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Title:
Bite force and occlusal stress production in hominin evolution
Authors:
Eng, Carolyn M.; Lieberman, Daniel E.; Zink, Katherine D.; Peters, Michael A.
Abstract:
Maximum bite force affects craniofacial morphology and an organism's ability to break down foods with different material properties. Humans are generally believed to produce low bite forces and spend less time chewing compared with other apes because advances in mechanical and thermal food processing techniques alter food material properties in such a way as to reduce overall masticatory effort. However, when hominins began regularly consuming mechanically processed or cooked diets is not known. Here, we apply a model for estimating maximum bite forces and stresses at the second molar in modern human, nonhuman primate, and hominin skulls that incorporates skeletal data along with species-specific estimates of jaw muscle architecture. The model, which reliably estimates bite forces, shows a significant relationship between second molar bite force and second molar area across species but does not confirm our hypothesis of isometry. Specimens in the genus Homo fall below the regression line describing the relationship between bite force and molar area for nonhuman anthropoids and australopiths. These results suggest that Homo species generate maximum bite forces below those predicted based on scaling among australopiths and nonhuman primates. Because this decline occurred before evidence for cooking, we hypothesize that selection for lower bite force production was likely made possible by an increased reliance on nonthermal food processing. However, given substantial variability among in vivo bite force magnitudes measured in humans, environmental effects, especially variations in food mechanical properties, may also be a factor. The results also suggest that australopiths had ape-like bite force capabilities.
Published:
2013-08
Title:
Dietary lipid modification for mild and severe dyslipidaemias. [Review]
Authors:
Marais, A. David
Abstract:
The aim of this review is to place a historical perspective on linking dyslipidaemia with atherosclerosis and emphasises previous knowledge about the impact on the lipoprotein profile and health in persons with mild dyslipidaemia and in those with defined genetic disorders. CVD is becoming the leading cause of death and disability in developed and developing countries and is strongly related to lifestyle factors that influence plasma lipoprotein concentrations. It is established that risk of complications from atherosclerosis increases with increasing LDL and decreasing HDL and that there is potentiation of risk when these and other risk factors co-exist. High-fat diets used for losing body mass may increase risk through dyslipidaemia. Pharmaceutical modulation of the lipoproteins has lowered risk powerfully but residual risk persists, possibly relating to existing disease as well as progression relating in many instances to dietary lipids. The impact of various dietary lipids is reviewed as they relate to the conventional lipoprotein profile in persons who do not have significant metabolic defects, as well as the impact on inherited metabolic disease such as familial hypercholesterolaemia, hypertriglyceridaemia and phytosterolaemia. For most persons with dyslipidaemias a significant benefit will be seen on the lipid profile by adopting a low saturated fat diet with less cholesterol intake.
Published:
2013-08
Title:
Effects of a short-term carbohydrate-restricted diet on strength and power performance
Authors:
Sawyer, Jason C.; Wood, Richard J.; Davidson, Patrick W.; Collins, Sean M.; Matthews, Tracey D.; Gregory, Sara M.; Paolone, Vincent J.
Abstract:
The purpose of the study was to examine the effects of switching from a habitual diet to a carbohydrate-restricted diet (CRD) on strength and power performance in trained men (n = 16) and women (n = 15). Subjects performed handgrip dynamometry, vertical jump, 1RM bench press and back squat, maximum-repetition bench press, and a 30-second Wingate anaerobic cycling test after consuming a habitual diet (40.7% carbohydrate, 22.2% protein, and 34.4% fat) for 7 days and again after following a CRD (5.4% carbohydrate, 35.1% protein, and 53.6% fat) for 7 days. Before both testing sessions, body weight and composition were examined using bioelectrical impedance analysis. Three 2 × 2 multiple analyses of variance were used to compare performance variables between the habitual diet and CRD. Subjects consumed significantly fewer (p < 0.05) total kilocalories during the CRD (2,156.55 ± 126.7) compared with the habitual diet (2,537.43 ± 99.5). Body mass decreased significantly (p
Published:
2013-08
Title:
Effects of whey proteins and carbohydrates on the efficacy of resistance training in elderly people: double blind, randomised controlled trial
Authors:
Arnarson, A.; Gudny Geirsdottir, O.; Ramel, A.; Briem, K.; Jonsson, P. V.; Thorsdottir, I.
Abstract:
BACKGROUND/OBJECTIVES: A few previous studies indicate that protein supplementation increases gains in muscle mass and strength during a resistance exercise program. The purpose of this study was to investigate whether whey protein supplementation results in greater increases in lean body mass, muscle strength and physical function in elderly individuals during 12 weeks of resistance exercise when compared to isocaloric carbohydrate supplementation. SUBJECTS/METHODS: A total of 161 men and women, 65-91 years old, participated in a randomized, controlled, double-blind intervention study, involving dietary supplementation and a 12-week resistance exercise program, designed to increase muscle mass and strength of all major muscle groups. Participants exercised three times a week and received either 20 g of whey protein (n=83) or isocaloric carbohydrate (n=78) in liquid form immediately after each workout. Data were obtained at baseline and end point. RESULTS: The primary outcomes, lean body mass, strength and physical function increased significantly during the course of the study. Type of dietary supplementation did not influence gains in lean body mass (P=0.365), quadriceps strength (P=0.776) or performance during a 6-min walk (P=0.726) or a timed up-and-go test (P=0.151). Twenty participants discontinued the intervention. CONCLUSIONS: Ingestion of 20 g of whey protein immediately after resistance exercise three times per week, does not lead to greater gains in lean body mass, strength and physical function in elderly people with sufficient energy and protein intakes when compared to isocaloric carbohydrate.
Published:
2013-08
Title:
Epidemiology of alcoholic and nonalcoholic fatty liver disease in China
Authors:
Fan, Jian-Gao
Abstract:
The prevalence of patients presenting with fatty liver disease (FLD) in China has approximately doubled over the past two decades. At present, FLD, which is typically diagnosed by imaging, is highly prevalent (≈ 27% urban population) in China and is mainly related to obesity and metabolic syndrome (MetS). However, the percentage of alcoholic liver disease (ALD) among patients with chronic liver diseases in clinic is increasing as well, and a synergetic effect exists between heavy alcohol drinking and obesity in ALD. Prevalence figures reveal regional variations, with a median prevalence of ALD and nonalcoholic FLD (NAFLD) of 4.5% and 15.0%, respectively. The prevalence of NAFLD in children is 2.1%, although the prevalence increases to 68.2% among obese children. With the increasing pandemic of obesity and MetS in the general population, China is likely to harbor an increasing reservoir of patients with FLD. The risk factors for FLD resemble to those of Caucasian counterparts, but the ethnic-specific definitions of obesity and MetS are more useful in assessment of Chinese people. Therefore, FLD/NAFLD has become a most common chronic liver disease in China. Public health interventions are needed to halt the worldwide trend of obesity and alcohol abuse to ameliorate liver injury and to improve metabolic health.
