top of page
Published Science
Click Search to Filter.
Total Entries: 10690
Title:
Hypertension, Diabetes, And Elevated Cholesterol Among Insured And Uninsured U.S. Adults
Authors:
Wilper, Andrew P.; Woolhandler, Steffie; Lasser, Karen E.; McCormick, Danny; Bor, David H.; Himmelstein, David U.
Abstract:
:In this paper we explore whether uninsured Americans with three chronic conditions were less likely than the insured to be aware of their illness or to have it controlled. Among those with diabetes and elevated cholesterol, the uninsured were more often undiagnosed. Among hypertensives and people with elevated cholesterol, the uninsured more often had uncontrolled conditions. Undiagnosed and uncontrolled chronic illness, which is common among insured people, is even more frequent among the uninsured.
Published:
December 31, 2008
Title:
Internalization of the Receptor for Advanced Glycation End Products (RAGE) is Required to Mediate Intracellular Responses
Authors:
Sevillano, Natalia; Girón, María D.; Salido, Mercedes; Vargas, Alberto M.; Vilches, José; Salto, Rafael
Abstract:
Abstract. To dissect the rat receptor for advanced glycation end products (RAGE) subcellular distribution and trafficking in eukaryotic cells, an expression sy
Published:
December 31, 2008
Title:
Primate diets and gut morphology: Implications for hominid evolution
Authors:
Milton, Katharine
Abstract:
THERE IS CURRENTLY STRONG INTEREST IN DEVELOPING A BETTER understanding of the probable food habits and dietary niche of early humans (Isaac 1978; Peters and O'Brian 1981; Stahl 1984). Without such information, we are handicapped in our ability to interpret the significance of many features of human morphology and to construct viable models of early human ecology (Isaac 1978; Sussman 1978). Further, it is increasingly obvious that many of the major health problems faced today by more modern technological societies stem from factors related to diet. This strongly suggests that the average diet in such societies is not entirely suitable for human nutritional needs (Burkitt, Walker, and Painter, 1972; Trowell 1978; Truswell 1977). In this paper, I review information about dietary choice in primates, paying particular attention to members of the Hominoidea. I then examine features of the human gut, comparing it with the guts of other mammals, both primates and non-primates, to distinguish any features that appear to set humans apart. I conclude by speculating on the probable diet of early humans, using the behavior of extant pongids as a partial foundation for my speculations.
Published:
December 31, 2008
Title:
The preference for animal protein and fat: A cross-cultural survey
Authors:
Jr, H.L.
Abstract:
Published:
December 31, 2008
Title:
Plasma Isoflavones and Subsequent Risk of Prostate Cancer in a Nested Case-Control Study: The Japan Public Health Center
Authors:
Kurahashi, Norie; Iwasaki, Motoki; Inoue, Manami; Sasazuki, Shizuka; Tsugane, Shoichiro
Abstract:
Purpose The incidence of prostate cancer is much lower in Japanese than Western populations. Given the preventive effects of isoflavones on carcinogenesis in the prostate in many nonhuman studies and the high consumption of isoflavones in Japanese, this low incidence may be partly due to the effects of soy. Patients and Methods We conducted a nested case-control study within the Japan Public Health Center–based Prospective Study. A total of 14,203 men aged 40 to 69 years who had returned the baseline questionnaire and provided blood samples were observed from 1990 to 2005. During a mean of 12.8 years of follow-up, 201 newly diagnosed prostate cancers were identified. Two matched controls for each case were selected from the cohort. Conditional logistic regression model was used to estimate the odds ratios (ORs) and 95% CIs for prostate cancer in relation to plasma levels of isoflavone. Results Plasma genistein level tended to be inversely associated with the risk of total prostate cancer. Although plasma daidzein showed no association, the highest tertile for plasma equol, a metabolite of daidzein, was significantly associated with a decreased risk of total prostate cancer (OR = 0.60; 95% CI, 0.36 to 0.99; Ptrend = .04). These inverse associations were strengthened after analysis was confined to localized cases, with ORs in the highest group of plasma genistein and equol compared with the lowest of 0.54 (95% CI, 0.29 to 1.01; Ptrend = .03) and 0.43 (95% CI, 0.22 to 0.82; Ptrend = .02), respectively. Plasma isoflavone levels were not statistically significantly associated with the risk of advanced prostate cancer. Conclusion Isoflavones may prevent the development of prostate cancer.
Published:
December 19, 2008
Title:
The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus
Authors:
Westman, Eric C.; Yancy, William S.; Mavropoulos, John C.; Marquart, Megan; McDuffie, Jennifer R.
Abstract:
OBJECTIVE: Dietary carbohydrate is the major determinant of postprandial glucose levels, and several clinical studies have shown that low-carbohydrate diets improve glycemic control. In this study, we tested the hypothesis that a diet lower in carbohydrate would lead to greater improvement in glycemic control over a 24-week period in patients with obesity and type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: Eighty-four community volunteers with obesity and type 2 diabetes were randomized to either a low-carbohydrate, ketogenic diet (<20 g of carbohydrate daily; LCKD) or a low-glycemic, reduced-calorie diet (500 kcal/day deficit from weight maintenance diet; LGID). Both groups received group meetings, nutritional supplementation, and an exercise recommendation. The main outcome was glycemic control, measured by hemoglobin A1c. RESULTS: Forty-nine (58.3%) participants completed the study. Both interventions led to improvements in hemoglobin A1c, fasting glucose, fasting insulin, and weight loss. The LCKD group had greater improvements in hemoglobin A1c (-1.5% vs. -0.5%, p = 0.03), body weight (-11.1 kg vs. -6.9 kg, p = 0.008), and high density lipoprotein cholesterol (+5.6 mg/dL vs. 0 mg/dL, p < 0.001) compared to the LGID group. Diabetes medications were reduced or eliminated in 95.2% of LCKD vs. 62% of LGID participants (p
Published:
December 18, 2008
Title:
A Null Mutation in Human APOC3 Confers a Favorable Plasma Lipid Profile and Apparent Cardioprotection
Authors:
Pollin, T. I.; Damcott, C. M.; Shen, H.; Ott, S. H.; Shelton, J.; Horenstein, R. B.; Post, W.; McLenithan, J. C.; Bielak, L. F.; Peyser, P. A.; Mitchell, B. D.; Miller, M.; O'Connell, J. R.; Shuldiner, A. R.
Abstract:
Published:
December 11, 2008
Title:
Apolipoprotein B Is an innate barrier against invasive Staphylococcus aureus infection
Authors:
Peterson, M. Michal; Mack, Jessica L.; Hall, Pamela R.; Alsup, Anny A.; Alexander, Susan M.; Sully, Erin K.; Sawires, Youhanna S.; Cheung, Ambrose L.; Otto, Michael; Gresham, Hattie D.
Abstract:
Staphylococcus aureus is both a colonizer of humans and a cause of severe invasive infections. Although the genetic basis for phenotype switching from colonizing to invasive has received significant study, knowledge of host factors that antagonize the switch is limited. We show that VLDL and LDL lipoproteins interfere with this switch by antagonizing the S. aureus agr quorum-sensing system that upregulates genes required for invasive infection. The mechanism of antagonism entails binding of the major structural protein of these lipoproteins, apolipoprotein B, to an S. aureus autoinducing pheromone, preventing attachment of this pheromone to the bacteria and subsequent signaling through its receptor, AgrC. Mice deficient in plasma apolipoprotein B, either genetically or pharmacologically, are more susceptible to invasive agr+ bacterial infection, but not to infection with an agr deletion mutant. Therefore, apolipoprotein B at homeostatic levels in blood is an essential innate defense effector against invasive S. aureus infection.
