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Title:
DAT1, DRD4, and DRD5 polymorphisms are not associated with ADHD in Dutch families
Authors:
Bakker, Steven C.; van der Meulen, Emma M.; Oteman, Nicole; Schelleman, Hedi; Pearson, Peter L.; Buitelaar, Jan K.; Sinke, Richard J.
Abstract:
Recent meta-analyses have indicated that the dopamine transporter gene (DAT1) and the dopamine receptor genes D4 (DRD4) and D5 (DRD5) are associated with attention-deficit hyperactivity disorder (ADHD), although single studies frequently failed to show significant association. In a family-based sample of 236 Dutch children with ADHD, we have investigated the previously described variable number of tandem repeat (VNTR) polymorphisms and two additional microsatellites at the DAT1 and DRD4 loci. DRD5 was investigated using the microsatellite that was previously found to be associated. Transmission disequilibrium tests (TDTs) did not show preferential transmission of alleles or two-marker haplotypes to affected offspring. These data suggest that DAT1, DRD4, and DRD5 do not contribute substantially to ADHD in the Dutch population.
Published:
January 4, 2005
Title:
Is a calorie really a calorie? Metabolic advantage of low-carbohydrate diets
Authors:
Manninen, Anssi H.
Abstract:
The first law of thermodynamics dictates that body mass remains constant when caloric intake equals caloric expenditure. It should be noted, however, that different diets lead to different biochemical pathways that are not equivalent when correctly compared through the laws of thermodynamics. It is inappropriate to assume that the only thing that counts in terms of food consumption and energy balance is the intake of dietary calories and weight storage. Well-controlled studies suggest that calorie content may not be as predictive of fat loss as is reduced carbohydrate consumption. Biologically speaking, a calorie is certainly not a calorie. The ideal weight loss diet, if it even exists, remains to be determined, but a high-carbohydrate/low-protein diet may be unsatisfactory for many obese individuals.
Published:
December 30, 2004
Title:
Metabolic Effects of the Very-Low-Carbohydrate Diets: Misunderstood "Villains" of Human Metabolism
Authors:
Manninen, Anssi H
Abstract:
During very low carbohydrate intake, the regulated and controlled production of ketone bodies causes a harmless physiological state known as dietary ketosis. Ketone bodies flow from the liver to extra-hepatic tissues (e.g., brain) for use as a fuel; this spares glucose metabolism via a mechanism similar to the sparing of glucose by oxidation of fatty acids as an alternative fuel. In comparison with glucose, the ketone bodies are actually a very good respiratory fuel. Indeed, there is no clear requirement for dietary carbohydrates for human adults. Interestingly, the effects of ketone body metabolism suggest that mild ketosis may offer therapeutic potential in a variety of different common and rare disease states. Also, the recent landmark study showed that a very-low-carbohydrate diet resulted in a significant reduction in fat mass and a concomitant increase in lean body mass in normal-weight men. Contrary to popular belief, insulin is not needed for glucose uptake and utilization in man. Finally, both muscle fat and carbohydrate burn in an amino acid flame.
Published:
December 30, 2004
Title:
The antidepressant properties of the ketogenic diet
Authors:
Murphy, Patricia; Likhodii, Sergei; Nylen, Kirk; Burnham, W. M.
Abstract:
BACKGROUND: The ketogenic diet is used to treat epilepsy refractory to anticonvulsant medication. Individuals with epilepsy often have behavioral problems and deficits in attention and cognitive functioning. The ketogenic diet has been found to effect improvements in these domains. It has also been suggested that the ketogenic diet may act as a mood stabilizer. METHODS: The present research used the Porsolt test, an animal model of depression, to determine whether the ketogenic diet has antidepressant properties. Porsolt test scores of rats on the ketogenic diet were compared with those of rats on a control diet. RESULTS: The rats on the ketogenic diet spent less time immobile, suggesting that rats on the ketogenic diet, like rats treated with antidepressants, are less likely to exhibit "behavioral despair." CONCLUSIONS: It is concluded that the ketogenic diet may have antidepressant properties.
Published:
December 14, 2004
Title:
Thermodynamics of weight loss diets
Authors:
Fine, Eugene J.; Feinman, Richard D.
Abstract:
BACKGROUND: It is commonly held that "a calorie is a calorie", i.e. that diets of equal caloric content will result in identical weight change independent of macronutrient composition, and appeal is frequently made to the laws of thermodynamics. We have previously shown that thermodynamics does not support such a view and that diets of different macronutrient content may be expected to induce different changes in body mass. Low carbohydrate diets in particular have claimed a "metabolic advantage" meaning more weight loss than in isocaloric diets of higher carbohydrate content. In this review, for pedagogic clarity, we reframe the theoretical discussion to directly link thermodynamic inefficiency to weight change. The problem in outline: Is metabolic advantage theoretically possible? If so, what biochemical mechanisms might plausibly explain it? Finally, what experimental evidence exists to determine whether it does or does not occur? RESULTS: Reduced thermodynamic efficiency will result in increased weight loss. The laws of thermodynamics are silent on the existence of variable thermodynamic efficiency in metabolic processes. Therefore such variability is permitted and can be related to differences in weight lost. The existence of variable efficiency and metabolic advantage is therefore an empiric question rather than a theoretical one, confirmed by many experimental isocaloric studies, pending a properly performed meta-analysis. Mechanisms are as yet unknown, but plausible mechanisms at the metabolic level are proposed. CONCLUSIONS: Variable thermodynamic efficiency due to dietary manipulation is permitted by physical laws, is supported by much experimental data, and may be reasonably explained by plausible mechanisms.
