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  • 1
    Keywords: INTERVENTION ; BREAST-CANCER ; STRESS ; LYMPHOCYTES ; SKELETAL-MUSCLE ; POSTMENOPAUSAL WOMEN ; PHYSICAL-ACTIVITY ; OXIDATIVE DNA-DAMAGE ; alkaline comet assay ; WEIGHT-LOSS
    Abstract: INTRODUCTION: Maintenance of normal weight and higher levels of physical activity are associated with a reduced risk of several types of cancer. As genomic instability is regarded as a hallmark of cancer development, one proposed mechanism is improvement of DNA repair function. We investigated links between dietary weight loss, exercise, and strand break rejoining in an ancillary study to a randomized-controlled trial. METHODS: Overweight/obese postmenopausal women (n=439) were randomized to: a) reduced-calorie weight-loss diet ("diet" n=118); b) moderate-to-vigorous intensity aerobic exercise ("exercise" n=117); c) a combination ("diet+exercise" n=117); or d) control (n=87). The reduced-calorie diet had a 10% weight-loss goal. The exercise intervention consisted of 45 minutes of moderate-to-vigorous aerobic activity 5 days/week for 12 months. DNA repair capacity was measured in a subset of 226 women at baseline and 12 months, from cryopreserved peripheral mononuclear cells using the Comet assay. Anthropometric and body composition measures were performed at baseline and 12 months. RESULTS: DNA repair capacity did not change significantly with any of the 12 month interventions compared to control; there were also no significant changes when stratified by changes in body composition or aerobic fitness (VO2max). At baseline, DNA repair capacity was positively associated with weight, BMI, and fat mass (r=0.20, p=0.003; r=0.19, p=0.004; r=0.13, p=0.04, respectively) and inversely with lean body mass (r=-0.14, p=0.04). CONCLUSION: In conclusion, DNA repair capacity did not change with dietary weight loss or exercise interventions in postmenopausal women within a period of 12 months. Other assays that capture different facets of DNA repair function may be needed.
    Type of Publication: Journal article published
    PubMed ID: 25160845
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  • 2
    Keywords: COLORECTAL-CANCER ; microsatellite instability ; SYSTEMIC-LUPUS-ERYTHEMATOSUS ; METHYLENETETRAHYDROFOLATE REDUCTASE ; EPIGENETIC CHANGES ; FREE TESTOSTERONE ; RANDOMIZED CLINICAL-TRIAL ; LINE-1 HYPOMETHYLATION ; MODERATE FOLATE-DEPLETION ; NORMAL-TISSUES
    Abstract: DNA methylation is an epigenetic modification essential for the regulation of gene expression that has been implicated in many diseases, including cancer. Few studies have investigated the wide range of potential predictors of global DNA methylation, including biomarkers. Here, we investigated associations between DNA methylation and dietary factors, sex-steroid hormones, metabolic, lipid, inflammation, immune and one-carbon biomarkers. Data and baseline biomarker measurements were obtained from 173 overweight/obese postmenopausal women. Global DNA methylation in lymphocyte DNA was measured using the pyrosequencing assay for LINE-1 repeats. We used correlations and linear regression analyses to investigate associations between continuous data and DNA methylation, while t-tests were used for categorical data. Secondary analyses stratified by serum folate levels and multivitamin use were also conducted. There was little variability in LINE-1 methylation (66.3-79.5%). Mean LINE-1 methylation was significantly higher among women with elevated glucose levels. Mean LINE-1 methylation was also higher among women with high CD4+/CD8+ ratio, and lower among women with elevated vitamin B6, but neither reached statistical significance. In analyses stratified by folate status, DNA methylation was negatively associated with sex hormone concentrations (estrone, estradiol, testosterone and sex hormone binding globulin) among women with low serum folate levels (n = 53). Conversely, among women with high serum folate levels (n = 53), DNA methylation was positively associated with several immune markers (CD4/CD8 ratio, NK1656/lymphocytes and IgA). Results from this screening suggest that global DNA methylation is generally stable, with differential associations for sex hormones and immune markers depending on one-carbon status.
