top of page
Published Science
Click Search to Filter.
Total Entries: 10690
Title:
Does Being an Immigrant Make a Difference in Seeking Physician Services?
Authors:
Xu, Ke Tom; Borders, Tyrone F.
Abstract:
The current study investigated the effects of immigration status, acculturation, and health beliefs on the use of preventive and non-preventive visits, through use of a nationally representative sample of U.S.-born and foreign-born adults. U.S.-born adults were found to have significantly more preventive and non-preventive visits than immigrants. The effects on predicting preventive visits of education, having a usual source of care, and having other public insurance were stronger among immigrants than among the U.S.-born. Health confidence and believing in the need for health insurance significantly predicted the numbers of both preventive and non-preventive visits among the U.S.-born but correlated little with either type of visit among immigrants. Among immigrant adults, acculturation affected only the number of preventive visits. The lower utilization of both preventive and non-preventive care among immigrants may be associated with a combination of better health and more limited enabling resources.
Published:
May 7, 2008
Title:
Carbohydrate intake, glycemic index, glycemic load, and risk of postmenopausal breast cancer in a prospective study of French women
Authors:
Lajous, Martin; Boutron-Ruault, Marie-Christine; Fabre, Alban; Clavel-Chapelon, Françoise; Romieu, Isabelle
Abstract:
Background: Diets high in carbohydrates may result in chronically elevated insulin concentrations and may affect breast cancer risk by stimulation of insulin receptors or through insulin-like growth factor I (IGF-I)–mediated mitogenesis. Insulin response to carbohydrate intake is increased in insulin-resistant states such as obesity. Objective: We sought to evaluate carbohydrate intake, glycemic index (GI), and glycemic load (GL) and subsequent overall and hormone-receptor-defined breast cancer risk among postmenopausal women. Design: A prospective cohort analysis of dietary carbohydrate and fiber intakes was conducted among 62 739 postmenopausal women from the E3N French study who had completed a validated dietary history questionnaire in 1993. During a 9-y period, 1812 cases of pathology-confirmed breast cancer were documented through follow-up questionnaires. Nutrients were categorized into quartiles and energy-adjusted with the regression-residual method. Cox model– derived relative risks (RRs) were adjusted for known determinants in breast cancer. Results: Dietary carbohydrate and fiber intakes were not associated with overall breast cancer risk. Among overweight women, we observed an association between GI and breast cancer (RRQ1–Q4: 1.35; 95% CI: 1.00, 1.82; P for trend ҃ 0.04). For women in the highest category of waist circumference, the RRQ1–Q4 was 1.28 (95% CI: 0.98, 1.67; P for trend ҃ 0.10) for carbohydrates, 1.35 (95% CI: 1.04, 1.75; P for trend ҃ 0.01) for GI, and 1.37 (95% CI: 1.05, 1.77; P for trend ҃ 0.003) for GL. We also observed a direct association between carbohydrate intake, GL, and estrogen receptor–negative breast cancer risk. Conclusions: Rapidly absorbed carbohydrates are associated with postmenopausal breast cancer risk among overweight women and women with large waist circumference. Carbohydrate intake may also be associated with estrogen receptor–negative breast cancer. Am J Clin Nutr 2008;87:1384 –91.
Published:
April 30, 2008
Title:
Alteration of cardiovascular autonomic functions by vegetarian diets in postmenopausal women is related to LDL cholesterol levels
Authors:
Fu, Chin-Hua; Yang, Cheryl C. H.; Lin, Chin-Lon; Kuo, Terry B. J.
Abstract:
This study was designed to test the hypothesis that alteration of cardiovascular autonomic functions by vegetarian diets in healthy postmenopausal women is related to lipid metabolism. A total of 70 healthy postmenopausal women not on hormone therapy participated in this study: 35 were vegetarians (mean age 55.0 years) and 35 were omnivores (mean age 55.1 years). Cardiovascular autonomic functions and baroreflex sensitivity were evaluated by specific frequency-domain measures of heart rate variability (HRV) and arterial blood pressure fluctuation. The vegetarians had statistically significant lowered blood pressure, total cholesterol, low-density lipoprotein (LDL) cholesterol, triglyceride, and fasting glucose levels compared with the omnivores. The vegetarians exhibited a significant higher total power, low-frequency (LF; 0.04-0.15 Hz) and high-frequency (HF; 0.15-0.4 Hz) of HRV and increased baroreflex sensitivity measures [Brr(LF) and Brr(HF)] compared with the omnivores. Total power, LF and HF of HRV, Brr(LF), and Brr(HF) were significantly and negatively correlated with LDL-cholesterol concentrations (P
Published:
April 29, 2008
Title:
Has carbohydrate-restriction been forgotten as a treatment for diabetes mellitus? A perspective on the ACCORD study design
Authors:
Westman, Eric C.; Vernon, Mary C.
Abstract:
Prior to the discovery of medical treatment for diabetes, carbohydrate-restriction was the predominant treatment recommendation to treat diabetes mellitus. In this commentary we argue that carbohydrate-restriction should be reincorporated into contemporary treatment studies for diabetes mellitus.
Published:
April 8, 2008
Title:
Dietary carbohydrate restriction in type 2 diabetes mellitus and metabolic syndrome: time for a critical appraisal
Authors:
Accurso, Anthony; Bernstein, Richard K.; Dahlqvist, Annika; Draznin, Boris; Feinman, Richard D.; Fine, Eugene J.; Gleed, Amy; Jacobs, David B.; Larson, Gabriel; Lustig, Robert H.; Manninen, Anssi H.; McFarlane, Samy I.; Morrison, Katharine; Nielsen, Jørgen Vesti; Ravnskov, Uffe; Roth, Karl S.; Silvestre, Ricardo; Sowers, James R.; Sundberg, Ralf; Volek, Jeff S.; Westman, Eric C.; Wood, Richard J.; Wortman, Jay; Vernon, Mary C.
Abstract:
Current nutritional approaches to metabolic syndrome and type 2 diabetes generally rely on reductions in dietary fat. The success of such approaches has been limited and therapy more generally relies on pharmacology. The argument is made that a re-evaluation of the role of carbohydrate restriction, the historical and intuitive approach to the problem, may provide an alternative and possibly superior dietary strategy. The rationale is that carbohydrate restriction improves glycemic control and reduces insulin fluctuations which are primary targets. Experiments are summarized showing that carbohydrate-restricted diets are at least as effective for weight loss as low-fat diets and that substitution of fat for carbohydrate is generally beneficial for risk of cardiovascular disease. These beneficial effects of carbohydrate restriction do not require weight loss. Finally, the point is reiterated that carbohydrate restriction improves all of the features of metabolic syndrome.