Published:
2013-08
Title:
How does the ketogenic diet work? Four potential mechanisms
Authors:
Danial, Nika N.; Hartman, Adam L.; Stafstrom, Carl E.; Thio, Liu Lin
Abstract:
The ketogenic diet and its newer variants are clinically useful in treating epilepsy. They can also have antiepileptogenic properties and can eventually have a role in treating other neurologic and nonneurologic conditions. Despite being nearly a century old, identifying the molecular underpinnings of the ketogenic diet has been challenging. However, recent studies provide experimental evidence for 4 distinct mechanisms that could contribute to the antiseizure and other beneficial effects of these diets. These mechanisms include carbohydrate reduction, activation of adenosine triphosphate (ATP)-sensitive potassium channels by mitochondrial metabolism, inhibition of the mammalian target of rapamycin pathway, and inhibition of glutamatergic excitatory synaptic transmission.
Published:
2013-08
Title:
Ketosis proportionately spares glucose utilization in brain
Authors:
Zhang, Yifan; Kuang, Youzhi; Xu, Kui; Harris, Donald; Lee, Zhenghong; LaManna, Joseph; Puchowicz, Michelle A.
Abstract:
The brain is dependent on glucose as a primary energy substrate, but is capable of utilizing ketones such as β-hydroxybutyrate and acetoacetate, as occurs with fasting, starvation, or chronic feeding of a ketogenic diet. The relationship between changes in cerebral metabolic rates of glucose (CMRglc) and degree or duration of ketosis remains uncertain. To investigate if CMRglc decreases with chronic ketosis, 2-[(18)F]fluoro-2-deoxy-D-glucose in combination with positron emission tomography, was applied in anesthetized young adult rats fed 3 weeks of either standard or ketogenic diets. Cerebral metabolic rates of glucose (μmol/min per 100 g) was determined in the cerebral cortex and cerebellum using Gjedde-Patlak analysis. The average CMRglc significantly decreased in the cerebral cortex (23.0±4.9 versus 32.9±4.7) and cerebellum (29.3±8.6 versus 41.2±6.4) with increased plasma ketone bodies in the ketotic rats compared with standard diet group. The reduction of CMRglc in both brain regions correlates linearly by ∼9% for each 1 mmol/L increase of total plasma ketone bodies (0.3 to 6.3 mmol/L). Together with our meta-analysis, these data revealed that the degree and duration of ketosis has a major role in determining the corresponding change in CMRglc with ketosis.
Published:
2013-08
Title:
MYC, Metabolism, Cell Growth, and Tumorigenesis
Authors:
Dang, Chi V.
Abstract:
The MYC proto-oncogene is frequently activated in human cancers through a variety of mechanisms. Its deregulated expression, unconstrained by inactivation of key checkpoints, such as p53, contributes to tumorigenesis. Unlike its normal counterpart, which is restrained by negative regulators, the unleashed MYC oncogene produces a transcription factor that alters global gene expression through transcriptional regulation, resulting in tumorigenesis. Key genes involved in ribosomal and mitochondrial biogenesis, glucose and glutamine metabolism, lipid synthesis, and cell-cycle progression are robustly activated by MYC, contributing to the acquisition of bioenergetics substrates for the cancer cell to grow and proliferate., MYC is a master regulator of cell metabolism. In cells with deregulated MYC expression, key genes involved in cell growth and proliferation are robustly activated, resulting in tumorigenesis.
Published:
2013-08
Title:
Small molecule-induced mitochondrial disruption directs prostate cancer inhibition via UPR signaling
Authors:
Rico-Bautista, Elizabeth; Zhu, Wenhong; Kitada, Shinichi; Ganapathy, Suthakar; Lau, Eric; Krajewski, Stan; Ramirez, Joel; Bush, Jason A.; Yuan, Zhimin; Wolf, Dieter A.
Abstract:
We previously identified SMIP004 (N-(4-butyl-2-methyl-phenyl) acetamide) as a novel inducer of cancer-cell selective apoptosis of human prostate cancer cells. SMIP004 decreased the levels of positive cell cycle regulators, upregulated cyclin-dependent kinase inhibitors, and resulted in G1 arrest, inhibition of colony formation in soft agar, and cell death. However, the mechanism of SMIP004-induced cancer cell selective apoptosis remained unknown. Here, we used chemical genomic and proteomic profiling to unravel a SMIP004-induced pro-apoptotic pathway, which initiates with disruption of mitochondrial respiration leading to oxidative stress. This, in turn, activates two pathways, one eliciting cell cycle arrest by rapidly targeting cyclin D1 for proteasomal degradation and driving the transcriptional downregulation of the androgen receptor, and a second pathway that activates pro-apoptotic signaling through MAPK activation downstream of the unfolded protein response (UPR). SMIP004 potently inhibits the growth of prostate and breast cancer xenografts in mice. Our data suggest that SMIP004, by inducing mitochondrial ROS formation, targets specific sensitivities of prostate cancer cells to redox and bioenergetic imbalances that can be exploited in cancer therapy.
Published:
2013-08
Title:
Treatment of diabetes and diabetic complications with a ketogenic diet
Authors:
Mobbs, Charles V.; Mastaitis, Jason; Isoda, Fumiko; Poplawski, Michal
Abstract:
Accumulating evidence suggests that low-carbohydrate, high-fat diets are safe and effective to reduce glycemia in diabetic patients without producing significant cardiovascular risks. Most of these studies have been carried out specifically restricting carbohydrates, which tends to lead to increased protein intake, thus reducing the ketosis. However, diets that limit protein as well as carbohydrates, entailing a composition very high in fat, appear even more effective to reduce glucose and whole-body glucose metabolism in humans. In animal models, low-carbohydrate, high-protein diets do not produce ketosis or reduce glycemia but rather cause obesity. However, limiting both protein and carbohydrates as in a classic ketogenic diet remarkably reduces blood glucose in animal models of type 1 and type 2 diabetes and reverses diabetic nephropathy. Future studies should assess if ketogenic diets would be effective to reverse diabetic complications in humans.
Published:
2013-08
Title:
Updates in Diverticular Disease
Authors:
Templeton, Adam W.; Strate, Lisa L.