Published:
December 10, 2008
Title:
Genetic analyses of dopamine related genes in adult ADHD patients suggest an association with the DRD5-microsatellite repeat, but not with DRD4 or SLC6A3 VNTRs
Authors:
Johansson, S.; Halleland, H.; Halmøy, A.; Jacobsen, K. K.; Landaas, E. T.; Dramsdahl, M.; Fasmer, O. B.; Bergsholm, P.; Lundervold, A. J.; Gillberg, C.; Hugdahl, K.; Knappskog, P. M.; Haavik, J.
Abstract:
Attention deficit hyperactivity disorder (ADHD) is a common and highly heritable psychiatric disorder in children and adults. Recent meta-analyses have indicated an association between genes involved in dopaminergic signaling and childhood ADHD, but little is known about their possible role in adult ADHD. In this study of adults with ADHD, we evaluated the three most commonly studied ADHD candidate genetic polymorphisms; the dopamine receptor D4 (DRD4) exon 3 VNTR repeat, a microsatellite repeat 18.5 kb upstream of the DRD5 locus and the 3'UTR dopamine transporter SLC6A3 (DAT 1) VNTR. We examined 358 clinically diagnosed adult Norwegian ADHD patients (51% males) and 340 ethnically matched controls. We found a nominally significant overall association with adult ADHD for the DRD5 microsatellite marker (P = 0.04), and a trend toward increased risk associated with the 148-bp allele consistent with recent meta-analyses. The strongest overall association (P = 0.02) and increased risk for the 148-bp allele [odds ratio (OR) = 1.27 (95% CI: 1.00-1.61)] were seen in the inattentive and combined inattentive/hyperactive group as previously reported for childhood ADHD. No association was found for the DRD4 or SLC6A3 polymorphisms in this patient sample. In conclusion, our results among adults with a clinical diagnosis of ADHD support an association between ADHD and the DRD5 locus, but not the DRD4 or SLC6A3 loci. It is possible that the latter polymorphisms are associated with a transient form of ADHD with better long-term clinical outcome.
Published:
December 4, 2008
Title:
Interaction of the RAGE Cytoplasmic Domain with Diaphanous-1 Is Required for Ligand-stimulated Cellular Migration through Activation of Rac1 and Cdc42
Authors:
Hudson, Barry I.; Kalea, Anastasia Z.; del Mar Arriero, Maria; Harja, Evis; Boulanger, Eric; D'Agati, Vivette; Schmidt, Ann Marie
Abstract:
Cellular migration is a fundamental process linked to diverse pathological states such as diabetes and its complications, atherosclerosis, inflammation, and cancer. The receptor for advanced glycation end products (RAGE) is a multiligand cell surface macromolecule which binds distinct ligands that accumulate in these settings. RAGE-ligand interaction evokes central changes in key biological properties of cells, including proliferation, generation of inflammatory mediators, and migration. Although RAGE-dependent signal transduction is critically dependent on its short cytoplasmic domain, to date the proximate mechanism by which this RAGE domain engages and stimulates cytoplasmic signaling pathways has yet to be identified. Here we show that the RAGE cytoplasmic domain interacts with Diaphanous-1 (Dia-1) both in vitro and in vivo. We employed the human RAGE cytoplasmic domain as “bait” in the yeast two-hybrid assay and identified the formin homology (FH1) domain of Dia-1 as a potential binding partner of this RAGE domain. Immunoprecipitation studies revealed that the RAGE cytoplasmic domain interacts with the FH1 domain of Dia-1. Down-regulation of Dia-1 expression by RNA interference blocks RAGE-mediated activation of Rac-1 and Cdc42 and, in parallel, RAGE ligand-stimulated cellular migration. Taken together, these findings indicate that the interaction of the RAGE cytoplasmic domain with Dia-1 is required to transduce extracellular environmental cues evoked by binding of RAGE ligands to their cell surface receptor, a chief consequence of which is Rac-1 and Cdc42 activation and cellular migration. Because RAGE and Dia-1 are implicated in the regulation of inflammatory, vascular, and transformed cell migration, these findings highlight this interaction as a novel target for therapeutic intervention in inflammation, atherosclerosis, diabetes, and cancer.
Published:
December 4, 2008
Title:
Hypometabolism as a therapeutic target in Alzheimer's disease
Authors:
Costantini, Lauren C.; Barr, Linda J.; Vogel, Janet L.; Henderson, Samuel T.
Abstract:
The pathology of Alzheimer's disease (AD) is characterized by cerebral atrophy in frontal, temporal, and parietal regions, with senile plaques, dystrophic neurites, and neurofibrillar tangles within defined areas of the brain. Another characteristic of AD is regional hypometabolism in the brain. This decline in cerebral glucose metabolism occurs before pathology and symptoms manifest, continues as symptoms progress, and is more severe than that of normal aging. Ketone bodies are an efficient alternative fuel for cells that are unable to metabolize glucose or are 'starved' of glucose. AC-1202 is designed to elevate serum ketone levels safely. We previously showed that treatment with AC-1202 in patients with mild-to-moderate AD improves memory and cognition. Treatment outcomes were influenced by apolipoprotein E genotype status. These data suggest that AC-1202 may be an effective treatment for cognitive dysfunction by providing an alternative substrate for use by glucose-compromised neurons.
Published:
December 2, 2008
Title:
Trichinellosis: a possible link between human infection and the traditional earth-oven or ‘mumu’ method of cooking in Morehead District, Western Province, Papua New Guinea
Authors:
Owen, Ifor L.; Muke, Leslie; Davies, Hugh L.
Abstract:
Objective: To investigate if the traditional method of cooking pig meat in an earth-oven or mumu, as practiced by people in Morehead District, Western Province, Papua New Guinea (PNG), could be a source of infection with Trichinella papuae and of the disease trichinellosis. Procedure: As the locality lacks suitable river stones normally used in a mumu in PNG, people use various substitute materials, such as pieces of termite mounds, balls of dried clay and small rough stones. Samples of these were tested and compared with conventional mumu stones in their capacity to retain heat. Results: None of the substitute materials tested was as efficient in retaining heat as the conventional mumu stones. Conclusions: Cooking pig meat in a mumu in Morehead District has the potential to be a source of infection with T. papuae. Loss of heat in a Morehead mumu is accelerated probably as the mumu is prepared on the surface of the ground and not in a shallow pit or depression as is the custom elsewhere in the country.
Published:
November 30, 2008
Title:
Drug/diet synergy for managing malignant astrocytoma in mice: 2-deoxy-D-glucose and the restricted ketogenic diet
Authors:
Marsh, Jeremy; Mukherjee, Purna; Seyfried, Thomas N.