    Type of Publication: Journal article published
    PubMed ID: 22869041
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  • 3
  • 4
    Keywords: CLINICAL-TRIAL ; MARKERS ; C-REACTIVE PROTEIN ; NATIONAL-HEALTH ; CARDIOVASCULAR-DISEASE ; PHYSICAL-ACTIVITY ; METAANALYSIS ; NUTRITION EXAMINATION SURVEY ; ENDOMETRIAL CANCER-RISK ; LIFE-STYLE INTERVENTION
    Abstract: Obese and sedentary persons have increased risk for cancer; inflammation is a hypothesized mechanism. We examined the effects of a caloric restriction weight loss diet and exercise on inflammatory biomarkers in 439 women. Overweight and obese postmenopausal women were randomized to 1-year: caloric restriction diet (goal of 10% weight loss, N = 118), aerobic exercise (225 min/wk of moderate-to-vigorous activity, N = 117), combined diet + exercise (N = 117), or control (N = 87). Baseline and 1-year high-sensitivity C-reactive protein (hs-CRP), serum amyloid A (SAA), interleukin-6 (IL-6), leukocyte, and neutrophil levels were measured by investigators blind to group. Inflammatory biomarker changes were compared using generalized estimating equations. Models were adjusted for baseline body mass index (BMI), race/ethnicity, and age. Four hundred and thirty-eight (N = 1 in diet + exercise group was excluded) were analyzed. Relative to controls, hs-CRP decreased by geometric mean (95% confidence interval, P value): 0.92 mg/L (0.53-1.31, P 〈 0.001) in the diet and 0.87 mg/L (0.51-1.23, P 〈 0.0001) in the diet + exercise groups. IL-6 decreased by 0.34 pg/mL (0.13-0.55, P = 0.001) in the diet and 0.32 pg/mL (0.15-0.49, P 〈 0.001) in the diet + exercise groups. Neutrophil counts decreased by 0.31 x 10(9)/L (0.09-0.54, P = 0.006) in the diet and 0.30 x 10(9)/L (0.09-0.50, P = 0.005) in the diet + exercise groups. Diet and diet + exercise participants with 5% or more weight loss reduced inflammatory biomarkers (hs-CRP, SAA, and IL-6) compared with controls. The diet and diet + exercise groups reduced hs-CRP in all subgroups of baseline BMI, waist circumference, CRP level, and fasting glucose. Our findings indicate that a caloric restriction weight loss diet with or without exercise reduces biomarkers of inflammation in postmenopausal women, with potential clinical significance for cancer risk reduction.
    Type of Publication: Journal article published
    PubMed ID: 22549948
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  • 5
    Keywords: CLINICAL-TRIAL ; RISK ; BREAST-CANCER ; OBESITY ; COLON-CANCER ; CARDIOVASCULAR-DISEASE ; INSULIN-RESISTANCE ; metabolic syndrome ; BODY-MASS INDEX ; adipokines
    Abstract: BackgroundExcess body weight and a sedentary lifestyle are associated with the development of several diseases, including cardiovascular disease, diabetes and cancer in women. One proposed mechanism linking obesity to chronic diseases is an alteration in adipose-derived adiponectin and leptin levels. We investigated the effects of 12-month reduced calorie, weight loss and exercise interventions on adiponectin and leptin concentrations. MethodsOverweight/obese postmenopausal women (n=439) were randomized as follows: (i) a reduced calorie, weight-loss diet (diet; N=118), (ii) moderate-to-vigorous intensity aerobic exercise (exercise; N=117), (iii) a combination of a reduced calorie, weight-loss diet and moderate-to-vigorous intensity aerobic exercise (diet+exercise; N=117), and (iv) control (N=87). The reduced calorie diet had a 10% weight-loss goal. The exercise intervention consisted of 45min of moderate-to-vigorous aerobic activity 5days per week. Adiponectin and leptin levels were measured at baseline and after 12months of intervention using a radioimmunoassay. ResultsAdiponectin increased by 9.5% in the diet group and 6.6% in the diet+exercise group (both P0.0001 vs. control). Compared with controls, leptin decreased with all interventions (diet+exercise, -40.1%, P〈0.0001; diet, -27.1%, P〈0.0001; exercise, -12.7%, P=0.005). The results were not influenced by the baseline body mass index (BMI). The degree of weight loss was inversely associated with concentrations of adiponectin (diet, P-trend=0.0002; diet+exercise, P-trend=0.0005) and directly associated with leptin (diet, P-trend〈0.0001; diet+exercise, P-trend〈0.0001). ConclusionWeight loss through diet or diet+exercise increased adiponectin concentrations. Leptin concentrations decreased in all of the intervention groups, but the greatest reduction occurred with diet+exercise. Weight loss and exercise exerted some beneficial effects on chronic diseases via effects on adiponectin and leptin.