Published:
April 7, 2008
Title:
Disseminating Health Information and Diabetes Care for Latinos Via Electronic Information Kiosks
Authors:
Matthews, Paul H.; Darbisi, Carolina; Sandmann, Lorilee; Galen, Robert; Rubin, Donald
Abstract:
This study investigated the use of electronic, web-enabled touch-screen information kiosks as a tool to provide culturally and linguistically appropriate diabetes information to Latino audiences. Two kiosk models (high privacy sit-down, group enabled stand-up) in two locations (pharmacy, community center) in Northeast Georgia provided bilingual, read-aloud diabetes education and local resource information on health care. Data from public use and interviews with focus group participants showed that users found the kiosks and their functions helpful and usable, though usage was moderated by presence or absence of a peer health educator (promotora); participants also preferred the sit-down, multi-function kiosk model.
Published:
April 7, 2008
Title:
Angina pectoris and atherosclerotic risk factors in the multisite cardiac lifestyle intervention program
Authors:
Frattaroli, Joanne; Weidner, Gerdi; Merritt-Worden, Terri A.; Frenda, Steven; Ornish, Dean
Abstract:
Cardiovascular symptom relief is a major indicator for revascularization procedures. To examine the effects of intensive lifestyle modification on symptom relief, we investigated changes in angina pectoris, coronary risk factors, quality of life, and lifestyle behaviors in patients with stable coronary artery disease enrolled in the multisite cardiac lifestyle intervention program, an ongoing health insurance-covered lifestyle intervention conducted at 22 sites in the united states. Patients with coronary artery disease (nonsmokers; 757 men, 395 women; mean age 61 years) were asked to make changes in diet (10% calories from fat, plant based), engage in moderate exercise (3 hours/week), and practice stress management (1 hour/day). At baseline, 108 patients (43% women) reported mild angina and 174 patients (37% women) reported limiting angina. By 12 weeks, 74% of these patients were angina free, and an additional 9% moved from limiting to mild angina. This improvement in angina was significant for patients with mild and limiting angina at baseline regardless of gender (p <0.01). Significant improvements in cardiac risk factors, quality of life, and lifestyle behaviors were observed, and patients with angina who became angina free by 12 weeks showed the greatest improvements in exercise capacity, depression, and health-related quality of life (p
Published:
March 31, 2008
Title:
Dyslipidemia is a protective factor in amyotrophic lateral sclerosis
Authors:
Dupuis, L.; Corcia, P.; Fergani, A.; Gonzalez De Aguilar, J.-L.; Bonnefont-Rousselot, D.; Bittar, R.; Seilhean, D.; Hauw, J.-J.; Lacomblez, L.; Loeffler, J.-P.; Meininger, V.
Abstract:
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is the most serious form of degenerative motor neuron disease in adults, characterized by upper and lower motor neuron degeneration, skeletal muscle atrophy, paralysis, and death. High prevalence of malnutrition and weight loss adversely affect quality of life. Moreover, two thirds of patients develop a hypermetabolism of unknown cause, leading to increased resting energy expenditure. Inasmuch as lipids are the major source of energy for muscles, we determined the status of lipids in a population of patients with ALS and investigated whether lipid contents may have an impact on disease progression and survival. METHODS: Blood concentrations of triglycerides, cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were measured in a cohort of 369 patients with ALS and compared to a control group of 286 healthy subjects. Postmortem histologic examination was performed on liver specimens from 59 other patients with ALS and 16 patients with Parkinson disease (PD). RESULTS: The frequency of hyperlipidemia, as revealed by increased plasma levels of total cholesterol or LDL, was twofold higher in patients with ALS than in control subjects. As a result, steatosis of the liver was more pronounced in patients with ALS than in patients with PD. Correlation studies demonstrated that bearing an abnormally elevated LDL/HDL ratio significantly increased survival by more than 12 months. CONCLUSIONS: Hyperlipidemia is a significant prognostic factor for survival of patients with amyotrophic lateral sclerosis. This finding highlights the importance of nutritional intervention strategies on disease progression and claims our attention when treating these patients with lipid-lowering drugs.
Published:
March 24, 2008
Title:
Modeling the Local Dynamics of Cardiovascular Health: Risk Factors, Context, and Capacity
Authors:
Orenstein, Diane R; Homer, Jack; Milstein, Bobby; Wile, Kristina; Pratibhu, Parakash; Farris, Rosanne
Abstract:
Published:
March 14, 2008
Title:
Biglycan Is Required for Adaptive Remodeling After Myocardial Infarction
Authors:
Westermann, D.; Mersmann, J.; Melchior, A.; Freudenberger, T.; Petrik, C.; Schaefer, L.; Lüllmann-Rauch, R.; Lettau, O.; Jacoby, C.; Schrader, J.; Brand-Herrmann, S.-M.; Young, M.F.; Schultheiss, H.P.; Levkau, B.; Baba, H.A.; Unger, T.; Zacharowski, K.; Tschöpe, C.; Fischer, J.W.
Abstract:
Published:
March 10, 2008
Title:
Acculturation and Healthy Lifestyle Among Latinos With Diabetes
Authors:
Mainous, Arch G.; Diaz, Vanessa A.; Geesey, Mark E.
Abstract:
PURPOSE Latinos have a high prevalence of diabetes and disproportionately experience diabetic complications. We sought to examine the association of acculturation on healthy lifestyle habits among the Latino population in the United States with diabetes. METHODS We studied Latino adults (aged ≥20 years) with previously diagnosed diabetes in the 1999–2004 National Health and Nutrition Examination Survey (unweighted N = 467; weighted N = 1,957,778). Healthy lifestyle habits were those consistent with recommendations of the American Diabetes Association (ADA) regarding exercise, smoking, obesity, and diet. Acculturation was measured with the Short Acculturation Scale, a validated 5-item scale assessing use of the Spanish language. Logistic regression analyses of acculturation and healthy behaviors were computed controlling for access to care, demographics, and disease characteristics. RESULTS In bivariate analyses, compared with their less-acculturated counterparts, individuals who were more-acculturated to any extent were less likely to have a higher fiber intake (9.4% vs 35.4%, P = .001) and lower saturated fat intake (17.2% vs 46.5%, P = .03). More-acculturated individuals were more likely to report leisure time exercise (59.2% vs 19.3%, P
Published:
February 29, 2008
Title:
Effects of weight loss from a very-low-carbohydrate diet on endothelial function and markers of cardiovascular disease risk in subjects with abdominal obesity
Authors:
Keogh, Jennifer B.; Brinkworth, Grant D.; Noakes, Manny; Belobrajdic, Damien P.; Buckley, Jonathan D.; Clifton, Peter M.
