Dr. Dean Ornish
MED-2763
Facing the facelessness of public health: what's the public got to do with it?
Despite compelling statistics that show we could eliminate 80%of all heart disease and strokes, 90% of all diabetes, and 60% of all cancers with basic lifestyle changes, we have failed to motivate the public to make these changes and failed to motivate policy makers to make healthy choices the easiest choice. Dr. Katz suggests we have failed because we have focused too much on statistics and too little on passion. He implores all of us to tap into people's passion by connecting each of these statistics with a human story.
MED-3780
Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease
Metabolomics studies hold promise for discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. A metabolomics approach was used to generate unbiased small molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine, namely choline, trimethylamine N-oxide (TMAO), and betaine, were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted up-regulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases (FMOs), an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidemic mice. Discovery of a relationship between gut flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for development of both novel diagnostic tests and therapeutic approaches for atherosclerotic heart disease.
MED-3784
Choline and betaine intake and the risk of colorectal cancer in men
Dietary choline and betaine have been hypothesized to decrease the risk of cancer because of their role as methyl donors in the one-carbon metabolism. However, it remains unknown whether dietary intake of choline and betaine is associated with colorectal cancer risk. We prospectively examined the associations between dietary choline and betaine intake and risk of colorectal cancer in men in the Health Professionals Follow-up Study. We followed 47,302 men and identified a total of 987 incident colorectal cancer cases from 1986 to 2004. We assessed dietary and supplemental choline and betaine intake every four years using a validated semi-quantitative food frequency questionnaire. The Cox proportional hazards model was used to estimate multivariate relative risks (RRs) and 95% confidence intervals (95% CIs). All statistical tests were two-sided. We did not find any statistically significant associations between choline intake or betaine intake and risk of colorectal cancer. Comparing the top quintile with bottom quintile, multivariate RRs (95% CI) were 0.97 (0.79-1.20; Ptrend = 0.87) for choline intake and 0.94 (0.77-1.16; Ptrend = 0.79) for betaine intake. Similarly, we observed no associations between colorectal cancer risk and choline from free choline, glycerophosphocholine, phosphocholine, phosphatidylcholine, or sphingomyelin. Our data do not support that choline and betaine intake is inversely associated with colorectal cancer risk.
MED-3242
Macronutrient intake and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition.
Previous studies have suggested that dietary factors may be important in the development of bladder cancer. We examined macronutrient intake in relation to risk of urothelial cell carcinoma among 469,339 men and women in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by sex, age at recruitment and centre and further adjusted for smoking status and duration, body mass index and total energy intake. After an average of 11.3 years of follow-up, 1,416 new cases of urothelial cell carcinoma were identified. After allowing for measurement error, a 3% increase in the consumption of energy intake from animal protein was associated with a 15% higher risk (95% confidence interval [CI]: 3-30%; p(trend) = 0.01) and a 2% increase in energy from plant protein intake was associated with a 23% lower risk (95% CI: 36-7%, p(trend) = 0.006). Dietary intake of fat, carbohydrate, fibre or calcium was not associated with risk. These findings suggest that animal and/or plant protein may affect the risk of urothelial cell carcinoma, and examination of these associations in other studies is needed. Copyright © 2012 UICC.
MED-3244
A Novel Measure of Dietary Change in a Prostate Cancer Dietary Program Incorporating Mindfulness Training
Diet may represent a modifiable prostate cancer (CaP) risk factor, but a vegetable-based prostate-healthy diet is a major change for most men. We used a ratio of animal:vegetable proteins (A:V ratio) to evaluate whether a comprehensive dietary change was self-sustaining following completion of 11 weekly dietary and cooking classes that integrated mindfulness training (MT). Thirty-six men with recurring CaP were randomized to the intervention or wait-list control. Assessments were at baseline, three months and six months. Of the 17 men randomized to the intervention, 14 completed the requirements. Nineteen were randomized to control and 17 completed requirements. Compared to controls, a significant post-intervention (3 months) decrease in A:V ratio in the intervention group (p=.01) was self-maintained 3 months post-intervention (p=0.049). At each assessment, the A:V ratio was correlated with lycopene, fiber, saturated fat, and dietary cholesterol; four dietary components linked to clinically relevant outcomes in CaP. Change in A:V ratio was also significantly correlated with changes in fiber, saturated fat and dietary cholesterol intake. Participants reported regular MT practice and there was a significant correlation between MT practice and changes in both initiation and maintenance of the change in the A:V ratio. These pilot results provide encouraging evidence for the feasibility of a dietary program that includes MT in supporting dietary change for men with recurrent CaP and invite further study to explore the possible role of MT as a means of supporting both initiation of dietary changes and maintenance of those changes over time.
MED-3790
Intakes of meat, fish, poultry, and eggs and risk of prostate cancer progression
Background: Processed meat and fish have been shown to be associated with the risk of advanced prostate cancer, but few studies have examined diet after prostate cancer diagnosis and risk of its progression. Objective: We examined the association between postdiagnostic consumption of processed and unprocessed red meat, fish, poultry, and eggs and the risk of prostate cancer recurrence or progression. Design: We conducted a prospective study in 1294 men with prostate cancer, without recurrence or progression as of 2004–2005, who were participating in the Cancer of the Prostate Strategic Urologic Research Endeavor and who were followed for an average of 2 y. Results: We observed 127 events (prostate cancer death or metastases, elevated prostate-specific antigen concentration, or secondary treatment) during 2610 person-years. Intakes of processed and unprocessed red meat, fish, total poultry, and skinless poultry were not associated with prostate cancer recurrence or progression. Greater consumption of eggs and poultry with skin was associated with 2-fold increases in risk in a comparison of extreme quantiles: eggs [hazard ratio (HR): 2.02; 95% CI: 1.10, 3.72; P for trend = 0.05] and poultry with skin (HR: 2.26; 95% CI: 1.36, 3.76; P for trend = 0.003). An interaction was observed between prognostic risk at diagnosis and poultry. Men with high prognostic risk and a high poultry intake had a 4-fold increased risk of recurrence or progression compared with men with low/intermediate prognostic risk and a low poultry intake (P for interaction = 0.003). Conclusions: Our results suggest that the postdiagnostic consumption of processed or unprocessed red meat, fish, or skinless poultry is not associated with prostate cancer recurrence or progression, whereas consumption of eggs and poultry with skin may increase the risk.
MED-3245
Vegetable and fruit intake after diagnosis and risk of prostate cancer progression
Cruciferous vegetables, tomato sauce, and legumes have been associated with reduced risk of incident advanced prostate cancer. In vitro and animal studies suggest these foods may inhibit progression of prostate cancer, but there are limited data in men. Therefore, we prospectively examined whether intake of total vegetables, and specifically cruciferous vegetables, tomato sauce, and legumes, after diagnosis reduce risk of prostate cancer progression among 1,560 men diagnosed with non-metastatic prostate cancer and participating in the Cancer of the Prostate Strategic Urologic Research Endeavor, a United States prostate cancer registry. As a secondary analysis, we also examined other vegetable sub-groups, total fruit, and subgroups of fruits. The participants were diagnosed primarily at community-based clinics and followed from 2004–2009. We assessed vegetable and fruit intake via a semi-quantitative food frequency questionnaire, and ascertained prostate cancer outcomes via urologist report and medical records. We observed 134 events of progression (53 biochemical recurrences, 71 secondary treatments likely due to recurrence, six bone metastases, four prostate cancer deaths) during 3,171 person-yrs. Men in the fourth quartile of post-diagnostic cruciferous vegetable intake had a statistically significant 59% decreased risk of prostate cancer progression compared to men in the lowest quartile (hazard ratio (HR): 0.41; 95% confidence interval (CI): 0.22, 0.76; p-trend: 0.003). No other vegetable or fruit group was statistically significantly associated with risk of prostate cancer progression. In conclusion, cruciferous vegetable intake after diagnosis may reduce risk of prostate cancer progression.
MED-5337
Intensive lifestyle changes may affect the progression of prostate cancer.
PURPOSE: Men with prostate cancer are often advised to make changes in diet and lifestyle, although the impact of these changes has not been well documented. Therefore, we evaluated the effects of comprehensive lifestyle changes on prostate specific antigen (PSA), treatment trends and serum stimulated LNCaP cell growth in men with early, biopsy proven prostate cancer after 1 year. MATERIALS AND METHODS: Patient recruitment was limited to men who had chosen not to undergo any conventional treatment, which provided an unusual opportunity to have a nonintervention randomized control group to avoid the confounding effects of interventions such as radiation, surgery or androgen deprivation therapy. A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were randomly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group. RESULTS: None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and/or progression of disease on magnetic resonance imaging. PSA decreased 4% in the experimental group but increased 6% in the control group (p = 0.016). The growth of LNCaP prostate cancer cells (American Type Culture Collection, Manassas, Virginia) was inhibited almost 8 times more by serum from the experimental than from the control group (70% vs 9%, p <0.001). Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle. CONCLUSIONS: Intensive lifestyle changes may affect the progression of early, low grade prostate cancer in men. Further studies and longer term followup are warranted.
MED-3250
Improvement of endothelium-dependent coronary vasodilation after a single LDL apheresis in patients with hypercholesterolemia.
The purpose of this study was to determine whether a single LDL apheresis would improve impaired endothelium-dependent dilation of the coronary artery in patients with hypercholesterolemia. Hypercholesterolemia is associated with impaired endothelial function, and human studies using cholesterol-lowering drugs indicate that endothelial function in the coronary arteries improves with reduction of serum LDL cholesterol over 6 to 12 months. The internal diameter of the left coronary artery and the coronary blood flow were measured by intracoronary Doppler-wire measurement and quantitative angiography before and immediately after a single LDL apheresis in a population of 15 patients with familial hypercholesterolemia. Endothelium-dependent vasodilation was assessed by intracoronary infusion of acetylcholine (1, 10, and 50 microg/min), and endothelium-independent vasodilation was assessed by intracoronary bolus infusion of isosorbide dinitrate (2.5 mg) or papaverine (10 mg). A single 3-hour LDL apheresis reduced serum LDL cholesterol by an average of 86.6 +/- 1.7%. After the LDL apheresis, the changes in the coronary artery diameter and coronary blood flow in response to an infusion of 50 microg/min of acetylcholine increased significantly compared to the pre-apheresis values (from -19.7 +/- 4.8 to -2.9 +/- 3.0% [P < 0.01] and from 80.7 +/- 27.6 to 155.3 +/- 23.5% [P < 0.01], respectively). The LDL apheresis did not significantly change the response of either parameter to infusion with isosorbide dinitrate or papaverine. The endothelial function of the epicardial coronary artery and the coronary microvasculature improved in hypercholesterolemic patients after only a single LDL apheresis, a procedure that markedly reduces the serum level of LDL cholesterol. Copyright 2004 Wiley-Liss, Inc.
MED-3251
Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis.
CONTEXT: Interferon beta is widely prescribed to treat multiple sclerosis (MS); however, its relationship with disability progression has yet to be established. OBJECTIVE: To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study based on prospectively collected data (1985-2008) from British Columbia, Canada. Patients with relapsing-remitting MS treated with interferon beta (n = 868) were compared with untreated contemporary (n = 829) and historical (n = 959) cohorts. MAIN OUTCOME MEASURES: The main outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 m; confirmed at >150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability). A multivariable Cox regression model with interferon beta treatment included as a time-varying covariate was used to assess the hazard of disease progression associated with interferon beta treatment. Analyses also included propensity score adjustment to address confounding by indication. RESULTS: The median active follow-up times (first to last EDSS measurement) were as follows: for the interferon beta-treated cohort, 5.1 years (interquartile range [IQR], 3.0-7.0 years); for the contemporary control cohort, 4.0 years (IQR, 2.1-6.4 years); and for the historical control cohort, 10.8 years (IQR, 6.3-14.7 years). The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8%, 5.3%, and 23.1% in the 3 cohorts, respectively. After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort (hazard ratio, 1.30; 95% CI, 0.92-1.83; P = .14) or the historical control cohort (hazard ratio, 0.77; 95% CI, 0.58-1.02; P = .07) were considered. Further adjustment for comorbidities and socioeconomic status, where possible, did not change interpretations, and propensity score adjustment did not substantially change the results. CONCLUSION: Among patients with relapsing-remitting MS, administration of interferon beta was not associated with a reduction in progression of disability.
MED-3247
Evidence Report: The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis
Objective: The chemotherapeutic agent mitoxantrone was approved for use in multiple sclerosis (MS) in 2000. After a review of all the available evidence, the original report of the Therapeutics and Technology Assessment Subcommittee in 2003 concluded that mitoxantrone probably reduced clinical attack rates, MRI activity, and disease progression. Subsequent reports of decreased systolic function, heart failure, and leukemia prompted the US Food and Drug Administration to institute a “black box” warning in 2005. This review was undertaken to examine the available literature on the efficacy and safety of mitoxantrone use in patients with MS since the initial report. Methods: Relevant articles were obtained through a review of the medical literature and the strength of the available evidence was graded according to the American Academy of Neurology evidence classification scheme. Results: The accumulated Class III and IV evidence suggests an increased incidence of systolic dysfunction and therapy-related acute leukemia (TRAL) with mitoxantrone therapy. Systolic dysfunction occurs in ∼12% of patients with MS treated with mitoxantrone, congestive heart failure occurs in ∼0.4%, and leukemia occurs in ∼0.8%. The number needed to harm is 8 for systolic dysfunction and 123 for TRAL. There is no new efficacy evidence that would change the recommendation from the previous report. Conclusions: The risk of systolic dysfunction and leukemia in patients treated with mitoxantrone is higher than suggested at the time of the previous report, although comprehensive postmarketing surveillance data are lacking. GLOSSARY
MED-3248
Retinal arterial changes correlate with cerebral small-vessel disease.
OBJECTIVE: To examine the relation between retinal artery disease and cerebral small-vessel disease (SVD). METHODS: In a prospective cohort of patients with symptomatic atherosclerotic disease, the authors performed retinal photographs and brain MRI. Two ophthalmologists, not aware of the MR results, independently assessed retinal arterial narrowing, crossings, sclerosis, and tortuosity according to standard scoring lists. Two observers independently assessed white matter lesions (WML) and lacunar infarcts on the MR images. Lesions were considered abnormal only when both ophthalmologists or MR raters agreed. Cerebral SVD was defined as the presence of WML or lacunar infarcts. RESULTS: In 179 patients, retinal photographs and brain MRI were performed. Of the 108 patients with MR signs of SVD, 92% had at least one retinal vascular abnormality; of the 71 patients without SVD, 77% had retinal pathology (p < 0.01). All types of retinal vascular pathology occurred more frequently in patients with SVD, but only retinal arterial narrowing and sclerosis differed significantly. In the 109 normotensive patients, the presence of any retinal vascular change correlated with signs of SVD (p = 0.01). CONCLUSION: Pathologic changes in the retinal arteries parallel changes in the small cerebral arteries that cause WML and lacunes, both in hypertensive and in normotensive patients.
MED-3249
Effect of low saturated fat diet in early and late cases of multiple sclerosis.
144 multiple sclerosis patients took a low-fat diet for 34 years. For each of three categories of neurological disability (minimum, moderate, severe) patients who adhered to the prescribed diet (less than or equal to 20 g fat/day) showed significantly less deterioration and much lower death rates than did those who consumed more fat than prescribed (greater than 20 g fat/day). The greatest benefit was seen in those with minimum disability at the start of the trial; in this group, when those who died from non-MS diseases were excluded from the analysis, 95% survived and remained physically active.
MED-3254
Relation of serum lipoprotein levels and systolic blood pressure to early atherosclerosis. The Bogalusa Heart Study.
We assessed the relation of risk factors for cardiovascular disease to early atherosclerotic lesions in the aorta and coronary arteries in 35 persons (mean age at death, 18 years). Aortic involvement with fatty streaks was greater in blacks than in whites (37 vs. 17 percent, P less than 0.01). However, aortic fatty streaks were strongly related to antemortem levels of both total and low-density lipoprotein cholesterol (r = 0.67, P less than 0.0001 for each association), independently of race, sex, and age, and were inversely correlated with the ratio of high-density lipoprotein cholesterol to low-density plus very-low-density lipoprotein cholesterol (r = -0.35, P = 0.06). Coronary-artery fatty streaks were correlated with very-low-density lipoprotein cholesterol (r = 0.41, P = 0.04). Mean systolic blood-pressure levels also tended to be higher in the four subjects with coronary-artery fibrous plaques than in those without them: 112 mm Hg as compared with 104 (P = 0.09). These results document the importance of risk-factor levels to early anatomical changes in the aorta and coronary arteries. The progression of fatty streaks to fibrous plaques is uncertain, but these data suggest that a rational approach to the prevention of cardiovascular disease should begin early in life.
MED-3253
Pathobiological determinants of atherosclerosis in youth risk scores are associated with early and advanced atherosclerosis.
OBJECTIVES: Atherosclerosis begins in childhood and progresses during adolescence and young adulthood. The Pathobiological Determinants of Atherosclerosis in Youth Study previously reported risk scores to estimate the probability of advanced atherosclerotic lesions in young individuals aged 15 to 34 years using the coronary heart disease risk factors (gender, age, serum lipoprotein concentrations, smoking, hypertension, obesity, and hyperglycemia). In this study we investigated the relation of these risk scores to the early atherosclerotic lesions. METHODS: We measured atherosclerotic lesions in the left anterior descending coronary artery, right coronary artery, and abdominal aorta and the coronary heart disease risk factors in persons 15 to 34 years of age who died as a result of external causes and were autopsied in forensic laboratories. RESULTS: Risk scores computed from the modifiable risk factors were associated with prevalence of microscopically demonstrable lesions of atherosclerosis (American Heart Association grade 1) in the left anterior descending coronary artery and with the extent of the earliest detectable gross lesion (fatty streaks) in the right coronary artery and abdominal aorta. Risk scores computed from the modifiable risk factors also were associated with prevalence of lesions of higher degrees of microscopic severity (intermediate as well as advanced) in the left anterior descending coronary artery and with extent of lesions of higher degrees of severity (intermediate and raised lesions) in the right coronary artery and abdominal aorta. CONCLUSIONS: Risk scores calculated from traditional coronary heart disease risk factors to identify individual young persons with high probability of having advanced atherosclerotic lesions also are associated with earlier atherosclerotic lesions, including the earliest anatomically demonstrable atherosclerotic lesion. These results support lifestyle modification in youth to prevent development of the initial lesions and the subsequent progression to advanced lesions and, thereafter, to prevent or delay coronary heart disease.
MED-1399
Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Di...
BACKGROUND: The Lyon Diet Heart Study is a randomized secondary prevention trial aimed at testing whether a Mediterranean-type diet may reduce the rate of recurrence after a first myocardial infarction. An intermediate analysis showed a striking protective effect after 27 months of follow-up. This report presents results of an extended follow-up (with a mean of 46 months per patient) and deals with the relationships of dietary patterns and traditional risk factors with recurrence. METHODS AND RESULTS: Three composite outcomes (COs) combining either cardiac death and nonfatal myocardial infarction (CO 1), or the preceding plus major secondary end points (unstable angina, stroke, heart failure, pulmonary or peripheral embolism) (CO 2), or the preceding plus minor events requiring hospital admission (CO 3) were studied. In the Mediterranean diet group, CO 1 was reduced (14 events versus 44 in the prudent Western-type diet group, P=0.0001), as were CO 2 (27 events versus 90, P=0.0001) and CO 3 (95 events versus 180, P=0. 0002). Adjusted risk ratios ranged from 0.28 to 0.53. Among the traditional risk factors, total cholesterol (1 mmol/L being associated with an increased risk of 18% to 28%), systolic blood pressure (1 mm Hg being associated with an increased risk of 1% to 2%), leukocyte count (adjusted risk ratios ranging from 1.64 to 2.86 with count >9x10(9)/L), female sex (adjusted risk ratios, 0.27 to 0. 46), and aspirin use (adjusted risk ratios, 0.59 to 0.82) were each significantly and independently associated with recurrence. CONCLUSIONS: The protective effect of the Mediterranean dietary pattern was maintained up to 4 years after the first infarction, confirming previous intermediate analyses. Major traditional risk factors, such as high blood cholesterol and blood pressure, were shown to be independent and joint predictors of recurrence, indicating that the Mediterranean dietary pattern did not alter, at least qualitatively, the usual relationships between major risk factors and recurrence. Thus, a comprehensive strategy to decrease cardiovascular morbidity and mortality should include primarily a cardioprotective diet. It should be associated with other (pharmacological?) means aimed at reducing modifiable risk factors. Further trials combining the 2 approaches are warranted.
MED-1393
Changes in ultrasound-assessed carotid intima-media thickness and plaque with a Mediterranean diet: a substudy of the PREDIMED trial.
OBJECTIVE: The Prevención con Dieta Mediterránea (PREDIMED) trial showed that a Mediterranean diet (MedDiet) supplemented with either extra virgin olive oil or 30 g/d of mixed nuts reduced incident cardiovascular events compared with a control (low fat) diet. The mechanisms of cardiovascular protection afforded by MedDiets remain to be uncovered. We assessed the effect of both supplemented MedDiets on internal carotid intima-media thickness (ICA-IMT) and plaque height, the ultrasound features that best predict future cardiovascular events, in subjects at high cardiovascular risk. APPROACH AND RESULTS: In a PREDIMED subcohort (n=175), plaque height and carotid IMT of 3 prespecified segments (ICA, bifurcation, and common) were sonographically assessed at baseline and after intervention for a mean of 2.4 years. We evaluated 164 subjects with complete data. In a multivariate model, mean ICA-IMT progressed in the control diet group (mean [95% confidence interval], 0.052 mm [-0.014 to 0.118 mm]), whereas it regressed in the MedDiet+nuts group (-0.084 mm [-0.158 to -0.010 mm]; P=0.024 versus control). Similar results were observed for maximum ICA-IMT (control, 0.188 mm [0.077 to 0.299 mm]; MedDiet+nuts, -0.030 mm [-0.153 to 0.093 mm]; P=0.034) and maximum plaque height (control, 0.106 mm [0.001 to 0.210 mm]; MedDiet+nuts, -0.091 mm [-0.206 to 0.023 mm]; P=0.047). There were no changes in ICA-IMT or plaque after the MedDiet+extra virgin olive oil. CONCLUSIONS: Compared with a control diet, consumption of a MedDiet supplemented with nuts is associated with delayed progression of ICA-IMT and plaque. The results contribute mechanistic evidence for the reduction of cardiovascular events observed in the PREDIMED trial. CLINICAL TRIAL REGISTRATION URL: http://www.controlled-trials.com. Unique identifier: ISRCTN35739639.
MED-1394
Primary prevention of cardiovascular disease with a Mediterranean diet.
BACKGROUND: Observational cohort studies and a secondary prevention trial have shown an inverse association between adherence to the Mediterranean diet and cardiovascular risk. We conducted a randomized trial of this diet pattern for the primary prevention of cardiovascular events. METHODS: In a multicenter trial in Spain, we randomly assigned participants who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly individual and group educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was the rate of major cardiovascular events (myocardial infarction, stroke, or death from cardiovascular causes). On the basis of the results of an interim analysis, the trial was stopped after a median follow-up of 4.8 years. RESULTS: A total of 7447 persons were enrolled (age range, 55 to 80 years); 57% were women. The two Mediterranean-diet groups had good adherence to the intervention, according to self-reported intake and biomarker analyses. A primary end-point event occurred in 288 participants. The multivariable-adjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.54 to 0.92) and 0.72 (95% CI, 0.54 to 0.96) for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events). No diet-related adverse effects were reported. CONCLUSIONS: Among persons at high cardiovascular risk, a Mediterranean diet supplemented with extra-virgin olive oil or nuts reduced the incidence of major cardiovascular events. (Funded by the Spanish government's Instituto de Salud Carlos III and others; Controlled-Trials.com number, ISRCTN35739639.).
MED-1395
Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease.
In a prospective, randomised single-blinded secondary prevention trial we compared the effect of a Mediterranean alpha-linolenic acid-rich diet to the usual post-infarct prudent diet. After a first myocardial infarction, patients were randomly assigned to the experimental (n = 302) or control group (n = 303). Patients were seen again 8 weeks after randomisation, and each year for 5 years. The experimental group consumed significantly less lipids, saturated fat, cholesterol, and linoleic acid but more oleic and alpha-linolenic acids confirmed by measurements in plasma. Serum lipids, blood pressure, and body mass index remained similar in the 2 groups. In the experimental group, plasma levels of albumin, vitamin E, and vitamin C were increased, and granulocyte count decreased. After a mean follow up of 27 months, there were 16 cardiac deaths in the control and 3 in the experimental group; 17 non-fatal myocardial infarction in the control and 5 in the experimental groups: a risk ratio for these two main endpoints combined of 0.27 (95% CI 0.12-0.59, p = 0.001) after adjustment for prognostic variables. Overall mortality was 20 in the control, 8 in the experimental group, an adjusted risk ratio of 0.30 (95% CI 0.11-0.82, p = 0.02). An alpha-linolenic acid-rich Mediterranean diet seems to be more efficient than presently used diets in the secondary prevention of coronary events and death.
MED-1489
A way to reverse CAD?
PURPOSE: Plant-based nutrition achieved coronary artery disease (CAD) arrest and reversal in a small study. However, there was skepticism that this approach could succeed in a larger group of patients. The purpose of our follow-up study was to define the degree of adherence and outcomes of 198 consecutive patient volunteers who received counseling to convert from a usual diet to plant-based nutrition. METHODS: We followed 198 consecutive patients counseled in plant-based nutrition. These patients with established cardiovascular disease (CVD) were interested in transitioning to plant-based nutrition as an adjunct to usual cardiovascular care. We considered participants adherent if they eliminated dairy, fish, and meat, and added oil. RESULTS: Of the 198 patients with CVD, 177 (89%) were adherent. Major cardiac events judged to be recurrent disease totaled one stroke in the adherent cardiovascular participants—a recurrent event rate of .6%, significantly less than reported by other studies of plant-based nutrition therapy. Thirteen of 21 (62%) nonadherent participants experienced adverse events. CONCLUSION: Most of the volunteer patients with CVD responded to intensive counseling, and those who sustained plant-based nutrition for a mean of 3.7 years experienced a low rate of subsequent cardiac events. This dietary approach to treatment deserves a wider test to see if adherence can be sustained in broader populations. Plant-based nutrition has the potential for a large effect on the CVD epidemic.