Abstract:
Published:
2013-08
Title:
Video game use in boys with autism spectrum disorder, ADHD, or typical development
Authors:
Mazurek, Micah O.; Engelhardt, Christopher R.
Abstract:
OBJECTIVES: The study objectives were to examine video game use in boys with autism spectrum disorder (ASD) compared with those with ADHD or typical development (TD) and to examine how specific symptoms and game features relate to problematic video game use across groups. METHODS: Participants included parents of boys (aged 8-18) with ASD (n = 56), ADHD (n = 44), or TD (n = 41). Questionnaires assessed daily hours of video game use, in-room video game access, video game genres, problematic video game use, ASD symptoms, and ADHD symptoms. RESULTS: Boys with ASD spent more time than did boys with TD playing video games (2.1 vs 1.2 h/d). Both the ASD and ADHD groups had greater in-room video game access and greater problematic video game use than the TD group. Multivariate models showed that inattentive symptoms predicted problematic game use for both the ASD and ADHD groups; and preferences for role-playing games predicted problematic game use in the ASD group only. CONCLUSIONS: Boys with ASD spend much more time playing video games than do boys with TD, and boys with ASD and ADHD are at greater risk for problematic video game use than are boys with TD. Inattentive symptoms, in particular, were strongly associated with problematic video game use for both groups, and role-playing game preferences may be an additional risk factor for problematic video game use among children with ASD. These findings suggest a need for longitudinal research to better understand predictors and outcomes of video game use in children with ASD and ADHD.
Published:
2013-08
Title:
A Palaeolithic-type diet causes strong tissue-specific effects on ectopic fat deposition in obese postmenopausal women
Authors:
Ryberg, M.; Sandberg, S.; Mellberg, C.; Stegle, O.; Lindahl, B.; Larsson, C.; Hauksson, J.; Olsson, T.
Abstract:
CONCLUSIONS: A modified Palaeolithic-type diet has strong and tissue-specific effects on ectopic lipid deposition in postmenopausal women. Copyright © 2013 The Association for the Publication of the Journal of Internal Medicine.
Published:
2013-07
Title:
A meal high in saturated fat evokes postprandial dyslipemia, hyperinsulinemia, and altered lipoprotein expression in obese children with and without nonalcoholic fatty liver disease
Authors:
Mager, Diana R.; Mazurak, Vera; Rodriguez-Dimitrescu, Carla; Vine, Donna; Jetha, Mary; Ball, Geoff; Yap, Jason
Abstract:
CONCLUSION: A meal high in saturated fat evokes postprandial dyslipemia, hyperinsulinemia, and altered lipoprotein expression in obese children with and without NAFLD.
Published:
2013-07
Title:
A multicenter randomized controlled trial of a plant-based nutrition program to reduce body weight and cardiovascular risk in the corporate setting: the GEICO study
Authors:
Mishra, S.; Xu, J.; Agarwal, U.; Gonzales, J.; Levin, S.; Barnard, N. D.
Abstract:
BACKGROUND/OBJECTIVES: To determine the effects of a low-fat plant-based diet program on anthropometric and biochemical measures in a multicenter corporate setting. SUBJECTS/METHODS: Employees from 10 sites of a major US company with body mass index ≥ 25 kg/m(2) and/or previous diagnosis of type 2 diabetes were randomized to either follow a low-fat vegan diet, with weekly group support and work cafeteria options available, or make no diet changes for 18 weeks. Dietary intake, body weight, plasma lipid concentrations, blood pressure and glycated hemoglobin (HbA1C) were determined at baseline and 18 weeks. RESULTS: Mean body weight fell 2.9 kg and 0.06 kg in the intervention and control groups, respectively (P<0.001). Total and low-density lipoprotein (LDL) cholesterol fell 8.0 and 8.1 mg/dl in the intervention group and 0.01 and 0.9 mg/dl in the control group (P<0.01). HbA1C fell 0.6 percentage point and 0.08 percentage point in the intervention and control group, respectively (P<0.01).Among study completers, mean changes in body weight were -4.3 kg and -0.08 kg in the intervention and control groups, respectively (P<0.001). Total and LDL cholesterol fell 13.7 and 13.0 mg/dl in the intervention group and 1.3 and 1.7 mg/dl in the control group (P<0.001). HbA1C levels decreased 0.7 percentage point and 0.1 percentage point in the intervention and control group, respectively (P
Published:
2013-07
Title:
Alternate day fasting increases LDL particle size independently of dietary fat content in obese humans
Authors:
Klempel, M. C.; Kroeger, C. M.; Varady, K. A.
Abstract:
Alternate day fasting (ADF) with a low-fat (LF) diet increases low-density lipoprotein (LDL) particle size. Whether these beneficial effects can be reproduced by a high-fat (HF) ADF diet is unclear. This study compared an ADF-HF to an ADF-LF diet on plasma lipids, LDL size and high-density lipoprotein (HDL) size. Thirty-five obese subjects were randomized to an ADF-HF or ADF-LF diet for 10 weeks. Body weight decreased (P<0.0001) by 4.3+/-1.0 kg (4.8+/-1.1%) and 3.7+/-0.7 kg (4.2+/-0.8%) in the ADF-HF and ADF-LF group, respectively. LDL cholesterol was reduced (P<0.0001) by 19+/-8 mg/dl (18+/-5%) by ADF-HF and 28+/-7 mg/dl (25+/-3%) by ADF-LF. LDL particle size increased (P<0.005) by 3+/-1 A in both groups. The proportion of small LDL particles decreased (P
Published:
2013-07
Title:
Efficacy and safety of individual second-generation vs. first-generation antipsychotics in first-episode psychosis: a systematic review and meta-analysis
Authors:
Zhang, Jian-Ping; Gallego, Juan A.; Robinson, Delbert G.; Malhotra, Anil K.; Kane, John M.; Correll, Christoph U.
Abstract:
Published:
2013-07
Title:
Ketosis and appetite-mediating nutrients and hormones after weight loss
Authors:
Sumithran, P.; Prendergast, L. A.; Delbridge, E.; Purcell, K.; Shulkes, A.; Kriketos, A.; Proietto, J.