Abstract:
BACKGROUND: Astrocytomas are largely dependent on glycolysis to satisfy their bioenergetic requirements for growth and survival. Therapies that target glycolysis can potentially manage astrocytoma growth and progression. Dietary restriction of the high fat/low carbohydrate ketogenic diet (KD-R) reduces glycolysis and is effective in managing experimental mouse and human astrocytomas. The non-metabolizable glucose analogue, 2-deoxy-D-glucose (2-DG), is a potent glycolytic inhibitor that can mimic effects of energy restriction both in vitro and in vivo, but can also produce adverse effects when administered at doses greater than 200 mg/kg. The goal here was to determine if low doses of 2-DG could act synergistically with the KD-R to better manage growth of the CT-2A malignant mouse astrocytoma. METHODS: The therapeutic effect of a KD-R supplemented with a low dose of 2-DG (25 mg/kg) was examined in adult C57BL/6J mice bearing the syngeneic CT-2A malignant astrocytoma grown orthotopically. Mice were fed the standard unrestricted diet for the first 3 days after tumor implantation prior to their separation into one of four diet groups fed either a standard rodent diet in unrestricted amounts (SD-UR) or a KD-R with or without 2-DG for 10 days. The KD-R was restricted to reduce body weight by about 20%. 2-DG was initiated 6 days after tumor implantation and was continued for 7 days. Brain tumors were excised and weighed. RESULTS: Energy intake, body weights, and CT-2A tumor weights were similar in the SD-UR and the SD-UR+2-2DG mouse groups over the dietary treatment period (days 3-13). Tumor weights were about 48% and 80% lower in the KD-R and in the KD-R+2-DG groups, respectively, than in the SD-UR group. Mouse health and vitality was better in the KD-R group than in the KD-R+2-DG group. CONCLUSION: Astrocytoma growth was reduced more in the KD-R mouse group supplemented with 2-DG than in the mouse groups receiving either dietary restriction or 2-DG alone, indicating a synergistic interaction between the drug and the diet. The results suggest that management of malignant astrocytoma with restricted ketogenic diets could be enhanced when combined with drugs that inhibit glycolysis.
Published:
November 24, 2008
Title:
Gene Regulation in Primates Evolves under Tissue-Specific Selection Pressures
Authors:
Blekhman, Ran; Oshlack, Alicia; Chabot, Adrien E.; Smyth, Gordon K.; Gilad, Yoav
Abstract:
Regulatory changes have long been hypothesized to play an important role in primate evolution. To identify adaptive regulatory changes in humans, we performed a genome-wide survey for genes in which regulation has likely evolved under natural selection. To do so, we used a multi-species microarray to measure gene expression levels in livers, kidneys, and hearts from six humans, chimpanzees, and rhesus macaques. This comparative gene expression data allowed us to identify a large number of genes, as well as specific pathways, whose inter-species expression profiles are consistent with the action of stabilizing or directional selection on gene regulation. Among the latter set, we found an enrichment of genes involved in metabolic pathways, consistent with the hypothesis that shifts in diet underlie many regulatory adaptations in humans. In addition, we found evidence for tissue-specific selection pressures, as well as lower rates of protein evolution for genes in which regulation evolves under natural selection. These observations are consistent with the notion that adaptive circumscribed changes in gene regulation have fewer deleterious pleiotropic effects compared with changes at the protein sequence level., It has long been hypothesized that in addition to structural changes to proteins, changes in gene regulation might underlie many of the anatomic and behavioral differences between humans and other primates. However, to date, there are only a handful of examples of regulatory adaptations in humans. In this work, we present a genome-wide study of gene expression levels in livers, kidneys, and hearts from three species: humans, chimpanzees, and rhesus macaques. These data allowed us to identify genes and entire pathways in which regulation evolved under natural selection and therefore are likely to be functionally important. Our results provide some of the first examples of pathways that have been remodeled specifically in the human lineage. In particular, we find that the regulation of a large number of genes involved in metabolic pathways evolved under lineage-specific directional selection. This result is intriguing, because, in addition to the obvious cognitive and linguistic differences between humans and non-human apes, a clear lifestyle shift between us and other primates can be found in our diet. We also found evidence for tissue-specific selection pressures on gene regulation, an observation that provides strong support to the notion that adaptive circumscribed changes in gene regulation have fewer deleterious pleiotropic effects compared with changes at the protein sequence level.
Published:
November 20, 2008
Title:
Gene Regulation in Primates Evolves under Tissue-Specific Selection Pressures
Authors:
Blekhman, Ran; Oshlack, Alicia; Chabot, Adrien E.; Smyth, Gordon K.; Gilad, Yoav
Abstract:
Regulatory changes have long been hypothesized to play an important role in primate evolution. To identify adaptive regulatory changes in humans, we performed a genome-wide survey for genes in which regulation has likely evolved under natural selection. To do so, we used a multi-species microarray to measure gene expression levels in livers, kidneys, and hearts from six humans, chimpanzees, and rhesus macaques. This comparative gene expression data allowed us to identify a large number of genes, as well as specific pathways, whose inter-species expression profiles are consistent with the action of stabilizing or directional selection on gene regulation. Among the latter set, we found an enrichment of genes involved in metabolic pathways, consistent with the hypothesis that shifts in diet underlie many regulatory adaptations in humans. In addition, we found evidence for tissue-specific selection pressures, as well as lower rates of protein evolution for genes in which regulation evolves under natural selection. These observations are consistent with the notion that adaptive circumscribed changes in gene regulation have fewer deleterious pleiotropic effects compared with changes at the protein sequence level., It has long been hypothesized that in addition to structural changes to proteins, changes in gene regulation might underlie many of the anatomic and behavioral differences between humans and other primates. However, to date, there are only a handful of examples of regulatory adaptations in humans. In this work, we present a genome-wide study of gene expression levels in livers, kidneys, and hearts from three species: humans, chimpanzees, and rhesus macaques. These data allowed us to identify genes and entire pathways in which regulation evolved under natural selection and therefore are likely to be functionally important. Our results provide some of the first examples of pathways that have been remodeled specifically in the human lineage. In particular, we find that the regulation of a large number of genes involved in metabolic pathways evolved under lineage-specific directional selection. This result is intriguing, because, in addition to the obvious cognitive and linguistic differences between humans and non-human apes, a clear lifestyle shift between us and other primates can be found in our diet. We also found evidence for tissue-specific selection pressures on gene regulation, an observation that provides strong support to the notion that adaptive circumscribed changes in gene regulation have fewer deleterious pleiotropic effects compared with changes at the protein sequence level.
Published:
November 20, 2008
Title:
Moderate carbohydrate, moderate protein weight loss diet reduces cardiovascular disease risk compared to high carbohydrate, low protein diet in obese adults: A randomized clinical trial
Authors:
Lasker, Denise A. Walker; Evans, Ellen M.; Layman, Donald K.
Abstract:
BACKGROUND: To evaluate the metabolic effects of two weight loss diets differing in macronutrient composition on features of dyslipidemia and post-prandial insulin (INS) response to a meal challenge in overweight/obese individuals. METHODS: This study was a parallel-arm randomized 4 mo weight loss trial. Adults (n = 50, 47 +/- 7 y) matched on BMI (33.6 +/- 0.6 kg/m2, P = 0.79) consumed energy restricted diets (deficit ~500 kcal/d): PRO (1.6 g.kg-1.d-1 protein and 220 g/d carbohydrate) for 4 mos. Meal challenges of respective diets were utilized for determination of blood lipids and post-prandial INS and glucose response at the beginning and end of the study. RESULTS: There was a trend for PRO to lose more weight (-9.1% vs. -7.3%, P = 0.07) with a significant reduction in percent fat mass compared to CHO (-8.7% vs. -5.7%; P = 0.03). PRO also favored reductions in triacylglycerol (-34% vs. -14%; P < 0.05) and increases in HDL-C (+5% vs. -3%; P = 0.05); however, CHO favored reduction in LDL-C (-7% vs. +2.5%; P < 0.05). INS responses to the meal challenge were improved in PRO compared to CHO (P < 0.05) at both 1 hr (-34.3% vs. -1.0%) and 2 hr (-9.2% vs. +46.2%), an effect that remained significant after controlling for weight or fat loss (both P
Published:
November 6, 2008
Title:
Persistent epigenetic differences associated with prenatal exposure to famine in humans
Authors:
Heijmans, Bastiaan T.; Tobi, Elmar W.; Stein, Aryeh D.; Putter, Hein; Blauw, Gerard J.; Susser, Ezra S.; Slagboom, P. Eline; Lumey, L. H.