Published:
December 7, 2004
Title:
Cultural issues in disease management for chinese americans with type 2 diabetes
Authors:
Chun, Kevin M.; Chesla †, Catherine A.
Abstract:
The purpose of this study is to highlight culturally unique experiences and responses to type 2 diabetes among Chinese immigrant families. Patient and spouse narratives from 16 different families were elicited in a series of group interviews on this topic. Using interpretive phenomenology, 5 primary cultural considerations in diabetes management emerged from the narratives: (1) conceptualization of diabetes, illness and health, (2) significance and meaning of food, (3) perceptions of Chinese and Western medicines, (4) exercise and physical activity, and (5) effects of the disease on family dynamics. The relation of these cultural considerations to an interdependent view of the self, collectivistic social orientation, Chinese cultural beliefs and norms, and acculturation processes are discussed. Clinical recommendations for culturally appropriate disease management strategies are outlined.
Published:
November 30, 2004
Title:
Importance of advanced glycation end products in diabetes-associated cardiovascular and renal disease
Authors:
Cooper, Mark E.
Abstract:
Abstract. Although the features of diabetic cardiomyopathy, atherosclerosis, and nephropathy have been clinically characterized, the pathogenesis and the mecha
Published:
November 30, 2004
Title:
Flavonoid metabolites in human plasma and urine after the consumption of red onions: analysis by liquid chromatography with photodiode array and full scan tandem mass spectrometric detection
Authors:
Mullen, William; Boitier, Aurelie; Stewart, Amanda J.; Crozier, Alan
Abstract:
Blood was collected from six human volunteers 1 h after the ingestion of lightly fried red onions, which are rich in anthocyanins and flavonols. Urine excreted 0-4 h after ingestion was also collected. Plasma and urine were analysed by reversed-phase HPLC with photodiode array and tandem mass spectrometric detection. Twenty-three flavonols as a range of mixed sulphate, methyl, glucuronide and glucoside derivatives of quercetin were detected. The availability of reference compounds facilitated the identification of quercetin-3-glucuronide. quercetin-3'-glucuronide, quercetin-4'-glucuronide, quercetin-3'-sulphate and isorhamnetin-3-glucuronide in samples from all volunteers. Samples from one volunteer also contained trace amounts of quercetin-3,4'-diglucoside, quercetin-3-glucoside, isorhamnetin-3-glucoside and the aglycone quercetin. Despite a high dosage, neither anthocyanins nor anthocyanin metabolites accumulated in either plasma or urine in detectable quantities.
Published:
November 25, 2004
Title:
Comparative Physiology of the Vertebrate Digestive System
Authors:
Stevens, C. Edward; Hume, Ian D.
Abstract:
This book is useful for anyone interested in the basic structural and functional characteristics of the digestive system and how these vary among vertebrate groups and species. It discusses all of the major aspects of nutrition, anatomy and physiology in all of the major groups of vertebrates. It contains numerous figures and tables to aid in their comparison, including many illustrations of gastrointestinal tracts of vertebrates prepared so as to allow for direct comparison. The terminology of scientific specialties and sub-specialties is defined and animals are referred to by both their common and scientific names. Relationships between digestive strategies and the diet and environment are discussed throughout the text, and brought together in a chapter on the evolution of the digestive system. The final chapter offers a brief summary of the major concepts and suggests future directions for research.
Published:
November 24, 2004
Title:
Metabonomics, dietary influences and cultural differences: a 1H NMR-based study of urine samples obtained from healthy British and Swedish subjects
Authors:
Lenz, E. M.; Bright, J.; Wilson, I. D.; Hughes, A.; Morrisson, J.; Lindberg, H.; Lockton, A.
Abstract:
The aim of this study was to assess the feasibility and comparability of metabonomic data in clinical studies conducted in different countries without dietary restriction. A (1)H NMR-based metabonomic analysis was performed on urine samples obtained from two separate studies, both including male and female subjects. The first was on a group of healthy British subjects (n = 120), whilst the second was on healthy subjects from two European countries (Britain and Sweden, n = 30). The subjects were asked to provide single, early morning urine samples collected on a single occasion. The (1)H NMR spectra obtained for urine samples were visually inspected and analysed chemometrically using principal components analysis (PCA). These inspections highlighted outliers within the urine samples and displayed interesting differences, revealing characteristic dietary and cultural features between the subjects of both countries, such as high trimethylamine-N-oxide (TMAO)-excretion in the Swedish population and high taurine-excretion, due to the Atkins diet. This study suggests that the endogenous urinary profile is subject to distinct cultural and severe dietary influences and that great care needs to be taken in the interpretation of 'biomarkers of disease and response to drug therapy' for diagnostic purposes.
Published:
November 18, 2004
Title:
Endurance running and the evolution of Homo
Authors:
Bramble, Dennis M.; Lieberman, Daniel E.
Abstract:
Striding bipedalism is a key derived behaviour of hominids that possibly originated soon after the divergence of the chimpanzee and human lineages. Although bipedal gaits include walking and running, running is generally considered to have played no major role in human evolution because humans, like apes, are poor sprinters compared to most quadrupeds. Here we assess how well humans perform at sustained long-distance running, and review the physiological and anatomical bases of endurance running capabilities in humans and other mammals. Judged by several criteria, humans perform remarkably well at endurance running, thanks to a diverse array of features, many of which leave traces in the skeleton. The fossil evidence of these features suggests that endurance running is a derived capability of the genus Homo, originating about 2 million years ago, and may have been instrumental in the evolution of the human body form.