Abstract:
BACKGROUND/OBJECTIVES: Diet-induced weight loss is accompanied by compensatory changes, which increase appetite and encourage weight regain. There is some evidence that ketogenic diets suppress appetite. The objective is to examine the effect of ketosis on a number of circulating factors involved in appetite regulation, following diet-induced weight loss. SUBJECTS/METHODS: Of 50 non-diabetic overweight or obese subjects who began the study, 39 completed an 8-week ketogenic very-low-energy diet (VLED), followed by 2 weeks of reintroduction of foods. Following weight loss, circulating concentrations of glucose, insulin, non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHB), leptin, gastrointestinal hormones and subjective ratings of appetite were compared when subjects were ketotic, and after refeeding. RESULTS: During the ketogenic VLED, subjects lost 13% of initial weight and fasting BHB increased from (mean±s.e.m.) 0.07±0.00 to 0.48±0.07 mmol/l (P<0.001). BHB fell to 0.19±0.03 mmol/l after 2 weeks of refeeding (P
Published:
2013-07
Title:
MCP-1 binds to oxidized LDL and is carried by lipoprotein(a) in human plasma
Authors:
Wiesner, Philipp; Tafelmeier, Maria; Chittka, Dominik; Choi, Soo-Ho; Zhang, Li; Byun, Young Sup; Almazan, Felicidad; Yang, Xiaohong; Iqbal, Navaid; Chowdhury, Punam; Maisel, Alan; Witztum, Joseph L.; Handel, Tracy M.; Tsimikas, Sotirios; Miller, Yury I.
Abstract:
Published:
2013-07
Title:
Sugar addiction: pushing the drug-sugar analogy to the limit
Authors:
Ahmed, Serge H.; Guillem, Karine; Vandaele, Youna
Abstract:
PURPOSE OF REVIEW: To review research that tests the validity of the analogy between addictive drugs, like cocaine, and hyperpalatable foods, notably those high in added sugar (i.e., sucrose). RECENT FINDINGS: Available evidence in humans shows that sugar and sweetness can induce reward and craving that are comparable in magnitude to those induced by addictive drugs. Although this evidence is limited by the inherent difficulty of comparing different types of rewards and psychological experiences in humans, it is nevertheless supported by recent experimental research on sugar and sweet reward in laboratory rats. Overall, this research has revealed that sugar and sweet reward can not only substitute to addictive drugs, like cocaine, but can even be more rewarding and attractive. At the neurobiological level, the neural substrates of sugar and sweet reward appear to be more robust than those of cocaine (i.e., more resistant to functional failures), possibly reflecting past selective evolutionary pressures for seeking and taking foods high in sugar and calories. SUMMARY: The biological robustness in the neural substrates of sugar and sweet reward may be sufficient to explain why many people can have difficultly to control the consumption of foods high in sugar when continuously exposed to them.
Published:
2013-07
Title:
The dynamics of mangrove ecosystems, changes in sea level and the strategies of Neolithic settlements along the coast of Oman (6000–3000 cal. BC)
Authors:
Berger, J.F.; Charpentier, V.; Crassard, R.; Martin, C.; Davtian, G.; López-Sáez, J.A.
Abstract:
Abstract This paper focus on the Holocene palaeogeography of the Ja'alan coast from the 6th to the 4th millennium cal. BC, integrating the dynamics of mangroves, lagoons, khors-estuaries and deltas, with sea-level change and the evidence from Neolithic shell middens. The distribution and maturation of mangrove ecosystems along the Arabian coasts has varied considerably, affected by physical forces such as sea-level changes, climate, tidal amplitude and duration as well as the quantity of fresh water inflow associated with the monsoon systems along the Arabian coast. Palaeo-mangroves and lagoons, today replaced by large sabkhas, appear to be correlated to mid-Holocene fossil deltas and estuaries that currently function episodically, depending on the rhythm of winter rains. All these parameters have determined and impacted the location of settlement networks and the economic strategies of the first Arabian farmers along the eastern Arabian coast. The mid-Holocene sea-level highstand stability (5th millennium BC) can be considered to be an optimum period for mangrove development and can be correlated with Neolithic sites around the mangroves. The decline of mangroves since 3000/2500 cal. BC and further degradation is mainly attributed to the prevailing arid climate that reduced summer monsoon effects in the tropical area by favouring the extension of sabkhas. We discuss these aspects based on new archaeological surveys, excavations and geoarchaeological studies.
Published:
2013-07
Title:
Vitamin D for health: a global perspective
Authors:
Hossein-nezhad, Arash; Holick, Michael F.
Abstract:
It is now generally accepted that vitamin D deficiency is a worldwide health problem that affects not only musculoskeletal health but also a wide range of acute and chronic diseases. However, there remains cynicism about the lack of randomized controlled trials to support the association studies regarding the nonskeletal health benefits of vitamin D. This review was obtained by searching English-language studies published up to April 1, 2013, in PubMed, MEDLINE, and the Cochrane Central Register of Controlled Trials (search terms: vitamin D and supplementation) and focuses on recent challenges regarding the definition of vitamin D deficiency and how to achieve optimal serum 25-hydroxyvitamin D concentrations from dietary sources, supplements, and sun exposure. The effect of vitamin D on fetal programming epigenetics and gene regulation could potentially explain why vitamin D has been reported to have such wide-ranging health benefits throughout life. There is potentially a great upside to increasing the vitamin D status of children and adults worldwide for improving musculoskeletal health and reducing the risk of chronic illnesses, including some cancers, autoimmune diseases, infectious diseases, type 2 diabetes mellitus, neurocognitive disorders, and mortality.
Published:
2013-07
Title:
A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer's disease
Authors:
Kashiwaya, Yoshihiro; Bergman, Christian; Lee, Jong-Hwan; Wan, Ruiqian; King, M. Todd; Mughal, Mohamed R.; Okun, Eitan; Clarke, Kieran; Mattson, Mark P.; Veech, Richard L.
Abstract:
Published:
2013-06
Title:
Dietary modification dampens liver inflammation and fibrosis in obesity-related fatty liver disease
Authors:
Larter, Claire Z.; Yeh, Matthew M.; Haigh, W. Geoffrey; Van Rooyen, Derrick M.; Brooling, John; Heydet, Deborah; Nolan, Christopher J.; Teoh, Narci C.; Farrell, Geoffrey C.