Abstract:
Extensive epidemiologic studies have suggested that adult disease risk is associated with adverse environmental conditions early in development. Although the mechanisms behind these relationships are unclear, an involvement of epigenetic dysregulation has been hypothesized. Here we show that individuals who were prenatally exposed to famine during the Dutch Hunger Winter in 1944-45 had, 6 decades later, less DNA methylation of the imprinted IGF2 gene compared with their unexposed, same-sex siblings. The association was specific for periconceptional exposure, reinforcing that very early mammalian development is a crucial period for establishing and maintaining epigenetic marks. These data are the first to contribute empirical support for the hypothesis that early-life environmental conditions can cause epigenetic changes in humans that persist throughout life.
Published:
November 3, 2008
Title:
Recommendations for the Diagnosis and Management of Prader-Willi Syndrome
Authors:
Goldstone, A. P; Holland, A. J; Hauffa, B. P; Hokken-Koelega, A. C; Tauber, M.
Abstract:
Objective: The objective of the study was to provide recommendations for the diagnosis and management of Prader-Willi syndrome throughout the life span to guide clinical practice. Participants: An open international multidisciplinary expert meeting was held in October 2006 in Toulouse, France, with 37 invited speakers and session chairs (see Acknowledgments) and 85 additional registered participants. The meeting was supported by an unrestricted educational grant from Pfizer. Evidence: Invited participants with particular expertise reviewed the published evidence base for their specialist topic and unpublished data from personal experience, previous national and international PWS conferences, and PWS Association clinical advisory groups. Sessions covered epidemiology, psychiatric, and behavioral disorders; breathing and sleep abnormalities; genetics; endocrinology; and management in infancy, childhood, transition, and adulthood. Consensus Process: This included group meetings including open discussion after each session. The guidelines were written by the Scientific Committee (authors), using the conclusions provided by the sessions chairs and summary provided by each speaker, including incorporation of changes suggested after review by selected meeting participants (see Acknowledgments). Conclusions: The diagnosis and management of this complex disorder requires a multidisciplinary approach with particular emphasis on the importance of early diagnosis using accredited genetic testing, use and monitoring of GH therapy from early childhood, control of the food environment and regular exercise, appropriate management of transition, consideration of group home placement in adulthood, and distinction of behavioral problems from psychiatric illness.
Published:
October 31, 2008
Title:
Dietary omega 3 fatty acids and the developing brain
Authors:
Innis, Sheila M.
Abstract:
The omega-3 fatty acids are essential dietary nutrients and one of their important roles is providing the fatty acid with 22 carbons and 6 double bonds known as docosahexaenoic acid (DHA) for nervous tissue growth and function. Inadequate intakes of omega-3 fatty acids decrease DHA and increase omega-6 fatty acids in the brain. Decreased DHA in the developing brain leads to deficits in neurogenesis, neurotransmitter metabolism, and altered learning and visual function in animals. Western diets are low in omega-3 fatty acids, including the 18 carbon omega-3 fatty acid alpha linolenic acid found mainly in plant oils, and DHA, which is found mainly in fish. The DHA status of the newborn and breast-fed infant depends on the maternal intake of DHA and varies widely. Epidemiological studies have linked low maternal DHA to increased risk of poor child neural development. Intervention studies have shown improving maternal DHA nutrition decreases the risk of poor infant and child visual and neural development. Thus, sufficient evidence is available to conclude that maternal fatty acid nutrition is important to DHA transfer to the infant before and after birth, with short and long-term implications for neural function. However, genetic variation in genes encoding fatty acid desaturases also influence essential fatty acid metabolism, and may increase requirements in some individuals. Consideration of omega-3 fatty acid to include brain development, optimizing omega-3 and omega-6 fatty acids in gestation and lactation, and in fatty acid nutrition support for intravenous and formula-fed neonates is important.
Published:
October 26, 2008
Title:
Spanish Ketogenic Mediterranean diet: a healthy cardiovascular diet for weight loss
Authors:
Pérez-Guisado, Joaquín; Muñoz-Serrano, Andrés; Alonso-Moraga, Ángeles
Abstract:
Ketogenic diets are an effective healthy way of losing weight since they promote a non-atherogenic lipid profile, lower blood pressure and decrease resistance to insulin with an improvement in blood levels of glucose and insulin. On the other hand, Mediterranean diet is well known to be one of the healthiest diets, being the basic ingredients of such diet the olive oil, red wine and vegetables. In Spain the fish is an important component of such diet. The objective of this study was to determine the dietary effects of a protein ketogenic diet rich in olive oil, salad, fish and red wine.
Published:
October 25, 2008
Title:
Structural basis for pattern recognition by the receptor for advanced glycation end products (RAGE)
Authors:
Xie, Jingjing; Reverdatto, Sergey; Frolov, Andrej; Hoffmann, Ralf; Burz, David S.; Shekhtman, Alexander
Abstract:
The receptor for advanced glycated end products (RAGE) is a multiligand receptor that is implicated in the pathogenesis of various diseases, including diabetic complications, neurodegenerative disorders, and inflammatory responses. The ability of RAGE to recognize advanced glycated end products (AGEs) formed by nonenzymatic glycoxidation of cellular proteins places RAGE in the category of pattern recognition receptors. The structural mechanism of AGE recognition was an enigma due to the diversity of chemical structures found in AGE-modified proteins. Here, using NMR spectroscopy we showed that the immunoglobulin V-type domain of RAGE is responsible for recognizing various classes of AGEs. Three distinct surfaces of the V domain were identified to mediate AGE-V domain interactions. They are located in the positively charged areas of the V domain. The first interaction surface consists of strand C and loop CC ', the second interaction surface consists of strand C ', strand F, and loop FG, and the third interaction surface consists of strand A ' and loop EF. The secondary structure elements of the interaction surfaces exhibit significant flexibility on the ms-micros time scale. Despite highly specific AGE-V domain interactions, the binding affinity of AGEs for an isolated V domain is low, approximately 10 microm. Using in-cell fluorescence resonance energy transfer we show that RAGE is a constitutive oligomer on the plasma membrane. We propose that constitutive oligomerization of RAGE is responsible for recognizing patterns of AGE-modified proteins with affinities less than 100 nm.
Published:
October 2, 2008
Title:
Comparison of CYP1A2 and NAT2 phenotypes between black and white smokers
Authors:
Muscat, Joshua E.; Pittman, Brian; Kleinman, Wayne; Lazarus, Philip; Stellman, Steven D.; Richie, John P.