MED-1397
Omega-3 fatty acids and antioxidants in edible wild plants.
Human beings evolved on a diet that was balanced in the omega-6 and omega-3 polyunsaturated fatty acids (PUFA), and was high in antioxidants. Edible wild plants provide alpha-linolenic acid (ALA) and higher amounts of vitamin E and vitamin C than cultivated plants. In addition to the antioxidant vitamins, edible wild plants are rich in phenols and other compounds that increase their antioxidant capacity. It is therefore important to systematically analyze the total antioxidant capacity of wild plants and promote their commercialization in both developed and developing countries. The diets of Western countries have contained increasingly larger amounts of linoleic acid (LA), which has been promoted for its cholesterol-lowering effect. It is now recognized that dietary LA favors oxidative modification of low density lipoprotein (LDL) cholesterol and increases platelet response to aggregation. In contrast, ALA intake is associated with inhibitory effects on the clotting activity of platelets, on their response to thrombin, and on the regulation of arachidonic acid (AA) metabolism. In clinical studies, ALA contributed to lowering of blood pressure, and a prospective epidemiological study showed that ALA is inversely related to the risk of coronary heart disease in men. Dietary amounts of LA as well as the ratio of LA to ALA appear to be important for the metabolism of ALA to longer-chain omega-3 PUFAs. Relatively large reserves of LA in body fat. as are found in vegans or in the diet of omnivores in Western societies, would tend to slow down the formation of long-chain omega-3 fatty acids from ALA. Therefore, the role of ALA in human nutrition becomes important in terms of long-term dietary intake. One advantage of the consumption of ALA over omega-3 fatty acids from fish is that the problem of insufficient vitamin E intake does not exist with high intake of ALA from plant sources.
MED-1398
Mediterranean diet and cardiovascular disease: historical perspective and latest evidence.
The concept that the Mediterranean diet was associated with a lower incidence of cardiovascular disease (CVD) was first proposed in the 1950s. Since then, there have been randomized controlled trials and large epidemiological studies that reported associations with lower CVD: in 1994 and 1999, the reports of the intermediate and final analyses of the trial Lyon Diet Heart Study; in 2003, a major epidemiological study in Greece showing a strong inverse association between a Mediterranean score and the risk of cardiovascular complications; in 2011-2012, several reports showing that even non-Mediterranean populations can gain benefits from long-term adhesion to the Mediterranean diet; and in 2013, the PREDIMED trial showing a significant risk reduction in a low-risk population. Contrary to the pharmacological approach of cardiovascular prevention, the adoption of the Mediterranean diet has been associated with a significant reduction in new cancers and overall mortality. Thus, in terms of evidence-based medicine, the full adoption of a modern version of the Mediterranean diet pattern can be considered one of the most effective approaches for the prevention of fatal and nonfatal CVD complications.
MED-1400
Accruing evidence on benefits of adherence to the Mediterranean diet on health: an updated systematic review and meta-analysis.
BACKGROUND: The Mediterranean diet has long been reported to be protective against the occurrence of several different health outcomes. OBJECTIVE: We aimed to update our previous meta-analysis of published cohort prospective studies that investigated the effects of adherence to the Mediterranean diet on health status. DESIGN: We conducted a comprehensive literature search through electronic databases up to June 2010. RESULTS: The updated review process showed 7 prospective studies published in the past 2 y that were not included in the previous meta-analysis (1 study for overall mortality, 3 studies for cardiovascular incidence or mortality, 1 study for cancer incidence or mortality, and 2 studies for neurodegenerative diseases). These recent studies included 2 health outcomes not previously investigated (ie, mild cognitive impairment and stroke). The meta-analysis for all studies with a random-effects model that was conducted after the inclusion of these recent studies showed that a 2-point increase in adherence to the Mediterranean diet was associated with a significant reduction of overall mortality [relative risk (RR) = 0.92; 95% CI: 0.90, 0.94], cardiovascular incidence or mortality (RR = 0.90; 95% CI: 0.87, 0.93), cancer incidence or mortality (RR = 0.94; 95% CI: 0.92, 0.96), and neurodegenerative diseases (RR = 0.87; 95% CI: 0.81, 0.94). The meta-regression analysis showed that sample size was the most significant contributor to the model because it significantly influenced the estimate of the association for overall mortality. CONCLUSION: This updated meta-analysis confirms, in a larger number of subjects and studies, the significant and consistent protection provided by adherence to the Mediterranean diet in relation to the occurrence of major chronic degenerative diseases.
MED-1476
Neanderthal cannibalism at Moula-Guercy, Ardèche, France.
The cave site of Moula-Guercy, 80 meters above the modern Rhone River, was occupied by Neanderthals approximately 100,000 years ago. Excavations since 1991 have yielded rich paleontological, paleobotanical, and archaeological assemblages, including parts of six Neanderthals. The Neanderthals are contemporary with stone tools and faunal remains in the same tightly controlled stratigraphic and spatial contexts. The inference of Neanderthal cannibalism at Moula-Guercy is based on comparative analysis of hominid and ungulate bone spatial distributions, modifications by stone tools, and skeletal part representations.
MED-2432
The Garden of Eden--plant based diets, the genetic drive to conserve cholesterol and its implications for heart disease in the 21st century.
It is likely that plant food consumption throughout much of human evolution shaped the dietary requirements of contemporary humans. Diets would have been high in dietary fiber, vegetable protein, plant sterols and associated phytochemicals, and low in saturated and trans-fatty acids and other substrates for cholesterol biosynthesis. To meet the body's needs for cholesterol, we believe genetic differences and polymorphisms were conserved by evolution, which tended to raise serum cholesterol levels. As a result modern man, with a radically different diet and lifestyle, especially in middle age, is now recommended to take medications to lower cholesterol and reduce the risk of cardiovascular disease. Experimental introduction of high intakes of viscous fibers, vegetable proteins and plant sterols in the form of a possible Myocene diet of leafy vegetables, fruit and nuts, lowered serum LDL-cholesterol in healthy volunteers by over 30%, equivalent to first generation statins, the standard cholesterol-lowering medications. Furthermore, supplementation of a modern therapeutic diet in hyperlipidemic subjects with the same components taken as oat, barley and psyllium for viscous fibers, soy and almonds for vegetable proteins and plant sterol-enriched margarine produced similar reductions in LDL-cholesterol as the Myocene-like diet and reduced the majority of subjects' blood lipids concentrations into the normal range. We conclude that reintroduction of plant food components, which would have been present in large quantities in the plant based diets eaten throughout most of human evolution into modern diets can correct the lipid abnormalities associated with contemporary eating patterns and reduce the need for pharmacological interventions.
MED-1478
Paleolithic nutrition: twenty-five years later.
A quarter century has passed since the first publication of the evolutionary discordance hypothesis, according to which departures from the nutrition and activity patterns of our hunter-gatherer ancestors have contributed greatly and in specifically definable ways to the endemic chronic diseases of modern civilization. Refinements of the model have changed it in some respects, but anthropological evidence continues to indicate that ancestral human diets prevalent during our evolution were characterized by much lower levels of refined carbohydrates and sodium, much higher levels of fiber and protein, and comparable levels of fat (primarily unsaturated fat) and cholesterol. Physical activity levels were also much higher than current levels, resulting in higher energy throughput. We said at the outset that such evidence could only suggest testable hypotheses and that recommendations must ultimately rest on more conventional epidemiological, clinical, and laboratory studies. Such studies have multiplied and have supported many aspects of our model, to the extent that in some respects, official recommendations today have targets closer to those prevalent among hunter-gatherers than did comparable recommendations 25 years ago. Furthermore, doubts have been raised about the necessity for very low levels of protein, fat, and cholesterol intake common in official recommendations. Most impressively, randomized controlled trials have begun to confirm the value of hunter-gatherer diets in some high-risk groups, even as compared with routinely recommended diets. Much more research needs to be done, but the past quarter century has proven the interest and heuristic value, if not yet the ultimate validity, of the model.
MED-1479
BEYOND THE PALEOLITHIC PRESCRIPTION: INCORPORATING DIVERSITY AND FLEXIBILITY IN THE STUDY OF HUMAN DIET EVOLUTION
Evolutionary paradigms of human health and nutrition center on the evolutionary discordance or “mismatch” model whereby human bodies, reflecting adaptations established in the Paleolithic era, are ill-suited to modern industrialized diets resulting in rapidly increasing rates of chronic metabolic disease. Whereas this model remains useful, we argue that its utility in explaining the evolution of human dietary tendencies is limited. The assumption that human diets are mismatched to our evolved biology implies that they are instinctual or genetically determined and rooted in the Paleolithic. We review current research indicating that human eating habits are primarily learned through behavioral, social and physiological mechanisms starting in utero and extending throughout the life course. Those adaptations that appear to be strongly genetic likely reflect Neolithic, rather than Paleolithic, adaptations and are significantly influenced by human niche-constructing behavior. Incorporating a broader understanding of the evolved mechanisms by which humans learn and imprint eating habits and the reciprocal effects of those habits on physiology would provide useful tools for structuring more lasting nutrition interventions.
MED-1486
Patient expectations on lipid-lowering drugs.
OBJECTIVE: The objective of this study was to assess expectations of effect when using statins in a treatment population. Further the aim was to examine factors, including history and concurrent risk of coronary heart disease, associated with a higher and lower treatment belief. METHODS: Eight hundred and twenty-nine (829) Swedish patients using statins completed postal questionnaires about their health, life style, cardiovascular risk factors and expectation of the treatment. Expected treatment benefit was used as outcome measurement. RESULTS: A medical history of coronary heart disease did not affect treatment expectations. Patients with a high risk of cardiovascular disease reported a slightly lower expectation of the treatment effect at a 10-year perspective (p<0.01) but not at shorter time perspectives. Low satisfaction with the explanation of the purpose of the treatment and a poor perceived control of own health was associated with a more negative view on treatment benefit. CONCLUSION: The rationale applied by physicians prescribing statins does not seem to relate to the patients' expectations, whereas factors relating to the patient-physician relationship, the social situation and the perceived control of health seem to affect patient belief. PRACTICE IMPLICATIONS: The association between patients' poor satisfaction of treatment explanation and a low belief in treatment benefits emphasizes the importance of the patient-physician communication. It is suggested that clinical tools are developed in order to identify patients with poor belief in treatment benefit since tailored education for this group might reduce the risk of non-compliance and subsequently reduce the risk of coronary heart disease.
MED-1487
Patients' Expectations of Screening and Preventive Treatments
PURPOSE An informed decision to accept a health care intervention requires an understanding of its likely benefit. This study assessed participants' estimates of the benefit, as well as minimum acceptable benefit, of screening for breast and bowel cancer and medication to prevent hip fracture and cardiovascular disease. METHODS Three general practitioners sent questionnaires to all registered patients aged 50 to 70 years. Patients agreeing to participate in the study were asked to estimate the number of events (fractures or deaths) prevented in a group of 5,000 patients undergoing each intervention over a period of 10 years, and to indicate the minimum number of events avoided by the intervention that they considered justified its use. The proportions of participants that overestimated each intervention's benefit were calculated, and univariate and multivariable analyses of predictors of response were performed. RESULTS The participation rate was 36%: 977 patients were invited to participate in the study, and 354 returned a completed questionnaire. Participants overestimated the degree of benefit conferred by all interventions: 90% of participants overestimated the effect of breast cancer screening, 94% overestimated the effect of bowel cancer screening, 82% overestimated the effect of hip fracture preventive medication, and 69% overestimated the effect of preventive medication for cardiovascular disease. Estimates of minimum acceptable benefit were more conservative, but other than for cardiovascular disease mortality prevention, most respondents indicated a minimum benefit greater than these interventions achieve. A lower level of education was associated with higher estimates of minimum acceptable benefit for all interventions. CONCLUSION Patients overestimated the risk reduction achieved with 4 examples of screening and preventive medications. A lower level of education was associated with higher minimum benefit to justify intervention use. This tendency to overestimate benefits may affect patients' decisions to use such interventions, and practitioners should be aware of this tendency when discussing these interventions with patients.
MED-1488
What benefit do patients expect from adding second and third antihypertensive drugs?
Aims To discover whether patients have the same expectations of benefit from taking the first and any additional drugs for the treatment of hypertension and to investigate any patient characteristics which predict willingness to take treatment. Methods This was an anonymous questionnaire survey carried out in a single primary care group. A random sample of patients from the practice list stratified by age and gender were surveyed to determine what benefit they required before deciding to receive first and subsequent drugs to treat hypertension. They were asked to indicate the largest number needing treatment for 5 years (NNT5) to prevent myocardial infarction in 1 (smallest benefit) that would persuade them of the need for treatment. Demographic information which might explain variability in enthusiasm for treatment was also collected. Results Participants required far higher benefit to consider drug treatment than expected with a mean NNT5 for the first treatment of 15.0 (95% CI 12.3, 17.8). Marginal benefit demanded for the addition of second and third treatments was at least as great with an NNT5 of 13.2 (95% CI 10.8, 15.7) and NNT5 of 11.0 (95% CI 8.6, 13.4). Additional factors influencing willingness to take treatment were gender with a difference in NNT5 between men and women of 7.1 (95% CI 1.7, 12.5), difficulty in making the decision (very easy vs very difficult) of 14.9 (95% CI 6.0, 23.8), and years in full time education 2.0 (95% CI 0.9, 3.0) for each additional year of education. Any slope of NNT5 with increasing number of tablets disappeared when gender, years in education, and difficulty in reaching a decision were taken into account simultaneously. Conclusions People may have greater expectation of benefit from antihypertensive drug treatment than it provides. They certainly do not view the addition of subsequent drugs as any lesser step than starting the first in terms of the benefit expected. Full understanding of both the risks and benefits may be of critical importance with those spending longer in full time education and those expending more effort in making the decision accepting more treatment. The discrepancy between benefit expected and that available demands further research into methods of determining patients’ expectations and informing individual patient decisions.
MED-1490
Are preventive drugs preventive enough? A study of patients' expectation of benefit from preventive drugs.
OBJECTIVES: The study aimed to find the threshold of benefit for a hypothetical cholesterol-lowering drug below which the subject would not be prepared to take the drug. We also looked at whether proximity to the target event (myocardial infarction) and the subjects' views on drug taking affected this threshold. DESIGN: We studied 307 subjects using a written questionnaire and interview. Group 1 (102 subjects) had just been discharged from the coronary care unit. Group 2 (105 subjects) were taking cardio-protective drugs but had no recent history of myocardial infarction. Group 3 (100 subjects) had no history of myocardial infarction and were taking no cardio-protective drugs. RESULTS: Median values for the threshold of benefit below which the subject would not take the preventive drug were 20%, 20%, and 30% absolute risk reduction for Groups 1, 2 and 3 respectively. Median values for expectation of average prolongation of life were 12, 12 and 18 months respectively. Only 27% of subjects would take a drug offering 5% or less absolute risk reduction over five years. Subjects' views on medicinal drug taking in general and proximity to the target event were predictors of the acceptance of preventive drugs. Eighty percent of subjects wished to be told the numerical benefit of a preventive drug before starting on it. CONCLUSION: For the majority, the expectation of benefit from a preventive drug is higher than the actual benefit provided by current drug strategies. There is a tension between the patient's right to know about the chance of benefiting from a preventive drug and the likely reduction in uptake if they are so informed.
MED-1914
Early life stress and telomere length: Investigating the connection and possible mechanisms
How can adverse experiences in early life, such as maltreatment, exert such powerful negative effects on health decades later? The answer may lie in changes to DNA. New research suggests that exposure to stress can accelerate the erosion of DNA segments called telomeres. Shorter telomere length correlates with chronological age and also disease morbidity and mortality. Thus, telomere erosion is a potential mechanism linking childhood stress to health problems later in life. However, an array of mechanistic, methodological, and basic biological questions must be addressed in order to translate telomere discoveries into clinical applications for monitoring health and predicting disease risk. This paper covers the current state of the science and lays out new research directions.
MED-1915
Work-Related Exhaustion and Telomere Length: A Population-Based Study
Background Psychological stress is suggested to accelerate the rate of biological aging. We investigated whether work-related exhaustion, an indicator of prolonged work stress, is associated with accelerated biological aging, as indicated by shorter leukocyte telomeres, that is, the DNA-protein complexes that cap chromosomal ends in cells. Methods We used data from a representative sample of the Finnish working-age population, the Health 2000 Study. Our sample consisted of 2911 men and women aged 30–64. Work-related exhaustion was assessed using the Maslach Burnout Inventory - General Survey. We determined relative leukocyte telomere length using a quantitative real-time polymerase chain reaction (PCR) -based method. Results After adjustment for age and sex, individuals with severe exhaustion had leukocyte telomeres on average 0.043 relative units shorter (standard error of the mean 0.016) than those with no exhaustion (p = 0.009). The association between exhaustion and relative telomere length remained significant after additional adjustment for marital and socioeconomic status, smoking, body mass index, and morbidities (adjusted difference 0.044 relative units, standard error of the mean 0.017, p = 0.008). Conclusions These data suggest that work-related exhaustion is related to the acceleration of the rate of biological aging. This hypothesis awaits confirmation in a prospective study measuring changes in relative telomere length over time.
MED-1916
The association between physical activity in leisure time and leukocyte telomere length.
BACKGROUND: Physical inactivity is an important risk factor for many aging-related diseases. Leukocyte telomere dynamics (telomere length and age-dependent attrition rate) are ostensibly a biological indicator of human aging. We therefore tested the hypothesis that physical activity level in leisure time (over the past 12 months) is associated with leukocyte telomere length (LTL) in normal healthy volunteers. METHODS: We studied 2401 white twin volunteers, comprising 2152 women and 249 men, with questionnaires on physical activity level, smoking status, and socioeconomic status. Leukocyte telomere length was derived from the mean terminal restriction fragment length and adjusted for age and other potential confounders. RESULTS: Leukocyte telomere length was positively associated with increasing physical activity level in leisure time (P< .001); this association remained significant after adjustment for age, sex, body mass index, smoking, socioeconomic status, and physical activity at work. The LTLs of the most active subjects were 200 nucleotides longer than those of the least active subjects (7.1 and 6.9 kilobases, respectively; P= .006). This finding was confirmed in a small group of twin pairs discordant for physical activity level (on average, the LTL of more active twins was 88 nucleotides longer than that of less active twins; P= .03). CONCLUSIONS: A sedentary lifestyle (in addition to smoking, high body mass index, and low socioeconomic status) has an effect on LTL and may accelerate the aging process. This provides a powerful message that could be used by clinicians to promote the potentially antiaging effect of regular exercise.
MED-1917
Effect of healthy lifestyle behaviors on the association between leukocyte telomere length and coronary artery calcium.
The telomere length is an indicator of biologic aging, and shorter telomeres have been associated with coronary artery calcium (CAC), a validated indicator of coronary atherosclerosis. It is unclear, however, whether healthy lifestyle behaviors affect the relation between telomere length and CAC. In a sample of subjects aged 40 to 64 years with no previous diagnosis of coronary heart disease, stroke, diabetes mellitus, or cancer (n = 318), healthy lifestyle behaviors of greater fruit and vegetable consumption, lower meat consumption, exercise, being at a healthy weight, and the presence of social support were examined to determine whether they attenuated the association between a shorter telomere length and the presence of CAC. Logistic regression analyses controlling for age, gender, race/ethnicity, and Framingham risk score revealed that the relation between having shorter telomeres and the presence of CAC was attenuated in the presence of high social support, low meat consumption, and high fruit and vegetable consumption. Those with shorter telomeres and these characteristics were not significantly different from those with longer telomeres. Conversely, the subjects with shorter telomeres and less healthy lifestyles had a significantly increased risk of the presence of CAC: low fruit and vegetable consumption (odds ratio 3.30, 95% confidence interval 1.61 to 6.75), high meat consumption (odds ratio 3.33, 95% confidence interval 1.54 to 7.20), and low social support (odds ratio 2.58, 95% confidence interval 1.24 to 5.37). Stratification by gender yielded similar results for men; however, among women, only fruit and vegetable consumption attenuated the shorter telomere length and CAC relation. In conclusion, the results of the present study suggest that being involved in healthy lifestyle behaviors might attenuate the association between shorter telomere length and coronary atherosclerosis, as identified using CAC. 2010 Elsevier Inc. All rights reserved.
MED-1918
Intensive meditation training, immune cell telomerase activity, and psychological mediators.
BACKGROUND: Telomerase activity is a predictor of long-term cellular viability, which decreases with chronic psychological distress (Epel et al., 2004). Buddhist traditions claim that meditation decreases psychological distress and promotes well-being (e.g., Dalai Lama and Cutler, 2009). Therefore, we investigated the effects of a 3-month meditation retreat on telomerase activity and two major contributors to the experience of stress: Perceived Control (associated with decreased stress) and Neuroticism (associated with increased subjective distress). We used mediation models to test whether changes in Perceived Control and Neuroticism explained meditation retreat effects on telomerase activity. In addition, we investigated whether two qualities developed by meditative practice, increased Mindfulness and Purpose in Life, accounted for retreat-related changes in the two stress-related variables and in telomerase activity. METHODS: Retreat participants (n=30) meditated for ∼6 h daily for 3 months and were compared with a wait-list control group (n=30) matched for age, sex, body mass index, and prior meditation experience. Retreat participants received instruction in concentrative meditation techniques and complementary practices used to cultivate benevolent states of mind (Wallace, 2006). Psychological measures were assessed pre- and post-retreat. Peripheral blood mononuclear cell samples were collected post-retreat for telomerase activity. Because there were clear, a priori hypotheses, 1-tailed significance criteria were used throughout. RESULTS: Telomerase activity was significantly greater in retreat participants than in controls at the end of the retreat (p<0.05). Increases in Perceived Control, decreases in Neuroticism, and increases in both Mindfulness and Purpose in Life were greater in the retreat group (p<0.01). Mediation analyses indicated that the effect of the retreat on telomerase was mediated by increased Perceived Control and decreased Neuroticism. In turn, changes in Perceived Control and Neuroticism were both partially mediated by increased Mindfulness and Purpose in Life. Additionally, increases in Purpose in Life directly mediated the telomerase group difference, whereas increases in Mindfulness did not. CONCLUSIONS: This is the first study to link meditation and positive psychological change with telomerase activity. Although we did not measure baseline telomerase activity, the data suggest that increases in perceived control and decreases in negative affectivity contributed to an increase in telomerase activity, with implications for telomere length and immune cell longevity. Further, Purpose in Life is influenced by meditative practice and directly affects both perceived control and negative emotionality, affecting telomerase activity directly as well as indirectly. Copyright © 2010 Elsevier Ltd. All rights reserved.
MED-1919
Human telomerase model shows the role of the TEN domain in advancing the double helix for the next polymerization step
Telomerases constitute a group of specialized ribonucleoprotein enzymes that remediate chromosomal shrinkage resulting from the “end-replication” problem. Defects in telomere length regulation are associated with several diseases as well as with aging and cancer. Despite significant progress in understanding the roles of telomerase, the complete structure of the human telomerase enzyme bound to telomeric DNA remains elusive, with the detailed molecular mechanism of telomere elongation still unknown. By application of computational methods for distant homology detection, comparative modeling, and molecular docking, guided by available experimental data, we have generated a three-dimensional structural model of a partial telomerase elongation complex composed of three essential protein domains bound to a single-stranded telomeric DNA sequence in the form of a heteroduplex with the template region of the human RNA subunit, TER. This model provides a structural mechanism for the processivity of telomerase and offers new insights into elongation. We conclude that the RNA∶DNA heteroduplex is constrained by the telomerase TEN domain through repeated extension cycles and that the TEN domain controls the process by moving the template ahead one base at a time by translation and rotation of the double helix. The RNA region directly following the template can bind complementarily to the newly synthesized telomeric DNA, while the template itself is reused in the telomerase active site during the next reaction cycle. This first structural model of the human telomerase enzyme provides many details of the molecular mechanism of telomerase and immediately provides an important target for rational drug design.
MED-1920
Look AHEAD (Action for Health in Diabetes): design and methods for a clinical trial of weight loss for the prevention of cardiovascular disease in ...
Overweight and obesity are major contributors to both type 2 diabetes and cardiovascular disease (CVD). Moreover, individuals with type 2 diabetes who are overweight or obese are at particularly high risk for CVD morbidity and mortality. Although short-term weight loss has been shown to ameliorate obesity-related metabolic abnormalities and CVD risk factors, the long-term consequences of intentional weight loss in overweight or obese individuals with type 2 diabetes have not been adequately examined. The primary objective of the Look AHEAD clinical trial is to assess the long-term effects (up to 11.5 years) of an intensive weight loss program delivered over 4 years in overweight and obese individuals with type 2 diabetes. Approximately 5000 male and female participants who have type 2 diabetes, are 45-74 years of age, and have a body mass index >or=25 kg/m(2) will be randomized to one of the two groups. The intensive lifestyle intervention is designed to achieve and maintain weight loss through decreased caloric intake and increased physical activity. This program is compared to a control condition given diabetes support and education. The primary study outcome is time to incidence of a major CVD event. The study is designed to provide a 0.90 probability of detecting an 18% difference in major CVD event rates between the two groups. Other outcomes include components of CVD risk, cost and cost-effectiveness, diabetes control and complications, hospitalizations, intervention processes, and quality of life.
MED-1921
Intake of Small-to-Medium-Chain Saturated Fatty Acids Is Associated with Peripheral Leukocyte Telomere Length in Postmenopausal Women
Dietary factors, including dietary fat, may affect the biological aging process, as reflected by the shortening of telomere length (TL), by affecting levels of oxidative stress and inflammatory responses. We examined the direct relations of total and types of dietary fats and fat-rich foods to peripheral leukocyte TL. In 4029 apparently healthy postmenopausal women who participated in the Women’s Health Initiative, intakes of total fat, individual fatty acids, and fat-rich foods were assessed by a questionnaire. TL was measured by quantitative polymerase chain reaction. Intake of short-to-medium-chain saturated fatty acids (SMSFAs; aliphatic tails of ≤12 carbons) was inversely associated with TL. Compared with participants in other quartiles of SMSFA intake, women who were in the highest quartile (median: 1.29% of energy) had shorter TLs [mean: 4.00 kb (95% CI: 3.89, 4.11 kb)], whereas women in the lowest quartile of intake (median: 0.29% of energy) had longer TLs [mean: 4.13 kb (95% CI: 4.03, 4.24 kb); P-trend = 0.046]. Except for lauric acid, all other individual SMSFAs were inversely associated with TL (P < 0.05). In isoenergetic substitution models, the substitution of 1% of energy from SMSFAs with any other energy source was associated with 119 bp longer TLs (95% CI: 21, 216 bp). Intakes of nonskim milk, butter, and whole-milk cheese (major sources of SMSFAs) were all inversely associated with TL. No significant associations were found with long-chain saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids. In conclusion, we found that higher intakes of SMSFAs and SMSFA-rich foods were associated with shorter peripheral leukocyte TL among postmenopausal women. These findings suggest the potential roles of SMSFAs in the rate of biological aging.