Published:
November 17, 2004
Title:
Comparison of energy-restricted very low-carbohydrate and low-fat diets on weight loss and body composition in overweight men and women
Authors:
Volek, JS; Sharman, MJ; Gómez, AL; Judelson, DA; Rubin, MR; Watson, G; Sokmen, B; Silvestre, R; French, DN; Kraemer, WJ
Abstract:
Objective To compare the effects of isocaloric, energy-restricted very low-carbohydrate ketogenic (VLCK) and low-fat (LF) diets on weight loss, body composition, trunk fat mass, and resting energy expenditure (REE) in overweight/obese men and women. Design Randomized, balanced, two diet period clinical intervention study. Subjects were prescribed two energy-restricted (-500 kcal/day) diets: a VLCK diet with a goal to decrease carbohydrate levels below 10% of energy and induce ketosis and a LF diet with a goal similar to national recommendations (%carbohydrate:fat:protein = ~60:25:15%). Subjects 15 healthy, overweight/obese men (mean ± s.e.m.: age 33.2 ± 2.9 y, body mass 109.1 ± 4.6 kg, body mass index 34.1 ± 1.1 kg/m2) and 13 premenopausal women (age 34.0 ± 2.4 y, body mass 76.3 ± 3.6 kg, body mass index 29.6 ± 1.1 kg/m2). Measurements Weight loss, body composition, trunk fat (by dual-energy X-ray absorptiometry), and resting energy expenditure (REE) were determined at baseline and after each diet intervention. Data were analyzed for between group differences considering the first diet phase only and within group differences considering the response to both diets within each person. Results Actual nutrient intakes from food records during the VLCK (%carbohydrate:fat:protein = ~9:63:28%) and the LF (~58:22:20%) were significantly different. Dietary energy was restricted, but was slightly higher during the VLCK (1855 kcal/day) compared to the LF (1562 kcal/day) diet for men. Both between and within group comparisons revealed a distinct advantage of a VLCK over a LF diet for weight loss, total fat loss, and trunk fat loss for men (despite significantly greater energy intake). The majority of women also responded more favorably to the VLCK diet, especially in terms of trunk fat loss. The greater reduction in trunk fat was not merely due to the greater total fat loss, because the ratio of trunk fat/total fat was also significantly reduced during the VLCK diet in men and women. Absolute REE (kcal/day) was decreased with both diets as expected, but REE expressed relative to body mass (kcal/kg), was better maintained on the VLCK diet for men only. Individual responses clearly show the majority of men and women experience greater weight and fat loss on a VLCK than a LF diet. Conclusion This study shows a clear benefit of a VLCK over LF diet for short-term body weight and fat loss, especially in men. A preferential loss of fat in the trunk region with a VLCK diet is novel and potentially clinically significant but requires further validation. These data provide additional support for the concept of metabolic advantage with diets representing extremes in macronutrient distribution.
Published:
November 7, 2004
Title:
Dietary fats, carbohydrate, and progression of coronary atherosclerosis in postmenopausal women
Authors:
Mozaffarian, Dariush; Rimm, Eric B.; Herrington, David M.
Abstract:
ABSTRACT. Background: The influence of diet on atherosclerotic progression is not well established, particularly in postmenopausal women, in whom risk factors
Published:
October 31, 2004
Title:
Dietary fats, carbohydrate, and progression of coronary atherosclerosis in postmenopausal women
Authors:
Mozaffarian, Dariush; Rimm, Eric B.; Herrington, David M.
Abstract:
ABSTRACT. Background: The influence of diet on atherosclerotic progression is not well established, particularly in postmenopausal women, in whom risk factors
Published:
October 31, 2004
Title:
Saturated fat prevents coronary artery disease? An American paradox
Authors:
Knopp, Robert H.; Retzlaff, Barbara M.
Abstract:
It is an article of faith that saturated fat raises LDL cholesterol and accelerates coronary artery disease, whereas unsaturated fatty acids have the opposite e
Published:
October 31, 2004
Title:
The National Cholesterol Education Program Diet vs a Diet Lower in Carbohydrates and Higher in Protein and Monounsaturated Fat: A Randomized Trial
Authors:
Aude, Y. Wady; Agatston, Arthur S.; Lopez-Jimenez, Francisco; Lieberman, Eric H.; Almon, Marie; Hansen, Melinda; Rojas, Gerardo; Lamas, Gervasio A.; Hennekens, Charles H.
Abstract:
Background
In the United States, obesity is a major clinical and public health problem causing diabetes, dyslipidemia, and hypertension, as well as increasing cardiovascular and total mortality. Dietary restrictions of calories and saturated fat are beneficial. However, it remains unclear whether replacement of saturated fat with carbohydrates (as in the US National Cholesterol Education Program [NCEP] diet) or protein and monounsaturated fat (as in our isocaloric modified low-carbohydrate [MLC] diet, which is lower in total carbohydrates but higher in protein, monounsaturated fat, and complex carbohydrates) is optimal.
Methods
We randomized 60 participants (29 women and 31 men) to the NCEP or the MLC diet and evaluated them every 2 weeks for 12 weeks. They were aged 28 to 71 years (mean age, 44 years in the NCEP and 46 years in the MLC group). A total of 36% of participants from the NCEP group and 35% from the MLC group had a body mass index (calculated as weight in kilograms divided by the square of height in meters) greater than 27. The primary end point was weight loss, and secondary end points were blood lipid levels and waist-to-hip ratio.
Results
Weight loss was significantly greater in the MLC (13.6 lb) than in the NCEP group (7.5 lb), a difference of 6.1 lb (P = .02). There were no significant differences between the groups for total, low density, and high-density lipoprotein cholesterol, triglycerides, or the proportion of small, dense low-density lipoprotein particles. There were significantly favorable changes in all lipid levels within the MLC but not within the NCEP group. Waist-to-hip ratio was not significantly reduced between the groups (P = .27), but it significantly decreased within the MLC group (P = .009).