    Type of Publication: Journal article published
    PubMed ID: 23432360
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  • 6
    Keywords: cancer prevention ; NECROSIS-FACTOR-ALPHA ; POSTMENOPAUSAL WOMEN ; PHYSICAL-ACTIVITY ; INSULIN-RESISTANCE ; RANDOMIZED CONTROLLED-TRIAL ; LOW-CALORIE DIET ; OBESE WOMEN ; MACROPHAGE INFILTRATION ; HYPOCALORIC DIETS
    Abstract: Adipose tissue plays a role in obesity-related cancers via increased production of inflammatory factors, steroid hormones, and altered adipokines. The impact of weight loss on adipose-tissue gene expression may provide insights into pathways linking obesity with cancer risk. We conducted an ancillary study within a randomized trial of diet, exercise, or combined diet+exercise vs. control among overweight/obese postmenopausal women. In 45 women, subcutaneous adipose-tissue biopsies were performed at baseline and after 6 months and changes in adipose-tissue gene expression were determined by microarray with an emphasis on pre-specified candidate pathways, as well as by unsupervised clustering of 〉37,000 transcripts (Illumina). Analyses were conducted first by randomization group, and then by degree of weight change at 6-months in all women combined. At 6 months, diet, exercise and diet+exercise participants lost a mean of 8.8 kg, 2.5 kg, and 7.9 kg (all p〈0.05 vs. no change in controls). There was no significant change in candidate-gene expression by intervention group. In analysis by weight-change category, greater weight loss was associated a decrease in 17beta-hydroxysteroid dehydrogenase-1 (HSD17B1, p-trend〈0.01) and leptin (LEP, p-trend〈0.01) expression, and marginally significant increased expression of estrogen receptor-1 (ESR1, p-trend=0.08) and insulin-like growth factor binding protein-3 (IGFBP3, p-trend=0.08). Unsupervised clustering revealed 83 transcripts with statistically significant changes. Multiple gene-expression changes correlated with changes in associated serum biomarkers. Weight-loss was associated with changes in adipose-tissue gene expression after 6 months, particularly in two pathways postulated to link obesity and cancer, i.e., steroid-hormone metabolism and IGF signaling.
    Type of Publication: Journal article published
    PubMed ID: 23341572
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  • 7
    Keywords: CLINICAL-TRIAL ; MARKER ; BIOMARKERS ; BODY-WEIGHT ; INTERVENTION ; TRIAL ; HEALTH ; STRESS ; WOMEN ; SURFACE ; MUSCLE ; FAT ; OXIDATIVE STRESS ; POSTMENOPAUSAL WOMEN ; exercise ; lipid peroxidation ; PRODUCTS ; WEIGHT ; SCIENCE ; methods ; WAIST CIRCUMFERENCE ; F-2-ISOPROSTANE ; AREA ; AEROBIC ; MAXIMAL OXYGEN UPTAKE ; OVERWEIGHT/OBESE
    Abstract: Campbell, p. T., M. D. Gross, j. D. Potter, k. H. Schmitz, c. Duggan, a. Mctiernan, and c. M. Ulrich. Effect of exercise on oxidative stress: A 12-month randomized, controlled trial. Med. Sci. Sports exerc., Vol. 42, No. 8, Pp. 1448-1453, 2010. Purpose: This study examined the effect of a yearlong exercise intervention on f-2-isoprostane, a specific marker of lipid peroxidation and a general marker of oxidative stress. Methods: In a randomized, controlled trial, 173 overweight or obese, postmenopausal, sedentary women were randomized either to an aerobic exercise intervention (60%-75% Observed maximal hr) For 〉= 45 Min.D(-1), 5 D.Wk(-1) (N = 87), Or to a stretching control group (N = 86), On an intent-to-treat basis. Baseline and 12-month measures included urinary f-2-isoprostane, maximal o-2 uptake, body weight, body fat percentage, waist circumference, and intra-abdominal fat surface area. Urine samples were available from 172 and 168 women at baseline and 12 months, respectively. Results: During the 12-month study, controls minimally changed maximal o-2 uptake (+0.2%) And body weight (+0.1 Kg), Whereas exercisers increased maximal o-2 uptake (+13.6%; P 〈 0.0001 Vs controls) And decreased body weight (-1.3 Kg; P = 0.007 Vs controls). F-2-isoprostane increased slightly among controls (+ 3.3%) And decreased in exercisers (-6.2%), Although the effect was not statistically significant (P = 0.26). In planned subgroup analyses, f-2-isoprostane decreased linearly with gain in maximal o-2 uptake (P-trend = 0.005) Relative to controls; Exercisers who increased maximal o-2 uptake by 915% decreased f-2-isoprostane by 14.1% (P = 0.005 Vs controls). A borderline statistically significant trend was observed between decreased waist circumference and f-2-isoprostane (P = 0.06). Similar subgroup analyses by 12-month changes in body fat percentage, weight, and intra-abdominal fat were not statistically significant. Conclusions: These findings suggest that aerobic exercise, when accompanied by relatively marked gains in aerobic fitness, decreases oxidative stress among previously sedentary older women and that these effects occur with minimal change in mass or body composition