MED-1922
Stress and Telomere Biology: A Lifespan Perspective
In the past decade, the growing field of telomere science has opened exciting new avenues for understanding the cellular and molecular substrates of stress and stress-related aging processes ver the lifespan. Shorter telomere length is associated with advancing chronological age and also increased disease morbidity and mortality. Emerging studies suggest that stress accelerates the erosion of telomeres from very early in life and possibly even influences the initial (newborn) setting of telomere length. In this review, we highlight recent empirical evidence linking stress and mental illnesses at various times across the lifespan with telomere erosion. We first present findings in the developmental programming of telomere biology linking prenatal stress to newborn and adult telomere length. We then present findings linking exposure to childhood trauma and to certain mental disorders with telomere shortening. Last, we review studies that characterize the relationship between related health-risk behaviors with telomere shortening over the lifespan, and how this process may further buffer the negative effects of stress on telomeres. A better understanding of the mechanisms that govern and regulate telomere biology throughout the lifespan may inform our understanding of etiology and the long-term consequences of stress and mental illnesses on aging processes in diverse populations and settings.
MED-1923
Loving-Kindness Meditation practice associated with longer telomeres in women.
Relatively short telomere length may serve as a marker of accelerated aging, and shorter telomeres have been linked to chronic stress. Specific lifestyle behaviors that can mitigate the effects of stress might be associated with longer telomere lengths. Previous research suggests a link between behaviors that focus on the well-being of others, such as volunteering and caregiving, and overall health and longevity. We examined relative telomere length in a group of individuals experienced in Loving-Kindness Meditation (LKM), a practice derived from the Buddhist tradition which utilizes a focus on unselfish kindness and warmth towards all people, and control participants who had done no meditation. Blood was collected by venipuncture, and Genomic DNA was extracted from peripheral blood leukocytes. Quantitative real time PCR was used to measure relative telomere length (RTL) (Cawthon, 2002) in fifteen LKM practitioners and 22 control participants. There were no significant differences in age, gender, race, education, or exposure to trauma, but the control group had a higher mean body mass index (BMI) and lower rates of past depression. The LKM practitioners had longer RTL than controls at the trend level (p=.083); among women, the LKM practitioners had significantly longer RTL than controls, (p=.007), which remained significant even after controlling for BMI and past depression. Although limited by small sample size, these results offer the intriguing possibility that LKM practice, especially in women, might alter RTL, a biomarker associated with longevity. Copyright © 2013 Elsevier Inc. All rights reserved.
MED-1924
Saturated fatty acid metabolism is key link between cell division, cancer, and senescence in cellular and whole organism aging
Cellular senescence is an in vivo and in vitro phenomenon, accompanied by physiological changes including cessation of division and disturbances of organelle structure and function. Review of the literature was undertaken to determine whether there is evidence that whole organism aging and cell senescence share a common initiation pathway. In vivo aged cells of different lineages, including aged T lymphocytes, show high expression of the INK4A-p16 gene. In cell culture when telomeres are shortened past a key length or state, the Arf/Ink gene system (p16/p14 humans, p16/p19 mice) switches on and activates p53, which suppresses further cell division. The p53 gene is a key tumor suppressor and its deletion or mutation allows cancerous growth. The switching on of p53 also causes changes in fatty acid metabolism, especially down-regulation of both fatty acid synthase and stearoyl-CoA (delta-9) desaturase. The co-suppression of these genes together with enhanced uptake of extracellular fatty acids, leads to raised levels of cellular palmitate and induction of either apoptosis or senescence. In senescent cells, the fatty acid composition of the cellular membranes alters and leads to changes in both structure and function of organelles, especially mitochondria. Animal models of accelerated aging exhibit repression of stearoyl-CoA desaturase activity while anti-aging calorie restriction stimulates the same enzyme system. It is concluded that aging in cells and whole organisms share a common initiation pathway and that cellular senescence is protective against cancer. Healthy longevity is likely to be most enhanced by factors that actively suppress excessive cell division.
MED-4877
Increased telomerase activity and comprehensive lifestyle changes: a pilot study.
BACKGROUND: Telomeres are protective DNA-protein complexes at the end of linear chromosomes that promote chromosomal stability. Telomere shortness in human beings is emerging as a prognostic marker of disease risk, progression, and premature mortality in many types of cancer, including breast, prostate, colorectal, bladder, head and neck, lung, and renal cell. Telomere shortening is counteracted by the cellular enzyme telomerase. Lifestyle factors known to promote cancer and cardiovascular disease might also adversely affect telomerase function. However, previous studies have not addressed whether improvements in nutrition and lifestyle are associated with increases in telomerase activity. We aimed to assess whether 3 months of intensive lifestyle changes increased telomerase activity in peripheral blood mononuclear cells (PBMC). METHODS: 30 men with biopsy-diagnosed low-risk prostate cancer were asked to make comprehensive lifestyle changes. The primary endpoint was telomerase enzymatic activity per viable cell, measured at baseline and after 3 months. 24 patients had sufficient PBMCs needed for longitudinal analysis. This study is registered on the ClinicalTrials.gov website, number NCT00739791. FINDINGS: PBMC telomerase activity expressed as natural logarithms increased from 2.00 (SD 0.44) to 2.22 (SD 0.49; p=0.031). Raw values of telomerase increased from 8.05 (SD 3.50) standard arbitrary units to 10.38 (SD 6.01) standard arbitrary units. The increases in telomerase activity were significantly associated with decreases in low-density lipoprotein (LDL) cholesterol (r=-0.36, p=0.041) and decreases in psychological distress (r=-0.35, p=0.047). INTERPRETATION: Comprehensive lifestyle changes significantly increase telomerase activity and consequently telomere maintenance capacity in human immune-system cells. Given this finding and the pilot nature of this study, we report these increases in telomerase activity as a significant association rather than inferring causation. Larger randomised controlled trials are warranted to confirm the findings of this study.
MED-1926
Habitual physical exercise has beneficial effects on telomere length in postmenopausal women.
OBJECTIVE: It has been reported that women benefit from the maintenance of telomere length by estrogen. Exercise may favorably influence telomere length, although results are inconsistent regarding the duration and type of exercise and the cell type used to measure telomere length. The purpose of this study was to investigate the relationship between habitual physical exercise and telomere length in peripheral blood mononuclear cells (PBMCs) in postmenopausal women. Postmenopausal women were chosen as study participants because they are typically estrogen deficient. METHODS: This experimental-control, cross-sectional study included 44 healthy, nondiabetic, nonsmoking, postmenopausal women. Habitual exercisers and sedentary participants were matched for age and body mass index. Body weight, height, blood pressure, and waist and hip circumference were measured. Mitochondrial DNA copy number and telomere length in PBMCs were determined, and biochemical tests were performed. Habitual physical exercise was defined as combined aerobic and resistance exercise performed for at least 60 minutes per session more than three times a week for more than 12 months. RESULTS: The mean age of all participants was 58.11 ± 6.84 years, and participants in the habitual exercise group had been exercising more than three times per week for an average of 19.23 ± 5.15 months. Serum triglyceride levels (P = 0.01), fasting insulin concentrations (P < 0.01), and homeostasis model assessment of insulin resistance (P < 0.01) were significantly lower and high-density lipoprotein cholesterol levels (P < 0.01), circulating adiponectin (P < 0.01), mitochondrial DNA copy number (P < 0.01), and telomere length (P < 0.01) were significantly higher in the habitual exercise group than in the sedentary group. In a stepwise multiple regression analysis, habitual exercise (β = 0.522, P < 0.01) and adiponectin levels (β = 0.139, P = 0.03) were the independent factors associated with the telomere length of PBMCs in postmenopausal women. CONCLUSIONS: Habitual physical exercise is associated with greater telomere length in postmenopausal women. This finding suggests that habitual physical exercise in postmenopausal women may reduce telomere attrition.
MED-4878
Dietary patterns, food groups, and telomere length in the Multi-Ethnic Study of Atherosclerosis (MESA)
Background Telomere length reflects biological aging and may be influenced by environmental factors, including those that affect inflammatory processes. Objective With data from 840 white, black, and Hispanic adults from the Multi-Ethnic Study of Atherosclerosis, we studied cross-sectional associations between telomere length and dietary patterns and foods and beverages that were associated with markers of inflammation. Design Leukocyte telomere length was measured by quantitative polymerase chain reaction. Length was calculated as the amount of telomeric DNA (T) divided by the amount of a single-copy control DNA (S) (T/S ratio). Intake of whole grains, fruit and vegetables, low-fat dairy, nuts or seeds, nonfried fish, coffee, refined grains, fried foods, red meat, processed meat, and sugar-sweetened soda were computed with responses to a 120-item food-frequency questionnaire completed at baseline. Scores on 2 previously defined empirical dietary patterns were also computed for each participant. Results After adjustment for age, other demographics, lifestyle factors, and intakes of other foods or beverages, only processed meat intake was associated with telomere length. For every 1 serving/d greater intake of processed meat, the T/S ratio was 0.07 smaller (β ± SE: −0.07 ± 0.03, P = 0.006). Categorical analysis showed that participants consuming ≥1 serving of processed meat each week had 0.017 smaller T/S ratios than did nonconsumers. Other foods or beverages and the 2 dietary patterns were not associated with telomere length. Conclusions Processed meat intake showed an expected inverse association with telomere length, but other diet features did not show their expected associations.
MED-1928
Telomeres, lifestyle, cancer, and aging
Purpose of review There has been growing evidence that lifestyle factors may affect the health and lifespan of an individual by affecting telomere length. The purpose of this review was to highlight the importance of telomeres in human health and aging and to summarize possible lifestyle factors that may affect health and longevity by altering the rate of telomere shortening. Recent findings Recent studies indicate that telomere length, which can be affected by various lifestyle factors, can affect the pace of aging and onset of age-associated diseases. Summary Telomere length shortens with age. Progressive shortening of telomeres leads to senescence, apoptosis, or oncogenic transformation of somatic cells, affecting the health and lifespan of an individual. Shorter telomeres have been associated with increased incidence of diseases and poor survival. The rate of telomere shortening can be either increased or decreased by specific lifestyle factors. Better choice of diet and activities has great potential to reduce the rate of telomere shortening or at least prevent excessive telomere attrition, leading to delayed onset of age-associated diseases and increased lifespan. This review highlights the role of telomeres in aging and describes the lifestyle factors which may affect telomeres, human health, and aging.
MED-1929
A pilot study of yogic meditation for family dementia caregivers with depressive symptoms: Effects on mental health, cognition, and telomerase activity
BACKGROUND This study examined the effects of brief daily yogic meditation on mental health, cognitive functioning, and immune cell telomerase activity in family dementia caregivers with mild depressive symptoms. METHODS Thirty-nine family dementia caregivers (mean age 60.3 years old (SD=10.2)) were randomized to practicing Kirtan Kriya or listening to relaxation music for 12 minutes per day for eight weeks. The severity of depressive symptoms, mental and cognitive functioning were assessed at baseline and follow-up. Telomerase activity in peripheral blood mononuclear cells (PMBC) was examined in peripheral PBMC pre- and post-intervention. RESULTS The meditation group showed significantly lower levels of depressive symptoms and greater improvement in mental health and cognitive functioning compared to the relaxation group. In the meditation group, 65.2% showed 50% improvement on the Hamilton Depression Rating scale and 52% of the participants showed 50% improvement on the Mental Health Composite Summary score (MCS) of the SF-36 scale; compared to 31.2% and 19% respectively in the relaxation group (pp<0.05). The meditation group showed 43% improvement in telomerase activity compared to 3.7% in the relaxation group (p=0.05). CONCLUSION This pilot study found that brief daily meditation practices by family dementia caregivers can lead to improved mental and cognitive functioning, and lower levels of depressive symptoms. This improvement is accompanied by an increase in telomerase activity suggesting improvement in stress-induced cellular aging. These results need to be confirmed in a larger sample.
MED-1930
Leukocyte telomere length and its relation to food and nutrient intake in an elderly population.
BACKGROUND/OBJECTIVES: Shorter leukocyte telomere length (LTL) is associated with several chronic diseases, but only a few studies have assessed the association between dietary factors and LTL. Our objective was to study the association between fats, fruits, vegetables and LTL in a cross-sectional study design. We hypothesized that intakes of fruits and vegetables would be positively associated with LTL and that intakes of fats, and especially saturated fatty acids (SFAs), would be negatively associated with LTL. SUBJECTS/METHODS: LTL was measured by quantitative real-time polymerase chain reaction in 1942 men and women aged 57-70 years from the Helsinki Birth Cohort Study. We assessed the whole diet by a validated semiquantitative 128-item food-frequency questionnaire. RESULTS: In general, there were only a few significant results. However, total fat and SFA intake (P=0.04 and 0.01, respectively) were inversely associated with LTL in men adjusting for age and energy intake. In women, vegetable intake was positively associated with LTL (P=0.05). Men consuming the most butter and least fruits had significantly shorter telomeres than those consuming the lowest amounts of butter and highest amounts of fruits (P=0.05). We found no association between LTL and body mass index, waist-hip ratio, smoking, physical activity or educational attainment. CONCLUSIONS: In this cross-sectional study of elderly men and women, there were only a few statistically significant effects of diet, but in general they support the hypothesis that fat and vegetable intakes were associated with LTL.
MED-1931
Accelerated Telomere Erosion Is Associated with a Declining Immune Function of Caregivers of Alzheimer’s Disease Patients
Caregivers of Alzheimer’s disease patients endure chronic stress associated with a decline of immune function. To assess the psychological and immunological changes of caregivers, we compared depressive symptoms, PBMC composition, in vitro activation-induced proliferation and cytokine production, and telomere length and telomerase activity of 82 individuals (41 caregivers and 41 age- and gender-matched controls). We found depressive symptoms were significantly higher in caregivers than in controls (p < 0.001). Correspondingly, caregivers had significantly lower T cell proliferation but higher production of immune-regulatory cytokines (TNF-α and IL-10) than controls in response to stimulation in vitro. We examined the impact of these changes on cellular replicative lifespan and found that caregivers had significantly shorter telomere lengths in PBMC than controls (6.2 and 6.4 kb, respectively, p < 0.05) with similar shortening in isolated T cells and monocytes and that this telomere attrition in caregivers was not due to an increase of shorter telomere possessing T cell subsets in PBMC. Finally, we showed that basal telomerase activity in PBMC and T cells was significantly higher in caregivers than in controls (p < 0.0001), pointing to an unsuccessful attempt of cells to compensate the excessive loss of telomeres in caregivers. These findings demonstrate that chronic stress is associated with altered T cell function and accelerated immune cell aging as suggested by excessive telomere loss.
MED-1932
Exposure to violence during childhood is associated with telomere erosion from 5 to 10 years of age: a longitudinal study
There is increasing interest in discovering mechanisms that mediate the effects of childhood stress on late-life disease morbidity and mortality. Previous studies have suggested one potential mechanism linking stress to cellular aging, disease and mortality in humans: telomere erosion. We examined telomere erosion in relation to children’s exposure to violence, a salient early-life stressor, which has known long-term consequences for well-being and is a major public-health and social-welfare problem. In the first prospective-longitudinal study with repeated telomere measurements in children while they experienced stress, we tested the hypothesis that childhood violence exposure would accelerate telomere erosion from age 5 to age 10 years. Violence was assessed as exposure to maternal domestic violence, frequent bullying victimization and physical maltreatment by an adult. Participants were 236 children (49% females; 42% with one or more violence exposures) recruited from the Environmental-Risk Longitudinal Twin Study, a nationally representative 1994–1995 birth cohort. Each child’s mean relative telomere length was measured simultaneously in baseline and follow-up DNA samples, using the quantitative PCR method for T/S ratio (the ratio of telomere repeat copy numbers to single-copy gene numbers). Compared with their counterparts, the children who experienced two or more kinds of violence exposure showed significantly more telomere erosion between age-5 baseline and age-10 follow-up measurements, even after adjusting for sex, socioeconomic status and body mass index (B = −0.052, s.e. = 0.021, P = 0.015). This finding provides support for a mechanism linking cumulative childhood stress to telomere maintenance, observed already at a young age, with potential impact for life-long health.
MED-1933
From the Cover: Accelerated telomere shortening in response to life stress
Numerous studies demonstrate links between chronic stress and indices of poor health, including risk factors for cardiovascular disease and poorer immune function. Nevertheless, the exact mechanisms of how stress gets “under the skin” remain elusive. We investigated the hypothesis that stress impacts health by modulating the rate of cellular aging. Here we provide evidence that psychological stress— both perceived stress and chronicity of stress—is significantly associated with higher oxidative stress, lower telomerase activity, and shorter telomere length, which are known determinants of cell senescence and longevity, in peripheral blood mononuclear cells from healthy premenopausal women. Women with the highest levels of perceived stress have telomeres shorter on average by the equivalent of at least one decade of additional aging compared to low stress women. These findings have implications for understanding how, at the cellular level, stress may promote earlier onset of age-related diseases.
MED-1934
Independent and Combined Effects of Dietary Weight Loss and Exercise on Leukocyte Telomere Length in Postmenopausal Women
Objective Investigate the effects of 12 months of dietary weight loss and/or aerobic exercise on leukocyte telomere length in postmenopausal women. Design and Methods 439 overweight or obese women (50–75 y) were randomized to: i) dietary weight loss (N=118); ii) aerobic exercise (N=117), iii) diet + exercise (N=117), or iv) control (N=87). The diet intervention was a group-based program with a 10% weight loss goal. The exercise intervention was 45 mins/day, 5 days/week of moderate-to-vigorous aerobic activity. Fasting blood samples were taken at baseline and 12 months. DNA was extracted from isolated leukocytes and telomere length was measured by quantitative-polymerase chain reaction (qPCR). Mean changes were compared between groups (intent-to-treat) using generalized estimating equations. Results Baseline telomere length was inversely associated with age (r=−0.12 p<0.01) and positively associated with maximal oxygen uptake (r=0.11, p=0.03), but not with BMI or %body fat. Change in telomere length was inversely correlated with baseline telomere length (r=−0.47, p<0.0001). No significant difference in leukocyte telomere length was detected in any intervention group compared to controls, nor was the magnitude of weight loss associated with telomere length at 12 months. Conclusions Twelve-months of dietary weight loss and exercise did not change telomere length in postmenopausal women.
MED-1935
Diet-related telomere shortening and chromosome stability
Recent evidences have highlighted an influence of micronutrients in the maintenance of telomere length (TL). In order to explore whether diet-related telomere shortening had any physiological relevance and was accompanied by significant damage in the genome, in the present study, TL was assessed by terminal restriction fragment (TRF) analysis in peripheral blood lymphocytes of 56 healthy subjects for which detailed information on dietary habits was available and data were compared \with the incidence of nucleoplasmic bridges (NPBs), a marker of chromosomal instability related to telomere dysfunction visualised with the cytokinesis-blocked micronucleus assay. To increase the capability to detect even slight impairment of telomere function, the incidence of NPBs was also evaluated on cells exposed in vitro to ionising radiation. Care was taken to control for potential confounding factors that might influence TL, viz. age, hTERT genotype and smoking status. Data showed that higher consumption of vegetables was related with significantly higher mean TL (P = 0.013); in particular, the analysis of the association between micronutrients and mean TL highlighted a significant role of antioxidant intake, especially beta-carotene, on telomere maintenance (P = 0.004). However, the diet-related telomere shortening did not result in associated increased spontaneous or radiation-induced NPBs. The distribution of TRFs was also analysed and a slight prevalence of radiation-induced NPBs (P = 0.03) was observed in subjects with higher amount of very short TRFs (<2 kb). The relative incidence of very short TRFs was positively associate with ageing (P = 0.008) but unrelated to vegetables consumption and daily intake of micronutrients, suggesting that the degree of telomere erosion related with low dietary intake of antioxidants observed in this study was not so extensive to lead to chromosome instability.
MED-1936
Physical exercise prevents cellular senescence in circulating leukocytes and in the vessel wall.
BACKGROUND: The underlying molecular mechanisms of the vasculoprotective effects of physical exercise are incompletely understood. Telomere erosion is a central component of aging, and telomere-associated proteins regulate cellular senescence and survival. This study examines the effects of exercising on vascular telomere biology and endothelial apoptosis in mice and the effects of long-term endurance training on telomere biology in humans. METHODS AND RESULTS: C57/Bl6 mice were randomized to voluntary running or no running wheel conditions for 3 weeks. Exercise upregulated telomerase activity in the thoracic aorta and in circulating mononuclear cells compared with sedentary controls, increased vascular expression of telomere repeat-binding factor 2 and Ku70, and reduced the expression of vascular apoptosis regulators such as cell-cycle-checkpoint kinase 2, p16, and p53. Mice preconditioned by voluntary running exhibited a marked reduction in lipopolysaccharide-induced aortic endothelial apoptosis. Transgenic mouse studies showed that endothelial nitric oxide synthase and telomerase reverse transcriptase synergize to confer endothelial stress resistance after physical activity. To test the significance of these data in humans, telomere biology in circulating leukocytes of young and middle-aged track and field athletes was analyzed. Peripheral blood leukocytes isolated from endurance athletes showed increased telomerase activity, expression of telomere-stabilizing proteins, and downregulation of cell-cycle inhibitors compared with untrained individuals. Long-term endurance training was associated with reduced leukocyte telomere erosion compared with untrained controls. CONCLUSIONS: Physical activity regulates telomere-stabilizing proteins in mice and in humans and thereby protects from stress-induced vascular apoptosis.
MED-2109
Extracorporeal membrane oxygenation and conventional medical therapy in neonates with persistent pulmonary hypertension of the newborn: a prospecti...
Thirty-nine newborn infants with severe persistent pulmonary hypertension and respiratory failure who met criteria for 85% likelihood of dying were enrolled in a randomized trial in which extracorporeal membrane oxygenation (ECMO) therapy was compared with conventional medical therapy (CMT). In phase I, 4 of 10 babies in the CMT group died and 9 of 9 babies in the ECMO group survived. Randomization was halted after the fourth CMT death, as planned before initiating the study, and the next 20 babies were treated with ECMO (phase II). Of the 20, 19 survived. All three treatment groups (CMT and ECMO in phase I and ECMO, phase II) were comparable in severity of illness and mechanical ventilator support. The overall survival of ECMO-treated infants was 97% (28 of 29) compared with 60% (6 of 10) in the CMT group (P less than .05).
MED-2110
Extracorporeal membrane oxygenation for newborn respiratory failure: forty-five cases.
Almost all types of newborn respiratory failure are reversible. However, supportive treatment (oxygen and positive airway pressure) can damage the lung, and newborn respiratory failure remains a major cause of morbidity and death in infants. Prolonged extracorporeal membrane oxygenation (ECMO) provides life support while allowing the lung to "rest." We have used ECMO in 45 moribund newborn infants; 25 survived. Neonatologists referred patients who were unresponsive to maximal therapy. The right atrium and aortic arch were cannulated via the jugular vein and carotid artery. Heparin was infused continuously to main activated clotting time at 200 to 300 seconds. Airway oxygenation and pressure were reduced to low levels. Primary diagnoses were hyaline membrane disease, 14 (6 survived, 8 died); meconium aspiration, 22 (15 survived, 7 died); persistent fetal circulation including diaphragmatic hernia, 5 (3 survived, 2 died); and sepsis, 4 (1 survived, 3 died). Growth, development, and brain and lung function are normal in 20 of 25 survivors. ECMO decreased newborn respiratory failure mortality and morbidity rates in this phase I trial. A controlled randomized study is underway. The results suggest that ECMO may be effective in older patients if used before irreversible lung damage occurs.
MED-2111
Updating a 12-year experience with arrest and reversal therapy for coronary heart disease (an overdue requiem for palliative cardiology).
Coronary artery disease is essentially nonexistent in cultures whose nutrition assures cholesterol levels <150 mg/dl. Patients with advanced coronary artery disease may abolish disease progression through a plant-based diet and cholesterol-lowering medication to achieve and maintain a total cholesterol <150 mg/dl.
MED-2112
How evidence-based medicine biases physicians against nutrition.
Medical students in the United States are taught little about nutrition and dietetics. Worse yet, their training biases them against the studies that show the power of dietary approaches to managing disease. The current approach to evidence-based medicine encourages physicians to ignore any information that does not come from a double-blind, randomized controlled trial. Yet human beings cannot be blinded to a dietary intervention. As a result, physicians are biased toward drug treatments and against dietary interventions for the management of chronic disease. Copyright © 2013 Elsevier Ltd. All rights reserved.
MED-4255
Resolving the Coronary Artery Disease Epidemic Through Plant-Based Nutrition.
The world's advanced countries have easy access to plentiful high-fat food; ironically, it is this rich diet that produces atherosclerosis. In the world's poorer nations, many people subsist on a primarily plant-based diet, which is far healthier, especially in terms of heart disease. To treat coronary heart disease, a century of scientific investigation has produced a device-driven, risk factor-oriented strategy. Nevertheless, many patients treated with this approach experience progressive disability and death. This strategy is a rear-guard defensive one. In contrast, compelling data from nutritional studies, population surveys, and interventional studies support the effectiveness of a plant-based diet and aggressive lipid lowering to arrest, prevent, and selectively reverse heart disease. In essence, this is an offensive strategy. The single biggest step toward adopting this strategy would be to have United States dietary guidelines support a plant-based diet. An expert committee purged of industrial and political influence is required to assure that science is the basis for dietary recommendations. (c)2001 CHF, Inc.
MED-3113
The emergence of "lifestyle medicine" as a structured approach for management of chronic disease.