Conclusions
Compared with the NCEP diet, the MLC diet, which is lower in total carbohydrates but higher in complex carbohydrates, protein, and monounsaturated fat, caused significantly greater weight loss over 12 weeks. There were no significant differences between the groups in blood lipid levels, but favorable changes were observed within the MLC diet group.
Published:
October 24, 2004
Title:
Perceived personal, social and environmental barriers to weight maintenance among young women: A community survey
Authors:
Andajani-Sutjahjo, Sari; Ball, Kylie; Warren, Narelle; Inglis, Victoria; Crawford, David
Abstract:
Background Young women are a group at high risk of weight gain. This study examined a range of perceived personal, social and environmental barriers to physical activity and healthy eating for weight maintenance among young women, and how these varied by socioeconomic status (SES), overweight status and domestic situation. Methods In October-December 2001, a total of 445 women aged 18–32 years, selected randomly from the Australian electoral roll, completed a mailed self-report survey that included questions on 11 barriers to physical activity and 11 barriers to healthy eating (relating to personal, social and environmental factors). Height, weight and socio-demographic details were also obtained. Statistical analyses were conducted mid-2003. Results The most common perceived barriers to physical activity and healthy eating encountered by young women were related to motivation, time and cost. Women with children were particularly likely to report a lack of social support as an important barrier to physical activity, and lack of social support and time as important barriers to healthy eating. Perceived barriers did not differ by SES or overweight status. Conclusions Health promotion strategies aimed at preventing weight gain should take into account the specific perceived barriers to physical activity and healthy eating faced by women in this age group, particularly lack of motivation, lack of time, and cost. Strategies targeting perceived lack of time and lack of social support are particularly required for young women with children.
Published:
October 4, 2004
Title:
Diet and relapsing ulcerative colitis: take off the meat?
Authors:
Tilg, H.; Kaser, A.
Abstract:
Dietary factors such as red meat, high protein intake, and alcohol are associated with relapse in ulcerative colitis, probably mediated via hydrogen sulphide production. Major advances in the understanding of the aetiopathogenesis and genetics of inflammatory bowel disease (IBD) have been accompanied by an increase in the therapeutic armamentarium, including immunosuppressants and anticytokine drugs. Whereas patients are in many cases highly motivated to use prescribed drugs in those chronic disorders, they would be even more willing to change lifestyle and dietary habits so they could actively influence the course of their disease. Therefore, one of the most common questions physicians treating patients with IBD are asked is whether changing diet could positively affect the course of their disease. So far, and this has been especially true for patients with ulcerative colitis (UC), our answer had been “we do not know and there are no special recommendations”. This may now change as Jowett and colleagues1 in this issue of Gut present interesting and clinically novel data studying the role of dietary factors on the clinical course of UC (see page 1479) . In this prospective cohort study, they investigated the effects of habitual diet on relapses of disease. Impressively, 96% of patients (n = 191) completed the study. Dietary factors such as red and processed meat, protein, and alcohol, as well as sulphur and sulphate intake were positively associated with relapses. Even though dietary factors in this study were less important than measures of prior disease activity in determining the risk of relapse,2 clinically this information is extremely valuable as it may open the perspective of lifestyle modification in the treatment of UC. As discussed in detail by the authors, these effects may be related to sulphur and sulphate contents of food. Most importantly, to continue to prove this important …
Published:
September 30, 2004
Title:
Prevalence of diabetes mellitus and related conditions in Asian Indians living in the United States
Authors:
Venkataraman, Rajesh; Nanda, Navin C.; Baweja, Gurpreet; Parikh, Naresh; Bhatia, Vishal
Abstract:
This study is the first attempt to evaluate the prevalence of diabetes mellitus and related conditions in Asian Indians living in the United States. A community-based survey of 1,046 Asian Indian immigrants living in and around the Atlanta metro area of Georgia was conducted and found an overall prevalence of diabetes mellitus of 18.3% (22.5% in men and 13.6% in women). This prevalence of diabetes mellitus in Asian Indians is much higher than in whites, blacks, and Hispanics living in the United States.
Published:
September 30, 2004
Title:
Yonnondio
Authors:
Olsen, Tillie
Abstract:
Published:
September 30, 2004
Title:
Effects of dietary glycaemic index on adiposity, glucose homoeostasis, and plasma lipids in animals
Authors:
Pawlak, Dorota B.; Kushner, Jake A.; Ludwig, David S.
Abstract:
BACKGROUND: Clinical studies suggest a role for dietary glycaemic index (GI) in bodyweight regulation and diabetes risk. However, partly because manipulation of GI can produce changes in potentially confounding dietary factors such as fibre content, palatability, and energy density, its relevance to human health remains controversial. This study examined the independent effects of GI in animals. METHODS: Partially pancreatectomised male Sprague-Dawley rats were given diets with identical nutrients, except for the type of starch: high-GI (n=11) or low-GI (n=10). The animals were fed in a controlled way to maintain the same mean bodyweight in the two groups for 18 weeks. Further experiments examined the effects of GI in rats in a cross-over design and C57BL/6J mice in a parallel design. FINDINGS: Despite having similar mean bodyweight (547.9 [SE 13.4] vs 549.2 [15.2] g), rats given high-GI food had more body fat (97.8 [13.6] vs 57.3 [7.2] g; p=0.0152) and less lean body mass (450.1 [9.6] vs 491.9 [11.7] g; p=0.0120) than those given low-GI food. The high-GI group also had greater increases over time in the areas under the curve for blood glucose and plasma insulin after oral glucose, lower plasma adiponectin concentrations, higher plasma triglyceride concentrations, and severe disruption of islet-cell architecture. Mice on the high-GI diet had almost twice the body fat of those on the low-GI diet after 9 weeks. INTERPRETATION: These findings provide a mechanistic basis for interpretation of studies of GI in human beings. RELEVANCE TO PRACTICE: The term GI describes how a food, meal, or diet affects blood sugar during the postprandial period. GI as an independent factor can cause obesity and increase risks of diabetes and heart disease in animals. Use of low-GI diets in prevention and treatment of human disease merits thorough examination.
