts, p < 0.0001), and fat 19.4 +/- 5.1 vs 22.8 +/- 3.2, Egg vs Bagel breakfasts, p < 0.0001) for lunch. Energy intake following the egg breakfast remained lower for the entire day (p < 0.05) as well as for the next 36 hours (p

Testotoxicosis is a form of gonadotropin-independent (peripheral) precocious puberty in which boys experience early onset and progression of puberty. Patients have accelerated growth, early development of secondary sexual characteristics and usually reduced adult height. Testotoxicosis is caused by an activating mutation of the luteinizing hormone (LH) receptor, leading to increased levels of sex steroids in the context of low LH. Therapy has, therefore, traditionally targeted steroidogenesis. However, the drugs used have been associated with side effects. More recently, a combination of an oral anti-androgen (spironolactone) and an aromatase inhibitor (testolactone) decreased height velocity and improved predicted height. A phase II study in testotoxicosis is currently underway,exploring the combination of a highly selective anti-androgen, bicalutamide, and the potent aromatase inhibitor, anastrozole. These agents are well tolerated in the populations in which they have been studied and effectively inhibit testosterone activity and estrogen production, in adult patients.

Vitamin B12 deficiency can cause serious developmental regression, hypotonia and cerebral atrophy in infants. We report a 6-month-old infant, with insidious developmental regression and brain atrophy showed by CT scan, secondarily to vitamin B12 deficiency. His mother was a strict vegetarian and the patient was exclusively breastfed. The clinical symptoms and the brain CT were normalized after vitamin B12 administration.

In several recent studies, athletes experienced substantial gains in sprint and endurance performance when explosive training or high-intensity interval training was added in the noncompetitive phase of a season. Here we report the effect of combining these 2 types of training on performance in the competitive phase. We randomized 18 road cyclists to an experimental (n = 9) or control (n = 9) group for 4-5 weeks of training. The experimental group replaced part of their usual training with twelve 30-minute sessions consisting of 3 sets of explosive single-leg jumps (20 for each leg) alternating with 3 sets of high-resistance cycling sprints (5 x 30 seconds at 60-70 min(-1) with 30-second recoveries between repetitions). Performance measures, obtained over 2-3 days on a cycle ergometer before and after the intervention, were mean power in a 1- and 4-km time trial, peak power in an incremental test, and lactate-profile power and oxygen cost determined from 2 fixed submaximal workloads. The control group showed little mean change in performance. Power output sampled in the training sprints of the experimental group indicated a plateau in the training effect after 8-12 sessions. Relative to the control group, the mean changes (+/-90% confidence limits) in the experimental group were: 1-km power, 8.7% (+/-2.5%); 4-km power, 8.1% (+/-4.1%); peak power, 6.8% (+/-3.6); lactate-profile power, 3.7% (+/-4.8%); and oxygen cost, -3.0% (+/-2.6%). Individual responses to the training were apparent only for 4-km and lactate-profile power (standard deviations of 2.5% and 2.8%, respectively). The addition of explosive training and high-resistance interval training to the programs of already well-trained cyclists produces major gains in sprint and endurance performance, partly through improvements in exercise efficiency and anaerobic threshold.

The human c-myc proto-oncogene, implicated in the control of many cellular processes including cell growth and apoptosis, encodes three isoforms which differ in their N-terminal region. The functions of these isoforms have never been addressed in vivo. Here, we used Drosophila melanogaster to examine their functions in a fully integrated system. First, we established that the human c-Myc protein can rescue lethal mutations of the Drosophila myc ortholog, dmyc, demonstrating the biological relevance of this model. Then, we characterized a new lethal dmyc insertion allele, which permits expression of human c-Myc in place of dMyc and used it to compare physiological activities of these isoforms in whole-organism rescue, transcription, cell growth, and apoptosis. These isoforms differ both quantitatively and qualitatively. Most remarkably, while the small c-MycS form truncated for much of its N-terminal trans-activation domain efficiently rescued viability and cell growth, it did not induce detectable programmed cell death. Our data indicate that the main functional difference between c-Myc isoforms resides in their apoptotic properties and that the N-terminal region, containing the conserved MbI motif, is decisive in governing the choice between growth and death.

Variations in the size and density distributions of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles have been related to risk for cardiovascular disease. In particular, increased levels of small, dense LDL particles, together with reduced levels of large HDL and increases in small HDL, are integral features of the atherogenic dyslipidemia found in patients with insulin resistance, obesity, and metabolic syndrome. Increased dietary carbohydrates, particularly simple sugars and starches with high glycemic index, can increase levels of small, dense LDL and HDL, primarily by mechanisms that involve increasing plasma triglyceride concentrations. Low-carbohydrate diets may have the opposite effects. Diets with differing fatty acid composition can also influence LDL and HDL particle distributions.