Abstract:
ABSTRACT. Background: The effects of a very-low-carbohydrate, high-saturated-fat weight-loss diet (LC) on brachial artery flow-mediated dilatation (FMD) and ma
Published:
February 29, 2008
Title:
Role of Mitochondrial Dysfunction in Insulin Resistance
Authors:
Kim, Jeong-a; Wei, Yongzhong; Sowers, James R.
Abstract:
Insulin resistance is characteristic of obesity, type 2 diabetes, and components of the cardiometabolic syndrome, including hypertension and dyslipidemia, that collectively contribute to a substantial risk for cardiovascular disease. Metabolic actions of insulin in classic insulin target tissues (eg, skeletal muscle, fat, and liver), as well as actions in nonclassic targets (eg, cardiovascular tissue), help to explain why insulin resistance and metabolic dysregulation are central in the pathogenesis of the cardiometabolic syndrome and cardiovascular disease. Glucose and lipid metabolism are largely dependent on mitochondria to generate energy in cells. Thereby, when nutrient oxidation is inefficient, the ratio of ATP production/oxygen consumption is low, leading to an increased production of superoxide anions. Reactive oxygen species formation may have maladaptive consequences that increase the rate of mutagenesis and stimulate proinflammatory processes. In addition to reactive oxygen species formation, genetic factors, aging, and reduced mitochondrial biogenesis all contribute to mitochondrial dysfunction. These factors also contribute to insulin resistance in classic and nonclassic insulin target tissues. Insulin resistance emanating from mitochondrial dysfunction may contribute to metabolic and cardiovascular abnormalities and subsequent increases in cardiovascular disease. Furthermore, interventions that improve mitochondrial function also improve insulin resistance. Collectively, these observations suggest that mitochondrial dysfunction may be a central cause of insulin resistance and associated complications. In this review, we discuss mechanisms of mitochondrial dysfunction related to the pathophysiology of insulin resistance in classic insulin-responsive tissue, as well as cardiovascular tissue.
Published:
February 28, 2008
Title:
Eggs modulate the inflammatory response to carbohydrate restricted diets in overweight men
Authors:
Ratliff, Joseph C.; Mutungi, Gisella; Puglisi, Michael J.; Volek, Jeff S.; Fernandez, Maria Luz
Abstract:
BACKGROUND: Carbohydrate restricted diets (CRD) consistently lower glucose and insulin levels and improve atherogenic dyslipidemia [decreasing triglycerides and increasing HDL cholesterol (HDL-C)]. We have previously shown that male subjects following a CRD experienced significant increases in HDL-C only if they were consuming a higher intake of cholesterol provided by eggs compared to those individuals who were taking lower concentrations of dietary cholesterol. Here, as a follow up of our previous study, we examined the effects of eggs (a source of both dietary cholesterol and lutein) on adiponectin, a marker of insulin sensitivity, and on inflammatory markers in the context of a CRD. METHODS: Twenty eight overweight men [body mass index (BMI) 26-37 kg/m2] aged 40-70 y consumed an ad libitum CRD (% energy from CHO:fat:protein = 17:57:26) for 12 wk. Subjects were matched by age and BMI and randomly assigned to consume eggs (EGG, n = 15) (640 mg additional cholesterol/day provided by eggs) or placebo (SUB, n = 13) (no additional dietary cholesterol). Fasting blood samples were drawn before and after the intervention to assess plasma lipids, insulin, adiponectin and markers of inflammation including C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1(VCAM-1). RESULTS: Body weight, percent total body fat and trunk fat were reduced for all subjects after 12 wk (P < 0.0001). Increases in adiponectin were also observed (P < 0.01). Subjects in the EGG group had a 21% increase in this adipokine compared to a 7% increase in the SUB group (P < 0.05). Plasma CRP was significantly decreased only in the EGG group (P < 0.05). MCP-1 levels were decreased for the SUB group (P
Published:
February 19, 2008
Title:
Specialized Perinodal Fat Fuels and Fashions Immunity
Authors:
Knight, Stella C.
Abstract:
Adipose tissue around lymph nodes is usually removed prior to the study of immune activity—but is it time to reconsider this practice? Perinodal adipose tissue may provide not only a specific lipid resource but also fatty acids, dendritic cells, and soluble mediators that modulate local immunity.
Published:
February 14, 2008
Title:
Evidence of different metabolic phenotypes in humans
Authors:
Assfalg, Michael; Bertini, Ivano; Colangiuli, Donato; Luchinat, Claudio; Schäfer, Hartmut; Schütz, Birk; Spraul, Manfred
Abstract:
The study of metabolic responses to drugs, environmental changes, and diseases is a new promising area of metabonomic research. Metabolic fingerprints can be obtained by analytical techniques such as nuclear magnetic resonance (NMR). In principle, alterations of these fingerprints due to appearance/disappearance or concentration changes of metabolites can provide early evidences of, for example, onset of diseases. A major drawback in this approach is the strong day-to-day variability of the individual metabolic fingerprint, which should be rather called a metabolic “snapshot.” We show here that a thorough statistical analysis performed on NMR spectra of human urine samples reveals an invariant part characteristic of each person, which can be extracted from the analysis of multiple samples of each single subject. This finding (i) provides evidence that individual metabolic phenotypes may exist and (ii) opens new perspectives to metabonomic studies, based on the possibility of eliminating the daily “noise” by multiple sample collection.
Published:
February 4, 2008
Title:
Low-carbohydrate-diet score and risk of type 2 diabetes in women
Authors:
Halton, Thomas L.; Liu, Simin; Manson, JoAnn E.; Hu, Frank B.
Abstract:
ABSTRACT. Background: Low-carbohydrate weight-loss diets remain popular; however, the long-term effects of these diets are not known.Objective: The objective w
Published:
January 31, 2008
Title:
On the Ideology of Nutritionism
Authors:
Scrinis, Gyorgy
Abstract:
This essay introduces and defines the ideology or paradigm of nutritionism, which is generally characterized by a reductive focus on the nutrient composition of food. More specifically, it is where the nutri-biochemical level of engagement with food and the body becomes the dominant way of understanding the relationship between food and bodily health, and at the expense of other levels and ways of understanding and engaging with food. Nutritionism is the dominant paradigm within nutrition science, informs much dietary advice, and has become a primary means for the engineering and marketing of food products. A number of characteristics of nutritionism are defined, including nutritional reductionism, biomarker reductionism, genetic nutritionism, the functional body, the myth of nutritional precision, the nutritional gaze, and nutritional tinkering, nutri-quantification, the erasure of qualitatative food distinctions, nutrient fetishism, the 'good and bad nutrient' discourses, nutri-commodification, and the nutricentric person. A number of types of foods and types of food marketing are also introduced and defined, including nutritionally engineered foods, transnutric foods, nutritionally marketed foods and functionally marketed foods.