Published:
September 27, 2004
Title:
Redox modulation of chromatin remodeling: impact on histone acetylation and deacetylation, NF-κB and pro-inflammatory gene expression
Authors:
Rahman, Irfan; Marwick, John; Kirkham, Paul
Abstract:
Reactive oxygen species (ROS), either directly or via the formation of lipid peroxidation products, such as 4-hydroxy-2-nonenal, acrolein and F2-isoprostanes, may play a role in enhancing inflammation through the activation and phosphorylation of stress kinases (JNK, ERK, p38) and redox-sensitive transcription factors such as NF-κB and AP-1. This increases the expression of genes regulating a battery of distinct pro-inflammatory mediators. Acetylation by histone acetyltransferase (HAT) of specific lysine residues on the N-terminal tail of core histones, results in uncoiling of the DNA and increased accessibility to transcription factor binding. In contrast, histone deacetylation by histone deacetylase (HDAC) represses gene transcription by promoting DNA winding thereby limiting access to transcription factors. Oxidative stress activates NF-κB resulting in expression of pro-inflammatory mediators through the activation of intrinsic HAT activity on co-activator molecules. In addition, oxidative stress also inhibits HDAC activity and in doing so enhances inflammatory gene expression which leads to a chronic inflammatory response. Oxidative stress can also increase complex formation between the co-activator CBP/p300 and the p65 subunit of NF-κB suggesting a further role of oxidative stress in chromatin remodeling. The antioxidant and/or anti-inflammatory effects of thiol molecules (glutathione, N-acetyl-l-cysteine and N-acystelyn), dietary polyphenols (curcumin-diferuloylmethane and resveratrol), the bronchodilator theophylline and glucocorticoids have all been shown to play a role in either controlling NF-κB activation or chromatin remodeling through modulation of HDAC activity and subsequently inflammatory gene expression in lung epithelial cells. Thus, oxidative stress regulates both signal transduction and chromatin remodeling which in turn impacts on pro-inflammatory responses in the lungs.
Published:
September 14, 2004
Title:
Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents With Depression Study (TADS) randomized controlled trial
Authors:
March, John; Silva, Susan; Petrycki, Stephen; Curry, John; Wells, Karen; Fairbank, John; Burns, Barbara; Domino, Marisa; McNulty, Steven; Vitiello, Benedetto; Severe, Joanne; Treatment for Adolescents With Depression Study (TADS) Team
Abstract:
CONTEXT: Initial treatment of major depressive disorder in adolescents may include cognitive-behavioral therapy (CBT) or a selective serotonin reuptake inhibitor (SSRI). However, little is known about their relative or combined effectiveness. OBJECTIVE: To evaluate the effectiveness of 4 treatments among adolescents with major depressive disorder. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial of a volunteer sample of 439 patients between the ages of 12 to 17 years with a primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of major depressive disorder. The trial was conducted at 13 US academic and community clinics between spring 2000 and summer 2003. INTERVENTIONS: Twelve weeks of (1) fluoxetine alone (10 to 40 mg/d), (2) CBT alone, (3) CBT with fluoxetine (10 to 40 mg/d), or (4) placebo (equivalent to 10 to 40 mg/d). Placebo and fluoxetine alone were administered double-blind; CBT alone and CBT with fluoxetine were administered unblinded. MAIN OUTCOME MEASURES: Children's Depression Rating Scale-Revised total score and, for responder analysis, a (dichotomized) Clinical Global Impressions improvement score. RESULTS: Compared with placebo, the combination of fluoxetine with CBT was statistically significant (P =.001) on the Children's Depression Rating Scale-Revised. Compared with fluoxetine alone (P =.02) and CBT alone (P =.01), treatment of fluoxetine with CBT was superior. Fluoxetine alone is a superior treatment to CBT alone (P =.01). Rates of response for fluoxetine with CBT were 71.0% (95% confidence interval [CI], 62%-80%); fluoxetine alone, 60.6% (95% CI, 51%-70%); CBT alone, 43.2% (95% CI, 34%-52%); and placebo, 34.8% (95% CI, 26%-44%). On the Clinical Global Impressions improvement responder analysis, the 2 fluoxetine-containing conditions were statistically superior to CBT and to placebo. Clinically significant suicidal thinking, which was present in 29% of the sample at baseline, improved significantly in all 4 treatment groups. Fluoxetine with CBT showed the greatest reduction (P =.02). Seven (1.6%) of 439 patients attempted suicide; there were no completed suicides. CONCLUSION: The combination of fluoxetine with CBT offered the most favorable tradeoff between benefit and risk for adolescents with major depressive disorder.
Published:
August 17, 2004
Title:
Ketogenic diets and physical performance
Authors:
Phinney, Stephen D.
Abstract:
Impaired physical performance is a common but not obligate result of a low carbohydrate diet. Lessons from traditional Inuit culture indicate that time for adaptation, optimized sodium and potassium nutriture, and constraint of protein to 15–25 % of daily energy expenditure allow unimpaired endurance performance despite nutritional ketosis.