Variations in the size and density distributions of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles have been related to risk for cardiovascular disease. In particular, increased levels of small, dense LDL particles, together with reduced levels of large HDL and increases in small HDL, are integral features of the atherogenic dyslipidemia found in patients with insulin resistance, obesity, and metabolic syndrome. Increased dietary carbohydrates, particularly simple sugars and starches with high glycemic index, can increase levels of small, dense LDL and HDL, primarily by mechanisms that involve increasing plasma triglyceride concentrations. Low-carbohydrate diets may have the opposite effects. Diets with differing fatty acid composition can also influence LDL and HDL particle distributions.

UDP-glucuronosyltransferases (UGTs) catalyze the glucuronidation of many different chemicals. Glucuronidation is especially important for detoxifying reactive intermediates from metabolic reactions, which otherwise can be biotransformed into highly reactive cytotoxic or carcinogenic species. Detoxification of certain food-borne-carcinogenic heterocyclic amines (HAs) is highly dependent on UGT1A-mediated glucuronidation. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most mass abundant carcinogenic HA found in well-done cooked meat, is extensively glucuronidated by UGT1A proteins. In humans, CYP1A2 catalyzed N-hydroxylation and subsequent UGT1A-mediated glucuronidation is a dominant pathway in the metabolism of PhIP. Therefore, changes in glucuronidation rates could significantly alter PhIP metabolism. To determine the importance of UGT1A-mediated glucuronidation in the biotransformation of PhIP, hepatic UGT1A deficient Gunn and UGT1A proficient Wistar rats were exposed to a 100 microg/kg oral dose of [(14)C]PhIP. Urine was collected over 24 h and the PhIP urinary metabolite profiles were compared between the two strains. After the 24 h exposure, livers and colons were removed and analyzed for DNA adduct formation by accelerator mass spectrometry. Wistar rats produced several PhIP and N-hydroxy-PhIP glucuronides that accounted for approximately 25% of the total amount of recovered urinary metabolites. In the Gunn rats, PhIP and N-hydroxy-PhIP glucuronides were reduced by 68-92%, compared with the Wistar rats. PhIP-DNA adduct analysis from the Gunn rats revealed a correlation between reduced urinary PhIP and N-hydroxy-PhIP glucuronide levels and increased hepatic DNA adducts, compared with the Wistar rats. In the colon, DNA adduct levels were lower in the Gunn rats compared with the Wistar rats, suggesting deficient hepatic UGT1A activity provides protection against DNA adduct formation in peripheral tissue. Due to differences in PhIP metabolism between humans and rodents, extrapolation of these results to the human situation must be done with caution. These results indicate that UGT1A-mediated glucuronidation of PhIP and N-hydroxy-PhIP is an important pathway for PhIP detoxification, and demonstrate the importance of tissue-specific metabolism. Tissues with reduced UGT1A activity can have a higher rate of PhIP activation and be more inclined to form DNA adducts compared with tissues with normal UGT1A activity.

Advanced glycation end products (AGEs), S100/calgranulins, HMGB1-proteins, amyloid-beta peptides, and the family of beta-sheet fibrils have been shown to contribute to a number of chronic diseases such as diabetes, amyloidoses, inflammatory conditions, and tumors by promoting cellular dysfunction via binding to cellular surface receptors. The receptor for AGEs (RAGE) is a multiligand receptor of the immunoglobulin superfamily of cell surface molecules acting as counter-receptor for these diverse molecules. Engagement of RAGE converts a brief pulse of cellular activation to sustained cellular dysfunction and tissue destruction. The involvement of RAGE in pathophysiologic processes has been demonstrated in murine models of chronic disease using either a receptor decoy such as soluble RAGE (sRAGE), RAGE neutralizing antibodies, or a dominant-negative form of the receptor. Studies with RAGE-/- mice confirmed that RAGE contributes, at least in part, to the development of late diabetic complications, such as neuropathy and nephropathy, macrovascular disease, and chronic inflammation. Furthermore, deletion of RAGE provided protection from the lethal effects of septic shock caused by cecal ligation and puncture (CLP). In contrast, deletion of RAGE had no effect on the host response in delayed-type hypersensitivity (DTH). Despite the lack of effect seen in adaptive immunity by the deletion of RAGE, administration of the receptor decoy, sRAGE, still afforded a protective effect in RAGE-/- mice. Thus, sRAGE is likely to sequester ligands, thereby preventing their interaction with other receptors in addition to RAGE. These data suggest that, just as RAGE is a multiligand receptor, its ligands are also likely to recognize several receptors in mediating their biologic effects.