Chronic diseases with a lifestyle-based aetiology currently make up a significant proportion of primary care consultations, but management often falls between the demands of public and clinical health. A modified clinical approach, based around the concept of "lifestyle medicine", helps fill the gap by adding behavioural, motivational and environmental skills to conventional medical practice. When used in a multidisciplinary setting, lifestyle medicine offers potential cost and effectiveness benefits, which are beginning to be realised.
MED-4247
Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial.
In a prospective, randomised, controlled trial to determine whether comprehensive lifestyle changes affect coronary atherosclerosis after 1 year, 28 patients were assigned to an experimental group (low-fat vegetarian diet, stopping smoking, stress management training, and moderate exercise) and 20 to a usual-care control group. 195 coronary artery lesions were analysed by quantitative coronary angiography. The average percentage diameter stenosis regressed from 40.0 (SD 16.9)% to 37.8 (16.5)% in the experimental group yet progressed from 42.7 (15.5)% to 46.1 (18.5)% in the control group. When only lesions greater than 50% stenosed were analysed, the average percentage diameter stenosis regressed from 61.1 (8.8)% to 55.8 (11.0)% in the experimental group and progressed from 61.7 (9.5)% to 64.4 (16.3)% in the control group. Overall, 82% of experimental-group patients had an average change towards regression. Comprehensive lifestyle changes may be able to bring about regression of even severe coronary atherosclerosis after only 1 year, without use of lipid-lowering drugs.
MED-3786
Choline- and betaine-defined diets for use in clinical research and for the management of trimethylaminuria.
This article describes the development of a series of choline- and betaine-controlled diets that were served to research subjects as part of an ongoing study of diet requirements in humans. These diets were developed based on the analysis of choline and betaine in individual foods. The calculated diets were compared with analyses of all foods combined into a single sample for each day. The laboratory analyses of choline and betaine in the whole-diet aliquots matched the estimated amounts in the diets that were calculated from the analyses of individual foods. These diets were adjusted for several levels of choline and betaine and were well accepted by research subjects who consumed them for a time period of up to 2 months. This article describes applications of this diet for use in clinical research on methyl-group requirements in humans and for use in clinical practice for counseling the client who requires a choline-controlled diet.
MED-3781
Detection of increased choline compounds with proton nuclear magnetic resonance spectroscopy subsequent to malignant transformation of human prosta...
In this study, a panel of normal human prostate cells (HPCs) and tumor cells derived from metastases were studied by (1)H NMR spectroscopy to determine whether the malignant transformation of HPCs results in the elevation of choline compounds. Although an elevated choline signal has been observed previously in clinical studies, the contribution of the different Cho compounds to this elevation, as well as their quantification, has not been established until now. Here we have shown that HPCs derived from metastases exhibit significantly higher phosphocholine as well as glycerophosphocholine levels compared with normal prostate epithelial and stromal cells. Thus the elevation of the choline peak observed clinically in prostate cancer is attributable to an alteration of phospholipid metabolism and not simply to increased cell density, doubling time, or other nonspecific effects. Androgen deprivation of the androgen receptor-positive cell lines resulted in a significant increase of choline compounds after chronic androgen deprivation of the LNCaP cell line and in a decrease of choline compounds after a more acute androgen deprivation of the LAPC-4 cell line. These data strongly support the use of proton magnetic resonance spectroscopic imaging to detect the presence of prostate cancer for diagnosis, to detect response subsequent to androgen ablation therapy, and to detect recurrence.
MED-3789
Choline intake and risk of lethal prostate cancer: incidence and survival
Background: Meat, milk, and eggs have been inconsistently associated with the risk of advanced prostate cancer. These foods are sources of choline—a nutrient that may affect prostate cancer progression through cell membrane function and one-carbon metabolism. No study has examined dietary choline and the risk of lethal prostate cancer. Objective: Our objective was to examine whether dietary choline, choline-containing compounds, and betaine (a choline metabolite) increase the risk of lethal prostate cancer. Design: We prospectively examined the intake of these nutrients and the risk of lethal prostate cancer among 47,896 men in the Health Professionals Follow-Up Study. In a case-only survival analysis, we examined the postdiagnostic intake of these nutrients and the risk of lethal prostate cancer among 4282 men with an initial diagnosis of nonmetastatic disease during follow-up. Diet was assessed with a validated questionnaire 6 times during 22 y of follow-up. Results: In the incidence analysis, we observed 695 lethal prostate cancers during 879,627 person-years. Men in the highest quintile of choline intake had a 70% increased risk of lethal prostate cancer (HR: 1.70; 95% CI: 1.18, 2.45; P-trend = 0.005). In the case-only survival analysis, we observed 271 lethal cases during 33,679 person-years. Postdiagnostic choline intake was not statistically significantly associated with the risk of lethal prostate cancer (HR for quintile 5 compared with quintile 1: 1.69; 95% CI: 0.93, 3.09; P-trend = 0.20). Conclusion: Of the 47,896 men in our study population, choline intake was associated with an increased risk of lethal prostate cancer.
MED-3193
11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma
Background Multiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. Aim As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. Methods Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. Results Four patients (40%) had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20%) had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042). Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8). Conclusion According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.
MED-3783
Fish odour syndrome
Fish odour syndrome (trimethylaminuria) is a metabolic syndrome caused by abnormal excretion of trimethylamine in the breath, urine, sweat, saliva and vaginal secretions. Trimethylamine is derived from the intestinal bacterial degradation of foods rich in choline and carnitine and is normally oxidised by the liver to odourless trimethylamine N-oxide which is then excreted in the urine. Impaired oxidation of trimethylamine is thought to be the cause of the fish odour syndrome and is responsible for the smell of rotting fish. Certain foods rich in choline exacerbate the condition and the patients have a variety of psychological problems. Recognition of the condition is important as dietary adjustments reduce the excretion of trimethylamine and may reduce the odour. Occasionally, a short course of metronidazole, neomycin and lactulose may suppress production of trimethylamine by reducing the activity of gut microflora. Keywords: fish odour syndrome; trimethylaminuria
MED-3785
One-carbon metabolism and prostate cancer risk: prospective investigation of seven circulating B vitamins and metabolites.
PURPOSE: Components of one-carbon metabolism are believed to influence cancer development with suggested mechanisms, including DNA methylation and DNA repair mechanisms. However, few prospective studies have investigated one-carbon metabolism in relation to prostate cancer risk, and the results have been conflicting. The aim of this study was to do a comprehensive investigation of the components of one-carbon metabolism in relation to prostate cancer risk. A panel of seven circulating B vitamins and related metabolites was selected, most of which have not been studied before. MATERIALS AND METHODS: We analyzed plasma concentrations of betaine, choline, cysteine, methionine, methylmalonic acid (MMA), vitamin B2, and vitamin B6 in 561 cases and 1,034 controls matched for age and recruitment date, nested within the population-based Northern Sweden Health and Disease Cohort. Relative risks of prostate cancer were estimated by conditional logistic regression. RESULTS: Positive associations with prostate cancer risk were observed for choline and vitamin B2, and an inverse association was observed for MMA. The relative risks for a doubling in concentrations were 1.46 [95% confidence interval (95% CI), 1.04-2.05; P(trend) = 0.03] for choline, 1.11 (95% CI, 1.00-1.23; P(trend) = 0.04) for vitamin B2, and 0.78 (95% CI, 0.63-0.97; P(trend) = 0.03) for MMA. Concentrations of betaine, cysteine, methionine, and vitamin B6 were not associated with prostate cancer risk. CONCLUSION: The results of this large prospective study suggest that elevated plasma concentrations of choline and vitamin B2 may be associated with an increased risk of prostate cancer. These novel findings support a role of one-carbon metabolism in prostate cancer etiology and warrant further investigation.
MED-3243
A dietary intervention for recurrent prostate cancer after definitive primary treatment: results of a randomized pilot trial.
OBJECTIVES: Considerable evidence has shown that diet can affect both the incidence and the progression of prostate cancer. The objective of this study was to determine whether men in this situation could make a change to a diet emphasizing plant-based foods and fish and to examine the effect on quality of life (QOL) and prostate-specific antigen (PSA) velocity. METHODS: A total of 36 men and their partners were randomly assigned to attend a series of 11 dietary and cooking classes that also integrated mindfulness practice as a support in making the change or a wait-list control group. Assessments were made of dietary intake, QOL, and PSA at baseline, after intervention (11 weeks), and 3 months after intervention. RESULTS: The intervention group showed significant reductions in the consumption of saturated fat and increased consumption of vegetable proteins with accompanying reductions in animal proteins, including dairy products. They also showed increased QOL. Although no significant change was found in the rate of PSA increase between the two groups, the mean PSA doubling time for the intervention group was substantially longer at the 3-month follow-up visit than that of the controls. CONCLUSIONS: Men with a increasing PSA level after primary treatment were able to make a change to a prostate-healthy diet, accompanied by increases in QOL. No significant difference was found in the log PSA slope between the two groups; however, the PSA doubling time increased substantially in the intervention group compared with that in the controls. Future trials should examine the effect of the prostate-healthy diet with a larger sample of men for a longer period.
MED-3252
The molecular basis of nutritional intervention in multiple sclerosis: a narrative review.
It is commonly accepted that nutrition is one of the possible environmental factors involved in the pathogenesis of multiple sclerosis (MS), but its role as complementary MS treatment is unclear and largely disregarded. At present, MS therapy is not associated to a particular diet, probably due to lack of information on the effects of nutrition on the disease. To overcome the distrust of the usefulness of dietary control in MS and to encourage nutritional interventions in the course of the disease, it is necessary to assess the nature and the role of bioactive dietary molecules and their targets, and establish how a dietary control can influence cell metabolism and improve the wellness of MS patients. The aim of this review is to provide a rationale for a nutritional intervention in MS by evaluating at the molecular level the effects of dietary molecules on the inflammatory and autoimmune processes involved in the disease. Present data reveal that healthy dietary molecules have a pleiotropic role and are able to change cell metabolism from anabolism to catabolism and down-regulate inflammation by interacting with enzymes, nuclear receptors and transcriptional factors. The control of gut dysbiosis and the combination of hypo-caloric, low-fat diets with specific vitamins, oligoelements and dietary integrators, including fish oil and polyphenols, may slow-down the progression of the disease and ameliorate the wellness of MS patients. Copyright © 2011 Elsevier Ltd. All rights reserved.
MED-3255
Endothelial function in healthy 11-year-old children after dietary intervention with onset in infancy: the Special Turku Coronary Risk Factor Inter...
BACKGROUND: Early childhood introduction of nutritional habits aimed at atherosclerosis prevention reduces children's serum total cholesterol concentration, but its effect on vascular endothelial function is unknown. METHODS AND RESULTS: Between 1990 and 1992, we randomized healthy 7-month-old infants (n=1062) to intervention (low-saturated-fat diet) and control (unrestricted diet) groups. At the age of 11 years, endothelium-dependent (flow-mediated) and endothelium-independent (nitrate-mediated) vasodilatory responses of the brachial artery were measured with high-resolution ultrasound in 179 intervention and 190 control children. The effect of intervention on endothelial function was significant in boys (P=0.0034) but not in girls (P=0.69). The maximum endothelium-dependent dilation response (mean+/-SD) was 9.62+/-3.53% and 8.36+/-3.85% in intervention boys and control boys and 8.84+/-4.00% and 8.44+/-3.60% in intervention girls and control girls, respectively. Intervention had no effect on nitrate-mediated dilation. The difference in endothelial function in boys remained significant after adjustment for current serum total or LDL cholesterol but became nonsignificant after adjustment for mean cholesterol measured under 3 years of age (adjusted means: 9.46% [CI 8.68% to 10.24%] versus 8.54% [CI 7.75% to 9.32%], P=0.11). CONCLUSIONS: A low-saturated-fat diet introduced in infancy and maintained during the first decade of life is associated with enhanced endothelial function in boys. The effect is explained in part by the diet-induced reduction in serum cholesterol concentration.
MED-3722
Dietary patterns and the risk of esophageal cancer.
BACKGROUND: The role of dietary habits on esophageal cancer risk has been rarely considered in terms of dietary patterns. PATIENTS AND METHODS: We analyzed data from an Italian case-control study, including 304 cases with squamous cell carcinoma of the esophagus and 743 hospital controls. Dietary habits were evaluated using a food frequency questionnaire. A posteriori dietary patterns were identified through principal component factor analysis performed on 28 selected nutrients. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained from multiple logistic regression models applied on quartiles of factor scores, adjusting for potential confounding variables. RESULTS: We identified five major dietary patterns, named 'animal products and related components', 'vitamins and fiber', 'starch-rich', 'other polyunsaturated fatty acids and vitamin D', and 'other fats'. The 'animal products and related components' pattern was positively related to esophageal cancer (OR = 1.64, 95% CI:1.06-2.55, for the highest versus the lowest quartile of factor scores category). The 'vitamins and fiber' (OR = 0.50, 95% CI: 0.32-0.78) and the 'other polyunsaturated fatty acids and vitamin D' (OR = 0.48, 95% CI: 0.31-0.74) were inversely related to esophageal cancer. No significant association was observed for the other patterns. CONCLUSION: Our findings suggest that a diet rich in foods from animal origin and poor in foods containing vitamins and fiber increase esophageal cancer risk.
MED-3723
Dietary patterns and risk of oesophageal cancers: a population-based case-control study.
Epidemiological studies investigating the association between dietary intake and oesophageal cancer have mostly focused on nutrients and food groups instead of dietary patterns. We conducted a population-based case-control study, which included 365 oesophageal adenocarcinoma (OAC), 426 oesophagogastric junction adenocarcinoma (OGJAC) and 303 oesophageal squamous cell carcinoma (OSCC) cases, with frequency matched on age, sex and geographical location to 1580 controls. Data on demographic, lifestyle and dietary factors were collected using self-administered questionnaires. We used principal component analysis to derive three dietary patterns: 'meat and fat', 'pasta and pizza' and 'fruit and vegetable', and unconditional logistic regression models to estimate risks of OAC, OGJAC and OSCC associated with quartiles (Q) of dietary pattern scores. A high score on the meat-and-fat pattern was associated with increased risk of all three cancers: multivariable-adjusted OR 2·12 (95 % CI 1·30, 3·46) for OAC; 1·88 (95% CI 1·21, 2·94) for OGJAC; 2·84 (95% CI 1·67, 4·83) for OSCC (P-trend <0·01 for all three cancers). A high score on the pasta-and-pizza pattern was inversely associated with OSCC risk (OR 0·58, 95 % CI 0·36, 0·96, P for trend=0·009); and a high score on the fruit-and-vegetable pattern was associated with a borderline significant decreased risk of OGJAC (OR for Q4 v. Q1 0·66, 95% CI 0·42, 1·04, P=0·07) and significantly decreased risk of OSCC (OR 0·41, 95% CI 0·24, 0·70, P for trend=0·002). High-fat dairy foods appeared to play a dominant role in the association between the meat-and-fat pattern and risk of OAC and OGJAC. Further investigation in prospective studies is needed to confirm these findings.
MED-3724
Synergism from sequenced combinations of curcumin and epigallocatechin-3-gallate with cisplatin in the killing of human ovarian cancer cells.
Drug resistance remains an on-going challenge in ovarian cancer chemotherapy. The objective of this study was to determine the effect on synergism in activity from the sequenced combinations of cisplatin (Cis) with curcumin (Cur) and epigallocatechin-3-gallate (EGCG) in the human ovarian cancer cell lines. The drugs were added in binary combinations: Cis combined with Cur, and Cis combined with EGCG to the human ovarian A2780 and A2780(cisR) cancer cell lines, using five different sequences of administration: 0/0 h, 4/0 h, 0/4 h, 24/0 h and 0/24 h. The combination index (CI) was used to assess the combined action of the drugs. CIs <1, =1 and >1 indicated synergism, additiveness and antagonism respectively. Cellular accumulation of platinum and platinum-DNA binding levels from Cis and its combination with the phytochemicals were determined using graphite furnace atomic absorption spectrometry. Addition of Cis 4 h before Cur and EGCG (0/4 h combination) produced the most synergistic outcomes in both the A2780 and A2780(cisR) cell lines. The cellular accumulations of platinum and platinum-DNA binding resulting from the 0/4 h combinations were greater as compared to the values using Cis alone, thus providing an explanation for the synergistic action. When sequenced combinations of Cis with Cur and with EGCG are applied to human ovarian A2780 and A2780(cisR) cancer cell lines, lower concentrations and shorter time gap between the two additions seem to produce a higher cytotoxic effect.
MED-3744
Antioxidant and antiproliferative activities of common fruits.
Consumption of fruits and vegetables has been associated with reduced risk of chronic diseases such as cardiovascular disease and cancer. Phytochemicals, especially phenolics, in fruits and vegetables are suggested to be the major bioactive compounds for the health benefits. However, the phenolic contents and their antioxidant activities in fruits and vegetables were underestimated in the literature, because bound phenolics were not included. This study was designed to investigate the profiles of total phenolics, including both soluble free and bound forms in common fruits, by applying solvent extraction, base digestion, and solid-phase extraction methods. Cranberry had the highest total phenolic content, followed by apple, red grape, strawberry, pineapple, banana, peach, lemon, orange, pear, and grapefruit. Total antioxidant activity was measured using the TOSC assay. Cranberry had the highest total antioxidant activity (177.0 +/- 4.3 micromol of vitamin C equiv/g of fruit), followed by apple, red grape, strawberry, peach, lemon, pear, banana, orange, grapefruit, and pineapple. Antiproliferation activities were also studied in vitro using HepG(2) human liver-cancer cells, and cranberry showed the highest inhibitory effect with an EC(50) of 14.5 +/- 0.5 mg/mL, followed by lemon, apple, strawberry, red grape, banana, grapefruit, and peach. A bioactivity index (BI) for dietary cancer prevention is proposed to provide a new alternative biomarker for future epidemiological studies in dietary cancer prevention and health promotion.
MED-3726
Combinatorial strategies employing nutraceuticals for cancer development.
Cancer is the second leading cause of death worldwide. Therefore, the fight against cancer is one of the most important areas of research in medicine, and one that possibly contributes to the increased interest in chemoprevention as an alternative approach to the control of cancer. Cancer prevention by nutraceuticals present in fruits and vegetables has received considerable attention because of their low cost and wide safety margin. A substantial amount of evidence from human, animal, and cell culture studies has shown cancer chemopreventive effects from these natural products. However, single-agent intervention has failed to produce the expected outcome in clinical trials; therefore, combinations of nutraceuticals are gaining increasing popularity. Thus, combinations of nutraceuticals that mimic real-life situations and are competent in targeting multiple targets with very little or virtually no toxicity are needed. In this review, we summarize the results of those studies that report combinatorial cancer chemopreventive action of various nutraceuticals and their combinations with anticancer drugs. © 2011 New York Academy of Sciences.
MED-4481
Dietary fat and meat intakes and risk of reflux esophagitis, Barrett’s esophagus and esophageal adenocarcinoma
The aim of this study was to investigate whether dietary fat and meat intakes are associated with reflux esophagitis (RE), Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). In this all-Ireland case-control study, dietary intake data was collected using a food frequency questionnaire in 219 RE patients, 220 BE patients, 224 EAC patients, and 256 frequency-matched controls between 2002 and 2005. Unconditional multiple logistic regression analysis was used to examine the association between dietary variables and disease risk using quartiles of intake, to attain odds ratios (OR) and 95% confidence intervals (95%CI), while adjusting for potential confounders. Patients in the highest quartile of total fat intake had a higher risk of RE (OR=3.54; 95%CI=1.32–9.46) and EAC (OR=5.44; 95%CI=2.08–14.27). A higher risk of RE and EAC was also reported for patients in the highest quartile of saturated fat intake (OR=2.79; 95%CI=1.11–7.04; OR=2.41; 95%CI=1.14–5.08, respectively) and monounsaturated fat intake (OR=2.63; 95%CI=1.01–6.86; OR=5.35; 95%CI=2.14–13.34, respectively). Patients in the highest quartile of fresh red meat intake had a higher risk of EAC (OR=3.15; 95%CI=1.38–7.20). Patients in the highest category of processed meat intake had a higher risk of RE (OR=4.67; 95%CI=1.71–12.74). No consistent associations were seen for BE with either fat or meat intakes. Further studies, investigating the association between dietary fat and food sources of fat are needed to confirm these results.
MED-3728
Strawberry fields forever?
On the basis of copious preclinical data supporting the preventive efficacy of small fruits such as berries and grapes, Chen and colleagues conducted a randomized (noncomparative) phase II trial evaluating two doses of strawberry powder (60 g/d or 30 g/d for six months) to prevent esophageal cancer in China (reported in this issue of the journal, beginning on page 41); 60 g/d reduced the histologic grade of dysplastic lesions and reduced localized biomarkers, whereas 30 g/d was not effective. Fundamental questions remain such as the best formulation of strawberry powder, the active components associated with powder, and the actual mechanism of action, and standardized preparations will be required to permit the widespread use of strawberry powder with a predicable outcome. Clearly, however, this work is a good example of proof-of-principle and highlights the important role of diet, nutrition, and natural products in cancer prevention. ©2012 AACR.
MED-3729
Role of antioxidants in cancer therapy.
Oxidative stress is a key component in linking environmental toxicity to the multistage carcinogenic process. Reactive oxygen species (ROS) are generated in response to both endogenous and exogenous stimuli. To counterbalance ROS-mediated injury, an endogenous antioxidants defense system exists; however, when oxidation exceeds the control mechanisms, oxidative stress arises. Chronic and cumulative oxidative stress induces deleterious modifications to a variety of macromolecular components, such as DNA, lipids, and proteins. A primary mechanism of many chemotherapy drugs against cancer cells is the formation of ROS, or free radicals. Radiotherapy is based on the fact that ionizing radiation destroys tumor cells. Radiotherapy induces direct lesions in the DNA or biological molecules, which eventually affect DNA. Free radicals produced by oncology therapy are often a source of serious side effects as well. The objective of this review is to provide information about the effects of antioxidants during oncology treatments and to discuss the possible events and efficacy. Much debate has arisen about whether antioxidant supplementation alters the efficacy of cancer chemotherapy. There is still limited evidence in both quality and sample size, suggesting that certain antioxidant supplements may reduce adverse reactions and toxicities. Significant reductions in toxicity may alleviate dose-limiting toxicities so that more patients are able to complete prescribed chemotherapy regimens and thus, in turn, improve the potential for success in terms of tumor response and survival. Copyright © 2013 Elsevier Inc. All rights reserved.
MED-3730
Randomized phase II trial of lyophilized strawberries in patients with dysplastic precancerous lesions of the esophagus.
Dysplasia is a histologic precursor of esophageal squamous cell carcinoma (SCC). We previously showed that dietary freeze-dried, or lyophilized, strawberry powder inhibits N-nitrosomethylbenzylamine-induced SCC in the rat esophagus. On the basis of this observation, we conducted a randomized (noncomparative) phase II trial in China to investigate the effects of two doses of freeze-dried strawberries in patients with esophageal dysplastic lesions in a high-risk area for esophageal cancer. We randomly assigned 75 patients identified by endoscopy to have dysplastic esophageal premalignant lesions to receive freeze-dried strawberry powder at either 30 g/d (37 patients) or 60 g/d (38 patients) for six months; the powder was mixed with water and drunk. After six months, we assessed the changes in histologic grade of these lesions (primary endpoint) in a blinded fashion. The dose of 30 g/d, did not significantly affect histology or any other measured parameter. The dose of 60 g/d, however, reduced the histologic grade of dysplastic premalignant lesions in 29 (80.6%) of the 36 patients at this dose who were evaluated for histology (P < 0.0001). The strawberry powder was well tolerated, with no toxic effects or serious adverse events. Strawberries (60 g/d) also reduced protein expression levels of inducible nitric oxide synthase (iNOS) by 79.5% (P < 0.001), cyclooxygenase-2 (COX-2) by 62.9% (P < 0.001), phospho-nuclear factor kappa B (NFκB)-p65 (pNFκB-p65) by 62.6% (P < 0.001), and phospho-S6 (pS6) by 73.2% (P < 0.001). Freeze-dried strawberries (60 g/d) also significantly inhibited the Ki-67 labeling index by 37.9% (P = 0.023). Our present results indicate the potential of freeze-dried strawberry powder for preventing human esophageal cancer, supporting further clinical testing of this natural agent in this setting. ©2011 AACR.
MED-3731
Esophageal cancer: epidemiology, pathogenesis and prevention.
Esophageal cancer is highly aggressive and is a common cancer both worldwide and in the US. In the past two decades, the incidence and mortality of esophageal cancer in the US have both increased, where as the incidence and mortality of other cancers have decreased. Although esophageal squamous cell carcinoma and esophageal adenocarcinoma differ in their histology and epidemiologic distribution, some of their risk factors (e.g. dietary deficiencies and tobacco) and underlying mechanisms of carcinogenesis are the same. Intensive research into risk factors combined with the ability to identify precursor lesions (e.g.squamous dysplasia in esophageal squamous cell carcinoma and Barrett's esophagus in esophageal adenocarcinoma) has paved the way for studies of chemoprevention for esophageal cancer, some of which have shown promising results.
MED-3732
Rectal laterally spreading tumors successfully treated in two steps by endoscopic submucosal dissection and endoscopic mucosal resection
Background Endoscopic submucosal dissection (ESD) is an advanced technique of therapeutic endoscopy alternative to endoscopic mucosal resection (EMR) for superficial gastrointestinal neoplasms >2 cm. ESD allows for the direct dissection of the submucosa and large lesions can be resected en bloc. ESD is not limited by resection size, increases histologically complete resection rates and may reduce the local recurrence. Nevertheless, the technique is time-consuming, technically demanding and associated with a high complication rate. To reduce the risk of complications, different devices and technical advances have been proposed with conflicting results and, still, ESD en bloc resections of huge lesions are associated with increased complications. Case Presentation We successfully used a combined ESD/EMR technique for huge rectal laterally spreading tumors (LSTs). ESD was used for circumferential resection of 2/3 of the lesion followed by piecemeal resection (2-3 pieces) of the central part of the tumour. In all three patients we obtained the complete dissection of the polyp and the complete histological evaluation in absence of complications and recurrence at 6 months' follow up. Conclusions In the treatment of rectal LSTs, the combined treatment - ESD/EMR resection may be considered a suitable therapeutic option, indicated in selected cases as an alternative to surgery, in which the two techniques are neither reliable nor safe separately. However, to confirm our results, larger trials with longer follow up are required together with improvement of the technique and of the technical devices.