Published:
August 16, 2004
Title:
What is Nutrition & Metabolism?
Authors:
Feinman, Richard D.; Hussain, M. Mahmood
Abstract:
A new Open Access journal, Nutrition & Metabolism (N&M) will publish articles that integrate nutrition with biochemistry and molecular biology. The open access process is chosen to provide rapid and accessible dissemination of new results and perspectives in a field that is of great current interest. Manuscripts in all areas of nutritional biochemistry will be considered but three areas of particular interest are lipoprotein metabolism, amino acids as metabolic signals, and the effect of macronutrient composition of diet on health. The need for the journal is identified in the epidemic of obesity, diabetes, dyslipidemias and related diseases, and a sudden increase in popular diets, as well as renewed interest in intermediary metabolism.
Published:
August 16, 2004
Title:
"A calorie is a calorie" violates the second law of thermodynamics
Authors:
Feinman, Richard D.; Fine, Eugene J.
Abstract:
The principle of "a calorie is a calorie," that weight change in hypocaloric diets is independent of macronutrient composition, is widely held in the popular and technical literature, and is frequently justified by appeal to the laws of thermodynamics. We review here some aspects of thermodynamics that bear on weight loss and the effect of macronutrient composition. The focus is the so-called metabolic advantage in low-carbohydrate diets--greater weight loss compared to isocaloric diets of different composition. Two laws of thermodynamics are relevant to the systems considered in nutrition and, whereas the first law is a conservation (of energy) law, the second is a dissipation law: something (negative entropy) is lost and therefore balance is not to be expected in diet interventions. Here, we propose that a misunderstanding of the second law accounts for the controversy about the role of macronutrient effect on weight loss and we review some aspects of elementary thermodynamics. We use data in the literature to show that thermogenesis is sufficient to predict metabolic advantage. Whereas homeostasis ensures balance under many conditions, as a general principle, "a calorie is a calorie" violates the second law of thermodynamics.
Published:
July 27, 2004
Title:
Animal Protein, Animal Fat, and Cholesterol Intakes and Risk of Cerebral Infarction Mortality in the Adult Health Study
Authors:
Sauvaget Catherine; Nagano Jun; Hayashi Mikiko; Yamada Michiko
Abstract:
Background and Purpose— A traditional diet that is poor in animal products is thought to explain the high rate of stroke in Asian populations. The purpose of the present study was to examine the effect of a diet rich in animal protein, animal fat, and cholesterol on the risk of cerebral infarction mortality in a Japanese population.Methods— A prospective study of 3731 Japanese men and women aged 35 to 89 years was conducted from 1984 to 2001. Nutrient intake was estimated at baseline from the responses to a 24-hour diary. During the follow-up period, cases of cerebral infarction deaths (as entered on death certificates) were monitored.Results— During the follow-up period, 60 deaths were attributed to cerebral infarction. A high intake of animal fat and cholesterol was significantly associated with a reduced risk of cerebral infarction death. The risk was reduced by 62% (CI, 82% to 18%) for those in the third tertile of animal fat intake, compared with those in the first tertile, with a significant linear dose-response relationship (P=0.0073). The risk of death from infarction was reduced by 63% (CI, 82% to 22%) in the high cholesterol consumption group, compared with the low consumption group. A significant linear dose–response relationship was observed. Animal protein was not significantly associated with infarction mortality after adjustment for animal fat and cholesterol.Conclusions— This study suggests that in Japan, where animal product intake is lower than in Western countries, a high consumption of animal fat and cholesterol was associated with a reduced risk of cerebral infarction death.
Published:
June 30, 2004
Title:
Selective pressures on the olfactory receptor repertoire since the human-chimpanzee divergence
Authors:
Gimelbrant, Alexander A.; Skaletsky, Helen; Chess, Andrew
Abstract:
The availability of the sequence of the chimpanzee genome provides an opportunity to examine human genes and their chimpanzee orthologs and to analyze selective pressures that have been shaping the olfactory receptor repertoire since the human-chimpanzee divergence. We determined the ratio of nonsynonymous to synonymous changes for each of 186 orthologous pairs and then examined how the distribution of these ratios compares with the distribution expected under neutral drift. Consistent with the diminishing importance of olfaction for these species, we find no evidence for positive selection and we find evidence of weak purifying selection affecting over half of the repertoire.
Published:
June 14, 2004
Title:
Yessotoxin, a shellfish biotoxin, is a potent inducer of the permeability transition in isolated mitochondria and intact cells
Authors:
Bianchi, Cristina; Fato, Romana; Angelin, Alessia; Trombetti, Fabiana; Ventrella, Vittoria; Borgatti, Anna Rosa; Fattorusso, Ernesto; Ciminiello, Patrizia; Bernardi, Paolo; Lenaz, Giorgio; Parenti Castelli, Giovanna
Abstract:
The diarrhetic poisoning by bivalve molluscs, diarrhetic shellfish poisoning, is due to consumption of mussels containing biotoxins produced by some Dinoflagellate species. Toxic effects of yessotoxin (YTX) include morphological alterations of mitochondria from heart and liver but the biochemical basis for these alterations is completely unknown. This paper demonstrates that YTX is a very powerful compound that opens the permeability transition pore (PTP) of the inner mitochondrial membrane of rat liver mitochondria at nanomolar concentrations. The effect requires the presence of a permissive level of calcium, by itself incapable of opening the pore. The direct effect of YTX on PTP is further confirmed by the inhibition exerted by cyclosporin A (CsA) that is known as a powerful inhibitor of PTP opening. Moreover, YTX induces membrane depolarization as shown by the quenching of tetramethylrhodamine methyl ester (TMRM), also prevented by the addition of CsA. YTX caused PTP opening in Morris Hepatoma 1C1 cells, as shown by the occurrence of CsA-sensitive depolarization within minutes of the addition of submicromolar concentrations of the toxin. These results provide a biochemical basis for the mitochondrial alterations observed in the course of intoxication with YTX, offering the first clue into the pathogenesis of diseases caused by YTX, and providing a novel tool to study the PTP in situ.