Abstract:
The lower incidence rate of transitional cell carcinoma of the urinary bladder in blacks than in whites may be due to racial differences in the catalytic activity of enzymes that metabolize carcinogenic arylamines in tobacco smoke. To examine this, we compared cytochrome P4501A2 (CYP1A2) and N-acetyltransferase-2 activities (NAT2) in black and white smokers using urinary caffeine metabolites as a probe for enzyme activity in a community-based study of 165 black and 183 white cigarette smokers. The paraxanthine (1,7-dimethylxanthine, 17X)/caffeine (trimethylxanthine, 137X) ratio or [17X+1,7-dimethyluric acid (17U)]/137X ratio was used as an indicator of CYP1A2 activity. The 5-acetyl-amino-6-formylamino-3-methyluracil (AFMU)/1-methylxanthine (1X) ratio indicated NAT2 activity. The odds ratio for the slow NAT2 phenotype associated with black race was 0.4; 95% confidence intervals 0.2-0.7. The putative combined low risk phenotype (slow CYP1A2/rapid NAT2) was more common in blacks than in whites (25% vs. 15%, P
Published:
September 30, 2008
Title:
Effectiveness of Long-term Psychodynamic Psychotherapy: A Meta-analysis
Authors:
Leichsenring, Falk
Abstract:
Objective To examine the effects of LTPP, especially in complex mental disorders, ie, patients with personality disorders, chronic mental disorders, multiple mental disorders, and complex depressive and anxiety disorders (ie, associated with chronic course and/or multiple mental disorders), by performing a meta-analysis. Data Sources Studies of LTPP published between January 1, 1960, and May 31, 2008, were identified by a computerized search using MEDLINE, PsycINFO, and Current Contents, supplemented by contact with experts in the field. Study Selection Only studies that used individual psychodynamic psychotherapy lasting for at least a year, or 50 sessions; had a prospective design; and reported reliable outcome measures were included. Randomized controlled trials (RCTs) and observational studies were considered. Twenty-three studies involving a total of 1053 patients were included (11 RCTs and 12 observational studies). Data Extraction Information on study characteristics and treatment outcome was extracted by 2 independent raters. Effect sizes were calculated for overall effectiveness, target problems, general psychiatric symptoms, personality functioning, and social functioning. To examine the stability of outcome, effect sizes were calculated separately for end-of-therapy and follow-up assessment. Results According to comparative analyses of controlled trials, LTPP showed significantly higher outcomes in overall effectiveness, target problems, and personality functioning than shorter forms of psychotherapy. With regard to overall effectiveness, a between-group effect size of 1.8 (95% confidence interval [CI], 0.7-3.4) indicated that after treatment with LTPP patients with complex mental disorders on average were better off than 96% of the patients in the comparison groups (P=.002). According to subgroup analyses, LTPP yielded significant, large, and stable within-group effect sizes across various and particularly complex mental disorders (range, 0.78-1.98). Conclusions There is evidence that LTPP is an effective treatment for complex mental disorders. Further research should address the outcome of LTPP in specific mental disorders and should include cost-effectiveness analyses.
Published:
September 30, 2008
Title:
Vitamin A Deficiency and Clinical Disease: An Historical Overview
Authors:
Sommer, Alfred
Abstract:
Vitamin A deficiency has a plethora of clinical manifestations, ranging from xerophthalmia (practically pathognomonic) to disturbances in growth and susceptibility to severe infection (far more protean). Like other classical vitamin deficiency states (scurvy, rickets), some of the signs and symptoms of xerophthalmia were recognized long ago. Reports related to vitamin A and/or manifestations of deficiency might conveniently be divided into “ancient” accounts; eighteenth to nineteenth century clinical descriptions (and their purported etiologic associations); early twentieth century laboratory animal experiments and clinical and epidemiologic observations that identified the existence of this unique nutrient and manifestations of its deficiency; and, most recently, a flowering of carefully conducted clinical studies and field-based randomized trials that documented the full extent and impact of deficiency among the poor of low- and middle-income countries, which in turn changed global health policy.
Published:
September 30, 2008
Title:
Comparison of Waist Circumference, Body Mass Index, Percent Body Fat and Other Measure of Adiposity in Identifying Cardiovascular Disease Risks among Thai Adults
Authors:
Paniagua, Linda; Lohsoonthorn, Vitool; Lertmaharit, Somrat; Jiamjarasrangsi, Wiroj; Williams, Michelle A.
Abstract:
Objective To compare the abilities of body mass index (BMI), percent body fat (%BF), waist circumference (WC), waist-hip ratio (WHR) and waist-height ratio (WHtR) to identify cardiovascular disease risk factors. Methods This cross-sectional study is comprised of 1,391 Thai participants (451 men and 940 women) receiving annual health check-ups. Spearman’s rank correlation was used to determine the association of the five anthropometric indices with metabolic parameters including fasting plasma glucose, triglyceride, high density lipoprotein and blood pressure. The prevalence of cardiovascular disease risk factors was determined according to tertile of each anthropometric measure. Receiver operating characteristic (ROC) curves were plotted to compare anthropometric measure as predictors of the prevalence of cardiovascular risk factors. Results Metabolic parameters were more strongly associated with %BF and WHR and least correlated with BMI in men. Among women, BMI was most strongly correlated with metabolic parameters. In both genders, the prevalence of cardiovascular disease risk factors increased across successive tertiles for each anthropometric measure. Review of ROC curves indicated that %BF and WHR performed slightly better than other measures in identifying differences in CVD risk factors among men. BMI performed at least as well or better than other measures of adiposity among women. Conclusions These findings confirm high correlations between anthropometric measures and metabolic parameters. BMI, WC and other measures were not materially different in identifying cardiovascular disease risk factors. Although small differences were observed, the magnitudes of those differences are not likely to be of public health or clinical significance.
Published:
August 31, 2008
Title:
Food: The Key Concepts
Authors:
Belasco, Warren
Abstract:
Food: The Key Concepts presents an exciting, coherent and interdisciplinary introduction to food studies for the beginning reader. Food Studies is an increasingly complex field, drawing on disciplines as diverse as Sociology, Anthropology and Cultural Studies at one end and Economics, Politics and Agricultural Science at the other. In order to clarify the issues, Food: The Key Concepts distills food choices down to three competing considerations: consumer identity; matters of convenience and price; and an awareness of the consequences of what is consumed. The book concludes with an examination of two very different future scenarios for feeding the world's population: the technological fix, which looks to science to provide the solution to our future food needs; and the anthropological fix, which hopes to change our expectations and behaviors. Throughout, the analysis is illustrated with lively case studies. Bulleted chapter summaries, questions and guides to further reading are also provided.
Published:
August 31, 2008
Title:
Analysis of dietary interventions. A simple payoff matrix for display of comparative dietary trials
Authors:
Feinman, Richard D.; Fine, Eugene J.; Volek, Jeff S.
Abstract:
OBJECTIVE: To provide a simple method for presentation of data in comparative dietary trials. METHODS: Individual data from each diet are ranked and all possible paired comparisons are made and displayed in a pay-off matrix which can be color-coded according to the magnitude of the differences between the two diets. Probability of outcome can be calculated from the fraction of matrix elements corresponding to specified conditions. The method has the advantage of emphasizing differences and providing the maximum amount of information. RESULTS: The method was tested with values from the literature and allows intuitive sense of the comparative effectiveness of the two diets. In a test case in which a cross-over study had been performed the matrix derived from theoretical paired comparisons (treating the data as two parallel studies) was consistent with the results from the actual pairing in the cross-over. CONCLUSION: The matrix method is a simple way of providing access to the differences between dietary trials. It exaggerates differences but can be used in combination with group statistics that, conversely, provide reliability at the expense of detailed information.
Published:
August 28, 2008
Title:
Effect of protein, fat, carbohydrate and fibre on gastrointestinal peptide release in humans
Authors:
Karhunen, L. J.; Juvonen, K. R.; Huotari, A.; Purhonen, A. K.; Herzig, K. H.