Abstract:
BACKGROUND: Alms1 mutant (foz/foz) mice develop hyperphagic obesity, diabetes, metabolic syndrome, and fatty liver (steatosis). High-fat (HF) feeding converts pathology from bland steatosis to nonalcoholic steatohepatitis (NASH) with fibrosis, which leads to cirrhosis in humans. OBJECTIVE: We sought to establish how dietary composition contributes to NASH pathogenesis. DESIGN AND METHODS: foz/foz mice were fed HF diet or chow 24 weeks, or switched HF to chow after 12 weeks. Serum ALT, NAFLD activity score (NAS), fibrosis severity, neutrophil, macrophage and apoptosis immunohistochemistry, uncoupling protein (UCP)2, ATP, NF-κB activation/expression of chemokines/adhesion molecules/fibrogenic pathways were determined. RESULT: HF intake upregulated liver fatty acid and cholesterol transporter, CD36. Dietary switch expanded adipose tissue and decreased hepatomegaly by lowering triglyceride, cholesterol ester, free cholesterol and diacylglyceride content of liver. There was no change in lipogenesis or fatty acid oxidation pathways; instead, CD36 was suppressed. These diet-induced changes in hepatic lipids improved NAS, reduced neutrophil infiltration, normalized UCP2 and increased ATP; this facilitated apoptosis with a change in macrophage phenotype favoring M2 cells. Dietary switch also abrogated NF-κB activation and chemokine/adhesion molecule expression, and arrested fibrosis by dampening stellate cell activation. CONCLUSION: Reversion to a physiological dietary composition after HF feeding in foz/foz mice alters body weight distribution but not obesity. This attenuates NASH severity and fibrotic progression by suppressing NF-κB activation and reducing neutrophil and macrophage activation. However, adipose inflammation persists and is associated with continuing apoptosis in the residual fatty liver disease. Taken together, these findings indicate that other measures, such as weight reduction, may be required to fully reverse obesity-related NASH.
Published:
2013-06
Title:
Dietary modification of the microbiome affects risk for cardiovascular disease
Authors:
Mendelsohn, Andrew R; Larrick, James W
Abstract:
Abstract The incidence of cardiovascular disease (CVD) increases with age and is associated with some syndromes that exhibit aspects of premature aging, such as progeria. Various factors are thought to contribute to the progression of CVD, including hypertension, hypercholesterolemia, diets rich in saturated and trans fats, etc. Recent reports have uncovered an important connection between diet, the microbiome, and CVD. Dietary carnitine (present predominately in red meat) and lecithin (phosphatidyl choline) are shown to be metabolized by gut microbes to trimethylamine (TMA), which in turn is metabolized by liver flavin monoxygenases (especially FMO3 and FMO1) to form trimethylamine-N-oxide (TMAO). High levels of TMAO in the blood strongly correlate with CVD and associated acute clinical events. Plasma TMAO levels may be an important clinical biomarker for CVD. The data suggest that that presence of specific as yet unidentified microorganisms in the gut linked to diet are required for high TMAO levels and TMAO-mediated CVD progression. Development of novel therapeutic approaches to manipulate gut flora may help treat CVD.
Published:
2013-06
Title:
Effectiveness and Mood Conversion Rate of Short-Term Fluoxetine Monotherapy in Patients With Rapid Cycling Bipolar II Depression Versus Patients With Nonrapid Cycling Bipolar II Depression:
Authors:
Amsterdam, Jay D.; Luo, Lola; Shults, Justine
Abstract:
Objective: We examined the effectiveness and mood conversion rate of fluoxetine monotherapy in patients with rapid cycling bipolar II depression versus patients with nonrapid cycling bipolar II depression. We hypothesized that there would be reduced antidepressant effectiveness and a greater mood conversion rate over time in patients with rapid cycling. Methods: Open-label fluoxetine monotherapy 10 to 80 mg daily was administered for up to 14 weeks in 42 outpatients with rapid cycling versus 124 outpatients with nonrapid cycling. Outcome measures included the change over time in depression ratings, the proportion of treatment responders and remitters, change over time in mania ratings, and frequency of syndromal and subsyndromal hypomanic episodes. Results: There was a greater reduction in depression rating scores in the patients with rapid cycling versus those with nonrapid cycling (P = 0.04), with similar rates of response (P = 0.18) and remission (P = 0.69). Change in mean mania rating scores was similar in the patients with rapid cycling versus those with nonrapid cycling (P = 0.28). Hypomanic symptoms occurred in a similar proportion of the patients with rapid cycling versus those with nonrapid cycling (P = 0.99). Hypomanic episodes occurred in 5.4% (95% confidence interval [CI], 0.7Y18.2) of the patients with rapid cycling versus 3.6% (95% CI, 1.0Y8.9) of those with nonrapid cycling (P = 0.65). Subsyndromal hypomania occurred in 13.5% (95% CI, 4.5Y28.8) of the patients with rapid cycling versus 9.0% (95% CI, 4.4Y15.9) of those with nonrapid cycling (P = 0.43). Conclusion: In contrast to reports of reduced effectiveness and increased mood conversion rates in patients with rapid cycling bipolar disorder taking antidepressants, we found greater effectiveness and similar hypomania rates during fluoxetine monotherapy in the patients with rapid cycling bipolar II depression versus those with nonrapid cycling bipolar II depression.
Published:
2013-06
Title:
Egg consumption modulates HDL lipid composition and increases the cholesterol-accepting capacity of serum in metabolic syndrome
Authors:
Andersen, Catherine J.; Blesso, Christopher N.; Lee, Jiyoung; Barona, Jacqueline; Shah, Dharika; Thomas, Michael J.; Fernandez, Maria Luz
Abstract:
We recently demonstrated that daily whole egg consumption during moderate carbohydrate restriction leads to greater increases in plasma HDL-cholesterol (HDL-C) and improvements in HDL profiles in metabolic syndrome (MetS) when compared to intake of a yolk-free egg substitute. We further investigated the effects of this intervention on HDL composition and function, hypothesizing that the phospholipid species present in egg yolk modulate HDL lipid composition to increase the cholesterol-accepting capacity of subject serum. Men and women classified with MetS were randomly assigned to consume either three whole eggs (EGG, n = 20) per day or the equivalent amount of egg substitute (SUB, n = 17) throughout a 12-week moderate carbohydrate-restricted (25-30 % of energy) diet. Relative to other HDL lipids, HDL-cholesteryl ester content increased in all subjects, with greater increases in the SUB group. Further, HDL-triacylglycerol content was reduced in EGG group subjects with normal baseline plasma HDL-C, resulting in increases in HDL-CE/TAG ratios in both groups. Phospholipid analysis by mass spectrometry revealed that HDL became enriched in phosphatidylethanolamine in the EGG group, and that EGG group HDL better reflected sphingomyelin species present in the whole egg product at week 12 compared to baseline. Further, macrophage cholesterol efflux to EGG subject serum increased from baseline to week 12, whereas no changes were observed in the SUB group. Together, these findings suggest that daily egg consumption promotes favorable shifts in HDL lipid composition and function beyond increasing plasma HDL-C in MetS.