Published:
January 31, 2008
Title:
Proximal, Distal, and the Politics of Causation: What’s Level Got to Do With It?
Authors:
Krieger, Nancy
Abstract:
Causal thinking in public health, and especially in the growing literature on social determinants of health, routinely employs the terminology of proximal (or downstream) and distal (or upstream).I argue that the use of these terms is problematic and adversely affects public health research, practice, and causal accountability. At issue are distortions created by conflating measures of space, time, level, and causal strength.To make this case, I draw on an ecosocial perspective to show how public health got caught in the middle of the problematic proximal–distal divide—surprisingly embraced by both biomedical and social determinist frameworks—and propose replacing the terms proximal and distal with explicit language about levels, pathways, and power.
Published:
January 31, 2008
Title:
Human and Chimpanzee Gene Expression Differences Replicated in Mice Fed Different Diets
Authors:
Somel, Mehmet; Creely, Hilliary; Franz, Henriette; Mueller, Uwe; Lachmann, Michael; Khaitovich, Philipp; Pääbo, Svante
Abstract:
Although the human diet is markedly different from the diets of closely related primate species, the influence of diet on phenotypic and genetic differences between humans and other primates is unknown. In this study, we analyzed gene expression in laboratory mice fed diets typical of humans and of chimpanzees. The effects of human diets were found to be significantly different from that of a chimpanzee diet in the mouse liver, but not in the brain. Importantly, 10% of the genes that differ in their expression between humans and chimpanzee livers differed also between the livers of mice fed the human and chimpanzee diets. Furthermore, both the promoter sequences and the amino acid sequences of these diet-related genes carry more differences between humans and chimpanzees than random genes. Our results suggest that the mouse can be used to study at least some aspects of human-specific traits.
Published:
January 29, 2008
Title:
Carbohydrate restriction, prostate cancer growth, and the insulin-like growth factor axis
Authors:
Freedland, Stephen J.; Mavropoulos, John; Wang, Amy; Darshan, Medha; Demark-Wahnefried, Wendy; Aronson, William J.; Cohen, Pinchas; Hwang, David; Peterson, Bercedis; Fields, Timothy; Pizzo, Salvatore V.; Isaacs, William B.
Abstract:
BACKGROUND: Recent evidence suggests carbohydrate intake may influence prostate cancer biology. We tested whether a no-carbohydrate ketogenic diet (NCKD) would delay prostate cancer growth relative to Western and low-fat diets in a xenograft model. METHODS: Seventy-five male SCID mice were fed a NCKD (84% fat-0% carbohydrate-16% protein kcal), low-fat (12% fat-72% carbohydrate-16% protein kcal), or Western diet (40% fat-44% carbohydrate-16% protein kcal). Low-fat mice were fed ad libitum and the other arms fed via a modified-paired feeding protocol. After 24 days, all mice were injected with LAPC-4 cells and sacrificed when tumors approached 1,000 mm(3). RESULTS: Despite consuming equal calories, NCKD-fed mice lost weight (up to 15% body weight) relative to low-fat and Western diet-fed mice and required additional kcal to equalize body weight. Fifty-one days after injection, NCKD mice tumor volumes were 33% smaller than Western mice (rank-sum, P = 0.009). There were no differences in tumor volume between low-fat and NCKD mice. Dietary treatment was significantly associated with survival (log-rank, P = 0.006), with the longest survival among the NCKD mice, followed by the low-fat mice. Serum IGFBP-3 was highest and IGF-1:IGFBP-3 ratio was lowest among NCKD mice while serum insulin and IGF-1 levels were highest in Western mice. NCKD mice had significantly decreased hepatic fatty infiltration relative to the other arms. CONCLUSIONS: In this xenograft model, despite consuming more calories, NCKD-fed mice had significantly reduced tumor growth and prolonged survival relative to Western mice and was associated with favorable changes in serum insulin and IGF axis hormones relative to low-fat or Western diet.
Published:
December 31, 2007
Title:
Challenges of existing pediatric dyslipidemia guidelines: call for reappraisal
Authors:
Steinberger, Julia; Kelly, Aaron S
Abstract:
Published:
December 31, 2007
Title:
Metabolic Effects of Weight Loss on a Very-Low-Carbohydrate Diet Compared With an Isocaloric High-Carbohydrate Diet in Abdominally Obese Subjects
Authors:
Tay, Jeannie; Brinkworth, Grant D.; Noakes, Manny; Keogh, Jennifer; Clifton, Peter M.
Abstract:
Objectives This study was designed to compare the effects of an energy-reduced, isocaloric very-low-carbohydrate, high-fat (VLCHF) diet and a high-carbohydrate, low-fat (HCLF) diet on weight loss and cardiovascular disease (CVD) risk outcomes. Background Despite the popularity of the VLCHF diet, no studies have compared the chronic effects of weight loss and metabolic change to a conventional HCLF diet under isocaloric conditions. Methods A total of 88 abdominally obese adults were randomly assigned to either an energy-restricted (∼6 to 7 MJ, 30% deficit), planned isocaloric VLCHF or HCLF diet for 24 weeks in an outpatient clinical trial. Body weight, blood pressure, fasting glucose, lipids, insulin, apolipoprotein B (apoB), and C-reactive protein (CRP) were measured at weeks 0 and 24. Results Weight loss was similar in both groups (VLCHF −11.9 ± 6.3 kg, HCLF −10.1 ± 5.7 kg; p = 0.17). Blood pressure, CRP, fasting glucose, and insulin reduced similarly with weight loss in both diets. The VLCHF diet produced greater decreases in triacylglycerols (VLCHF −0.64 ± 0.62 mmol/l, HCLF −0.35 ± 0.49 mmol/l; p = 0.01) and increases in high-density lipoprotein cholesterol (HDL-C) (VLCHF 0.25 ± 0.28 mmol/l, HCLF 0.08 ± 0.17 mmol/l; p = 0.002). Low-density lipoprotein cholesterol (LDL-C) decreased in the HCLF diet but remained unchanged in the VLCHF diet (VLCHF 0.06 ± 0.58 mmol/l, HCLF −0.46 ± 0.71 mmol/l; p
Published:
December 31, 2007
Title:
Receptor for advanced glycation endproducts and atherosclerosis: From basic mechanisms to clinical implications
Authors:
Basta, Giuseppina
Abstract:
The receptor for advanced glycation endproducts (RAGE) is a member of the immunoglobulin superfamily of cell-surface molecules with a diverse repertoire of ligands. In the atherosclerotic milieu, three classes of RAGE ligands, i.e., products of non-enzymatic glycoxidation, S100 proteins and amphoterin, appear to drive receptor-mediated cellular activation and potentially, acceleration of vascular disease. The interaction of RAGE–ligands effectively modulates several steps of atherogenesis, triggering an inflammatory-proliferative process and furthermore, critically contributing to propagation of vascular perturbation, mainly in diabetes. RAGE has a circulating truncated variant isoform, soluble RAGE (sRAGE), corresponding to its extracellular domain only. By competing with cell-surface RAGE for ligand binding, sRAGE may contribute to the removal/neutralization of circulating ligands thus functioning as a decoy. The critical role of RAGE in the chronic vascular inflammation processes highlights this receptor–ligand axis as a possible and attractive candidate for therapeutic intervention to limit vascular damage and its associated clinical disorders.