Abstract:
Short-term regulation of food intake controls what, when and how much we eat within a single day or a meal. This regulation results from an integrated response to neural and humoral signals that originate from the brain, gastrointestinal (GI) tract and adipose tissue. In the GI tract, multiple sites including the stomach, duodenum, distal small intestine, colon, and pancreas are involved in this process. Ingested food evokes satiety by mechanical stimulation and by release of peptides in the GI tract. The intestine in particular plays a key role in satiety through various peptides secreted in response to food. Many of the intestinal peptides inhibit also gastric emptying thus enhancing gastric mechanoreceptor stimulation. In this review, the current knowledge about the effects of different macronutrients and fibre on the release of GI satiety-related peptides in humans is discussed.
Published:
August 6, 2008
Title:
Preliminary Evidence for an Emerging Nonmetropolitan Mortality Penalty in the United States
Authors:
Cosby, Arthur G.; Neaves, Tonya T.; Cossman, Ronald E.; Cossman, Jeralynn S.; James, Wesley L.; Feierabend, Neal; Mirvis, David M.; Jones, Carol A.; Farrigan, Tracey
Abstract:
We discovered an emerging non-metropolitan mortality penalty by contrasting 37 years of age-adjusted mortality rates for metropolitan versus nonmetropolitan US counties. During the 1980s, annual metropolitan–nonmetropolitan differences averaged 6.2 excess deaths per 100000 nonmetropolitan population, or approximately 3600 excess deaths; however, by 2000 to 2004, the difference had increased more than 10 times to average 71.7 excess deaths, or approximately 35 000 excess deaths. We recommend that research be undertaken to evaluate and utilize our preliminary findings of an emerging US nonmetropolitan mortality penalty.
Published:
July 31, 2008
Title:
The US Department of Agriculture Automated Multiple-Pass Method reduces bias in the collection of energy intakes
Authors:
Moshfegh, Alanna J.; Rhodes, Donna G.; Baer, David J.; Murayi, Theophile; Clemens, John C.; Rumpler, William V.; Paul, David R.; Sebastian, Rhonda S.; Kuczynski, Kevin J.; Ingwersen, Linda A.; Staples, Robert C.; Cleveland, Linda E.
Abstract:
ABSTRACT. Background: The US Department of Agriculture Automated Multiple-Pass Method (AMPM) is used for collecting 24-h dietary recalls in What We Eat In Amer
Published:
July 31, 2008
Title:
Mechanisms of ROS modulated cell survival during carcinogenesis
Authors:
Clerkin, J. S.; Naughton, R.; Quiney, C.; Cotter, T. G.
Abstract:
There is increasing evidence within the literature that the decreased susceptibility of tumour cells to stimuli that induce apoptosis can be linked to their inherently increased redox potential. The review primarily focuses on the PI3-kinase/Akt pathway, and the multiple points along this signalling pathway that may be redox regulated. The PI3-kinase/Akt pathway can influence a cells' sensitivity to death inducing signals, through direct manipulation of apoptosis regulating molecules or by regulating the activity of key transcription factors. Proteins involved in the control of apoptosis that are directly regulated by the PI3-kinase/Akt pathway include caspase-9, Bad and the transcription factor GSK-3beta. Lately, it is becoming increasingly obvious that phosphatases are a major counter balance to the PI3-kinase/Akt pathway. Phosphatases such as PP2A and PP1alpha can dephosphorylate signalling molecules within the PI3-kinase/Akt pathway, blocking their activity. It is the balance between the kinase activity and the phosphatase activity that determines the presence and strength of the PI3-kinase/Akt signal. This is why any protein modifications that hinder dephosphorylation can increase the tumours survival advantage. One such modification is the oxidation of the sulphydryl group in key cysteine residues present within the active site of the phosphatases. This highlights the link between the increased redox stress in tumours with the PI3-kinase/Akt pathway. This review will discuss the various sources of reactive oxygen species within a tumour and the effect of these radicals on the PI3-kinase/Akt pathway.
Published:
July 17, 2008
Title:
Metastatic cancer cells with macrophage properties: evidence from a new murine tumor model
Authors:
Huysentruyt, Leanne C.; Mukherjee, Purna; Banerjee, Dia; Shelton, Laura M.; Seyfried, Thomas N.
Abstract:
Metastasis is the process by which cancer cells disseminate from the primary neoplasm and invade surrounding tissue and distant organs, and is the primary cause of morbidity and mortality for cancer patients. Most conventional cancer therapies are ineffective in managing tumor metastasis. This has been due in large part to the absence of in vivo metastatic models that represent the full spectrum of metastatic disease. Here we identify 3 new spontaneously arising tumors in the inbred VM mouse strain, which has a relatively high incidence of CNS tumors. Two of the tumors (VM-M2 and VM-M3) reliably expressed all of the major biological processes of metastasis to include local invasion, intravasation, immune system survival, extravasation and secondary tumor formation involving liver, kidney, spleen, lung and brain. Metastasis was assessed through visual organ inspection, histology, immunohistochemistry and bioluminescence imaging. The metastatic VM tumor cells also expressed multiple properties of macrophages including morphological appearance, surface adhesion, phagocytosis, total lipid composition (glycosphingolipids and phospholipids) and gene expression (CD11b, Iba1, F4/80, CD68, CD45 and CXCR4). The third tumor (VM-NM1) grew rapidly and expressed properties of neural stem/progenitor cells, but was neither invasive nor metastatic. Our data indicate that spontaneous brain tumors can arise from different cell types in VM mice and that metastatic cancer can represent a disease of macrophage-like cells similar to those described in several human metastatic cancers. The new VM tumor model will be useful for defining the biological processes of cancer metastasis and for evaluating potential therapies for tumor management.
Published:
June 30, 2008
Title:
New evidence for hominin carcass processing strategies at 1.5Ma, Koobi Fora, Kenya
Authors:
Pobiner, Briana L.; Rogers, Michael J.; Monahan, Christopher M.; Harris, John W. K.
Abstract:
Reconstruction of early Pleistocene hominin carcass acquisition and processing behaviors are necessarily based at least in part on butchered fossil bones. This paper provides zooarchaeological and taphonomic analyses and behavioral interpretations of three ∼1.5 million-year-old archaeofaunas from areas 1A and 103 in the Okote Member of the Koobi Fora Formation, northern Kenya: FwJj14A, FwJj14B, and GaJi14. These sites are all located in similar paleoenvironmental contexts, near shallow water with swampy, seasonally flooded areas, and some evidence for more wooded or gallery forest settings. Both individual specimen- and assemblage-level analyses of butchery-marked bones indicate that the hominins appear to have practiced similar butchery strategies at all of these sites, with butchery (defleshing, disarticulation, and marrow extraction) of both high- and low-ranked skeletal elements with no apparent preference for prey size, skeletal region, limb class, or limb portion. Only four tooth-marked specimens, including one likely crocodile-tooth-marked bone, are preserved in all three archaeofaunas. A paucity of limb epiphyses suggests that bone-crunching hyenids may have deleted these portions subsequent to hominin butchery. Strangely, there are no stone tools preserved with the 292 cut-marked and 27 percussion-marked faunal specimens (out of a total of 6,039 specimens), suggesting that raw material availability may have conditioned hominin lithic discard patterns at these locales. These assemblages increase our knowledge of the dietary behavior and ecology of Homo erectus, and provide support for variability in early Pleistocene hominin carcass foraging patterns.