Published:
2013-06
Title:
Estimation of usual intake and food sources of choline and betaine in New Zealand reproductive age women
Authors:
Mygind, Vanessa L; Evans, Sophie E; Peddie, Meredith C; Miller, Jody C; Houghton, Lisa A
Abstract:
Recently, choline has been associated with neurodevelopment, cognitive function and neural tube defect incidence. However, data on usual intakes are limited, and estimates of dietary intakes of choline and its metabolite betaine, are not available for New Zealanders. The objective of the present study was to determine usual intake and food sources of choline and betaine in a group of New Zealand reproductive age women. Dietary intake data were collected from a sample of 125 women, aged 18-40 years, by means of a 3-day weighed food record, and usual choline and betaine intake distributions were determined. The mean (SD) daily intakes of choline and betaine were 316 (66) mg and 178 (66) mg, respectively. The total choline intake relative to energy intake and body weight was 0.18 mg/kcal and 5.1 mg/kg, respectively. Only 16% of participants met or exceeded the Adequate Intake (AI) for adult women of 425 mg of choline. The top five major food contributors of choline were eggs, red meat, milk, bread and chicken; and of betaine were bread, breakfast cereal, pasta, grains and root vegetables (carrots, parsnips, beetroot, swedes). Our findings contribute towards the recent emergence of published reports on the range of dietary choline and betaine intakes consumed by free-living populations. In our sample of New Zealand women, few participants were meeting or exceeding the AI level. Given recent epidemiological evidence suggesting health benefits of increased choline and betaine intakes, recommendations should be made to encourage the consumption of choline and betaine-rich foods.
Published:
2013-06
Title:
Evaluation of a campaign to improve awareness and attitudes of young people towards mental health issues
Authors:
Livingston, James D.; Tugwell, Andrew; Korf-Uzan, Kimberly; Cianfrone, Michelle; Coniglio, Connie
Abstract:
Purpose This study evaluated the effectiveness of the In One Voice campaign for raising mental health awareness and improving attitudes of youth and young adults towards mental health issues. The campaign featured a prominent male sports figure talking about mental health issues and used online social media.
Published:
2013-06
Title:
Frameworks for learner assessment in medicine: AMEE Guide No. 78
Authors:
Pangaro, Louis; ten Cate, Olle
Abstract:
In any evaluation system of medical trainees there is an underlying set of assumptions about what is to be evaluated (i.e., which goals reflect the values of the system or institution), what kind of observations or assessments are useful to allow judgments1; and how these are to be analyzed and compared to a standard of what is to be achieved by the learner. These assumptions can be conventionalized into a framework for evaluation. Frameworks encompass, or ‘‘frame,’’ a group of ideas or categories to reflect the educational goals against which a trainee’s level of competence or progress is gauged. Different frameworks provide different ways of looking at the practice of medicine and have different purposes. In the first place, frameworks should enable educators to determine to what extent trainees are ready for advancement, that is, whether the desired competence has been attained. They should provide both a valid mental model of competence and also terms to describe successful performance, either at the end of training or as milestones during the curriculum. Consequently, such frameworks drive learning by providing learners with a guide for what is expected. Frameworks should also enhance consistency and reliability of ratings across staff and settings. Finally, they determine the content of, and resources needed for, rater training to achieve consistency of use. This is especially important in clinical rotations, in which reliable assessments have been most difficult to achieve. Because the limitations of workplace-based assessment have persisted despite the use of traditional frameworks (such as those based on knowledge, skills, and attitudes), this Guide will explore the assumptions and characteristics of traditional and newer frameworks. In this AMEE Guide, we make a distinction between analytic, synthetic, and developmental frameworks. Analytic frameworks deconstruct competence into individual pieces, to evaluate each separately. Synthetic frameworks attempt to view competence holistically, focusing evaluation on the performance in real-world activities. Developmental frameworks focus on stages of, or milestones, in the progression toward competence. Most frameworks have one predominant perspective; some have a hybrid nature.
Published:
2013-06
Title:
Genome-wide meta-analysis of observational studies shows common genetic variants associated with macronutrient intake
Authors:
Tanaka, Toshiko; Ngwa, Julius S.; van Rooij, Frank J. A.; Zillikens, M. Carola; Wojczynski, Mary K.; Frazier-Wood, Alexis C.; Houston, Denise K.; Kanoni, Stavroula; Lemaitre, Rozenn N.; Luan, Jian'an; Mikkilä, Vera; Renstrom, Frida; Sonestedt, Emily; Zhao, Jing Hua; Chu, Audrey Y.; Qi, Lu; Chasman, Daniel I.; de Oliveira Otto, Marcia C.; Dhurandhar, Emily J.; Feitosa, Mary F.; Johansson, Ingegerd; Khaw, Kay-Tee; Lohman, Kurt K.; Manichaikul, Ani; McKeown, Nicola M.; Mozaffarian, Dariush; Singleton, Andrew; Stirrups, Kathleen; Viikari, Jorma; Ye, Zheng; Bandinelli, Stefania; Barroso, Inês; Deloukas, Panos; Forouhi, Nita G.; Hofman, Albert; Liu, Yongmei; Lyytikäinen, Leo-Pekka; North, Kari E.; Dimitriou, Maria; Hallmans, Goran; Kähönen, Mika; Langenberg, Claudia; Ordovas, Jose M.; Uitterlinden, André G.; Hu, Frank B.; Kalafati, Ioanna-Panagiota; Raitakari, Olli; Franco, Oscar H.; Johnson, Andrew; Emilsson, Valur; Schrack, Jennifer A.; Semba, Richard D.; Siscovick, David S.; Arnett, Donna K.; Borecki, Ingrid B.; Franks, Paul W.; Kritchevsky, Stephen B.; Lehtimäki, Terho; Loos, Ruth J. F.; Orho-Melander, Marju; Rotter, Jerome I.; Wareham, Nicholas J.; Witteman, Jacqueline C. M.; Ferrucci, Luigi; Dedoussis, George; Cupples, L. Adrienne; Nettleton, Jennifer A.