Published:
December 31, 2007
Title:
The composition of mesolithic food - Evidence from the submerged settlement on the Argus Bank, Denmark
Authors:
Fischer, Anders; Richards, Michael; Olsen, Jesper; Robinson, DavidEarle; Bennike, Pia; Kubiak-Martens, Lucy; Heinemeier, J.
Abstract:
Well preserved food remains from a submerged settlement on the Argus Bank bear witness to the human consumption of fish, game, nuts and fruit. 15N data derived from the bones of the inhabitants show that aquatic food was the dominant source of their dietary protein. The 13C measurements demonstrate that much of this protein derived from marine animals, probably high trophic level fish. The isotopic data also imply that the two children represented in the analyses were predominantly breast-fed up to the age of 2-3 years. In addition these data indicate that an adult female consumed more marine protein than two males, while a dog consumed food of a lower trophic level than the humans.
Published:
November 30, 2007
Title:
The ligand activity of AGE-proteins to scavenger receptors is dependent on their rate of modification by AGEs
Authors:
Nagai, Ryoji; Mera, Katsumi; Nakajou, Keisuke; Fujiwara, Yukio; Iwao, Yasunori; Imai, Hiroki; Murata, Toshinori; Otagiri, Masaki
Abstract:
The cellular interaction of proteins modified with advanced glycation end-products (AGEs) is believed to induce several different biological responses, which are involved in the development of diabetic vascular complications. We report here that the ratio of protein glycation is implicated in its ligand activity to scavenger receptors. Although highly-modified AGE-bovine serum albumin (high-AGE-BSA) was significantly recognized by human monocyte-derived macrophages and Chinese hamster ovary cells which overexpress such scavenger receptors as CD36, SR-BI (scavenger receptor class B type-I), and LOX-1 (Lectin-like Ox-LDL receptor-1), the mildly-modified-AGE-BSA (mild-AGE-BSA) did not show any ligand activity to these cells. Furthermore, when 111In-labeled high- or mild-AGE-BSA were injected into the tail vein of mice, the high-AGE-BSA was rapidly cleared from the circulation whereas the clearance rate of the mild-AGE-BSA was very slow, similar to the native BSA. These results demonstrate the first evidence that the ligand activity of the AGE-proteins to the scavenger receptors and its pharmacokinetic properties depend on their rate of modification by AGEs, and we should carefully prepare the AGE-proteins in vitro to clarify the physiological significance of the interaction between the AGE-receptors and AGE-proteins.
Published:
November 30, 2007
Title:
ADHD-like hyperactivity, with no attention deficit, in adult rats after repeated hypoxia during the equivalent of extreme prematurity
Authors:
Oorschot, Dorothy E.; Voss, Logan; Covey, Matthew V.; Bilkey, David K.; Saunders, Sarah E.
Abstract:
The most common behavioural disorder seen in children and adolescents born extremely prematurely is attention deficit hyperactivity disorder (ADHD). The hyperactive/impulsive sub-type of ADHD or the inattentive sub-type or the hyperactive/impulsive/inattentive sub-type can be evident. These sub-types of ADHD can persist into adulthood. The aim of this study was to investigate the relevance of a new immature rat model of repeated hypoxic exposure to these behavioural characteristics of extreme prematurity. More specifically, this study aimed to measure ADHD-like hyperactivity in response to delayed reward, and inattention, in repeated hypoxic versus repeated normoxic rats. Sprague-Dawley rats were exposed to either repeated hypoxia or repeated normoxia during postnatal days (PN) 1-3. The rat brain during PN1-3 is generally considered to be developmentally equivalent to the human brain during extreme prematurity. The rats were then behaviourally tested at 16 months-of-age on a multiple component fixed interval-extinction test. This test detects ADHD-like hyperactivity in response to delayed reward, as well as inattention. It was found that the repeated hypoxic rats exhibited ADHD-like hyperactivity in response to delayed reward, but no attention deficit, when compared to repeated normoxic rats. These findings provide a new animal model to investigate the biological mechanisms and treatment of ADHD-like hyperactivity due to repeated hypoxia during the equivalent of extreme prematurity.
Published:
November 29, 2007
Title:
Is plasma vitamin C an appropriate biomarker of vitamin C intake? A systematic review and meta-analysis
Authors:
Dehghan, Mahshid; Akhtar-Danesh, Noori; McMillan, Catherine R.; Thabane, Lehana
Abstract:
BACKGROUND: As the primary source of dietary vitamin C is fruit and to some extent vegetables, the plasma level of vitamin C has been considered a good surrogate or predictor of vitamin C intake by fruit and vegetable consumption. The purpose of this systematic review was to investigate the relationship between dietary vitamin C intakes measured by different dietary methods and plasma levels of vitamin C. METHOD: We searched the literature up to May 2006 through the OVID interface: MEDLINE (from 1960) and EMBASE (from 1988). We also reviewed the reference lists in the articles, reviews, and textbooks retrieved. A total of 26 studies were selected and their results were combined using meta-analytic techniques with random-effect model approach. RESULTS: The overall result of this study showed a positive correlation coefficient between Food Frequency Questionnaire (FFQ) and biomarker (r = 0.35 for "both" genders, 0.39 for females, and 0.46 for males). Also the correlation between Dietary Recalls (DR)/diary and biomarker was 0.46 for "both" genders, 0.44 for females, and 0.36 for males. An overall correlation of 0.39 was found when using the weight record method. Adjusting for energy intake improved the observed correlation for FFQ from 0.31 to 0.41. In addition, we compared the correlation for smokers and non-smokers for both genders (FFQ: for non-smoker r = 0.45, adjusted for smoking r = 0.33). CONCLUSION: Our findings show that FFQ and DR/diary have a moderate relationship with plasma vitamin C. The correlation may be affected/influenced by the presence of external factors such as vitamin bioavailability, absorption condition, stress and food processing and storage time, or by error in reporting vitamin C intake.