Published:
June 30, 2008
Title:
Physiology and Pathophysiology of Potassium Channels in Gastrointestinal Epithelia
Authors:
Heitzmann, Dirk; Warth, Richard
Abstract:
Epithelial cells of the gastrointestinal tract are an important barrier between the “milieu interne” and the luminal content of the gut. They perform transport of nutrients, salts, and water, which is essential for the maintenance of body homeostasis. In these epithelia, a variety of K+ channels are expressed, allowing adaptation to different needs. This review provides an overview of the current literature that has led to a better understanding of the multifaceted function of gastrointestinal K+ channels, thereby shedding light on pathophysiological implications of impaired channel function. For instance, in gastric mucosa, K+ channel function is a prerequisite for acid secretion of parietal cells. In epithelial cells of small intestine, K+ channels provide the driving force for electrogenic transport processes across the plasma membrane, and they are involved in cell volume regulation. Fine tuning of salt and water transport and of K+ homeostasis occurs in colonic epithelia cells, where K+ channels are involved in secretory and reabsorptive processes. Furthermore, there is growing evidence for changes in epithelial K+ channel expression during cell proliferation, differentiation, apoptosis, and, under pathological conditions, carcinogenesis. In the future, integrative approaches using functional and postgenomic/proteomic techniques will help us to gain comprehensive insights into the role of K+ channels of the gastrointestinal tract.
Published:
June 30, 2008
Title:
Evolution of mammals and their gut microbes
Authors:
Ley, Ruth E.; Hamady, Micah; Lozupone, Catherine; Turnbaugh, Peter; Ramey, Rob Roy; Bircher, J. Stephen; Schlegel, Michael. L.; Tucker, Tammy A.; Schrenzel, Mark D.; Knight, Rob; Gordon, Jeffrey I.
Abstract:
Mammals are metagenomic in that they are composed not only of their own gene complements but also those of all of their associated microbes. To understand the co-evolution of the mammals and their indigenous microbial communities, we conducted a network-based analysis of bacterial 16S rRNA gene sequences from the fecal microbiota of humans and 59 other mammalian species living in two zoos and the wild. The results indicate that host diet and phylogeny both influence bacterial diversity, which increases from carnivory to omnivory to herbivory, that bacterial communities co-diversified with their hosts, and that the gut microbiota of humans living a modern lifestyle is typical of omnivorous primates.
Published:
June 19, 2008
Title:
Hypovitaminosis D Among Healthy Children in the United States: A Review of the Current Evidence
Authors:
Rovner, Alisha J.; O'Brien, Kimberly O.
Abstract:
Objective To review the published literature on serum 25-hydroxyvitamin D concentrations in US children. Data Sources Articles were identified by searching MEDLINE using 25-hydroxyvitamin D, vitamin D, hypovitaminosis D, vitamin D insufficiency, vitamin D deficiency, children, and adolescents as key words and by screening references from original studies. Study Selection Studies were included if they fulfilled the following a priori criteria: contained a well-defined sample of children, included only healthy children, presented data on serum 25-hydroxyvitamin D concentrations, were published in the past 10 years, and were conducted in the United States. Data Extraction Serum 25-hydroxyvitamin D concentrations and prevalence of low vitamin D status (hypovitaminosis D). Data Synthesis Fourteen articles fulfilled the criteria. There were no consistent definitions of hypovitaminosis D; values corresponding to vitamin D deficiency ranged from less than 5 ng/mL to less than 12 ng/mL, and those for vitamin D insufficiency ranged from less than 10 ng/mL to less than 32 ng/mL (to convert 25-hydroxyvitamin D concentrations to nanomoles per liter, multiply by 2.496). The following assays were used: radioimmunoassay (7 studies), competitive binding protein assay (3 studies), automated chemiluminescence protein-binding assay (3 studies), and enzyme-linked immunosorbent assay (1 study). Breastfed infants in winter who did not receive vitamin D supplementation were the most severely vitamin D deficient (78%). Estimates of the prevalence of hypovitaminosis D ranged from 1% to 78%. Older age, winter season, higher body mass index, black race/ethnicity, and elevated parathyroid hormone concentrations were associated with lower 25-hydroxyvitamin D concentrations. Conclusion Although overt vitamin D deficiency is no longer common in US children, lesser degrees of vitamin D insufficiency are widespread.
Published:
May 31, 2008
Title:
Role of reactive oxygen species in the neurotoxicity of environmental agents implicated in Parkinson's disease
Authors:
Drechsel, Derek A.; Patel, Manisha
Abstract:
Among age-related neurodegenerative diseases, Parkinson's disease (PD) represents the best example for which oxidative stress has been strongly implicated. The etiology of PD remains unknown, yet recent epidemiological studies have linked exposure to environmental agents, including pesticides, with an increased risk of developing the disease. As a result, the environmental hypothesis of PD has developed, which speculates that chemical agents in the environment are capable of producing selective dopaminergic cell death, thus contributing to disease development. The use of environmental agents such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, rotenone, paraquat, dieldrin, and maneb in toxicant-based models of PD has become increasingly popular and provided valuable insight into the neurodegenerative process. Understanding the unique and shared mechanisms by which these environmental agents act as selective dopaminergic toxicants is critical in identifying pathways involved in PD pathogenesis. In this review, we discuss the neurotoxic properties of these compounds with specific focus on the induction of oxidative stress. We highlight landmark studies along with recent advances that support the role of reactive oxygen and reactive nitrogen species from a variety of cellular sources as potent contributors to the neurotoxicity of these environmental agents. Finally, human risk and the implications of these studies in our understanding of PD-related neurodegeneration are discussed.
Published:
May 31, 2008
Title:
Protein-induced satiety: effects and mechanisms of different proteins
Authors:
Veldhorst, M.; Smeets, A.; Soenen, S.; Hochstenbach-Waelen, A.; Hursel, R.; Diepvens, K.; Lejeune, M.; Luscombe-Marsh, N.; Westerterp-Plantenga, M.
Abstract:
Relatively high protein diets, i.e. diets that maintain the absolute number of grams of protein ingested as compared to before dieting, are a popular strategy for weight loss and weight maintenance. Research into multiple mechanisms regulating body weight has focused on the effects of different quantities and types of dietary protein. Satiety and energy expenditure are important in protein-enhanced weight loss and weight maintenance. Protein-induced satiety has been shown acutely, with single meals, with contents of 25% to 81% of energy from protein in general or from specific proteins, while subsequent energy intake reduction was significant. Protein-induced satiety has been shown with high protein ad libitum diets, lasting from 1 to 6 days, up to 6 months. Also significantly greater weight loss has been observed in comparison with control. Mechanisms explaining protein-induced satiety are nutrient-specific, and consist mainly of synchronization with elevated amino acid concentrations. Different proteins cause different nutrient related responses of (an)orexigenic hormones. Protein-induced satiety coincides with a relatively high GLP-1 release, stimulated by the carbohydrate content of the diet, PYY release, while ghrelin does not seem to be especially affected, and little information is available on CCK. Protein-induced satiety is related to protein-induced energy expenditure. Finally, protein-induced satiety appears to be of vital importance for weight loss and weight maintenance. With respect to possible adverse events, chronic ingestion of large amounts of sulphur-containing amino acids may have an indirect effect on blood pressure by induction of renal subtle structural damage, ultimately leading to loss of nephron mass, and a secondary increase in blood pressure. The established synergy between obesity and low nephron number on induction of high blood pressure and further decline of renal function identifies subjects with obesity, metabolic syndrome and diabetes mellitus II as particularly susceptible groups.