MED-4245
The effectiveness and efficacy of an intensive cardiac rehabilitation program in 24 sites.
PURPOSE: The purpose of this study is to test the efficacy and effectiveness of an intensive cardiac rehabilitation program in improving health outcomes in multiple sites. METHODS: This study employs a nonexperimental (prospective time series) design to investigate changes in cardiovascular disease in 2974 men and women from 24 socioeconomically diverse sites who participated in an intensive cardiac rehabilitation program at baseline, 12 weeks, and 1 year. Paired t-tests were used to assess differences by comparing baseline values to those after 12 weeks, baseline values to those after 1 year, and values after 12 weeks to those after 1 year. RESULTS: Eighty-eight percent of patients remained enrolled in the program after 12 weeks, and 78.1% remained enrolled in the program after 1 year. Patients showed statistically significant improvements after 12 weeks in body mass index (BMI), triglycerides, low density lipoprotein cholesterol, total cholesterol, hemoglobin A1c, systolic blood pressure, diastolic blood pressure, depression, hostility, exercise, and functional capacity. These differences also remained significant after 1 year. There was additional significant improvement between 12 weeks and 1 year only in BMI, high density lipoprotein cholesterol, functional capacity, and hostility, and significant recidivism between 12 weeks and 1 year in all other measures (except triglycerides) and depression, yet improvements from baseline to 1 year remained significant in all measures (except HDL, which was unchanged) (p < .005). CONCLUSIONS: This intensive cardiac rehabilitation program was feasible and sustainable for most patients who enrolled and was associated with numerous subjective and objective improvements in health outcomes. It demonstrates that the intervention works when it is administered by staff at multiple clinical/commmunity sites in four different states. These improvements were also seen in patients 65 years of age or older.
MED-4246
A multicomponent intervention reduces body weight and cardiovascular risk at a GEICO corporate site.
PURPOSE: To determine whether a multicomponent nutrition intervention program at a corporate site reduces body weight and improves other cardiovascular risk factors in overweight individuals. DESIGN: Prospective clinical intervention study. SUBJECTS/SETTING: Employees of the Government Employees Insurance Company (GEICO) (N = 113), aged 21 to 65 years, with a body mass index > or =25 kg/m(2) and/or previous diagnosis of type 2 diabetes. INTERVENTION: A 22-week intervention including a low-fat, vegan diet. MEASURES: Changes in body weight, anthropometric measures, blood pressure, lipid profile, and dietary intake. ANALYSIS: Multivariate analyses of variance were calculated for clinical and nutrient measures, followed by univariate analyses of variance, to determine the significance of differences between groups in changes over time. RESULTS: Intervention-group participants experienced greater weight changes compared with control-group participants (mean, -5.1 [SE, .6] kg vs. + .1 [SE, .6] kg, p < .0001), as well as greater changes in waist circumference (mean, -4.7 [SE, .6] cm vs. + .8 [SE, .6] cm, p < .0001) and waistratiohip ratio (mean, -.006 [SE, .003] vs. + .014 [SE, .005], p = .0007). Weight loss of 5% of body weight was more frequently observed in the intervention group (48.5%) compared with the control group (11.1%) (chi(2)[1, N = 113] = 16.99, p < .0001). CONCLUSIONS: Among individuals volunteering for a 22-week worksite research study, an intervention using a low-fat, vegan diet effectively reduced body weight and waist circumference.
MED-4613
Resolving the Coronary Artery Disease Epidemic Through Plant-Based Nutrition.
The world's advanced countries have easy access to plentiful high-fat food; ironically, it is this rich diet that produces atherosclerosis. In the world's poorer nations, many people subsist on a primarily plant-based diet, which is far healthier, especially in terms of heart disease. To treat coronary heart disease, a century of scientific investigation has produced a device-driven, risk factor-oriented strategy. Nevertheless, many patients treated with this approach experience progressive disability and death. This strategy is a rear-guard defensive one. In contrast, compelling data from nutritional studies, population surveys, and interventional studies support the effectiveness of a plant-based diet and aggressive lipid lowering to arrest, prevent, and selectively reverse heart disease. In essence, this is an offensive strategy. The single biggest step toward adopting this strategy would be to have United States dietary guidelines support a plant-based diet. An expert committee purged of industrial and political influence is required to assure that science is the basis for dietary recommendations. (c)2001 CHF, Inc.
MED-4617
Systematic Review of the Incidence of Sudden Cardiac Death in the United States
The need for consistent and current data describing the true incidence of SCA and/or SCD was highlighted during the most recent Sudden Cardiac Arrest Thought Leadership Alliance’s (SCATLA) Think Tank meeting of national experts with broad representation of key stakeholders including thought leaders and representatives from the American College of Cardiology, American Heart Association, and the Heart Rhythm Society. As such, to evaluate the true magnitude of this public health problem, we performed a systematic literature search in MEDLINE using the MeSH headings, “death, sudden” OR the terms “sudden cardiac death” OR “sudden cardiac arrest” OR “cardiac arrest” OR “cardiac death” OR “sudden death” OR “arrhythmic death.” Study selection criteria included peer-reviewed publications of primary data used to estimate SCD incidence in the U.S. We used Web of Science®’s Cited Reference Search to evaluate the impact of each primary estimate on the medical literature by determining the number of times each “primary source” has been cited. The estimated U.S. annual incidence of SCD varied widely from 180,000 to > 450,000 among 6 included studies. These different estimates were in part due to different data sources (with data age ranging from 1980 to 2007), definitions of SCD, case ascertainment criteria, methods of estimation/extrapolation, and sources of case ascertainment. The true incidence of SCA and/or SCD in the U.S. remains unclear with a wide range in the available estimates, which are badly dated. As reliable estimates of SCD incidence are important for improving risk stratification and prevention, future efforts are clearly needed to establish uniform definitions of SCA and SCD and then to prospectively and precisely capture cases of SCA and SCD in the overall U.S. population.
MED-4615
Diet, lifestyle, and the etiology of coronary artery disease: the Cornell China study.
Investigators collected and analyzed mortality data for >50 diseases, including 7 different cancers, from 65 counties and 130 villages in rural mainland China. Blood, urine, food samples, and detailed dietary data were collected from 50 adults in each village and analyzed for a variety of nutritional, viral, hormonal, and toxic chemical factors. In rural China, fat intake was less than half that in the United States, and fiber intake was 3 times higher. Animal protein intake was very low, only about 10% of the US intake. Mean serum total cholesterol was 127 mg/dL in rural China versus 203 mg/dL for adults aged 20-74 years in the United States. Coronary artery disease mortality was 16.7-fold greater for US men and 5.6-fold greater for US women than for their Chinese counterparts. The combined coronary artery disease mortality rates for both genders in rural China were inversely associated with the frequency of intake of green vegetables and plasma erythrocyte monounsaturated fatty acids, but positively associated with a combined index of salt intake plus urinary sodium and plasma apolipoprotein B. These apolipoproteins, in turn, are positively associated with animal protein intake and the frequency of meat intake and inversely associated with plant protein, legume, and light-colored vegetable intake. Rates of other diseases were also correlated with dietary factors. There was no evidence of a threshold beyond which further benefits did not accrue with increasing proportions of plant-based foods in the diet.
MED-4616
Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial.
In a prospective, randomised, controlled trial to determine whether comprehensive lifestyle changes affect coronary atherosclerosis after 1 year, 28 patients were assigned to an experimental group (low-fat vegetarian diet, stopping smoking, stress management training, and moderate exercise) and 20 to a usual-care control group. 195 coronary artery lesions were analysed by quantitative coronary angiography. The average percentage diameter stenosis regressed from 40.0 (SD 16.9)% to 37.8 (16.5)% in the experimental group yet progressed from 42.7 (15.5)% to 46.1 (18.5)% in the control group. When only lesions greater than 50% stenosed were analysed, the average percentage diameter stenosis regressed from 61.1 (8.8)% to 55.8 (11.0)% in the experimental group and progressed from 61.7 (9.5)% to 64.4 (16.3)% in the control group. Overall, 82% of experimental-group patients had an average change towards regression. Comprehensive lifestyle changes may be able to bring about regression of even severe coronary atherosclerosis after only 1 year, without use of lipid-lowering drugs.
MED-4696
Modulation of inflammatory genes by natural dietary bioactive compounds.
Several epidemiologic studies have shown that chronic inflammation predisposes individuals to various types of cancer. Many cancers arise from sites of infection, chronic irritation, and inflammation. Conversely, an oncogenic change induces an inflammatory microenvironment that promotes the development of tumors. Natural bioactive compounds in dietary plant products including fruits, vegetables, grains, legumes, tea, and wine are claimed to help prevent cancer, degenerative diseases, and chronic and acute inflammation. Modern methods in cell and molecular biology allow us to understand the interactions of different natural bioactive compounds with basic mechanisms of inflammatory response. The molecular pathways of this cancer-related inflammation are now unraveled. Natural bioactive compounds exert anti-inflammatory activity by modulating pro-inflammatory gene expressions have shown promising chemopreventive activity. This review summarizes current knowledge on natural bioactive compounds that act through the signaling pathways and modulate inflammatory gene expressions, thus providing evidence for these substances in cancer chemopreventive action.
MED-4879
Estimating age of humans based on telomere shortening.
To estimate age using DNA based on telomere shortening, we determined the terminal restriction fragment (TRF) length, as telomere length, using Southern blot analysis of peripheral human blood and blood stains. All blood stains had been stored at room temperature for 5 months. The average TRF length clearly showed a tendency to shortening with aging. The formula for age estimation was based on a correlation between average TRF length and age of the subjects. The estimated age calculated from TRF length widely depends on environmental and genetic factors. However, as long as the DNA is well preserved, use of our method is feasible regardless of age of the subject and can give a rough estimation of age of subjects in forensic samples that carry no morphological information. Copyright 2002 Elsevier Science Ireland Ltd.
MED-4886
Clinical events in prostate cancer lifestyle trial: results from two years of follow-up.
OBJECTIVES: Previous research has demonstrated that patients with prostate cancer participating in the Prostate Cancer Lifestyle Trial had a reduction in prostate-specific antigen (PSA) levels, inhibition of LNCaP cell growth, and fewer prostate cancer-related clinical events at the end of 1 year compared with controls. The aim of this study was to examine the clinical events in this trial during a 2-year period. METHODS: The Prostate Cancer Lifestyle Trial was a 1-year randomized controlled clinical trial of 93 patients with early-stage prostate cancer (Gleason score <7, PSA 4-10 ng/mL) undergoing active surveillance. The patients in the experimental arm were encouraged to adopt a low-fat, plant-based diet, to exercise and practice stress management, and to attend group support sessions. The control patients received the usual care. RESULTS: By 2 years of follow-up, 13 of 49 (27%) control patients and 2 of 43 (5%) experimental patients had undergone conventional prostate cancer treatment (radical prostatectomy, radiotherapy, or androgen deprivation, P < .05). No differences were found between the groups in other clinical events (eg, cardiac), and no deaths occurred. Three of the treated control patients but none of the treated experimental patients had a PSA level of >or=10 ng/mL, and 1 treated control patient but no treated experimental patients had a PSA velocity of >2 ng/mL/y before treatment. No significant differences were found between the untreated experimental and untreated control patients in PSA change or velocity at the end of 2 years. CONCLUSIONS: Patients with early-stage prostate cancer choosing active surveillance might be able to avoid or delay conventional treatment for at least 2 years by making changes in their diet and lifestyle.
MED-4887
Angina pectoris and atherosclerotic risk factors in the multisite cardiac lifestyle intervention program.
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 <0.05). In conclusion, the observed improvements in angina in patients making intensive lifestyle changes could drastically reduce their need for revascularization procedures.
MED-4888
Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention
Epidemiological and prospective studies indicate that comprehensive lifestyle changes may modify the progression of prostate cancer. However, the molecular mechanisms by which improvements in diet and lifestyle might affect the prostate microenvironment are poorly understood. We conducted a pilot study to examine changes in prostate gene expression in a unique population of men with low-risk prostate cancer who declined immediate surgery, hormonal therapy, or radiation and participated in an intensive nutrition and lifestyle intervention while undergoing careful surveillance for tumor progression. Consistent with previous studies, significant improvements in weight, abdominal obesity, blood pressure, and lipid profile were observed (all P < 0.05), and surveillance of low-risk patients was safe. Gene expression profiles were obtained from 30 participants, pairing RNA samples from control prostate needle biopsy taken before intervention to RNA from the same patient's 3-month postintervention biopsy. Quantitative real-time PCR was used to validate array observations for selected transcripts. Two-class paired analysis of global gene expression using significance analysis of microarrays detected 48 up-regulated and 453 down-regulated transcripts after the intervention. Pathway analysis identified significant modulation of biological processes that have critical roles in tumorigenesis, including protein metabolism and modification, intracellular protein traffic, and protein phosphorylation (all P < 0.05). Intensive nutrition and lifestyle changes may modulate gene expression in the prostate. Understanding the prostate molecular response to comprehensive lifestyle changes may strengthen efforts to develop effective prevention and treatment. Larger clinical trials are warranted to confirm the results of this pilot study.
MED-4890
Effect of diet and exercise intervention on the growth of prostate epithelial cells.
Epidemiological studies suggest a positive association between nutrient intake, hyperinsulinemia and risk of Benign prostatic hyperplasis (BPH). This study tests the hypothesis that a low-fat, high-fiber diet and daily exercise would lower serum insulin and reduce the growth of serum-stimulated primary prostate epithelial cells in culture. Serum samples were obtained from eight overweight men before and after the Pritikin residential, 2-week diet and exercise intervention and from seven men who were long-term followers of the low-fat, high-fiber diet and regular exercise lifestyle. The serum was used to stimulate primary prostate epithelial cells in culture. Growth was measured after 48 and 96 h and apoptosis after 96 h. At 48 h there was no significant difference in growth within the Pre, 2-week or Long-Term groups. At 96 h growth was significantly reduced in the 2-week (13%) and in the Long-Term (14%) groups compared to the Pre data. At 96 h, apoptosis was not significantly different among the three groups. Fasting insulin was reduced by 30% in the 2-week group and by 52% in the Long-Term group compared to the Pre data. Testosterone was unchanged in the 2-week group. The results of this study indicate that a low-fat, high-fiber diet and daily exercise lowers insulin and reduces growth of prostate primary epithelial cells and suggests that lifestyle may be an important factor in the development or progression of BPH. Future prospective trials should address the effects of this lifestyle modification on BPH symptomatology and progression.
MED-4891
Epidemiology of Sudden Cardiac Death: Clinical and Research Implications
The current annual incidence of sudden cardiac death in the US is likely to be in the range of 180–250,000 per year. Coinciding with the decreased mortality from coronary artery disease, there is evidence pointing toward a significant decrease in rates of sudden cardiac death in the US during the second half of the twentieth century. However the alarming rise in prevalence of obesity and diabetes in the first decade of the new millennium both in the US and worldwide, would indicate that this favorable trend is unlikely to persist. We are likely to witness a resurgence of coronary artery disease and heart failure, as a result of which sudden cardiac death will have to be confronted as a shared and indiscriminate, worldwide public health problem. There is also increasing recognition of the fact that discovery of meaningful and relevant risk stratification and prevention methodologies will require careful prospective community-wide analyses, with access to large archives of DNA, serum and tissue that link with well-phenotyped databases. The purpose of this review is to summarize current knowledge of sudden cardiac death epidemiology. We will discuss the significance and strengths of community-wide evaluations of sudden cardiac death, summarize recent observations from such studies, and finally highlight specific potential predictors that warrant further evaluation as determinants of sudden cardiac death in the general population.
MED-1321
Phospholipids in rice: significance in grain quality and health benefits: a review.
Phospholipids (PLs) are a major class of lipid in rice grain. Although PLs are only a minor nutrient compared to starch and protein, they may have both nutritional and functional significance. We have systemically reviewed the literature on the class, distribution and variation of PLs in rice, their relation to rice end-use quality and human health, as well as available methods for analytical profiling. Phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and their lyso forms are the major PLs in rice. The deterioration of PC in rice bran during storage was considered as a trigger for the degradation of rice lipids with associated rancid flavour in paddy and brown rice. The lyso forms in rice endosperm represent the major starch lipid, and may form inclusion complexes with amylose, affecting the physicochemical properties and digestibility of starch, and hence its cooking and eating quality. Dietary PLs have a positive impact on several human diseases and reduce the side-effects of some drugs. As rice has long been consumed as a staple food in many Asian countries, rice PLs may have significant health benefits for those populations. Rice PLs may be influenced both by genetic (G) and environmental (E) factors, and resolving G×E interactions may allow future exploitation of PL composition and content, thus boosting rice eating quality and health benefits for consumers. We have identified and summarised the different methods used for rice PL analysis, and discussed the consequences of variation in reported PL values due to inconsistencies between methods. This review enhances the understanding of the nature and importance of PLs in rice and outlines potential approaches for manipulating PLs to improve the quality of rice grain and other cereals. Copyright © 2013 Elsevier Ltd. All rights reserved.
MED-1751
Commercial conspiracy theories: a pilot study
There are many ways to categorise conspiracy theories. In the present study, we examined individual and demographic predictors of beliefs in commercial conspiracy theories among a British sample of over 300 women and men. Results showed many people were cynical and sceptical with regard to advertising tricks, as well as the tactics of organisations like banks and alcohol, drug and tobacco companies. Beliefs sorted into four identifiable clusters, labelled sneakiness, manipulative, change-the-rules and suppression/prevention. The high alpha for the overall scale suggested general beliefs in commercial conspiracy. Regressions suggested that those people who were less religious, more left-wing, more pessimistic, less (self-defined as) wealthy, less Neurotic and less Open-to-Experience believed there was more commercial conspiracy. Overall the individual difference variables explained relatively little of the variance in these beliefs. The implications of these findings for the literature on conspiracy theories are discussed. Limitations of the study are also discussed.
MED-1575
Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease
Background Epithelial barrier function is impaired in Crohn's disease. Aim To define the underlying cellular mechanisms with special attention to tight junctions. Methods Biopsy specimens from the sigmoid colon of patients with mild to moderately active or inactive Crohn's disease were studied in Ussing chambers, and barrier function was determined by impedance analysis and conductance scanning. Tight junction structure was analysed by freeze fracture electron microscopy, and tight junction proteins were investigated immunohistochemically by confocal laser scanning microscopy and quantified in immunoblots. Epithelial apoptosis was analysed in terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick‐end labelling and 4′,6‐diamidino‐2‐phenylindole staining. Results Patients with active Crohn's disease showed an impaired intestinal barrier function as indicated by a distinct reduction in epithelial resistance. As distribution of conductivity was even, focal epithelial lesions (eg, microerosions) did not contribute to barrier dysfunction. Instead, freeze fracture electron microscopy analysis showed reduced and discontinuous tight junction strands. Occludin and the sealing tight junction proteins claudin 5 and claudin 8 were downregulated and redistributed off the tight junction, whereas the pore‐forming tight junctions protein claudin 2 was strongly upregulated, which constitute the molecular basis of tight junction changes. Other claudins were unchanged (claudins 1, 4 and 7) or not detectable in sigmoid colon (claudins 11, 12, 14, 15 and 16). Claudin 2 upregulation was less pronounced in active Crohn's disease compared with active ulcerative colitis and was inducible by tumour necrosis factor α. As a second source of impaired barrier function, epithelial apoptosis was distinctly increased in active Crohn's disease (mean (SD) 5.2 (0.5)% v 1.9 (0.2)% in control). By contrast, barrier function, tight junction proteins and apoptosis were unaffected in Crohn's disease in remission. Conclusion Upregulation of pore‐forming claudin 2 and downregulation and redistribution of sealing claudins 5 and 8 lead to altered tight junction structure and pronounced barrier dysfunction already in mild to moderately active Crohn's disease.
MED-4089
Antiproliferative effects of apple peel extract against cancer cells.
Studies have shown an inverse relationship between the consumption of apples and the risk of several cancers. The peels of apple, which have been shown to possess exceptionally high concentrations of antioxidants, are often discarded. In this study, we evaluated the antiproliferative effects of apple peel extract (APE) in variety of cancer cell types. Our data demonstrated that APE, obtained from organic Gala apples, imparted significant reduction in the viability of a variety of cancer cell lines. Further, our data showed a significant decrease in growth and clonogenic survival of human prostate carcinoma CWR22Rnu1 and DU145 cells and breast carcinoma Mcf-7 and Mcf-7:Her18 cells. Also, the antiproliferative effects of APE were found to be accompanied by a G0-G1 phase arrest of prostate and breast cancer cells. Furthermore, APE treatment resulted in a marked concentration-dependent decrease in the protein levels of proliferative cell nuclear antigen, a marker for proliferation. In addition, APE treatment resulted in a marked increase in maspin, a tumor suppressor protein that negatively regulates cell invasion, metastasis, and angiogenesis. Our data suggested that APE possesses strong antiproliferative effects against cancer cells, and apple peels should not be discarded from the diet. Detailed mechanistic studies, especially in appropriate in vivo animal models, are needed to further examine the antiproliferative and preventive effects of APE against cancer.
MED-3769
Energy density, nutrient adequacy, and cost per serving can provide insight into food choices in the lower Mississippi Delta.
OBJECTIVE: To compare differences across food groups for food cost, energy, and nutrient profiles of 100 items from a cross-sectional survey of 225 stores in 18 counties across the Lower Mississippi Delta of Arkansas, Louisiana, and Mississippi. METHODS: Energy, nutrient, and cost profiles for food items were calculated by using Naturally Nutrient Rich methodology and converting price per 100 g edible portion to price per serving. Foods were grouped into 6 food groups. Mean differences were compared with ANOVA. RESULTS: Significant differences existed by food group for each measure. Energy density was highest for fats/oils/sweets, whereas nutrient density was highest for vegetables. Price per serving was lowest for fats/oils/sweets and highest for meats. CONCLUSIONS AND IMPLICATIONS: Educational messages focusing on a complete diet should consider the role of food costs and provide specific recommendations for increasing nutrient-dense foods by replacing a portion of the meat serving at meals with culturally acceptable lower-cost nutrient-dense foods. Copyright Â© 2012 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.
MED-2982
Surgical management of bisphosphonate-related osteonecrosis of the jaw in oncologic patients: a challenging problem.
AIM: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious oral complication of supportive cancer therapy and the best method of treatment is still unclear. The purpose of this article is to analyze the type of treatment and outcome in a large patient cohort with BRONJ. PATIENTS AND METHODS: A total of 142 patients suffering from BRONJ at different sites were studied. All patients had been treated with intravenous bisphosphonates for various oncological disease. A descriptive analysis of all relevant patient data was performed with particular emphasis on surgical outcome. RESULTS: The mandible was affected in 58% of the patients. All but two patients had previous invasive dental procedures. The mean duration of bisphosphonate treatment was 37.1 months. A total of 86% of the patients were treated surgically, including sequestrectomies and mandibular resections. Soft-tissue reconstruction was achieved by local closure, myofascial flap using the mylohyoid muscle, and a vascularized fasciocutaneous flap in one patient. No bony reconstruction was performed. CONCLUSION: Surgical treatment of BRONJ remains challenging. There is only limited evidence that oncologic patients with BRONJ are candidates for vascularized bone reconstruction.
MED-4750
Assessment of endogenous androgen levels in meat, liver and testis of Iranian native cross-breed male sheep and bull by gas chromatography-mass spe...
Androgenic steroids always exist in different animal tissues at trace level, with significant numbers of interfering compounds, which makes their determination difficult. To solve some of the problems in quantification of the natural steroids in those tissues, a new GC-MS method was developed in this study. By using a surrogate analyte approach, which was developed in the authors' previous studies, and extensive sample preparation procedure, which successfully eliminates many of the interfering compounds and resulting in a cleaner extract, accuracy, precision, sensitivity and selectivity of the method for the determination of steroids in complex matrices such as meat, liver and testis were improved. By aid of this method, the levels of androgens in different tissues of Iranian native cross-breed bulls and male sheep were determined. According to the results obtained in the present study, although the androgenic profile (contents and ratios of precursors and metabolites to the main hormones) is similar between the same tissues of both animals, the total androgenic content of each tissue is higher in the bull than the same tissue in male sheep. In addition, in both animals higher amount of androgens were found in liver in comparison with meat and testis.
MED-4917
Soy consumption for reduction of menopausal symptoms.
AIMS: To review current research on the effects of soy consumption on menopausal symptoms. METHODS: To review results of recent meta-analyses and individual clinical trials. MAIN RESULTS: One recent meta-analysis reported that isoflavone supplementation was associated with a 34% reduction in hot flashes, with increased efficacy as the baseline number of flashes and isoflavone dose increased. A second review concluded that consumption of at least 15 mg genistein, rather than total isoflavones, is responsible for the reduction in symptoms. Results of these two reviews are supported by most subsequent randomized controlled trials. CONCLUSIONS: Consumption of 30 mg/day of soy isoflavones (or at least 15 mg genistein) reduces hot flashes by up to 50 %. This total reduction includes that provided by "the placebo effect". The greatest benefit may be realized when the isoflavone-rich food or supplement is taken in divided doses by subjects who experience at least four hot flashes/day.
MED-1123
Systematic literature review on economic implications and pharmacoeconomic issues of rheumatoid arthritis.
OBJECTIVES: To provide a state of the art of economic analyses applied to rheumatoid arthritis (RA). METHODS: A systematic literature review on economic consequences and pharmacoeconomic issues of RA was performed. RESULTS: 127 valid articles were examined in this review. Generally, the financial impact of RA is substantial for health-care systems and society worldwide, although differences exist among national economies. Both direct and indirect (i.e. loss of productivity) costs contribute to economic burden of RA and must be taken into account when estimating overall impact to society. Disease severity, disease activity, age and socioeconomic status have been found to be the most relevant predictors of cost increase in RA. Moreover, introduction of biological anti-rheumatic agents has significantly raised direct medical costs in certain patients, but has also led to marked improvements in reducing disease activity, joint damage, and productivity loss in many of these patients. RA has also a significant impact on all aspects of quality of life; recent publications on health utility scores showed RA to be one of the diseases associated with poorest quality of life. CONCLUSIONS: RA represents a clinical and economic burden for healthcare systems. Although attributable RA costs have been extensively evaluated over the last decades, several issues, especially concerning the use of expensive therapies, must be addressed and frequently updated. Future research should also provide health economic evidence from usual practice settings, and on the economic impact of different therapeutic approaches to pursue specific clinical targets in individual patients.