Published:
June 6, 2004
Title:
Down-regulation of macrophage inhibitory cytokine-1/prostate derived factor in benign prostatic hyperplasia
Authors:
Kakehi, Yoshiyuki; Segawa, Takehiko; Wu, Xiu-Xian; Kulkarni, Prakash; Dhir, Rajiv; Getzenberg, Robert H.
Abstract:
BACKGROUND: Macrophage inhibitory cytokine-1 (MIC-1) is a member of transforming growth factor-beta/bone morphogenetic protein (BMP) superfamily. Despite its potential role in prostatic regulation, little is known about its biological activity. METHODS: Expression profiling using 42K Affymetrix HuGeneFL array was conducted to compare symptomatic benign prostatatic hyperplasia (BPH), histological BPH without symptoms, and normal prostate samples from donors. MIC-1 gene expression was analyzed by RT-PCR in pure culture of prostate epithelial and stromal cells, and prostate cancer cells, LNCaP, PC-3, DU-145. Influence of androgens on MIC-1 expression in LNCaP cells was analyzed by Northern blot. Enhancement of promoter activity of MIC-1 by androgens was examined using reporter assays. RESULTS: In contrast to normal prostates, MIC-1 gene was down-regulated in BPH samples with symptoms and histological BPH obtained from cystoprostatectomy specimens (P < 0.005 and P
Published:
May 31, 2004
Title:
The Effects of Low-Carbohydrate versus Conventional Weight Loss Diets in Severely Obese Adults: One-Year Follow-up of a Randomized Trial
Authors:
Stern, Linda; Iqbal, Nayyar; Seshadri, Prakash; Chicano, Kathryn L.; Daily, Denise A.; McGrory, Joyce; Williams, Monica; Gracely, Edward J.; Samaha, Frederick F.
Abstract:
Published:
May 17, 2004
Title:
Meta-analysis of observational studies on fish intake and coronary heart disease
Authors:
Whelton, Seamus Paul; He, Jiang; Whelton, Paul Kieran; Muntner, Paul
Abstract:
Fish consumption has been associated with a lower risk of coronary heart disease (CHD) in some but not all studies. We conducted a meta-analysis of observational studies to determine if fish consumption is associated with lower fatal and total CHD. English language articles published before May 2003 were searched. In all, 19 observational studies (14 cohort and 5 case-control) in which there was a group that consumed fish on a regular basis and a comparison group that consumed little or no fish were included. With use of a standardized protocol and data extraction form, information on study design, sample size, participant characteristics, duration of follow-up, assessment of end points, and consumption of fish was abstracted. Using a random effects model, we pooled data from each study. Fish consumption versus little to no fish consumption was associated with a relative risk of 0.83 (95% confidence interval 0.76 to 0.90; p <0.005) for fatal CHD and a relative risk of 0.86 (95% confidence interval 0.81 to 0.92; p
Published:
April 30, 2004
Title:
Differential Enzyme Targeting As an Evolutionary Adaptation to Herbivory in Carnivora
Authors:
Birdsey, Graeme M.; Lewin, Jackie; Cunningham, Andrew A.; Bruford, Michael W.; Danpure, Christopher J.
Abstract:
Not all members of the order Carnivora are carnivorous. Some are omnivorous, and a few, such as the giant panda, Ailuropoda melanoleuca, are almost exclusively herbivorous. Although a number of adaptations to increased plant-eating are recognized within Carnivora, few have been studied at the molecular level. One molecular adaptation to diet that is spread widely across Mammalia is the differential intracellular targeting of the intermediary metabolic enzyme alanine:glyoxylate aminotransferase (AGT), which tends to be mitochondrial in carnivores, peroxisomal in herbivores, and both mitochondrial and peroxisomal in omnivores. In the present study, we have analyzed the targeting of AGT in Carnivora in relation to species' natural diets. We show not only that there has been an adaptive shift in AGT targeting from the mitochondrion toward the peroxisome as diets have shifted from being mainly carnivorous to ones that are more omnivorous and herbivorous but also that in one lineage, namely that of the giant panda, there is evidence for positive selection pressure at the molecular level on the AGT mitochondrial targeting sequence to decrease its efficiency, thereby allowing more AGT to be targeted to the peroxisomes.
Published:
March 31, 2004
Title:
Very Low-Carbohydrate and Low-Fat Diets Affect Fasting Lipids and Postprandial Lipemia Differently in Overweight Men
Authors:
Sharman, Matthew J.; Gómez, Ana L.; Kraemer, William J.; Volek, Jeff S.
Abstract:
ABSTRACT. Hypoenergetic very low-carbohydrate and low-fat diets are both commonly used for short-term weight loss; however, few studies have directly compared
Published:
March 31, 2004
Title:
PhIP metabolites in human urine after consumption of well-cooked chicken
Authors:
Kulp, K. S.; Knize, M. G.; Fowler, N. D.; Salmon, C. P.; Felton, J. S.