Published:
May 22, 2008
Title:
Low-carbohydrate diet in type 2 diabetes: stable improvement of bodyweight and glycemic control during 44 months follow-up
Authors:
Nielsen, Jörgen V.; Joensson, Eva A.
Abstract:
Low-carbohydrate diets, due to their potent antihyperglycemic effect, are an intuitively attractive approach to the management of obese patients with type 2 diabetes. We previously reported that a 20% carbohydrate diet was significantly superior to a 55–60% carbohydrate diet with regard to bodyweight and glycemic control in 2 groups of obese diabetes patients observed closely over 6 months (intervention group, n = 16; controls, n = 15) and we reported maintenance of these gains after 22 months. The present study documents the degree to which these changes were preserved in the low-carbohydrate group after 44 months observation time, without close follow-up. In addition, we assessed the performance of the two thirds of control patients from the high-carbohydrate diet group that had changed to a low-carbohydrate diet after the initial 6 month observation period. We report cardiovascular outcome for the low-carbohydrate group as well as the control patients who did not change to a low-carbohydrate diet.
Published:
May 21, 2008
Title:
Food-miles and the relative climate impacts of food choices in the United States
Authors:
Weber, Christopher L.; Matthews, H. Scott
Abstract:
Despite significant recent public concern and media attention to the environmental impacts of food, few studies in the United States have systematically compared the life-cycle greenhouse gas (GHG) emissions associated with food production against long-distance distribution, aka "food-miles." We find that although food is transported long distances in general (1640 km delivery and 6760 km life-cycle supply chain on average) the GHG emissions associated with food are dominated by the production phase, contributing 83% of the average U.S. household's 8.1 t CO2e/yr footprint for food consumption. Transportation as a whole represents only 11% of life-cycle GHG emissions, and final delivery from producer to retail contributes only 4%. Different food groups exhibit a large range in GHG-intensity; on average, red meat is around 150% more GHG-intensive than chicken or fish. Thus, we suggest that dietary shift can be a more effective means of lowering an average household's food-related climate footprint than "buying local." Shifting less than one day per week's worth of calories from red meat and dairy products to chicken, fish, eggs, or a vegetable-based diet achieves more GHG reduction than buying all locally sourced food.
Published:
May 14, 2008
Title:
Human metabolic phenotype diversity and its association with diet and blood pressure
Authors:
Holmes, Elaine; Loo, Ruey Leng; Stamler, Jeremiah; Bictash, Magda; Yap, Ivan K. S.; Chan, Queenie; Ebbels, Tim; De Iorio, Maria; Brown, Ian J.; Veselkov, Kirill A.; Daviglus, Martha L.; Kesteloot, Hugo; Ueshima, Hirotsugu; Zhao, Liancheng; Nicholson, Jeremy K.; Elliott, Paul
Abstract:
Metabolic phenotypes are the products of interactions among a variety of factors-dietary, other lifestyle/environmental, gut microbial and genetic. We use a large-scale exploratory analytical approach to investigate metabolic phenotype variation across and within four human populations, based on 1H NMR spectroscopy. Metabolites discriminating across populations are then linked to data for individuals on blood pressure, a major risk factor for coronary heart disease and stroke (leading causes of mortality worldwide). We analyse spectra from two 24-hour urine specimens for each of 4,630 participants from the INTERMAP epidemiological study, involving 17 population samples aged 40-59 in China, Japan, UK and USA. We show that urinary metabolite excretion patterns for East Asian and western population samples, with contrasting diets, diet-related major risk factors, and coronary heart disease/stroke rates, are significantly differentiated (P < 10(-16)), as are Chinese/Japanese metabolic phenotypes, and subgroups with differences in dietary vegetable/animal protein and blood pressure. Among discriminatory metabolites, we quantify four and show association (P < 0.05 to P
Published:
May 14, 2008
Title:
V domain of RAGE interacts with AGEs on prostate carcinoma cells
Authors:
Allmen, Edith Uetz-von; Koch, Michael; Fritz, Günter; Legler, Daniel F.
Abstract:
BACKGROUND: The expression of the scavenger receptor for advanced glycation end products (RAGE) and various ligands of RAGE correlate significantly with cancer progression. However, the mechanism of RAGE/sRAGE-induced cancer cell activation and ligand usage remain largely unknown. METHODS: Androgen-independent, highly invasive, as well as androgen-dependent, non-invasive human prostate carcinoma (CaP) cells were investigated for their interaction with the soluble form of RAGE (sRAGE). Using neutralizing antibodies and soluble proteins, the ligand for RAGE was identified on CaP cells and ligand binding with sRAGE was biochemically characterized. RESULTS: Both androgen-independent, highly invasive and androgen-dependent, non-invasive CaP cells interacted with immobilized sRAGE in a surprisingly strong manner. Using C-terminal truncation variants of RAGE we identified the V domain being responsible for the adhesion of CaP cells to sRAGE. Moreover, we demonstrate that this adhesion cannot be blocked by S100B or neutralizing antibodies against beta integrins, or amphoterin. However, the CaP cell-RAGE interaction was inhibited with either AGE-modified proteins, or with neutralizing antibodies against AGE or RAGE. Despite similar binding kinetics between AGE-modified BSA and different RAGE domains, only applying an excess of sRAGE, but not the VC1 or V domain of RAGE, was able to block the CaP cell-RAGE interaction. CONCLUSIONS: We identified AGEs as the ligand for RAGE on both invasive and non-invasive prostate cancer cells.
Published:
May 14, 2008
Title:
Site-specific blockade of RAGE-Vd prevents amyloid-beta oligomer neurotoxicity
Authors:
Sturchler, Emmanuel; Galichet, Arnaud; Weibel, Mirjam; Leclerc, Estelle; Heizmann, Claus W.
Abstract:
In the genesis of Alzheimer's disease (AD), converging lines of evidence suggest that amyloid-beta peptide (Abeta) triggers a pathogenic cascade leading to neuronal loss. It was long assumed that Abeta had to be assembled into extracellular amyloid fibrils or aggregates to exert its cytotoxic effects. Over the past decade, characterization of soluble oligomeric Abeta species in the brains of AD patients and in transgenic models has raised the possibility that different conformations of Abeta may contribute to AD pathology via different mechanisms. The receptor for advanced glycation end products (RAGE), a member of the Ig superfamily, is a cellular binding site for Abeta. Here, we investigate the role of RAGE in apoptosis induced by distinct well characterized Abeta conformations: Abeta oligomers (AbetaOs), Abeta fibrils (AbetaFs), and Abeta aggregates (AbetaAs). In our in vitro system, treatment with polyclonal anti-RAGE antibodies significantly improves SHSY-5Y cell and neuronal survival exposed to either AbetaOs or AbetaAs but does not affect AbetaF toxicity. Interestingly, using site-specific antibodies, we demonstrate that targeting of the V(d) domain of RAGE attenuates AbetaO-induced toxicity in both SHSY-5Y cells and rat cortical neurons, whereas inhibition of AbetaA-induced apoptosis requires the neutralization of the C(1d) domain of the receptor. Thus, our data indicate that distinct regions of RAGE are involved in Abeta-induced cellular and neuronal toxicity with respect to the Abeta aggregation state, and they suggest the blockage of particular sites of the receptor as a potential therapeutic strategy to attenuate neuronal death.
Published:
May 13, 2008
bottom of page