Ochratoxin A (OTA) is a secondary fungal metabolite produced by several moulds, mainly by Aspergillus ochraceus and by Penicillium verrucosum, that occurs in meat products. The aim of this work was to optimize an efficient extraction procedure for the determination of OTA in muscle tissue in order to assess its occurrence in meat samples. Three different apparatus, a Waring blender, a switching apparatus, and an ultrasonic processor, were evaluated to verify the efficiency of extraction. The analytical methods proposed involve the extraction with chloroform-orthophosphoric acid, cleanup through an immunoaffinity column, high-performance liquid chromatography/fluorescence detection for separation and identification of OTA, and confirmation with liquid chromatography/FD after methylation of OTA in muscle tissue. The limit of quantification of the proposed method was 0.04 microg kg(-1). Recoveries of OTA, using switching apparatus, ranged from 90.3 to 103.2% for chicken muscle spiked at 2.4 and 0.48 microg kg(-1), respectively, with a within-day relative standard deviation of 17 and 15.3%. The proposed method was applied to 38 chicken, swine, and turkey muscle samples and the presence of OTA was confirmed in five samples. Finally, the estimated daily intake of OTA in this study was between 23 pg kg(-1) body weight per day for swine samples and 18 pg kg(-1) body weight per day for turkey samples.

The principal biological role of alpha-linolenic acid (alphaLNA; 18:3n-3) appears to be as a precursor for the synthesis of longer chain n-3 polyunsaturated fatty acids (PUFA). Increasing alphaLNA intake for a period of weeks to months results in an increase in the proportion of eicosapentaenoic acid (EPA; 20:5n-3) in plasma lipids, in erythrocytes, leukocytes, platelets and in breast milk but there is no increase in docosahexaenoic acid (DHA; 22:6n-3), which may even decline in some pools at high alphaLNA intakes. Stable isotope tracer studies indicate that conversion of alphaLNA to EPA occurs but is limited in men and that further transformation to DHA is very low. The fractional conversion of alphaLNA to the longer chain n-3 PUFA is greater in women which may be due to a regulatory effect of oestrogen. A lower proportion of alphaLNA is used for beta-oxidation in women compared with men. Overall, alphaLNA appears to be a limited source of longer chain n-3 PUFA in humans. Thus, adequate intakes of preformed long chain n-3 PUFA, in particular DHA, may be important for maintaining optimal tissue function. Capacity to up-regulate alphaLNA conversion in women may be important for meeting the demands of the fetus and neonate for DHA.

OBJECTIVES: The objectives of the present study were to examine sociodemographic correlates of soy food consumption among women at increased risk of breast cancer, describe factors influencing soy food consumption or nonconsumption, and identify women's sources of information about soy foods. DESIGN: A cross-sectional, self-report survey was used to assess frequency of and factors influencing soy food consumption. Soy food intake was reported for the past year. SUBJECTS/SETTING: Participants were 452 women with family histories of breast cancer who were enrolled in a cancer risk assessment program. STATISTICAL ANALYSES PERFORMED: Comparisons between consumers and nonconsumers of soy foods were performed using multivariate logistic regression and chi(2) analyses. RESULTS: Thirty-two percent reported soy food consumption. Commonly consumed soy foods were vegetable burgers, tofu, and soymilk. Consumers of soy foods were more likely to have higher levels of education and report eating five or more daily servings of fruits and vegetables. The primary reason for consumption of soy foods was eating a healthful diet, whereas insufficient knowledge about soy food preparation was the primary reason stated for nonconsumption. Both consumers and nonconsumers reported obtaining information about soy foods from magazines, friends, and newspapers. Consumers also indicated using the Internet to seek information. CONCLUSIONS: These findings contribute to our understanding of the level of soy intake among women at increased risk for breast cancer and highlight potential factors that may influence women's decisions regarding soy food consumption. Women, particularly in this vulnerable population, would benefit from clear messages regarding the health effects of soy.

The suitability of a reverse transcriptase (RT) PCR assay was evaluated for the detection of bovine central nervous system (CNS) tissue specifically in liver sausages. Because of its emulsifying effect, CNS tissue was frequently added to this kind of meat product in the past. On standard samples, the RT-PCR technique reliably detected a concentration of 0.25% bovine CNS tissue in liver sausages stored for up to 28 days. Following the successful application of RT-PCR for the detection of bovine CNS tissue in these specially prepared samples, a field study was performed with a total of 258 liver sausages purchased in retail markets. All sausages were tested with both an RT-PCR assay and a commercial enzyme-linked immunosorbent assay (ELISA) kit. Nine (3.5%) of the retail liver sausage samples were positive for CNS tissue in the ELISA, but none were positive for this tissue in the RT-PCR assay. All positive ELISA results indicated the presence of 0.23 to 0.30% CNS tissue. Recent studies have indicated that the RT-PCR assay is not as sensitive for porcine CNS tissue as for bovine CNS tissue, which this assay can detect at 0.25%. Although the ELISA is not species specific, the CNS tissue detected by the ELISA is assumed to stem from a nonbovine species. The RT-PCR technique is a sensitive tool for the detection of bovine CNS tissues in a problematic matrix such as liver sausage. ELISA screening followed by a species-specific RT-PCR assay for bovine CNS tissue is a practical approach for monitoring meat products for compliance with European food regulations.