Abstract:
We devised an assay to quantify the metabolites of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in human urine following a single exposure to well-cooked meat. Our method uses LC/MS/MS to detect four metabolites and four deuterated internal standard peaks in a single chromatographic run. N2-OH-PhIP-N2-glucuronide was the most abundant urinary metabolite excreted by the 12 individuals who participated in our study. N2-PhIP glucuronide was the second most abundant metabolite for 8 of the 12 volunteers. The stability of PhIP metabolism over time was studied in three of the volunteers who repeated the assay eight times over a 2.5 year-period. PhIP metabolite excretion varied in each subject over time, although the rate of excretion was more constant. Our results suggest that quantifying PhIP metabolites should make future studies of individual susceptibility and dietary interventions possible.
Published:
March 24, 2004
Title:
Food and Nutritional Toxicology
Authors:
Omaye, Stanley T.
Abstract:
Published:
March 14, 2004
Title:
Prostate Pathology of Genetically Engineered Mice: Definitions and Classification. The Consensus Report from the Bar Harbor Meeting of the Mouse Models of Human Cancer Consortium Prostate Pathology Committee
Authors:
Shappell, Scott B.; Thomas, George V.; Roberts, Richard L.; Herbert, Ron; Ittmann, Michael M.; Rubin, Mark A.; Humphrey, Peter A.; Sundberg, John P.; Rozengurt, Nora; Barrios, Roberto; Ward, Jerrold M.; Cardiff, Robert D.
Abstract:
The Pathological Classification of Prostate Lesions in Genetically Engineered Mice (GEM) is the result of a directive from the National Cancer Institute Mouse Models of Human Cancer Consortium Prostate Steering Committee to provide a hierarchical taxonomy of disorders of the mouse prostate to facilitate classification of existing and newly created mouse models and the translation to human prostate pathology. The proposed Bar Harbor Classification system is the culmination of three meetings and workshops attended by various members of the Prostate Pathology Committee of the Mouse Models of Human Cancer Consortium. A 2-day Pathology Workshop was held at The Jackson Laboratory in Bar Harbor, Maine, in October 2001, in which study sets of 93 slides from 22 GEM models were provided to individual panel members. The comparison of mouse and human prostate anatomy and disease demonstrates significant differences and considerable similarities that bear on the interpretation of the origin and natural history of their diseases. The recommended classification of mouse prostate pathology is hierarchical, and includes developmental, inflammatory, benign proliferative, and neoplastic disorders. Among the neoplastic disorders, preinvasive, microinvasive, and poorly differentiated neoplasms received the most attention. Specific criteria were recommended and will be discussed. Transitions between neoplastic states were of particular concern. Preinvasive neoplasias of the mouse prostate were recognized as focal, atypical, and progressive lesions. These lesions were designated as mouse prostatic intraepithelial neoplasia (mPIN). Some atypical lesions were identified in mouse models without evidence of progression to malignancy. The panel recommended that mPIN lesions not be given histological grades, but that mPIN be further classified as to the absence or presence of documented associated progression to invasive carcinoma. Criteria for recognizing microinvasion, for classification of invasive gland-forming adenocarcinomas, and for characterizing poorly differentiated tumors, including neuroendocrine carcinomas, were developed and are discussed. The uniform application of defined terminology is essential for correlating results between different laboratories and models. It is recommended that investigators use the Bar Harbor Classification system when characterizing new GEM models or when conducting experimental interventions that may alter the phenotype or natural history of lesion progression in existing models.
Published:
March 14, 2004
Title:
Low-carbohydrate-high-protein diets: is there a place for them in clinical cardiology?
Authors:
Kappagoda, C. Tissa; Hyson, Dianne A.; Amsterdam, Ezra A.
Abstract:
Since the last meeting of the American Heart Association, a great deal of media attention has been focused on low-carbohydrate-high-protein diets (LC-HP) and their potential impact on the practice of cardiology. It has been suggested that these diets, which were introduced originally as weight-loss regimens, also have a significantly beneficial effect on a variety of cardiovascular risk factors. It is clear that people who consume such diets have a reduced intake of calories, resulting in a predictable degree of weight loss. These diets induce a moderate level of ketosis and, in some studies, have been shown to improve the lipid profile overall. There is also a reduction in the number of low-density lipoprotein particles. However, these trends also have been observed over periods of 24 weeks or less with low-calorie diets that already have an established record of safety and efficacy. Although there is a public perception that LC-HP diets have a near-perfect "success rate," the attrition rate on these diets varies from 20% to 43%, which is similar to other conventional weight-loss regimens. Additionally, from a nutritional standpoint, these diets are seriously deficient in several micronutrients and dietary fiber, thus creating a need for nutritional supplements. In contrast, the conventional weight-loss regimens have a favorable impact on serum lipids without the accompanying ketosis and have the potential to provide a nutritionally balanced diet without the need for supplements. Because of the nutritional deficiencies inherent in LC-HP diets and the absence of long-term data on their efficacy and safety, they cannot be recommended in place of currently advocated low-fat, low-calorie diets that have an established record of safety and efficacy.
Published:
March 2, 2004
Title:
The diet-heart hypothesis: a critique
Authors:
Weinberg, Sylvan Lee
Abstract:
The low-fat "diet-heart hypothesis" has been controversial for nearly 100 years. The low-fat-high-carbohydrate diet, promulgated vigorously by the National Cholesterol Education Program, National Institutes of Health, and American Heart Association since the Lipid Research Clinics-Primary Prevention Program in 1984, and earlier by the U.S. Department of Agriculture food pyramid, may well have played an unintended role in the current epidemics of obesity, lipid abnormalities, type II diabetes, and metabolic syndromes. This diet can no longer be defended by appeal to the authority of prestigious medical organizations or by rejecting clinical experience and a growing medical literature suggesting that the much-maligned low-carbohydrate-high-protein diet may have a salutary effect on the epidemics in question.
Published:
March 2, 2004
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