Abstract:
BACKGROUND: Macronutrient intake varies substantially between individuals, and there is evidence that this variation is partly accounted for by genetic variants. OBJECTIVE: The objective of the study was to identify common genetic variants that are associated with macronutrient intake. DESIGN: We performed 2-stage genome-wide association (GWA) meta-analysis of macronutrient intake in populations of European descent. Macronutrients were assessed by using food-frequency questionnaires and analyzed as percentages of total energy consumption from total fat, protein, and carbohydrate. From the discovery GWA (n = 38,360), 35 independent loci associated with macronutrient intake at P < 5 × 10(-6) were identified and taken forward to replication in 3 additional cohorts (n = 33,533) from the DietGen Consortium. For one locus, fat mass obesity-associated protein (FTO), cohorts with Illumina MetaboChip genotype data (n = 7724) provided additional replication data. RESULTS: A variant in the chromosome 19 locus (rs838145) was associated with higher carbohydrate (β ± SE: 0.25 ± 0.04%; P = 1.68 × 10(-8)) and lower fat (β ± SE: -0.21 ± 0.04%; P = 1.57 × 10(-9)) consumption. A candidate gene in this region, fibroblast growth factor 21 (FGF21), encodes a fibroblast growth factor involved in glucose and lipid metabolism. The variants in this locus were associated with circulating FGF21 protein concentrations (P
Published:
2013-06
Title:
Liquid chromatography-electrospray ionization tandem mass spectrometric analysis of 2-alkylcyclobutanones in irradiated chicken by precolumn derivatization with hydroxylamine
Authors:
Ye, Yuran; Liu, Hanxia; Horvatovich, Peter; Chan, Wan
Abstract:
Food irradiation is a common preservation method that is used in many countries. The ability to identify irradiated food is important for assuring compliance with regulatory policies, such as food labeling requirements, and for informed consumer choice. There is thus a significant demand for analytical methods of high sensitivity and selectivity to identify irradiated food, especially for foods subjected to low-dose irradiation and for processed or composite foods that contain small quantities of irradiated ingredients. 2-Alkylcyclobutanones (2-ACBs) are uniquely formed during food irradiation and have been adopted by the European Committee for Standardization as signature biomarkers for the identification of irradiated foods. We now report the development of a novel assay for quantification of 2-ACBs in gamma-irradiated food by liquid extraction of fat content followed by precolumn derivatization and liquid chromatography-tandem mass spectrometric (LC-MS/MS) detection. Precolumn derivatization with hydroxylamine introduced a polar functional group into the otherwise nonpolar 2-ACBs, which greatly enhanced ESI-MS response. The method was validated for extraction efficiency, precision, accuracy, and detection limit. In comparison with the current GC-MS based European official method (EN1785:2003) for 2-ACBs determination, our new LC-MS/MS method offers a more efficient sample processing protocol with reduced solvent consumption. More importantly, the combination of chemical derivatization and LC-MS/MS detection significantly enhanced the analytical sensitivity of the method, which allows confident identification of food irradiated with as little as 10 Gy. To the best of our knowledge, this is the first report of 2-ACB determination by LC-MS/MS and the first analytical method allowing confident identification of irradiated food at dosage of down to 10 Gy.
Published:
2013-06
Title:
Long-acting injectable formulations of antipsychotic drugs for the treatment of schizophrenia
Authors:
Park, Eun Ji; Amatya, Sarmila; Kim, Myung Sun; Park, Jong Hoon; Seol, Eunyoung; Lee, Heeyong; Shin, Young-Hee; Na, Dong Hee
Abstract:
Antipsychotic drugs have been used to treat patients with schizophrenia and other psychotic disorders. Long-acting injectable antipsychotic drugs are useful for improving medication compliance with a better therapeutic option to treat patients who lack insight or adhere poorly to oral medication. Several long-acting injectable antipsychotic drugs are clinically available. Haloperidol decanoate and fluphenazine decanoate are first-generation depot drugs, but the use of these medicines has declined since the advent of second-generation depot agents, such as longacting risperidone, paliperidone palmitate, and olanzapine pamoate. The second-generation depot drugs are better tolerated and have fewer adverse neurological side effects. Long-acting injectable risperidone, the first depot formulation of an atypical antipsychotic drug, was prepared by encapsulating risperidone into biodegradable microspheres. Paliperidone palmitate is an aqueous suspension of nanocrystal molecules, and olanzapine pamoate is a microcrystalline salt of olanzapine and pamoic acid suspended in aqueous solution. This review summarizes the characteristics and recent research of formulations of each longacting injectable antipsychotic drug.
Published:
2013-06
Title:
Meta-analysis of increased heart rate and blood pressure associated with CNS stimulant treatment of ADHD in adults
Authors:
Mick, Eric; McManus, David D.; Goldberg, Robert J.
Abstract:
Compared to children, adults with ADHD are at greater risk for developing adverse cardiovascular related outcomes and, if treated, may be likely to carry a greater burden of exposure to stimulant medications. The goal of this report is to critically review the available literature relevant to the cardiovascular safety of CNS stimulants for adult ADHD (aADHD). Twenty potential clinical trials of a CNS stimulant for aADHD have been published between 1979 and 2012. Of these, ten presented sufficient data to estimate the relative change in various cardiovascular parameters associated with ADHD treatment modalities. These trials were predominantly focused on long-acting stimulant preparations for acute symptom reduction (median duration=6 weeks, range: 4-24 weeks) and enrolled relatively young subjects (median age=36 years, range: 22-40). Using random effects meta-analysis, we found that subjects randomized to CNS stimulant treatment demonstrated a statistically significant increased resting heart rate [+5.7bpm (3.6, 7.8), p90bpm [4.2% (n=50) vs. 1.7% (n=8), OR=2.75 (1.3, 6.7), p=0.006] associated with CNS stimulant treatment. In light of prognostic value of resting heart rate with regard to cardiovascular morbidity in epidemiological studies, future research of adults with ADHD should focus on the potential clinical impact of the increase in heart rate observed in this meta-analysis.
Published:
2013-06
Title:
Modeling prostate cancer in mice: Something old, something new, something premalignant, something metastatic
Authors:
Irshad, Shazia; Abate-Shen, Cory
Abstract:
More than 15 years ago the first generation of genetically-engineered mouse (GEM) models of prostate cancer was introduced. These transgenic models utilized prostate-specific promoters to express SV40 oncogenes specifically in prostate epithelium. Since the description of these initial models, there have been a plethora of GEM models of prostate cancer, representing various perturbations of oncogenes or tumor suppressors, either alone or in combination. This review describes these GEM models, focusing on their relevance for human prostate cancer and highlighting their strengths and limitations, as well as opportunities for the future.
Published:
2013-06
Title:
Phenomenology and classification of dystonia: A consensus update
Authors:
Albanese, Alberto; Bhatia, Kailash; Bressman, Susan B.; Delong, Mahlon R.; Fahn, Stanley; Fung, Victor S.C.; Hallett, Mark; Jankovic, Joseph; Jinnah, Hyder A.; Klein, Christine; Lang, Anthony E.; Mink, Jonathan W.; Teller, Jan K.