Published:
November 12, 2007
Title:
Comparison of a low carbohydrate and low fat diet for weight maintenance in overweight or obese adults enrolled in a clinical weight management program
Authors:
Lecheminant, James D.; Gibson, Cheryl A.; Sullivan, Debra K.; Hall, Sandra; Washburn, Rik; Vernon, Mary C.; Curry, Chelsea; Stewart, Elizabeth; Westman, Eric C.; Donnelly, Joseph E.
Abstract:
BACKGROUND: Recent evidence suggests that a low carbohydrate (LC) diet may be equally or more effective for short-term weight loss than a traditional low fat (LF) diet; however, less is known about how they compare for weight maintenance. The purpose of this study was to compare body weight (BW) for participants in a clinical weight management program, consuming a LC or LF weight maintenance diet for 6 months following weight loss. METHODS: Fifty-five (29 low carbohydrate diet; 26 low fat diet) overweight/obese middle-aged adults completed a 9 month weight management program that included instruction for behavior, physical activity (PA), and nutrition. For 3 months all participants consumed an identical liquid diet (2177 kJ/day) followed by 1 month of re-feeding with solid foods either low in carbohydrate or low in fat. For the remaining 5 months, participants were prescribed a meal plan low in dietary carbohydrate (~20%) or fat (~30%). BW and carbohydrate or fat grams were collected at each group meeting. Energy and macronutrient intake were assessed at baseline, 3, 6, and 9 months. RESULTS: The LC group increased BW from 89.2 +/- 14.4 kg at 3 months to 89.3 +/- 16.1 kg at 9 months (P = 0.84). The LF group decreased BW from 86.3 +/- 12.0 kg at 3 months to 86.0 +/- 14.0 kg at 9 months (P = 0.96). BW was not different between groups during weight maintenance (P = 0.87). Fifty-five percent (16/29) and 50% (13/26) of participants for the LC and LF groups, respectively, continued to decrease their body weight during weight maintenance. CONCLUSION: Following a 3 month liquid diet, the LC and LF diet groups were equally effective for BW maintenance over 6 months; however, there was significant variation in weight change within each group.
Published:
October 31, 2007
Title:
Heterogeneity in Management of Diabetes Mellitus Among Latino Ethnic Subgroups in the United States
Authors:
Mainous, Arch G.; Diaz, Vanessa A.; Saxena, Sonia; Geesey, Mark E.
Abstract:
Background: Recent debate suggests that general racial/ethnic categories may obscure potentially important subgroup differences within minority groups. The purpose of this study was to examine the quality of diabetes care among ethnic subgroups of the Latino population in the United States while accounting for aspects of acculturation and access to care. Methods: We evaluated adults (≥18 years old) with previously diagnosed diabetes in the 2003 National Health Interview Survey (n = 2136; United States population estimate = 13,471,587). The Latino subgroups (n = 373; United States population estimate = 1,556,259) were Mexicans, Puerto Ricans, and Other Latinos. Through a series of logistic regressions we examined ethnic group and quality of care for diabetes while controlling for demographics, access to care, and acculturation. Results: Among Latinos, 43% conducted their interview in Spanish and 59% were immigrants to the United States. Ethnic group differences were apparent in the analyses. In a logistic regression analysis including all Latinos, with Puerto Ricans as the reference group, Mexicans (odds ratio, 0.24; 95% CI, 0.07–0.85) and Other Latinos (odds ratio, 0.15; 95% CI, 0.04–0.58) were significantly less likely to have only one doctor for their diabetes care. Mexicans were less likely than Puerto Ricans (odds ratio 0.39; 95% CI, 0.18- 0.84) to know about glycosylated hemoglobin. Similarly, among Latino immigrants, Mexicans (odds ratio, 0.13; 95% CI, 0.02–0.81) and Other Latinos (odds ratio, 0.09; 95% CI, 0.01–0.63) were significantly less likely than Puerto Ricans to have only one doctor for their diabetes care and management. Measures of acculturation and immigration were not independent predictors of diabetes quality of care. Conclusions: Differences in diabetes management exist between Latino ethnic subgroups; treating Latinos in the United States as one homogenous category may be a barrier to the appropriate provision of care.
Published:
October 31, 2007
Title:
How Heating Affects Extra Virgin Olive Oil Quality Indexes and Chemical Composition
Authors:
Allouche, Yosra; Jiménez, Antonio; Gaforio, José Juan; Uceda, Marino; Beltrán, Gabriel
Abstract:
Two monovarietal extra virgin olive oils from Arbequina and Picual cultivars were subjected to heating at 180 °C for 36 h. Oxidation progress was monitored by measuring oil quality changes (peroxide value and conjugated dienes and trienes), fatty acid composition, and minor compound content. Tocopherols and polyphenols were the most affected by the thermal treatment and showed the highest degradation rate although their behavior was different for each cultivar. α-Tocopherol loss was more important in Arbequina oil whereas, total phenol content loss was greater in Picual oil. The later showed an important decrease in hydroxytyrosol (3,4-DHPEA) and its secoiridoid derivatives (3,4-DHPEA-EDA and 3,4-DHPEA-EA), while lignans decrease was lesser. For Arbequina oil these compounds remained stable, and a lowering tendency was observed for tyrosol (p-HPEA) and its derivatives (p-HPEA-EDA and p-HPEA-EA). In general, flavone content showed a decrease during heating, being higher for Arbequina oil. On the other hand, oleic acid, sterols, squalene, and triterpenic alcohols (erythrodiol and uvaol) and acids (oleanolic and maslinic) were quite constant, exhibiting a high stability against oxidation. From these results, we can conclude that despite the heating conditions, VOO maintained most of its minor compounds and, therefore, most of its nutritional properties.