MED-1066
Dietary habits and their relations to insulin resistance and postprandial lipemia in nonalcoholic steatohepatitis.
The relations of dietary habits to insulin sensitivity and postprandial triglyceride metabolism were evaluated in 25 patients with nonalcoholic steatohepatitis (NASH) and 25 age-, body mass index (BMI)-, and gender-matched healthy controls. After a 7-day alimentary record, they underwent a standard oral glucose tolerance test (OGTT), and the insulin sensitivity index (ISI) was calculated from the OGTT; an oral fat load test was also performed in 15 patients and 15 controls. The dietary intake of NASH patients was richer in saturated fat (13.7% +/- 3.1% vs. 10.0% +/- 2.1% total kcal, respectively, P =.0001) and in cholesterol (506 +/- 108 vs. 405 +/- 111 mg/d, respectively, P =.002) and was poorer in polyunsaturated fat (10.0% +/- 3.5% vs. 14.5% +/- 4.0% total fat, respectively, P =.0001), fiber (12.9 +/- 4.1 vs. 23.2 +/- 7.8 g/d, respectively, P =.000), and antioxidant vitamins C (84.3 +/- 43.1 vs. 144.2 +/- 63.1 mg/d, respectively, P =.0001) and E (5.4 +/- 1.9 vs. 8.7 +/- 2.9 mg/d, respectively, P =.0001). The ISI was significantly lower in NASH patients than in controls. Postprandial total and very low density lipoproteins triglyceride at +4 hours and +6 hours, triglyceride area under the curve, and incremental triglyceride area under the curve were higher in NASH compared with controls. Saturated fat intake correlated with ISI, with the different features of the metabolic syndrome, and with the postprandial rise of triglyceride. Postprandial apolipoprotein (Apo) B48 and ApoB100 responses in NASH were flat and strikingly dissociated from the triglyceride response, suggesting a defect in ApoB secretion. In conclusion, dietary habits may promote steatohepatitis directly by modulating hepatic triglyceride accumulation and antioxidant activity as well as indirectly by affecting insulin sensitivity and postprandial triglyceride metabolism. Our findings provide further rationale for more specific alimentary interventions, particularly in nonobese, nondiabetic normolipidemic NASH patients.
MED-3952
Polyphenolics from açaí ( Euterpe oleracea Mart.) and red muscadine grape (Vitis rotundifolia ) protect human umbilical vascular Endothelial cell...
Endothelial anti-inflammatory effects of açaí (Ac) and red muscadine grape (Gp) polyphenolics have not been extensively investigated. It was hypothesized that polyphenolics from Ac and Gp exert comparable protective effects in human vascular endothelial cells (HUVEC) upon inflammatory stress. Furthermore, this study investigated whether microRNAs relevant to endothelial function might be regulated by Ac and Gp. Results showed that Ac and Gp (5-20 mg gallic acid equivalent/L) protected HUVEC against glucose-induced oxidative stress and inflammation. Glucose-induced expression of interleukin-6 and -8 was down-regulated by Ac and Gp at mRNA and protein levels. Upon lipopolysaccharide (LPS; 1 μg/L)-induced inflammation, Ac and Gp inhibited gene expression of adhesion molecules and NF-κB activation to similar extents, although Gp was more effective in decreasing PECAM-1 and ICAM-1 protein. Of the screened microRNAs, only microRNA-126 expression was found to be modulated by Ac and Gp as the underlying mechanism to inhibit gene and protein expression of VCAM-1.
MED-1500
Fruit, vegetables and prevention of cognitive decline or dementia: a systematic review of cohort studies.
BACKGROUND: Regular consumption of fruit and vegetables has been considered to be associated with a reduced risk of dementia and age-associated cognitive decline, although the association is currently unsupported by a systematic review of the literature. METHODS: We searched Medline, Embase, Biosis, ALOIS, the Cochrane library, different publisher databases as well as bibliographies of retrieved articles. All cohort studies with a follow-up of 6 months or longer were included if they reported an association of Alzheimer's disease or cognitive decline in regard to the frequency of fruit and vegetables consumption. FINDINGS: Nine studies with a total of 44,004 participants met the inclusion criteria. Six studies analyzed fruit and vegetables separately and five of them found that higher consumption of vegetables, but not fruit is associated with a decreased risk of dementia or cognitive decline. The same association was found by three further studies for fruit and vegetable consumption analytically combined. CONCLUSION: Increased intake of vegetables is associated with a lower risk of dementia and slower rates of cognitive decline in older age. Yet, evidence that this association is also valid for high fruit consumption is lacking.
MED-2437
Diet and breast cancer: understanding risks and benefits.
BACKGROUND: Breast cancer is the most commonly diagnosed cancer among women in the United States. Extensive research has been completed to evaluate the relationship between dietary factors and breast cancer risk and survival after breast cancer; however, a summary report with clinical inference is needed. Materials and METHODS: This review summarizes the current epidemiological and clinical trial evidence relating diet to breast cancer incidence, recurrence, survival, and mortality. The review includes emerging epidemiological studies that assess risk within breast cancer subtypes as well as a summary of previous and ongoing dietary intervention trials designed to modify breast cancer risk. RESULTS: The available literature suggests that both low-fat and high-fiber diets may be weakly protective against breast cancer, whereas total energy intake and alcohol appear to be positively associated. Fiber may be weakly protective possibly through modulation of estrogen, whereas fruit and vegetable intake is not clearly associated with risk. Obesity is a risk factor for postmenopausal disease, and adult weight gain should be avoided to reduce risk. In survivors, diet has the greatest potential influence on overall mortality rather than breast cancer-specific events. CONCLUSION: Diet is modestly associated with breast cancer risk; associations appear more pronounced for postmenopausal disease, and healthy choices after diagnosis and treatment likely support longevity more so than reduced risk for recurrent disease.
MED-1386
Communicating clinical research to reduce cancer risk through diet: Walnuts as a case example
Inflammation is one mechanism through which cancer is initiated and progresses, and is implicated in the etiology of other conditions that affect cancer risk and prognosis, such as type 2 diabetes, cardiovascular disease, and visceral obesity. Emerging human evidence, primarily epidemiological, suggests that walnuts impact risk of these chronic diseases via inflammation. The published literature documents associations between walnut consumption and reduced risk of cancer, and mortality from cancer, diabetes, and cardiovascular disease, particularly within the context of the Mediterranean Diet. While encouraging, follow-up in human intervention trials is needed to better elucidate any potential cancer prevention effect of walnuts, per se. In humans, the far-reaching positive effects of a plant-based diet that includes walnuts may be the most critical message for the public. Indeed, appropriate translation of nutrition research is essential for facilitating healthful consumer dietary behavior. This paper will explore the translation and application of human evidence regarding connections with cancer and biomarkers of inflammation to the development of dietary guidance for the public and individualized dietary advice. Strategies for encouraging dietary patterns that may reduce cancer risk will be explored.
MED-2309
Bridging the gap in life expectancy of the aborigines in Taiwan.
BACKGROUND: Similar to the general population in Taiwan, the health of aborigines has steadily improved over the last 30 years, but the gap remains wide, especially in males, despite an infusion of substantial medical resources. The objectives of this study are to quantify the contribution of major causes of death to the gap in life expectancy and to propose initiatives to bridge the health gap between aborigines and the general population. METHODS: This study included residents (slightly over 200000) from 30 'aboriginal townships' in Taiwan. The gap in life expectancy between aborigines and the general population was analysed by decomposing these gaps according to major causes of deaths. This analysis quantifies the contribution of different causes of deaths to the gap in life expectancy between the two populations. RESULTS: The overall mortality of aborigines in these townships was approximately 70% higher than the respective male and female general populations over the past 30 years. Mortality from infectious disease, cirrhosis of the liver, accidents, and suicide are substantially higher than the general population. The gap in life expectancy at birth in males was 8.5 years during 1971-1973, increasing to 13.5 years by 1998-2000, however, the gap in females remained relatively stable (8.0 years and 8.4 years, respectively). Of the 13.5-year difference in life expectancy in males, the differential mortality from diseases of the digestive system (mainly due to cirrhosis of the liver), accidents (from both motor vehicle and non-motor vehicle accidents), and infectious and parasitic disease contributed half (50%) of the gap in life expectancy. In females, the above primarily preventable causes of deaths accounted for 41% of the life expectancy gap. CONCLUSIONS: Based on the findings of this study, we suggest that future focus should be in the area of primary prevention in order to reduce the incidence of infectious and parasitic diseases, liver cirrhosis, and accidents.
MED-3977
Survival following an acute coronary syndrome: a pet theory put to the test.
OBJECTIVE: The aim of this study was to revisit findings from previous studies reporting that pet ownership improves outcome following an admission for acute coronary syndrome (ACS). METHOD: Four hundred and twenty-four patients admitted to a cardiac unit with an ACS completed questions regarding pet ownership in hospital. Rates of cardiac death and readmission were assessed 1 year following hospitalization. RESULTS: Pet owners were more likely to experience a death or readmission following their hospitalization, after controlling for key psychosocial and medical covariates. When dog and cat owners were considered separately, cat ownership was significantly associated with increased risk of death or readmission. CONCLUSION: In this independent study, pet ownership at baseline, and cat ownership in particular, was associated with increased cardiac morbidity and mortality in the year following an admission for an acute coronary syndrome, a finding contrary to previous reports.
MED-2677
Biological Clues to Potent DNA-Damaging Activities in Food and Flavoring
Population differences in age-related diseases and cancer could stem from differences in diet. To characterize DNA strand-breaking activities in selected foods/beverages, flavorings, and some of their constituent chemicals, we used p53R cells, a cellular assay sensitive to such breaks. Substances testing positive included reference chemicals: quinacrine (peak response, 51X) and etoposide (33X); flavonoids: EGCG (19X), curcumin (12X), apigenin (9X), and quercetin (7X); beverages: chamomile (11X), green (21X), and black tea (26X) and coffee (3 to 29X); and liquid smoke (4 to 28X). Damage occurred at dietary concentrations: etoposide near 5 μg/ml produced responses similar to a 1:1000 dilution of liquid smoke, a 1:20 dilution of coffee, and a 1:5 dilution of tea. Pyrogallol-related chemicals and tannins are present in dietary sources and individually produced strong activity: pyrogallol (30X), 3-methoxycatechol (25X), gallic acid (21X), and 1,2,4-benzenetriol (21X). From structure-activity relationships, high activities depended on specific orientations of hydroxyls on the benzene ring. Responses accompanied cellular signals characteristic of DNA breaks such as H2AX phosphorylation. Breaks were also directly detected by comet assay. Cellular toxicological effects of foods and flavorings could guide epidemiologic and experimental studies of potential disease risks from DNA strand-breaking chemicals in diets.
MED-5135
West syndrome in an infant with vitamin B12 deficiency in the absence of macrocytic anaemia.
Vitamin B(12) deficiency in infants often produces haematological and neurological deficits, including macrocytic anaemia, neurodevelopmental delay or regression, irritability, weakness, hypotonia, ataxia, apathy, tremor, and seizures. The diagnosis of vitamin B(12) deficiency can be difficult when the typical macrocytic anaemia is absent. We report the case of a 10-month-old female diagnosed with West syndrome associated with vitamin B(12) deficiency but without macrocytic anaemia caused by nutritional inadequacy in the mother. The patient's motor skills and cognitive development were normal until she was 9 months old, when she began to exhibit a series of sudden flexions of the head, trunk, arms, and legs. She was exclusively breast-fed and had received no vitamin supplementation. Results of electroencephalography (EEG) indicated modified hypsarrhythmia and the patient was diagnosed as having West syndrome. Synthetic adrenocorticotropic hormone was administered and although her spasms had resolved, the patient remained apathic and could not sit without assistance. EEG results indicated generalized slow activity. After she was diagnosed as having vitamin B(12) deficiency, parenteral treatment with vitamin B(12) was initiated. Her symptoms resolved and EEG was completely normal. When she was 20 months old she exhibited an age-appropriate developmental and neurological profile. To our knowledge, this is the first report of West syndrome as a presenting symptom of vitamin B(12) deficiency.
MED-2235
Bioavailability and inter-conversion of sulforaphane and erucin in human subjects consuming broccoli sprouts or broccoli supplement in a cross-over study design
Broccoli consumption may reduce the risk of various cancers and many broccoli supplements are now available. The bioavailability and excretion of the mercapturic acid pathway metabolites isothiocyanates after human consumption of broccoli supplements has not been tested. Two important isothiocyanates from broccoli are sulforaphane and erucin. We employed a cross-over study design in which 12 subjects consumed 40 grams of fresh broccoli sprouts followed by a 1 month washout period and then the same 12 subjects consumed 6 pills of a broccoli supplement. As negative controls for isothiocyanate consumption four additional subjects consumed alfalfa sprouts during the first phase and placebo pills during the second. Blood and urine samples were collected for 48 hours during each phase and analyzed for sulforaphane and erucin metabolites using LC-MS/MS. The bioavailability of sulforaphane and erucin is dramatically lower when subjects consume broccoli supplements compared to fresh broccoli sprouts. The peaks in plasma concentrations and urinary excretion were also delayed when subjects consumed the broccoli supplement. GSTP1 polymorphisms did not affect the metabolism or excretion of sulforaphane or erucin. Sulforaphane and erucin are able to interconvert in vivo and this interconversion is consistent within each subject but variable between subjects. This study confirms that consumption of broccoli supplements devoid of myrosinase activity does not produce equivalent plasma concentrations of the bioactive isothiocyanate metabolites compared to broccoli sprouts. This has implications for people who consume the recommended serving size (1 pill) of a broccoli supplement and believe they are getting equivalent doses of isothiocyanates.
MED-3945
International multidimensional authenticity specification (IMAS) algorithm for detection of commercial pomegranate juice adulteration.
The pomegranate fruit ( Punica granatum ) has become an international high-value crop for the production of commercial pomegranate juice (PJ). The perceived consumer value of PJ is due in large part to its potential health benefits based on a significant body of medical research conducted with authentic PJ. To establish criteria for authenticating PJ, a new International Multidimensional Authenticity Specifications (IMAS) algorithm was developed through consideration of existing databases and comprehensive chemical characterization of 45 commercial juice samples from 23 different manufacturers in the United States. In addition to analysis of commercial juice samples obtained in the United States, data from other analyses of pomegranate juice and fruits including samples from Iran, Turkey, Azerbaijan, Syria, India, and China were considered in developing this protocol. There is universal agreement that the presence of a highly constant group of six anthocyanins together with punicalagins characterizes polyphenols in PJ. At a total sugar concentration of 16 degrees Brix, PJ contains characteristic sugars including mannitol at >0.3 g/100 mL. Ratios of glucose to mannitol of 4-15 and of glucose to fructose of 0.8-1.0 are also characteristic of PJ. In addition, no sucrose should be present because of isomerase activity during commercial processing. Stable isotope ratio mass spectrometry as > -25 per thousand assures that there is no added corn or cane sugar added to PJ. Sorbitol was present at <0.025 g/100 mL; maltose and tartaric acid were not detected. The presence of the amino acid proline at >25 mg/L is indicative of added grape products. Malic acid at >0.1 g/100 mL indicates adulteration with apple, pear, grape, cherry, plum, or aronia juice. Other adulteration methods include the addition of highly concentrated aronia, blueberry, or blackberry juices or natural grape pigments to poor-quality juices to imitate the color of pomegranate juice, which results in abnormal anthocyanin profiles. To adjust the astringent taste of poor-quality juice or peel extract, addition of nonpomegranate sugars is a commonly detected adulteration method. The profile generated from these analyses combined with information from existing databases and published literature has been integrated into a validated IMAS for PJ, which can be utilized to detect PJ adulteration. In this survey of commercial pomegranate juices, only 6 of 23 strictly met all of the IMAS criteria.
MED-845
Boric acid inhibits embryonic histone deacetylases: a suggested mechanism to explain boric acid-related teratogenicity.
Histone deacetylases (HDAC) control gene expression by changing histonic as well as non histonic protein conformation. HDAC inhibitors (HDACi) are considered to be among the most promising drugs for epigenetic treatment for cancer. Recently a strict relationship between histone hyperacetylation in specific tissues of mouse embryos exposed to two HDACi (valproic acid and trichostatin A) and specific axial skeleton malformations has been demonstrated. The aim of this study is to verify if boric acid (BA), that induces in rodents malformations similar to those valproic acid and trichostatin A-related, acts through similar mechanisms: HDAC inhibition and histone hyperacetylation. Pregnant mice were treated intraperitoneally with a teratogenic dose of BA (1000 mg/kg, day 8 of gestation). Western blot analysis and immunostaining were performed with anti hyperacetylated histone 4 (H4) antibody on embryos explanted 1, 3 or 4 h after treatment and revealed H4 hyperacetylation at the level of somites. HDAC enzyme assay was performed on embryonic nuclear extracts. A significant HDAC inhibition activity (compatible with a mixed type partial inhibition mechanism) was evident with BA. Kinetic analyses indicate that BA modifies substrate affinity by a factor alpha=0.51 and maximum velocity by a factor beta=0.70. This work provides the first evidence for HDAC inhibition by BA and suggests such a molecular mechanism for the induction of BA-related malformations.
MED-2723
Health and economic burden of the projected obesity trends in the USA and the UK.
Rising prevalence of obesity is a worldwide health concern because excess weight gain within populations forecasts an increased burden from several diseases, most notably cardiovascular diseases, diabetes, and cancers. In this report, we used a simulation model to project the probable health and economic consequences in the next two decades from a continued rise in obesity in two ageing populations--the USA and the UK. These trends project 65 million more obese adults in the USA and 11 million more obese adults in the UK by 2030, consequently accruing an additional 6-8·5 million cases of diabetes, 5·7-7·3 million cases of heart disease and stroke, 492,000-669,000 additional cases of cancer, and 26-55 million quality-adjusted life years forgone for USA and UK combined. The combined medical costs associated with treatment of these preventable diseases are estimated to increase by $48-66 billion/year in the USA and by £1·9-2 billion/year in the UK by 2030. Hence, effective policies to promote healthier weight also have economic benefits. Copyright © 2011 Elsevier Ltd. All rights reserved.
MED-2356
The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose
Background In 2009, we reported a novel form of delayed anaphylaxis to red meat, which is related to serum IgE antibodies to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal). Most of these patients had tolerated meat for many years previously. The implication is that some exposure in adult life had stimulated the production of these IgE antibodies. Objectives To investigate possible causes of this IgE antibody response, focusing on evidence related to tick bites, which are common in the region where these reactions occur. Methods Serum assays were carried out using biotinylated proteins and extracts bound to a streptavidin ImmunoCAP. Results Prospective studies on IgE antibodies in three subjects following tick bites showed an increase in IgE to alpha-gal of twenty-fold or greater. Other evidence included i) a strong correlation between histories of tick bites and IgE to alpha-gal (χ2=26.8, p<0.001), ii) evidence that these IgE antibodies are common in areas where the tick Amblyomma americanum is common, and iii) a significant correlation between IgE antibodies to alpha-gal and IgE antibodies to proteins derived from A. americanum (rs=0.75, p<0.001). Conclusion The results presented here provide evidence that tick bites are a cause, or possibly the only cause, of IgE specific for alpha-gal in this area of the United States. Both the number of subjects becoming sensitized and the titer of IgE antibodies to alpha-gal are striking. Here we report the first example of a response to an ectoparasite giving rise to an important form of food allergy.
MED-4342
Animal protein intake and risk of inflammatory bowel disease: The E3N prospective study.
OBJECTIVES: Diet composition has long been suspected to contribute to inflammatory bowel disease (IBD), but has not been thoroughly assessed, and has been assessed only in retrospective studies that are prone to recall bias. The aim of the present study was to evaluate the role of dietary macronutrients in the etiology of IBD in a large prospective cohort. METHODS: The Etude Épidémiologique des femmes de la Mutuelle Générale de l'Education Nationale cohort consists of women living in France, aged 40-65 years, and free of major diseases at inclusion. A self-administered questionnaire was used to record dietary habits at baseline. Questionnaires on disease occurrence and lifestyle factors were completed every 24 months. IBDs were assessed in each questionnaire until June 2005, and subsequently validated using clinical and pathological criteria. We estimated the association between nutrients or foods and IBD using Cox proportional hazards models adjusted for energy intake. RESULTS: Among 67,581 participants (705,445 person-years, mean follow-up since completion of the baseline dietary questionnaire 10.4 years), we validated 77 incident IBD cases. High total protein intake, specifically animal protein, was associated with a significantly increased risk of IBD, (hazards ratio for the third vs. first tertile and 95% confidence interval being 3.31 and 1.41-7.77 (P trend=0.007), and 3.03 and 1.45-6.34 (P trend=0.005) for total and animal protein, respectively). Among sources of animal protein, high consumption of meat or fish but not of eggs or dairy products was associated with IBD risk. CONCLUSIONS: High protein intake is associated with an increased risk of incident IBD in French middle-aged women.
MED-4819
Mortality from malignant diseases-update of the Baltimore union poultry cohort.
We previously studied mortality up to 1989 in 2,639 members of a local union who had ever worked in poultry slaughtering and processing plants, because they were exposed to oncogenic viruses present in poultry. In this report, cancer mortality was updated to the year 2003 for 2,580 of the 2,639 subjects who worked exclusively in poultry plants. Mortality in poultry workers was compared with that in the US general population through the estimation of proportional mortality and standardized mortality ratios separately for each race/sex group and for the whole cohort. Compared to the US general population, an excess of cancers of the buccal and nasal cavities and pharynx (base of the tongue, palate and other unspecified mouth, tonsil and oropharynx, nasal cavity/middle ear/accessory sinus), esophagus, recto-sigmoid/rectum/anus, liver and intrabiliary system, myelofibrosis, lymphoid leukemia and multiple myeloma was observed in particular subgroups or in the entire poultry cohort. We hypothesize that oncogenic viruses present in poultry, and exposure to fumes, are candidates for an etiologic role to explain the excess occurrence of at least some of these cancers in the poultry workers. Larger studies which can control for confounding factors are urgently needed to determine the significance of these findings.
MED-5131
Vitamin B12 sources and bioavailability.
The usual dietary sources of vitamin B(12) are animal foods, meat, milk, egg, fish, and shellfish. As the intrinsic factor-mediated intestinal absorption system is estimated to be saturated at about 1.5-2.0 microg per meal under physiologic conditions, vitamin B(12) bioavailability significantly decreases with increasing intake of vitamin B(12) per meal. The bioavailability of vitamin B(12) in healthy humans from fish meat, sheep meat, and chicken meat averaged 42%, 56%-89%, and 61%-66%, respectively. Vitamin B(12) in eggs seems to be poorly absorbed (< 9%) relative to other animal food products. In the Dietary Reference Intakes in the United States and Japan, it is assumed that 50% of dietary vitamin B(12) is absorbed by healthy adults with normal gastro-intestinal function. Some plant foods, dried green and purple lavers (nori) contain substantial amounts of vitamin B(12), although other edible algae contained none or only traces of vitamin B(12). Most of the edible blue-green algae (cyanobacteria) used for human supplements predominantly contain pseudovitamin B(12), which is inactive in humans. The edible cyanobacteria are not suitable for use as vitamin B(12) sources, especially in vegans. Fortified breakfast cereals are a particularly valuable source of vitamin B(12) for vegans and elderly people. Production of some vitamin B(12)-enriched vegetables is also being devised.
MED-3535
Cherries and health: a review.
Cherries, and in particular sweet cherries, are a nutritionally dense food rich in anthocyanins, quercetin, hydroxycinnamates, potassium, fiber, vitamin C, carotenoids, and melatonin. UV concentration, degree of ripeness, postharvest storage conditions, and processing, each can significantly alter the amounts of nutrients and bioactive components. These constituent nutrients and bioactive food components support the potential preventive health benefits of cherry intake in relation to cancer, cardiovascular disease, diabetes, inflammatory diseases, and Alzheimer's disease. Mechanistically, cherries exhibit relatively high antioxidant activity, low glycemic response, COX 1 and 2 enzyme inhibition, and other anti-carcinogenic effects in vitro and in animal experiments. Well-designed cherry feeding studies are needed to further substantiate any health benefits in humans.
MED-955
Comparative assessment of human exposure to phthalate esters from house dust in China and the United States.
Because of volatilization and leaching from their application in consumer and personal care products, phthalate esters are ubiquitous contaminants in the indoor environment. In this study, we measured concentrations and profiles of 9 phthalate esters in indoor dust samples collected from six cities in China (n = 75). For comparison, we also analyzed samples collected from Albany, New York, USA (n = 33). The results indicated that concentrations, except for dicyclohexyl phthalate (DCHP) and bis(2-ethylhexyl) phthalate (DEHP), and profiles of phthalate esters varied significantly between the two countries. Concentrations of diethyl phthalate (DEP), di-n-hexyl phthalate (DNHP), and benzyl butyl phthalate (BzBP) were 5 to 10 times higher in dust samples collected from Albany than those from the Chinese cities. In contrast, concentrations of di-iso-butyl phthalate (DIBP) in dust samples from Albany were 5 times lower than those from the Chinese cities. We estimated the daily intake (DI) of phthalate esters through the routes of dust ingestion and dermal dust absorption. The extent of contribution of indoor dust to human exposures varied, depending on the type of phthalate esters. The contribution of dust to DEHP exposure was 2-5% and 10-58% of the estimated total DIs in China and the USA, respectively. On the basis of the estimates of total DIs of phthalates, extrapolated from urinary metabolite concentrations, the contributions of inhalation, dermal absorption, and dietary intake to total DIs were estimated. The results indicated that dietary intake is the main source of exposure to DEHP (especially in China), whereas dermal exposure was a major source for DEP. This is the first study to elucidate sources of human exposure to phthalates among the general population in China.