Abstract:
This report describes the consensus outcome of an international panel consisting of investigators with years of experience in this field that reviewed the definition and classification of dystonia. Agreement was obtained based on a consensus development methodology during 3 in-person meetings and manuscript review by mail. Dystonia is defined as a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Dystonic movements are typically patterned and twisting, and may be tremulous. Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation. Dystonia is classified along 2 axes: clinical characteristics, including age at onset, body distribution, temporal pattern and associated features (additional movement disorders or neurological features); and etiology, which includes nervous system pathology and inheritance. The clinical characteristics fall into several specific dystonia syndromes that help to guide diagnosis and treatment. We provide here a new general definition of dystonia and propose a new classification. We encourage clinicians and researchers to use these innovative definition and classification and test them in the clinical setting on a variety of patients with dystonia. © 2013 Movement Disorder Society.
Published:
2013-06
Title:
Risk Factors of Breast Cancer-Related Lymphedema
Authors:
Ugur, Saadet; Arıcı, Cumhur; Yaprak, Muhittin; Mescı, Ayhan; Arıcı, Gulbin Ayse; Dolay, Kemal; Ozmen, Vahit
Abstract:
Introduction: Secondary lymphedema is one of the major important long-term complications of breast cancer treatment. The aim of this study is to determine patient- and treatment-related risk factors of lymphedema in breast cancer patients. Patients and Methods: Patients, who had been operated on for primary breast cancer at Akdeniz University Hospital and followed regularly between August 1984 and December 2009 were included in the study. In order to evaluate the arm swelling objectively, measurements were performed with a flexible tape measure for both arms, and limb volume was calculated using a truncated cone volume formula. Participants, whose volume difference between the two arms was ‡5%, were considered as lymphedema-positive patients. The SPSS program (SPSS inc. Chicago, IL) was used for statistical analysis. Results: The mean age of 455 patients was 50.6 years and the median follow-up time was 53 months. Lymphedema was found in 124 (27%) patients. Most of the patients with a history of postoperative wound infection (52%) and lymphangitis (57%) had lymphedema ( p = 0.003 and p = 0.002, respectively). Addition of radiation therapy increased lymphedema risk 1.83 times ( p = 0.007). The mean duration of the axillary drainage and number of the removed lymph nodes were 7.8 days and 19, respectively. The rate of lymphedema in patients with early stage breast cancer was less than patients with advanced breast cancer (24% and 35.3%, respectively, p = 0.018). Most of the patients (92%) with lymphedema had a high body mass index (BMI ‡25 kg/m2), and obesity was another important factor for lymphedema ( p
Published:
2013-06
Title:
Dietary fat modification and the risk of future cardiovascular events and mortality
Authors:
Bui, Quynh
Abstract:
Published:
2013-05
Title:
Intermittent fasting: a "new" historical strategy for controlling seizures?
Authors:
Hartman, Adam L.; Rubenstein, James E.; Kossoff, Eric H.
Abstract:
In antiquity, fasting was a treatment for epilepsy and a rationale for the ketogenic diet (KD). Preclinical data indicate the KD and intermittent fasting do not share identical anticonvulsant mechanisms. We implemented an intermittent fasting regimen in six children with an incomplete response to a KD. Three patients adhered to the combined intermittent fasting/KD regimen for 2 months and four had transient improvement in seizure control, albeit with some hunger-related adverse reactions.
Published:
2013-05
Title:
Ketogenic diets and thermal pain: dissociation of hypoalgesia, elevated ketones, and lowered glucose in rats
Authors:
Ruskin, David N.; Suter, Tracey A. C. S.; Ross, Jessica L.; Masino, Susan A.
Abstract:
Ketogenic diets (KDs) are high-fat, low-carbohydrate formulations effective in treating medically refractory epilepsy, and recently we demonstrated lowered sensitivity to thermal pain in rats fed a KD for 3 to 4 weeks. Regarding anticonvulsant and hypoalgesic mechanisms, theories are divided as to direct effects of increased ketones and/or decreased glucose, metabolic hallmarks of these diets. To address this point, we characterized the time course of KD-induced thermal hypoalgesia, ketosis, and lowered glucose in young male rats fed ad libitum on normal chow or KDs. A strict 6.6:1 (fat:[carbohydrates + protein], by weight) KD increased blood ketones and reduced blood glucose by 2 days of feeding, but thermal hypoalgesia did not appear until 10 days. Thus, ketosis and decreased glucose are not sufficient for hypoalgesia. After feeding a 6.6:1 KD for 19 days, decreased thermal pain sensitivity and changes in blood chemistry reversed 1 day after return to normal chow. Effects were consistent between 2 different diet formulations: a more moderate and clinically relevant KD formula (3.0:1) produced hypoalgesia and similar changes in blood chemistry as the 6.6:1 diet, thus increasing translational potential. Furthermore, feeding the 3.0:1 diet throughout an extended protocol (10-11 weeks) revealed that significant hypoalgesia and increased ketones persisted whereas low glucose did not, demonstrating that KD-induced hypoalgesia does not depend on reduced glucose. In separate experiments we determined that effects on thermal pain responses were not secondary to motor or cognitive changes. Together, these findings dissociate diet-related changes in nociception from direct actions of elevated ketones or decreased glucose, and suggest mechanisms with a slower onset in this paradigm. Overall, our data indicate that metabolic approaches can relieve pain. PERSPECTIVE: Chronic pain is a common and debilitating condition. We show that a KD, a high-fat, very low carbohydrate diet well known for treating epilepsy, lowers sensitivity to thermal pain in rats. This reduced pain is not temporally correlated with hallmark diet-induced changes in blood glucose and ketones.
Published:
2013-05
Title:
Reduced adipose tissue lymphatic drainage of macromolecules in obese subjects: a possible link between obesity and local tissue inflammation?
Authors:
Arngrim, N.; Simonsen, L.; Holst, J. J.; Bülow, J.
Abstract:
The aim of this study was to investigate subcutaneous adipose tissue lymphatic drainage (ATLD) of macromolecules in lean and obese subjects and, furthermore, to evaluate whether ATLD may change in parallel with adipose tissue blood flow. Lean and obese male subjects were studied before and after an oral glucose load. Adipose-tissue blood flow was measured in the anterior subcutaneous abdominal adipose tissue by the 133Xe-washout technique. ATLD was measured as the disappearance rate of 99mTc-labelled nanoaggregated human albumin, during fasting and after an oral glucose load. A significant increase in ATLD was seen after the glucose load in the lean subjects. In the obese subjects, ATLD remained constant throughout the study and was significantly lower compared to the lean subjects. These results indicate a reduced ability to remove macromolecules from the interstitial space through the lymphatic system in obese subjects. Furthermore, they suggest that postprandial changes in ATLD taking place in lean subjects are not observed in obese subjects. This may have a role in the development of obesity-related inflammation in hypertrophic adipose tissue.
Published:
2013-05
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