Published:
October 31, 2007
Title:
Loss-of-Function Mutation in Carotenoid 15,15′-Monooxygenase Identified in a Patient with Hypercarotenemia and Hypovitaminosis A
Authors:
Lindqvist, Annika; Sharvill, John; Sharvill, Denis E.; Andersson, Stefan
Abstract:
Abstract. The enzyme carotenoid 15,15′-monooxygenase (CMO1) catalyzes the first step in the conversion of dietary provitamin A carotenoids to vitamin A in the
Published:
October 31, 2007
Title:
Macrophage scavenger receptors and host-derived ligands
Authors:
Plüddemann, Annette; Neyen, Claudine; Gordon, Siamon
Abstract:
The scavenger receptors are a large family of molecules that are structurally diverse and have been implicated in a range of functions. They are expressed by myeloid cells, selected endothelial cells and some epithelial cells and recognise many different ligands, including microbial pathogens as well as endogenous and modified host-derived molecules. This review will focus on the eight classes of scavenger receptors (class A–H) in terms of their structure, expression and recognition of host-derived ligands. Scavenger receptors have been implicated in a range of physiological and pathological processes, such as atherosclerosis and Alzheimer’s disease, and function in adhesion and tissue maintenance. More recently, some of the scavenger receptors have been shown to mediate binding and endocytosis of chaperone proteins, such as the heat shock proteins, thereby playing an important role in antigen cross-presentation.
Published:
October 31, 2007
Title:
Vinegar Ingestion at Bedtime Moderates Waking Glucose Concentrations in Adults With Well-Controlled Type 2 Diabetes
Authors:
White, Andrea M.; Johnston, Carol S.
Abstract:
Given the importance of maintaining acceptable blood glucose concentrations, there is much interest in identifying foods and diet patterns that will help individuals with diabetes manage their condition. Based on previous data indicating that vinegar ingestion at mealtime reduces postprandial glycemia (1–4), the aim of this pilot study was to examine whether vinegar ingestion at bedtime reduces the next-morning fasting glucose concentration in individuals with type 2 diabetes. Four men and seven women (aged 40–72 years) diagnosed with type 2 diabetes (by a physician) who were not taking insulin completed the study. Participants provided a clinically determined A1C reading from a recent (
Published:
October 31, 2007
Title:
Effects of low carbohydrate diets high in red meats or poultry, fish and shellfish on plasma lipids and weight loss
Authors:
Cassady, Bridget A.; Charboneau, Nicole L.; Brys, Emily E.; Crouse, Kristin A.; Beitz, Donald C.; Wilson, Ted
Abstract:
BACKGROUND: Low carbohydrate diets (LCDs) have been demonstrated to be effective tools for promoting weight loss and an improved plasma lipid profile. Such diets are often associated with increased meat consumption, either poultry, fish, and shellfish (PFS), which are generally high in polyunsaturated fat (PUFA) or red meats (RM), generally high in saturated fat (SFA). The fatty acid profile and content of a diet may influence the plasma lipid profile of humans. This study examined whether the type of meat consumed could influence the outcome of an LCD. METHODS: Moderately obese subjects consumed two different LCDs as part of a weight loss regimen: 1) a diet high in foods of mammalian origin (RM) intended to contain more SFA, or 2) a diet high in PFS intended to contain more PUFA. Diet dependent changes in body weight, nutritional intake, and plasma lipids were evaluated during a 28 day study period. RESULTS: Both diets were associated with significant weight loss after 28 days, -5.26 +/- 0.84 kg and -5.74 +/- 0.63 kg for RM and PFS groups, respectively. The PFS diet was associated with a significantly higher intake of PUFA and cholesterol. Despite high cholesterol and fat intakes, neither diet was associated with significant changes in plasma cholesterol or the plasma lipoprotein cholesterol profile. While plasma triglycerides were reduced in both groups, the effect was only statistically significant for the PFS diet.
Published:
October 30, 2007
Title:
Defining ETS transcription regulatory networks and their contribution to breast cancer progression
Authors:
Turner, David P.; Findlay, Victoria J.; Moussa, Omar; Watson, Dennis K.
Abstract:
ETS factors are members of one of the largest families of evolutionarily conserved transcription factors, regulating critical functions in normal cell homeostasis, that when perturbed contribute to tumor progression. The well documented alterations in ETS factor expression and function during breast cancer progression result in pleiotropic effects manifested by the downstream effect on their target genes. Multiple ETS factors bind to the same regulatory sites present on target genes, suggesting redundant or competitive functions. Furthermore, additional events contribute to, or may be necessary for, target gene regulation. In order to advance our understanding of the ETS-dependent regulation of breast cancer progression and metastasis, this prospect article puts forward a model for examining the effects of simultaneous expression of multiple transcription factors on the transcriptome of non-metastatic and metastatic breast cancer. Compared to existing RNA profiles defined following expression of individual transcription factors, the anti- and prometastatic signatures obtained by examining specific ETS regulatory networks will significantly improve our ability to accurately predict tumor progression and advance our understanding of gene regulation in cancer. Coordination of multiple ETS gene functions also mediates interactions between tumor and stromal cells and thus contributes to the cancer phenotype. As such, these new insights may provide a novel view of the ETS gene family as well as a focal point for studying the complex biological control involved in tumor progression. J. Cell. Biochem. 102: 549–559, 2007. ß 2007 Wiley-Liss, Inc.
Published:
October 14, 2007
Title:
No Potassium, No Acid: K+ Channels and Gastric Acid Secretion
Authors:
Heitzmann, Dirk; Warth, Richard
Abstract:
The gastric H+-K+-ATPase pumps H+ into the lumen and takes up K+ in parallel. In the acid-producing parietal cells, luminal KCNE2/KCNQ1 K+ channels play a pivotal role in replenishing K+ in the luminal fluid. Inactivation of KCNE2/KCNQ1 channels abrogates gastric acid secretion and dramatically modifies the architecture of gastric mucosa.
Published:
September 30, 2007
Title:
Predicting evolutionary patterns of mammalian teeth from development
Authors:
Kavanagh, Kathryn D.; Evans, Alistair R.; Jernvall, Jukka
Abstract:
One motivation in the study of development is the discovery of mechanisms that may guide evolutionary change. Here we report how development governs relative size and number of cheek teeth, or molars, in the mouse. We constructed an inhibitory cascade model by experimentally uncovering the activator-inhibitor logic of sequential tooth development. The inhibitory cascade acts as a ratchet that determines molar size differences along the jaw, one effect being that the second molar always makes up one-third of total molar area. By using a macroevolutionary test, we demonstrate the success of the model in predicting dentition patterns found among murine rodent species with various diets, thereby providing an example of ecologically driven evolution along a developmentally favoured trajectory. In general, our work demonstrates how to construct and test developmental rules with evolutionary predictability in natural systems.