MED-1511
Sedentary time and cardio-metabolic biomarkers in US adults: NHANES 2003–06
Aims Prolonged sedentary time is ubiquitous in developed economies and is associated with an adverse cardio-metabolic risk profile and premature mortality. This study examined the associations of objectively assessed sedentary time and breaks (interruptions) in sedentary time with continuous cardio-metabolic and inflammatory risk biomarkers, and whether these associations varied by sex, age, and/or race/ethnicity. Methods and results Cross-sectional analyses with 4757 participants (≥20 years) from the 2003/04 and 2005/06 US National Health and Nutrition Examination Survey (NHANES). An Actigraph accelerometer was used to derive sedentary time [<100 counts per minute (cpm)] and breaks in sedentary time. Independent of potential confounders, including moderate-to-vigorous exercise, detrimental linear associations (P for trends <0.05) of sedentary time with waist circumference, HDL-cholesterol, C-reactive protein, triglycerides, insulin, HOMA-%B, and HOMA-%S were observed. Independent of potential confounders and sedentary time, breaks were beneficially associated with waist circumference and C-reactive protein (P for trends <0.05). There was limited evidence of meaningful differences in associations with biomarkers by age, sex, or race/ethnicity. Notable exceptions were sex-differences in the associations of sedentary time and breaks with HDL-cholesterol, and race/ethnicity differences in the association of sedentary time with waist circumference with associations detrimental in non-Hispanic whites, null in Mexican Americans, and beneficial in non-Hispanic blacks. Conclusion These are the first population-representative findings on the deleterious associations of prolonged sedentary time with cardio-metabolic and inflammatory biomarkers. The findings suggest that clinical communications and preventive health messages on reducing and breaking up sedentary time may be beneficial for cardiovascular disease risk.
MED-3278
Sniffer dogs as part of a bimodal bionic research approach to develop a lung cancer screening
Lung cancer (LC) continues to represent a heavy burden for health care systems worldwide. Epidemiological studies predict that its role will increase in the near future. While patient prognosis is strongly associated with tumour stage and early detection of disease, no screening test exists so far. It has been suggested that electronic sensor devices, commonly referred to as ‘electronic noses’, may be applicable to identify cancer-specific volatile organic compounds in the breath of patients and therefore may represent promising screening technologies. However, three decades of research did not bring forward a clinically applicable device. Here, we propose a new research approach by involving specially trained sniffer dogs into research strategies by making use of their ability to identify LC in the breath sample of patients.
MED-1521
Effects of peppermint teas on plasma testosterone, follicle-stimulating hormone, and luteinizing hormone levels and testicular tissue in rats.
OBJECTIVES: To justify the effects of Mentha piperita labiatae and Mentha spicata labiatae herbal teas on plasma total testosterone, luteinizing hormone, and follicle-stimulating hormone levels and testicular histologic features. We performed this study because of major complaints in our area from men about the adverse effects of these herbs on male reproductive function. METHODS: The experimental study included 48 male Wistar albino rats (body weight 200 to 250 g). The rats were randomized into four groups of 12 rats each. The control group was given commercial drinking water, and the experimental groups were given 20 g/L M. piperita tea, 20 g/L M. spicata tea, or 40 g/L M. spicata tea. RESULTS: The follicle-stimulating hormone and luteinizing hormone levels had increased and total testosterone levels had decreased in the experimental groups compared with the control group; the differences were statistically significant. Also, the Johnsen testicular biopsy scores were significantly different statistically between the experimental groups and the control group. Although the mean seminiferous tubular diameter of the experimental groups was relatively greater than in the control group, the difference was not statistically significant. The only effects of M. piperita on testicular tissue was segmental maturation arrest in the seminiferous tubules; however, the effects of M. spicata extended from maturation arrest to diffuse germ cell aplasia in relation to the dose. CONCLUSIONS: Despite the beneficial effects of M. piperita and M. spicata in digestion, we should also be aware of the toxic effects when the herbs are not used in the recommended fashion or at the recommended dose.
MED-839
Omega-3 fatty acids for nutrition and medicine: considering microalgae oil as a vegetarian source of EPA and DHA.
Long-chain EPA/DHA omega-3 fatty acid supplementation can be co-preventative and co-therapeutic. Current research suggests increasing accumulated long chain omega-3s for health benefits and as natural medicine in several major diseases. But many believe plant omega-3 sources are nutritionally and therapeutically equivalent to the EPA/DHA omega-3 in fish oil. Although healthy, precursor ALA bio-conversion to EPA is inefficient and production of DHA is nearly absent, limiting the protective value of ALA supplementation from flax-oil, for example. Along with pollutants certain fish acquire high levels of EPA/DHA as predatory species. However, the origin of EPA/DHA in aquatic ecosystems is algae. Certain microalgae produce high levels of EPA or DHA. Now, organically produced DHA-rich microalgae oil is available. Clinical trials with DHA-rich oil indicate comparable efficacies to fish oil for protection from cardiovascular risk factors by lowering plasma triglycerides and oxidative stress. This review discusses 1) omega-3 fatty acids in nutrition and medicine; 2) omega-3s in physiology and gene regulation; 3) possible protective mechanisms of EPA/DHA in major diseases such as coronary heart disease, atherosclerosis, cancer and type 2 diabetes; 4) EPA and DHA requirements considering fish oil safety; and 5) microalgae EPA and DHA-rich oils and recent clinical results.
MED-2601
Curcumin induces apoptosis in human non-small cell lung cancer NCI-H460 cells through ER stress and caspase cascade- and mitochondria-dependent pat...
It has been reported that curcumin inhibited various types of cancer cells in vitro and in vivo. However, mechanisms of curcumin-inhibited cell growth and -induced apoptosis in human non-small cell lung cancer cells (NCI-H460) still remain unclear. In this study, NCI-H460 cells were treated with curcumin to determine its anticancer activity. Different concentrations of curcumin were used for different durations in NCI-H460 cells and the subsequent changes in the cell morphology, viability, cell cycle, mRNA and protein expressions were determined. Curcumin induced apoptotic morphologic changes in NCI-H460 cells in a dose-dependent manner. After curcumin treatment, BAX and BAD were up-regulated, BCL-2, BCL-X(L) and XIAP were down-regulated. In addition, reactive oxygen species (ROS), intracellular Ca(2+) and endoplasmic reticulum (ER) stress were increased in NCI-H460 cells after exposure to curcumin. These signals led to a loss of mitochondrial membrane potential (Delta Psi(m)) and culminated in caspase-3 activation. Curcumin-induced apoptosis was also stimulated through the FAS/caspase-8 (extrinsic) pathway and ER stress proteins, growth arrest- and DNA damage-inducible gene 153 (GADD153) and glucose-regulated protein 78 (GRP78) were activated in the NCI-H460 cells. Apoptotic cell death induced by curcumin was significantly reversed by pretreatment with ROS scavenger or caspase-8 inhibitor. Furthermore, the NCI-H460 cells tended to be arrested at the G(2)/M cell cycle stage after curcumin treatment and down-regulation of cyclin-dependent kinase 1 (CDK1) may be involved. In summary, curcumin exerts its anticancer effects on lung cancer NCI-H460 cells through apoptosis or cell cycle arrest.
MED-2077
Platelet dysfunction in vascular pathologies and how can it be treated.
Cardiovascular diseases are one of the leading causes of morbidity and mortality in industrialized countries, and although many processes play a role in the development of vascular disease, thrombosis is the primary event that precipitates stroke and acute coronary syndromes. The blood platelets are of significant importance in medicine. These cells are involved in many physiological processes, particularly haemostasis through their ability to aggregate and form clots in response to activation. In addition, these dynamic cells display activities that extend beyond thrombosis, including an important role in initiating and sustaining vascular inflammation. The expansion of knowledge from basic and clinical research has highlighted the critical position of platelets in several inflammatory diseases such as arthritis and atherosclerosis. Platelets are emerging as important mediators of inflammation and provide important signals to mediate phenotype of other blood and vascular cells. The important role of platelets in arterial thrombosis and the onset of acute myocardial infarction after atherosclerotic plaque rupture make inhibition of platelet aggregation a critical step in preventing thrombotic events associated with stroke, heart attack, and peripheral arterial thrombosis. However, the use of platelet inhibitors for thrombosis prevention must seek a delicate balance between inhibiting platelet activation and an associated increased bleeding risk. The aim of this review is to up-date the knowledge on platelets physiology and dysfunction in pathologies, such as diabetes mellitus, hypercholesterolemia, and hypertension, emphasizing the link between platelets and the inflammation-related atherosclerosis. The review evaluates the opportunities offered by the novel platelet inhibitors to efficiently alleviate the thrombotic events. Copyright © 2011 Elsevier Ltd. All rights reserved.
MED-2078
Dietary components and human platelet activity.
Platelet hyperactivity is one of the most important factors responsible for the incidence of cardiovascular disease. There are many nutritive and non-nutritive compounds present in the diet which may affect platelet function in various ways. Recent discovery of anti-platelet factors in plants, vegetables and fruits provides a new dietary means for a long-term strategy to favorably modify human blood platelet activity. This review summarises the effects of these dietary components on human platelet function both in vitro and in vivo.
MED-3683
Randomised, double-blind and placebo-controlled study using new probiotic lactobacilli for strengthening the body immune defence against viral infe...
BACKGROUND: The aim of this study was to investigate whether consumption of Lactobacillus plantarum HEAL 9 (DSM 15312) and Lactobacillus paracasei 8700:2 (DSM 13434) could affect naturally acquired common cold infections in healthy subjects. METHODS: A randomised, parallel, double-blind placebo-controlled study was performed to investigate whether intake of this probiotic mixture could reduce the risk of common cold episodes, number of days with common cold symptoms, frequency and severity of symptoms, and cellular immune response in common cold infections. A total of 272 subjects were supplemented daily with either 10(9) cfu (colony forming units) of probiotics (N = 135) or control (N = 137) for a 12-week period. RESULTS: The incidence of acquiring one or more common cold episode was reduced from 67% in the control group to 55% in the probiotic group (p < 0.05). Also, the number of days with common cold symptoms were significantly (p < 0.05) reduced from 8.6 days in the control group to 6.2 days, in the probiotic group, during the 12-week period. The total symptom score was reduced during the study period from a mean of 44.4 for the control group to 33.6 for the probiotic group. The reduction in pharyngeal symptoms was significant (p < 0.05). In addition, the proliferation of B lymphocytes was significantly counteracted in the probiotic group (p < 0.05) in comparison with the control group. CONCLUSION: In conclusion, intake of the probiotic strains Lactobacillus plantarum HEAL 9 (DSM 15312) and Lactobacillus paracasei 8700:2 (DSM 13434) reduces the risk of acquiring common cold infections.
MED-2679
Commercial hickory-smoke flavouring is a human lymphoblast mutagen but does not induce lung adenomas in newborn mice.
Commercial aqueous wood-smoke flavouring induced significant increases in the 6-thioguanine resistance mutation frequency of TK6 human lymphoblasts at 0.1 microliter flavouring/ml of cell suspension. This corresponds to 6 micrograms/ml of dissolved 'solids' as determined by fully drying the aqueous flavouring in a vacuum desiccator. In AHH-1 human lymphoblasts, which contain a cytochrome P-450 monooxygenase system, mutations were induced at 0.3 microliter/ml, corresponding to 18 microliters/ml of dissolved 'solids'. The flavouring did not induce 8-azaguanine resistant mutations in Salmonella typhimurium at concentrations up to 1.5 microliter/ml. At higher concentrations the flavouring was toxic to bacteria. The flavouring did not induce lung adenomas or other tumours in newborn mice when injected ip with total doses of up to 26 microliters over a 3-wk period. Toxicity to the kidney, colon and rectum was observed in some mice at 15 wk of age.
MED-4249
Crossover study of diets enriched with virgin olive oil, walnuts or almonds. Effects on lipids and other cardiovascular risk markers.
BACKGROUND AND AIMS: Virgin olive oil (VOO) and nuts are basic components of the Mediterranean diet, a heart-healthy dietary pattern. Nuts have well known cholesterol lowering effects, while evidence is unclear for VOO. We designed a study in hypercholesterolemic patients to assess the effects on serum lipids and other intermediate markers of cardiovascular risk of replacing 40% of the fat in the background diet with VOO, walnuts or almonds. METHODS AND RESULTS: After a 4 week run-in period with a healthy diet, eligible candidates were randomized into three diet sequences in a crossover design, with a common background diet enriched with VOO, walnuts or almonds, lasting 4 weeks each. Outcomes were changes of serum lipids and oxidation and inflammation markers, measured by standard methods. Plasma fatty acids were determined by gas chromatography to assess compliance. In 18 participants completing the study (9 women, mean age 56 y, BMI 25.7 kg/m(2)), LDL-cholesterol was reduced from baseline by 7.3%, 10.8% and 13.4% after the VOO, walnut and almond diets, respectively (P = 0.001, Friedman test). Total cholesterol and LDL/HDL ratios decreased in parallel. LDL-cholesterol decreases were greater than predicted from dietary fatty acid and cholesterol exchanges among diets. No changes of other lipid fractions, oxidation analytes or inflammatory biomarkers were observed. Plasma fatty acid changes after each diet sequence supported good compliance. CONCLUSION: The results confirm the cholesterol lowering properties of nut-enriched diets. They also suggest that phenolic-rich VOO has a cholesterol lowering effect independently of its fatty acid content, which clearly deserves further study. Copyright © 2010 Elsevier B.V. All rights reserved.
MED-2800
Curcumin: a new paradigm and therapeutic opportunity for the treatment of osteoarthritis: curcumin for osteoarthritis management
The management of osteoarthritis represents a real challenge. This complex and multi-factorial disease evolves over decades and requires not only the alleviation of symptoms, i.e. pain and joint function but also the preservation of articular structure without side effects. Nutraceuticals are good candidates for the management of OA due to their safety profile and potential efficacy. However, they are not part of the treatment guidelines and published recommendations. Curcumin is the yellow pigment isolated from the rhizomes of Curcuma longa, commonly known as turmeric. Curcumin is a highly pleiotropic molecule with an excellent safety profile. Strong molecular evidence has been published for its potency to target multiple inflammatory diseases. However, naturally occurring curcumin cannot achieve its optimum therapeutic outcomes due to its low solubility and poor bioavailability. Nevertheless, curcumin presents great potential for treating OA and has been categorized as having preclinical evidence of efficacy. This review aimed at gathering most of the available information to document the potential efficacy of curcumin based on the results obtained in in vitro models of cartilage and osteoarthritis and in other diseases.
MED-2646
Do fast foods cause asthma, rhinoconjunctivitis and eczema? Global findings from the International Study of Asthma and Allergies in Childhood (ISAA...
BACKGROUND: Certain foods may increase or decrease the risk of developing asthma, rhinoconjunctivitis and eczema. We explored the impact of the intake of types of food on these diseases in Phase Three of the International Study of Asthma and Allergies in Childhood. METHODS: Written questionnaires on the symptom prevalence of asthma, rhinoconjunctivitis and eczema and types and frequency of food intake over the past 12 months were completed by 13-14-year-old adolescents and by the parents/guardians of 6-7-year-old children. Prevalence ORs were estimated using logistic regression, adjusting for confounders, and using a random (mixed) effects model. RESULTS: For adolescents and children, a potential protective effect on severe asthma was associated with consumption of fruit ≥3 times per week (OR 0.89, 95% CI 0.82 to 0.97; OR 0.86, 95% CI 0.76 to 0.97, respectively). An increased risk of severe asthma in adolescents and children was associated with the consumption of fast food ≥3 times per week (OR 1.39, 95% CI 1.30 to 1.49; OR 1.27, 95% CI 1.13 to 1.42, respectively), as well as an increased risk of severe rhinoconjunctivitis and severe eczema. Similar patterns for both ages were observed for regional analyses, and were consistent with gender and affluence categories and with current symptoms of all three conditions. CONCLUSIONS: If the association between fast foods and the symptom prevalence of asthma, rhinoconjunctivitis and eczema is causal, then the findings have major public health significance owing to the rising consumption of fast foods globally.
MED-3279
Chitin synthesis and degradation as targets for pesticide action.
Various pesticides are being used to destabilize, perturb, or inhibit crucial biochemical and physiological targets related to metabolism, growth, development, nervous communication, or behavior in pestiferous organisms. Chitin is an eukaryotic extracellular aminosugar biopolymer, massively produced by most fungal systems and by invertebrates, notably arthropods. Being an integral supportive component in fungal cell wall, insect cuticle, and nematode egg shell, chitin has been considered as a selective target for pesticide action. Throughout the elaborate processes of chitin formation and deposition, only the polymerization events associated with the cell membrane compartment are so far available for chemical interference. Currently, the actinomycetes-derived nucleoside peptide fungicides such as the polyoxins and the insecticidal benzoylaryl ureas have reached commercial pesticide status. The polyoxins and other structurally-related antibiotics like nikkomycins are strong competitive inhibitors of the polymerizing enzyme chitin synthase. The exact biochemical lesion inflicted by the benzoylaryl ureas is still elusive, but a post-polymerization event, such as translocation of chitin chains across the cell membrane, is suggested. Hydrolytic degradation of the chitin polymer is essential for hyphal growth, branching, and septum formation in fungal systems as well as for the normal molting of arthropods. Recently, insect chitinase activity was strongly and specifically suppressed by allosamidin, an actimomycetes-derived metabolite. In part, the defense mechanism in plants against invasion of pathogens is associated with induced chitinases. Chitin, chitosan, and their oligomers are able to act as elicitors which induce enhanced levels of chitinases in various plants. Lectins which bind to N-acetyl-D-glucosamine strongly interfere with fungal and insect chitin synthases. Plant lectins with similar properties may be involved in plant-pathogen interaction inter alia by suppressing fungal invasion.
MED-2300
Exercise and longevity.
Aging is a natural and complex physiological process influenced by many factors, some of which are modifiable. As the number of older individuals continues to increase, it is important to develop interventions that can be easily implemented and contribute to "successful aging". In addition to a healthy diet and psychosocial well-being, the benefits of regular exercise on mortality, and the prevention and control of chronic disease affecting both life expectancy and quality of life are well established. We summarize the benefits of regular exercise on longevity, present the current knowledge regarding potential mechanisms, and outline the main recommendations. Exercise can partially reverse the effects of the aging process on physiological functions and preserve functional reserve in the elderly. Numerous studies have shown that maintaining a minimum quantity and quality of exercise decreases the risk of death, prevents the development of certain cancers, lowers the risk of osteoporosis and increases longevity. Training programs should include exercises aimed at improving cardiorespiratory fitness and muscle function, as well as flexibility and balance. Though the benefits of physical activity appear to be directly linked to the notion of training volume and intensity, further research is required in the elderly, in order to develop more precise recommendations, bearing in mind that the main aim is to foster long-term adherence to physical activity in this growing population. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
MED-4700
Association between manganese superoxide dismutase (MnSOD) Val-9Ala polymorphism and cancer risk - A meta-analysis.
A growing body of evidence suggests that reactive oxygen species (ROS) play an important role in human cancers. Manganese superoxide dismutase (MnSOD) is the major antioxidant in the mitochondria, catalysing the dismutation of superoxide radicals to form hydrogen peroxide. Since the identification of a well-characterised functional polymorphism, Val-9Ala of MnSOD, a number of molecular epidemiological studies have evaluated the association between Val-9Ala and cancer risk. However, the results remain conflicting rather than conclusive. This meta-analysis on 15,320 cancer cases and 19,534 controls from 34 published case-control studies shows no significant overall main effect of MnSOD Val-9Ala on cancer risk. However, we found that the MnSOD 9Ala allele was associated with an increased prostate cancer risk (Val/Ala versus Val/Val: odds ratio (OR)=1.1; 95% confidence intervals (CI): 1.0-1.3; Ala/Ala versus Val/Val: OR=1.3; 95% CI: 1.0-1.6; Val/Ala+Ala/Ala versus Val/Val: OR=1.2; 95% CI, 1.0-1.3). In addition, we found that the MnSOD Ala-9Ala genotype contributed to an increased breast cancer risk in premenopausal women who had low consumption of antioxidants (Ala/Ala versus Val/Ala+Val/Val: OR=2.6, 95% CI: 1.0-6.4 with low vitamin C consumption; OR=2.1, 95%CI: 1.3-3.4 with low vitamin E consumption and OR=2.9, 95%CI: 1.5-5.7 with low carotenoid consumption). These results suggest that the MnSOD Val-9Ala polymorphism may contribute to cancer development through a disturbed antioxidant balance.
MED-3878
Effect of Low-fat Diets on Plasma Levels of NFκB-regulated Inflammatory Cytokines and Angiogenic Factors in Men with Prostate Cancer
Diet, nutritional status, and certain dietary supplements are postulated to influence the development and progression of prostate cancer. Angiogenesis and inflammation are central to tumor growth and progression, but the effect of diet on these processes remains uncertain. We explored changes in 50 plasma cytokines and angiogenic factors (CAFs) in 145 men with prostate cancer enrolled in a pre-operative, randomized controlled phase-II trial with four arms: control (usual diet); low-fat (LF) diet; flaxseed-supplemented (FS) diet; and flaxseed-supplemented, low-fat diet. The mean duration of dietary intervention was 30–31 days. Among the individual arms, the largest number of significant changes (baseline vs pre-operative follow-up) was observed in the LF arm, with 19 CAFs decreasing and one increasing (p<.05). Compared to the control arm, 6 CAFs—including pro-angiogenic factors (stromal-cell derived-1α and myeloid factors (granulocyte-colony-stimulating factor, macrophage colony-stimulating factor — all decreased in the LF arm compared to controls; 3 and 4 CAFs changed in the FS and FS+LF arms, respectively. Weight loss occurred in the LF arms and significantly correlated with VEGF decreases (P <0.001). The CAFs that changed in the LF arm are all known to be regulated by nuclear factor-kappa B (NF-κB), and a pathway analysis identified NF-κB as the most likely regulatory network associated with these changes in the LF arm, but not in the FS-containing arms. These results suggest that a low-fat diet without flaxseed may reduce levels of specific inflammatory cytokines and angiogenic factors and suggests that the NF-κB pathway may be a mediator of these changes.
MED-4384
Glaucoma risk and the consumption of fruits and vegetables among older women in the study of osteoporotic fractures.
PURPOSE: To explore the association between the consumption of fruits and vegetables and the presence of glaucoma. DESIGN: Cross-sectional cohort study. METHODS: In a sample of 1,155 women located in multiple centers in the United States, glaucoma specialists diagnosed glaucoma in at least one eye by assessing optic nerve head photographs and 76-point suprathreshold screening visual fields. Consumption of fruits and vegetables was assessed using the Block Food Frequency Questionnaire. The relationship between selected fruit and vegetable consumption and glaucoma was investigated using adjusted logistic regression models. RESULTS: Among 1,155 women, 95 (8.2%) were diagnosed with glaucoma. In adjusted analysis, the odds of glaucoma risk were decreased by 69% (odds ratio [OR], 0.31; 95% confidence interval [CI], 0.11 to 0.91) in women who consumed at least one serving per month of green collards and kale compared with those who consumed fewer than one serving per month, by 64% (OR, 0.36; 95% CI, 0.17 to 0.77) in women who consumed more than two servings per week of carrots compared with those who consumed fewer than one serving per week, and by 47% (OR, 0.53; 95% CI, 0.29 to 0.97) in women who consumed at least one serving per week of canned or dried peaches compared with those who consumed fewer than one serving per month. CONCLUSIONS: A higher intake of certain fruits and vegetables may be associated with a decreased risk of glaucoma. More studies are needed to investigate this relationship.
MED-5041
Does Flavanol Intake Influence Mortality from Nitric Oxide-Dependent Processes? Ischemic Heart Disease, Stroke, Diabetes Mellitus, and Cancer in Panama
Substantial data suggest that flavonoid-rich food could help prevent cardiovascular disease and cancer. Cocoa is the richest source of flavonoids, but current processing reduces the content substantially. The Kuna living in the San Blas drink a flavanol-rich cocoa as their main beverage, contributing more than 900 mg/day and thus probably have the most flavonoid-rich diet of any population. We used diagnosis on death certificates to compare cause-specific death rates from year 2000 to 2004 in mainland and the San Blas islands where only Kuna live. Our hypothesis was that if the high flavanoid intake and consequent nitric oxide system activation were important the result would be a reduction in the frequency of ischemic heart disease, stroke, diabetes mellitus, and cancer – all nitric oxide sensitive processes. There were 77,375 deaths in mainland Panama and 558 deaths in the San Blas. In mainland Panama, as anticipated, cardiovascular disease was the leading cause of death (83.4 ± 0.70 age adjusted deaths/100,000) and cancer was second (68.4 ± 1.6). In contrast, the rate of CVD and cancer among island-dwelling Kuna was much lower (9.2 ± 3.1) and (4.4 ± 4.4) respectively. Similarly deaths due to diabetes mellitus were much more common in the mainland (24.1 ± 0.74) than in the San Blas (6.6 ± 1.94). This comparatively lower risk among Kuna in the San Blas from the most common causes of morbidity and mortality in much of the world, possibly reflects a very high flavanol intake and sustained nitric oxide synthesis activation. However, there are many risk factors and an observational study cannot provide definitive evidence.
MED-1013
Quality of life in patients with irritable bowel syndrome.
There has been an underestimation of the impact of irritable bowel syndrome (IBS) on an individual's functioning and quality of life (QoL). The general health status of both young and elderly individuals with IBS is generally found to be poorer than that of the general population. Patients with IBS seem to have worse health-related quality of life (HRQoL) than patients with certain other conditions such as gastroesophageal reflux disease, diabetes, and end-stage renal disease. Various disease-specific instruments are now available and are widely used in clinical trials to measure changes in QoL in patients with IBS after treatment intervention. Although few such data are presently available from clinical trials, it seems that patients who have a therapeutic response to therapy for IBS have a corresponding improvement in HRQoL. There seems to be no major differences in HRQoL based on IBS subtype (constipation-dominant or diarrhea-dominant). However, the severity of bowel symptoms in IBS is associated with a corresponding impact on HRQoL and patients with worse bowel symptoms have a greater diminished QoL compared with patients with milder symptoms. Evidence also indicates that HRQoL in patients with IBS is affected by sex and psychological conditions. Careful consideration of these factors may help to individualize a therapeutic strategy to optimize long-term outcomes.
MED-4028
Dietary advice in dental practice.