    Type of Publication: Journal article published
    PubMed ID: 20139793
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  • 8
    Abstract: BACKGROUND: The risk of musculoskeletal injury with the introduction of moderate-to-vigorous exercise in sedentary adults is not well established. The purpose of this report is to examine the effect of a 12-month exercise intervention on musculoskeletal injury and bodily pain in predominately overweight, sedentary men (n = 102) and women (n = 100), ages 40 to 75 years. METHODS: Participants were randomized to a moderate-to-vigorous aerobic exercise intervention (EX) (6 d/wk, 60 min/d, 60% to 85% max. heart rate) or usual lifestyle control (CON). Participants completed a self-report of musculoskeletal injury and body pain at baseline and 12-months. RESULTS: The number of individuals reporting an injury (CON; 28% vs. EX; 28%, P = .95) did not differ by group. The most commonly injured site was lower leg/ankle/foot. The most common causes of injury were sports/physical activity, home maintenance, or "other." In the control group, bodily pain increased over the 12 months compared with the exercise group (CON -7.9, EX -1.4, P = .05). Baseline demographics and volume of exercise were not associated with injury risk. CONCLUSIONS: Previously sedentary men and women randomized to a 12-month aerobic exercise intervention with a goal of 360 min/wk reported the same number of injuries as those in the control group and less bodily pain.
    Type of Publication: Journal article published
    PubMed ID: 22368219
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  • 9
    Electronic Resource
    Electronic Resource
    [s.l.] : Macmillian Magazines Ltd.
    Nature 416 (2002), S. 413-416 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Entangled polymer solutions and melts exhibit elastic, solid-like resistance to quick deformations and a viscous, fluid-like response to slow deformations. This viscoelastic behaviour reflects the dynamics of individual polymer chains driven by brownian motion: since individual chains can only ...
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background : Cystic fibrosis causes exocrine pancreatic insufficiency, leading to malabsorption. Supplemental pancreatic enzyme therapy alleviates the concomitant malnutrition experienced by cystic fibrosis patients. It is recognized that patients experience variations in clinical response to different brands of enzymes. This has prompted the US Food and Drug Administration to require that enzyme supplements be subjected to New Drug Applications.Aim : To investigate the safety and efficacy of supplemental pancreatic enzyme therapy in cystic fibrosis subjects.Methods : We compared two doses of one formulation of enteric-coated pancreatic enzymes: Ultrase MT12 (12 000 lipase units per capsule) and Ultrase MT20 (20 000 lipase units per capsule), to placebo in two separate safety and efficacy studies.Results : Mean total fat, protein and carbohydrate intake did not differ significantly between the groups. A significant difference in both fat and protein absorption occurred with the enzyme therapy groups. The Ultrase MT12 and Ultrase MT20 groups experienced a mean fat and protein absorption 79.4% and 83.8%, and 87.3% and 88.6%, respectively. No adverse events related to study drug were reported.Conclusions : This study further supports the use of enzymes to treat pancreatic insufficiency in cystic fibrosis. Excellent fat and protein absorption was achieved with minimal adverse events and safe doses.
    Type of Medium: Electronic Resource
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