Published:
September 26, 2007
Title:
Postcranial evidence from early Homo from Dmanisi, Georgia
Authors:
Lordkipanidze, David; Jashashvili, Tea; Vekua, Abesalom; Ponce de León, Marcia S; Zollikofer, Christoph P E; Rightmire, G Philip; Pontzer, Herman; Ferring, Reid; Oms, Oriol; Tappen, Martha; Bukhsianidze, Maia; Agusti, Jordi; Kahlke, Ralf; Kiladze, Gocha; Martinez-Navarro, Bienvenido; Mouskhelishvili, Alexander; Nioradze, Medea; Rook, Lorenzo
Abstract:
The Plio-Pleistocene site of Dmanisi, Georgia, has yielded a rich fossil and archaeological record documenting an early presence of the genus Homo outside Africa. Although the craniomandibular morphology of early Homo is well known as a result of finds from Dmanisi and African localities, data about its postcranial morphology are still relatively scarce. Here we describe newly excavated postcranial material from Dmanisi comprising a partial skeleton of an adolescent individual, associated with skull D2700/D2735, and the remains from three adult individuals. This material shows that the postcranial anatomy of the Dmanisi hominins has a surprising mosaic of primitive and derived features. The primitive features include a small body size, a low encephalization quotient and absence of humeral torsion; the derived features include modern-human-like body proportions and lower limb morphology indicative of the capability for long-distance travel. Thus, the earliest known hominins to have lived outside of Africa in the temperate zones of Eurasia did not yet display the full set of derived skeletal features.
Published:
September 19, 2007
Title:
Low- and high-carbohydrate weight-loss diets have similar effects on mood but not cognitive performance
Authors:
Halyburton, Angela K.; Brinkworth, Grant D.; Wilson, Carlene J.; Noakes, Manny; Buckley, Jonathan D.; Keogh, Jennifer B.; Clifton, Peter M.
Abstract:
Abstract. Background: Low-carbohydrate diets are often used to promote weight loss, but their effects on psychological function are largely unknown.Objective:
Published:
August 31, 2007
Title:
Skeletal and dental growth and development in chimpanzees of the Taï National Park, Côte D'Ivoire
Authors:
Zihlman, A. L.; Bolter, D. R.; Boesch, C.
Abstract:
Abstract An extraordinary collection of 22 immature skeletons from Taï National Park, Côte d'Ivoire, has provided a rare opportunity to establish the timing of dental eruption and its correlation with skeletal fusion and morphometrics in wild chimpanzees of known chronological ages. Comparison of the immature Taï chimpanzees Pan troglodytes verus with adults from the same population show that sex differences in skeletal maturation apparently appear during the Juvenile II stage, about age 8. A few skeletons from other chimpanzee field sites conform to the dental and skeletal growth in Taï chimpanzees. The tempo of wild chimpanzee growth contrasts sharply with the rate demonstrated for captive individuals. Captive chimpanzees may mature as much as 3?years earlier. The ability to link physical development with field observations of immature chimpanzees increases our understanding of their life-history stages. These data provide an improved dataset for comparing the rates of growth among chimpanzees, Homo sapiens and fossil hominids.
Published:
August 31, 2007
Title:
Statins and foam cell formation: Impact on LDL oxidation and uptake of oxidized lipoproteins via scavenger receptors
Authors:
Hofnagel, Oliver; Luechtenborg, Birgit; Weissen-Plenz, Gabriele; Robenek, Horst
Abstract:
The uptake of oxidized lipoproteins via scavenger receptors and the ensuing formation of foam cells are key events during atherogenesis. Foam cell formation can be reduced by treatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins). The efficacy of statins is evidently due not only to their cholesterol-lowering properties, but also to lipid-independent pleiotropic effects. This review focuses on lipid-independent pleiotropic effects of statins that influence foam cell formation during atherogenesis, with special emphasis on oxidative pathways and scavenger receptor expression.
Published:
August 31, 2007
Title:
[Floppy baby with macrocytic anemia and vegan mother]
Authors:
Schlapbach, L. J.; Schütz, B.; Nuoffer, J. M.; Brekenfeld, C.; Müller, G.; Fluri, S.
Abstract:
We report the case of a 7 month-old girl that presented with acute anemia, generalized muscular hypotonia and failure to thrive. Laboratory evaluation revealed cobalamin deficiency, due to a vegan diet of the mother. The clinical triad of an acquired floppy baby syndrome with megaloblastic anemia and failure to thrive is pathognomic for infantile cobalamin deficiency. Neurological abnormalities are often irreversible and may be associated with delayed myelinization in the MRI. A normal cobalamin level in maternal serum and absence of anemia do not exclude subclinical deficiency. If cobalamin deficiency is suspected, e.g. in pregnant women on vegan diet, urinary methylmalonic acid excretion and plasma homocysteine levels should be determined and cobalamin substitution should be started at an early stage to avoid potentially irreversible damage of the fetus.
Published:
August 28, 2007
Title:
Structural and functional insights into RAGE activation by multimeric S100B
Authors:
Ostendorp, Thorsten; Leclerc, Estelle; Galichet, Arnaud; Koch, Michael; Demling, Nina; Weigle, Bernd; Heizmann, Claus W.; Kroneck, Peter M. H.; Fritz, Günter
Abstract:
Nervous system development and plasticity require regulation of cell proliferation, survival, neurite outgrowth and synapse formation by specific extracellular factors. The EF-hand protein S100B is highly expressed in human brain. In the extracellular space, it promotes neurite extension and neuron survival via the receptor RAGE (receptor for advanced glycation end products). The X-ray structure of human Ca(2+)-loaded S100B was determined at 1.9 A resolution. The structure revealed an octameric architecture of four homodimeric units arranged as two tetramers in a tight array. The presence of multimeric forms in human brain extracts was confirmed by size-exclusion experiments. Recombinant tetrameric, hexameric and octameric S100B were purified from Escherichia coli and characterised. Binding studies show that tetrameric S100B binds RAGE with higher affinity than dimeric S100B. Analytical ultracentrifugation studies imply that S100B tetramer binds two RAGE molecules via the V-domain. In line with these experiments, S100B tetramer caused stronger activation of cell growth than S100B dimer and promoted cell survival. The structural and the binding data suggest that tetrameric S100B triggers RAGE activation by receptor dimerisation.
Published:
August 21, 2007
bottom of page