This paper aims to provide dental health professionals with practical advice to pass on to patients about diet and dental health. Sugars are the most important dietary factor contributing to dental caries. Different foods carry different dental health risks; those containing non-milk, extrinsic sugars are potentially the most damaging. In the UK, sugared soft drinks and confectionery contribute approximately 50% to total intake of non-milk extrinsic sugars. Patients should be encouraged to reduce the frequency of intake of sugary foods. Intake of acidic foods and drinks contributes to dental erosion and consumption of such foods should also be limited. Dietary advice to dental patients should be positive and personalized if possible and can be in line with dietary recommendations for general health. These are to increase the consumption of starchy staple foods (eg bread, potatoes and unsweetened cereals), vegetables and fruit and to reduce the consumption of sugary and fatty foods.
MED-3275
The Effect of Replacement of Methionine by Homocystine on Survival of Malignant and Normal Adult Mammalian Cells in Culture
In tissue cultures of normal adult and malignant mammalian cells, homocystine has been substituted for methionine in a medium rich in folic acid and cyanocobalamin. Normal adult cells thrive. Three highly malignant cell types from three different species, including man, die.
MED-4358
Bacteriophage biocontrol in animals and meat products
Summary Since their discovery almost a century ago, bacterial viruses (bacteriophages or ‘phages’) have been used to prevent and treat a multitude of bacterial infections (phage therapy: PT). In addition, they have been the basis for many advances in genetics and biochemistry. Phage therapy was performed on human subjects in the United States, Europe and Asia in the few decades following their discovery. However, Western countries largely abandoned PT in favour of antibiotics in the 1940s. The relatively recent renaissance of PT in the West can be attributed partly to the increasing prevalence of antibiotic resistance in human and animal pathogens. However, the stringent controls on human trials now required in the United States and Europe have led to a greater number of domestic animal and agricultural applications as an alternative to PT in man. This trend is set to continue, at least in the short term, with recent approval from the Food and Drug Administration allowing commercial phage treatments to be used in human food in the USA. Nevertheless, despite these significant milestones and the growing number of successful PT trials, significant obstacles remain to their widespread use in animals, food and ultimately medicine in many parts of the world. This review will provide a brief overview of the history of PT in the West and will summarize some of the key findings of phage biocontrol studies in animals and meat products.
MED-4239
A low-fat diet and/or strenuous exercise alters the IGF axis in vivo and reduces prostate tumor cell growth in vitro.
BACKGROUND: Prostate cancer is the most common solid-tumor cancer in US males but is rare in Asian males. When Asian men adopt the US lifestyle, clinical prostate cancer increases greatly. Epidemiological data from men in the US indicate that regular activity may reduce the risk for prostate cancer. METHODS: Serum was obtained from three groups of similar-aged men, Control, Diet and Exercise, and Exercise alone were used to stimulate LNCaP cells in culture. Growth and apoptosis of tumor cells were measured. Serum samples were also used to measure insulin, IGF-1, IGFBP-1. RESULTS: The Diet and Exercise and the Exercise alone groups had lower serum insulin and IGF-1 but higher IGFBP-1 compared to Controls. LNCaP cell growth was reduced in both groups compared to Control and there was a major increase in apoptosis of tumor cells. CONCLUSIONS: A low-fat diet and/or intensive exercise results in change in serum hormones and growth factors in vivo that can reduce growth and induce apoptosis of LNCaP prostate tumor cells in vitro. Copyright 2003 Wiley-Liss, Inc.
MED-4606
Does potassium sorbate induce genotoxic or mutagenic effects in lymphocytes?
The present study evaluates the genotoxic potential of potassium sorbate (PS) in cultured and isolated human lymphocytes. To assess the damage caused by PS in humans, we designed in vitro experiments by measuring chromosomal aberrations (CAs), sister-chromatid exchanges (SCEs), micronucleus (MN) and comet assays. Lymphocytes were treated with negative control (sterile distilled water), positive control (MMC for cultured lymphocytes, and H(2)O(2) for isolated lymphocytes) and four concentrations (125, 250, 500, and 1000 microg/ml) of PS. According to the results, PS treatment significantly increases the CAs (with or without gaps at 500 and 1000 microg/ml concentrations) and SCEs (at 250, 500, 1000 microg/ml for 24h and 125, 250, 500, 1000 microg/ml for 48h) compared with vehicle control. Following treatment of the isolated lymphocytes for 1h, significant PS-induced DNA strand breaks were observed, at all concentrations. However, PS failed to significantly affect the MN assay. On the contrary, PS does not cause cell cycle delay as noted by the non-significant decrease in the cytokinesis-block proliferation index (CBPI) and replicative index (RI). Only a slight decrease was observed in the mitotic index (MI) at the highest concentration for both treatment times. From the results, PS is clearly seen to be genotoxic to the human peripheral blood lymphocytes in vitro. Copyright (c) 2009 Elsevier Ltd. All rights reserved.
MED-4166
Concentrations of antibiotic residues vary between different edible muscle tissues in poultry.
Antibiotics are used by veterinarians and producers to treat disease and improve animal production. The federal government, to ensure the safety of the food supply, establishes antibiotic residue tolerances in edible animal tissues and determines the target tissues (e.g., muscle) for residue monitoring. However, when muscle is selected as the target tissue, the federal government does not specify which type of muscle tissue is used for monitoring (e.g., breast versus thigh). If specific muscle tissues incorporate residues at higher concentrations, these tissues should be selected for residue monitoring. To evaluate this possibility in poultry, chickens were divided into four groups and at 33 days of age were dosed with enrofloxacin (Baytril), as per label directions, at either 25 ppm for 3 days, 25 ppm for 7 days, 50 ppm for 3 days, or 50 ppm for 7 days. Breast and thigh muscle tissues were collected from each bird (n = 5 birds per day per group) during the dosing and withdrawal period, and fluoroquinolone concentrations were determined. The results indicate higher overall enrofloxacin concentrations in breast versus thigh muscle for each treatment group (P < 0.05). These data indicate, at least for enrofloxacin, that not all muscle tissues incorporate antibiotics at the same concentrations. These results may be helpful to regulatory agencies as they determine what tissues are to be monitored to ensure that the established residue safety tolerance levels are not exceeded.
MED-3013
Reducing the staggering costs of environmental disease in children, estimated at $76.6 billion in 2008.
A 2002 analysis documented $54.9 billion in annual costs of environmentally mediated diseases in US children. However, few important changes in federal policy have been implemented to prevent exposures to toxic chemicals. We therefore updated and expanded the previous analysis and found that the costs of lead poisoning, prenatal methylmercury exposure, childhood cancer, asthma, intellectual disability, autism, and attention deficit hyperactivity disorder were $76.6 billion in 2008. To prevent further increases in these costs, efforts are needed to institute premarket testing of new chemicals; conduct toxicity testing on chemicals already in use; reduce lead-based paint hazards; and curb mercury emissions from coal-fired power plants.
MED-1819
Potentiation of gemcitabine by Turmeric Force in pancreatic cancer cell lines.
Gemcitabine is a first line cancer drug widely used for the treatment of pancreatic cancer. However, its therapeutic efficiency is significantly limited by resistance of pancreatic cancer cells to this and other chemotherapeutic drugs. We have investigated the cytotoxic effect of Turmeric Force (TF), a supercritical and hydroethanolic extract of turmeric, alone and in combination with gemcitabine in two pancreatic carcinoma cell lines (BxPC3 and Panc-1). TF is highly cytotoxic to BxPC3 and Panc-1 cell lines with IC50 values of 1.0 and 1.22 microg/ml, respectively with superior cytotoxicity than curcumin. Gemcitabine IC50 value for both of these cell line is 0.03 microg/ml; however, 30-48% of the pancreatic cancer cells are resistant to gemcitabine even at concentrations >100 microg/ml. In comparison, TF induced cell death in 96% of the cells at 50 microg/ml. The combination of gemcitabine and TF was synergistic with IC90 levels achieved in both pancreatic cancer cell lines at lower concentrations. CalcuSyn analysis of cytotoxicity data showed that the Gemcitabine + Turmeric Force combination has strong synergism with combination index (CI) values of 0.050 and 0.183 in BxPC3 and Panc-1 lines, respectively at IC50 level. This synergistic effect is due to the increased inhibitory effect of the combination on nuclear factor-kappaB activity and signal transducer and activator of transcription factor 3 expression as compared to the single agent.
MED-4187
Organochlorine pesticide residues in bamboo shoot.
BACKGROUND: Xenobiotic organochlorine pesticides (OCPs) are a major environmental problem because of their historic widespread use, pronounced persistence against chemical and biological degradation, and bioaccumulation in the food chain. Pesticide use is prevalent in the production of edible bamboo shoots, which are exported widely from China. To evaluate the quality of Chinese bamboo shoots we determined the residual content of some OCPs in shoot samples. RESULTS: Three types of OCPs-hexachlorocyclohexane (HCH), 1,1,1-trichlor-2,2-bis(p-chlorophenyl)ethane (DDT) and pentachloronitrobenzene (PCNB)-were detected in bamboo shoots from Zhejiang province, China. Detection rates were 100%, 100% and 75% for HCH, DDT and PCNB, respectively. However, the average residue concentration did not exceed the maximum residue limit for pesticides detected in food in China (50 µg kg(-1) ). In terms of residue concentrations of the pesticides, 82.14% of the bamboo shoot samples could be classified as safe. CONCLUSION: While all sampled bamboo shoots contained OCP, most (82.14%) were safe for consumption. 2010 Society of Chemical Industry.
MED-2999
Western diseases and their emergence related to diet.
Many of the commonest diseases in the economically more developed communities are characteristic of modern Western culture. Evidence is presented suggesting that they represent a failure of adaptation to the dramatic changes in diet that have been associated with the emergence of modern Western culture. Dietary changes aimed at the alleviation and prevention of these diseases are discussed and recommended.
MED-958
A comparative review of thermography as a breast cancer screening technique.
Breast cancer is the most frequently diagnosed cancer of women in North America. Despite advances in treatment that have reduced mortality, breast cancer remains the second leading cause of cancer induced death. Several well established tools are used to screen for breast cancer including clinical breast exams, mammograms, and ultrasound. Thermography was first introduced as a screening tool in 1956 and was initially well accepted. However, after a 1977 study found thermography to lag behind other screening tools, the medical community lost interest in this diagnostic approach. This review discusses each screening tool with a focus brought to thermography. No single tool provides excellent predictability; however, a combination that incorporates thermography may boost both sensitivity and specificity. In light of technological advances and maturation of the thermographic industry, additional research is required to confirm the potential of this technology to provide an effective non-invasive, low risk adjunctive tool for the early detection of breast cancer.
MED-4157
Compounded bioidentical menopausal hormone therapy.
Although improvement in long-term health is no longer an indication for menopausal hormone therapy, evidence supporting fewer adverse events in younger women, combined with its high overall effectiveness, has reinforced its usefulness for short-term treatment of menopausal symptoms. Menopausal therapy has been provided not only by commercially available products but also by compounding, or creation of an individualized preparation in response to a health care provider's prescription to create a medication tailored to the specialized needs of an individual patient. The Women's Health Initiative findings, coupled with an increase in the direct-to-consumer marketing and media promotion of compounded bioidentical hormonal preparations as safe and effective alternatives to conventional menopausal hormone therapy, have led to a recent increase in the popularity of compounded bioidentical hormones as well as an increase in questions about the use of these preparations. Not only is evidence lacking to support superiority claims of compounded bioidentical hormones over conventional menopausal hormone therapy, but these claims also pose the additional risks of variable purity and potency and lack efficacy and safety data. The Committee on Gynecologic Practice of the American College of Obstetricians and Gynecologists and the Practice Committee of the American Society for Reproductive Medicine provide an overview of the major issues of concern surrounding compounded bioidentical menopausal hormone therapy and provide recommendations for patient counseling. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
MED-760
A High Antioxidant Spice Blend Attenuates Postprandial Insulin and Triglyceride Responses and Increases Some Plasma Measures of Antioxidant Activity in Healthy, Overweight Men
There is much interest in the potential of dietary antioxidants to attenuate in vivo oxidative stress, but little characterization of the time course of plasma effects exists. Culinary spices have demonstrated potent in vitro antioxidant properties. The objective of this study was to examine whether adding 14 g of a high antioxidant spice blend to a 5060-kJ (1200 kcal) meal exerted significant postprandial effects on markers of plasma antioxidant status and metabolism. Healthy overweight men (n = 6) consumed a control and spiced meal in a randomized crossover design with 1 wk between testing sessions. Blood was sampled prior to the meal and at 30-min intervals for 3.5 h (total of 8 samples). Mixed linear models demonstrated a treatment × time interaction (P < 0.05) for insulin and TG, corresponding with 21 and 31% reductions in postprandial levels with the spiced meal, respectively. Adding spices to the meal significantly increased the ferric reducing antioxidant power, such that postprandial increases following the spiced meal were 2-fold greater than after the control meal (P = 0.009). The hydrophilic oxygen radical absorbance capacity (ORAC) of plasma also was increased by spices (P = 0.02). There were no treatment differences in glucose, total thiols, lipophilic ORAC, or total ORAC. The incorporation of spices into the diet may help normalize postprandial insulin and TG and enhance antioxidant defenses.
MED-2120
ACNE AND RISK OF PROSTATE CANCER
In a recent study, prostatectomy specimens from which Propionibacterium acnes was cultured were more likely to have inflammation than culture-negative specimens or specimens positive for other bacteria, leading the authors to hypothesize that P. acnes-mediated inflammation may contribute to prostate carcinogenesis. To indirectly explore associations between P. acnes and prostate cancer, we investigated severe acne, as measured by tetracycline use for four or more years, in relation to incident prostate cancer in the Health Professionals Follow-up Study. On the 1992 follow-up questionnaire, participants were asked whether they had ever used “tetracycline for at least two months at a time (e.g., for acne or other reason)” and their duration of use. Prostate cancer diagnoses were ascertained on each subsequent biennial questionnaire and confirmed by medical record review. Between 1992 and 2002, 2,147 cases of prostate cancer were reported among 34,629 eligible participants. Men who used tetracycline for four or more years had a significantly higher risk of prostate cancer (16 cases, 1,569 person-years) than men who did not use tetracycline (2,071 cases, 304,822 person-years, multivariable-adjusted RR=1.70, 95% CI:1.03–2.80). Although intriguing, this finding should be viewed cautiously because of the small number of exposed cases, indirect assessment of severe acne, and complex etiology of acne, which is not limited to P. acnes infection. Therefore, additional biologic and epidemiologic studies are necessary to determine and elucidate the possible role of P. acnes infection in prostate carcinogenesis.
MED-3887
Food Animals and Antimicrobials: Impacts on Human Health
Summary: Antimicrobials are valuable therapeutics whose efficacy is seriously compromised by the emergence and spread of antimicrobial resistance. The provision of antibiotics to food animals encompasses a wide variety of nontherapeutic purposes that include growth promotion. The concern over resistance emergence and spread to people by nontherapeutic use of antimicrobials has led to conflicted practices and opinions. Considerable evidence supported the removal of nontherapeutic antimicrobials (NTAs) in Europe, based on the “precautionary principle.” Still, concrete scientific evidence of the favorable versus unfavorable consequences of NTAs is not clear to all stakeholders. Substantial data show elevated antibiotic resistance in bacteria associated with animals fed NTAs and their food products. This resistance spreads to other animals and humans—directly by contact and indirectly via the food chain, water, air, and manured and sludge-fertilized soils. Modern genetic techniques are making advances in deciphering the ecological impact of NTAs, but modeling efforts are thwarted by deficits in key knowledge of microbial and antibiotic loads at each stage of the transmission chain. Still, the substantial and expanding volume of evidence reporting animal-to-human spread of resistant bacteria, including that arising from use of NTAs, supports eliminating NTA use in order to reduce the growing environmental load of resistance genes.
MED-1849
Aluminum involvement in the progression of Alzheimer's disease.
The neuroanatomic specificity with which Alzheimer's disease (AD) progresses could provide clues to AD etiopathology. Magnetic resonance imaging studies of AD clinical progression have confirmed general conclusions from earlier studies of AD neuropathological progression wherein neurofibrillary tangle pathology was observed to spread along a well-defined sequence of corticocortical and corticosubcortical connections, preferentially affecting certain cell types, while sparing others. Identical and non-identical twin studies have consistently shown AD has mixed (environmental and genetic) etiopathogenesis. The decades-long prodromal phase over which AD develops suggests slow but progressive accumulation of a toxic or infective agent over time. Major environmental candidates are reviewed to assess which best fits the profile of an agent that slowly accrues in susceptible cell types of AD-vulnerable brain regions to toxic levels by old age, giving rise to AD neuropathology without rapid neuronal lysis. Chronic aluminum neurotoxicity best matches this profile. Many humans routinely ingest aluminum salts as additives contained in processed foods and alum-treated drinking water. The physical properties of aluminum and ferric iron ions are similar, allowing aluminum to use mechanisms evolved for iron to enter vulnerable neurons involved in AD progression, accumulate in those neurons, and cause neurofibrillary damage. The genetic component of AD etiopathogenesis apparently involves a susceptibility gene, yet to be identified, that increases aluminum absorption because AD and Down syndrome patients have higher than normal plasma, and brain, aluminum levels. This review describes evidence for aluminum involvement in AD neuropathology and the clinical progression of sporadic AD.
MED-4193
Crocus sativus L. (saffron) in the treatment of premenstrual syndrome: a double-blind, randomised and placebo-controlled trial.
OBJECTIVE: The aim of this double-blind and placebo-controlled trial was to investigate whether saffron (stigma of Crocus sativus L.) could relieve symptoms of premenstrual syndrome (PMS). DESIGN: Double-blind, randomised and placebo-controlled trial. SETTING: Departments of Gynaecology/Obstetrics and Psychiatry, Tehran and Zanjan University of Medical Sciences. POPULATION: Women aged 20-45 years with regular menstrual cycles and experience of PMS symptoms for at least 6 months were eligible for the study. METHOD: Women were randomly assigned to receive capsule saffron 30 mg/day (15 mg twice a day; morning and evening) (group A) or capsule placebo (twice a day) for a two menstrual cycles (cycles 3 and 4). MAIN OUTCOME MEASURES: The primary outcome measure was the Daily Symptom Report, and secondary outcome measure was the Hamilton Depression Rating Scale. RESULTS: In this trial, saffron was found to be effective in relieving symptoms of PMS. A significant difference was observed in efficacy of saffron in cycles 3 and 4 in the Total Premenstrual Daily Symptoms and Hamilton Depression Rating Scale. CONCLUSION: The results of this study indicate the efficacy of C. sativus L. in the treatment of PMS. However, a tolerable adverse effects profile of saffron may well confirm the application of saffron as an alternative treatment for PMS. These results deserved further investigations.
MED-1793
Concept and health-related properties of nonextractable polyphenols: the missing dietary polyphenols.
Most research studies in the field of dietary polyphenols or phenolic compounds use a chemical approach focusing exclusively on polyphenols extracted from plant foods with organic solvents. However, an appreciable part of polyphenols are not extracted with organic solvents and thus are ignored in biological, nutritional, and epidemiological studies. Recent studies have shown that these nonextractable polyphenols (NEPP) are a major part of total dietary polyphenols and that they exhibit a significant biological activity. A physiological approach is proposed on the basis that the bioavailability and health-related properties of polyphenols depend on their solubility in intestinal fluids, which is different from their solubility in organic solvents. This paper tries to clarify the concept of NEPP, distinguishing between chemical and physiological approaches and pointing out the main qualitative and quantitative differences between them. It is stressed that the literature and databases refer to only extractable polyphenols. Greater attention to NEPP may fill the current gap in the field of dietary polyphenols.
MED-4216
Relationship of dietary protein and soy isoflavones to serum IGF-1 and IGF binding proteins in the Prostate Cancer Lifestyle Trial.
High levels of insulin-like growth factor 1 (IGF-1) are associated with increased risk of prostate cancer, whereas increased levels of some of its binding proteins (IGFBPs) seem to be protective. High intakes of dietary protein, especially animal and soy protein, appear to increase IGF-1. However, soy isoflavones have demonstrated anti-proliferative and apoptotic effects both in vitro and in vivo. We evaluated dietary intakes of total protein and soy isoflavones in relation to the IGF axis in prostate cancer patients making comprehensive lifestyle changes including a very low-fat vegan diet supplemented with soy protein (58 g/day). After one year, intervention group patients reported significantly higher intakes of dietary protein and soy isoflavones compared to usual-care controls (P < 0.001). IGF-1 increased significantly in both groups, whereas IGFBP-1 rose in the experimental group only (P < 0.01). Increases in vegetable protein over one year were associated with increases in IGFBP-1 among intervention group patients (P < 0.05). These results suggest that dietary protein and soy isoflavones, in the context of comprehensive lifestyle changes, may not significantly alter IGF-1. However, given the recent literature indicating that high intake of protein rich in essential amino acids (animal or soy protein) may increase IGF-1, it may be prudent for men with early stage prostate cancer not to exceed dietary protein recommendations.
MED-2055
Intolerance of cow's milk and chronic constipation in children.
BACKGROUND: Chronic diarrhea is the most common gastrointestinal symptom of intolerance of cow's milk among children. On the basis of a prior open study, we hypothesized that intolerance of cow's milk can also cause severe perianal lesions with pain on defecation and consequent constipation in young children. METHODS: We performed a double-blind, crossover study comparing cow's milk with soy milk in 65 children (age range, 11 to 72 months) with chronic constipation (defined as having one bowel movement every 3 to 15 days). All had been referred to a pediatric gastroenterology clinic and had previously been treated with laxatives without success; 49 had anal fissures and perianal erythema or edema. After 15 days of observation, the patients received cow's milk or soy milk for two weeks. After a one-week washout period, the feedings were reversed. A response was defined as eight or more bowel movements during a treatment period. RESULTS: Forty-four of the 65 children (68 percent) had a response while receiving soy milk. Anal fissures and pain with defecation resolved. None of the children who received cow's milk had a response. In all 44 children with a response, the response was confirmed with a double-blind challenge with cow's milk. Children with a response had a higher frequency of coexistent rhinitis, dermatitis, or bronchospasm than those with no response (11 of 44 children vs. 1 of 21, P=0.05); they were also more likely to have anal fissures and erythema or edema at base line (40 of 44 vs. 9 of 21, P<0.001), evidence of inflammation of the rectal mucosa on biopsy (26 of 44 vs. 5 of 21, P=0.008), and signs of hypersensitivity, such as specific IgE antibodies to cow's-milk antigens (31 of 44 vs. 4 of 21, P<0.001). CONCLUSIONS: In young children, chronic constipation can be a manifestation of intolerance of cow's milk.
MED-5081
Raisins and additional walking have distinct effects on plasma lipids and inflammatory cytokines
Background Raisins are a significant source of dietary fiber and polyphenols, which may reduce cardiovascular disease (CVD) risk by affecting lipoprotein metabolism and inflammation. Walking represents a low intensity exercise intervention that may also reduce CVD risk. The purpose of this study was to determine the effects of consuming raisins, increasing steps walked, or a combination of these interventions on blood pressure, plasma lipids, glucose, insulin and inflammatory cytokines. Results Thirty-four men and postmenopausal women were matched for weight and gender and randomly assigned to consume 1 cup raisins/d (RAISIN), increase the amount of steps walked/d (WALK) or a combination of both interventions (RAISINS + WALK). The subjects completed a 2 wk run-in period, followed by a 6 wk intervention. Systolic blood pressure was reduced for all subjects (P = 0.008). Plasma total cholesterol was decreased by 9.4% for all subjects (P < 0.005), which was explained by a 13.7% reduction in plasma LDL cholesterol (LDL-C) (P < 0.001). Plasma triglycerides (TG) concentrations were decreased by 19.5% for WALK (P < 0.05 for group effect). Plasma TNF-α was decreased from 3.5 ng/L to 2.1 ng/L for RAISIN (P < 0.025 for time and group × time effect). All subjects had a reduction in plasma sICAM-1 (P < 0.01). Conclusion This research shows that simple lifestyle modifications such as adding raisins to the diet or increasing steps walked have distinct beneficial effects on CVD risk.
MED-4783
Childhood soy intake and breast cancer risk in Asian American women.
INTRODUCTION: Historically, breast cancer incidence has been substantially higher in the United States than in Asia. When Asian women migrate to the United States, their breast cancer risk increases over several generations and approaches that for U.S. Whites. Thus, modifiable factors, such as diet, may be responsible. METHODS: In this population-based case-control study of breast cancer among women of Chinese, Japanese, and Filipino descent, ages 20 to 55 years, and living in San Francisco-Oakland (California), Los Angeles (California) and Oahu (Hawaii), we interviewed 597 cases (70% of those eligible) and 966 controls (75%) about adolescent and adult diet and cultural practices. For subjects with mothers living in the United States (39% of participants), we interviewed mothers of 99 cases (43% of eligible) and 156 controls (40%) about the daughter's childhood exposures. Seventy-three percent of study participants were premenopausal at diagnosis. RESULTS: Comparing highest with lowest tertiles, the multivariate relative risks (95% confidence interval) for childhood, adolescent, and adult soy intake were 0.40 (0.18-0.83; P(trend) = 0.03), 0.80 (0.59-1.08; P(trend) = 0.12), and 0.76 (0.56-1.02; P(trend) = 0.04), respectively. Inverse associations with childhood intake were noted in all three races, all three study sites, and women born in Asia and the United States. Adjustment for measures of westernization attenuated the associations with adolescent and adult soy intake but did not affect the inverse relationship with childhood soy intake. DISCUSSION: Soy intake during childhood, adolescence, and adult life was associated with decreased breast cancer risk, with the strongest, most consistent effect for childhood intake. Soy may be a hormonally related, early-life exposure that influences breast cancer incidence.
MED-5170
Microbiological quality of sushi from sushi bars and retailers.
Sushi is a traditional Japanese food, mostly consisting of rice and raw fish. Fish is considered a healthy food, but as with other animal products, consumption of raw muscle incurs potential health risks such as ingestion of pathogenic bacteria or parasites. In this study, 250 sushi samples were analyzed for their microbiological status and the prevalence of pathogenic bacteria. A comparison was made between frozen sushi from supermarkets and fresh sushi from sushi bars. Aerobic mesophilic bacteria counts differed for sushi from these two sources, with means of 2.7 log CFU/g for frozen sushi and 6.3 log CFU/g for fresh sushi. The prevalence of Escherichia coli and Staphylococcus aureus was higher in the fresh samples. Salmonella was found in four (1.6%) of the sushi samples, and Listeria monocytogenes was found in three (1.2%) of the samples. These results indicate that the microbiological quality of industrially processed sushi is higher than that of freshly prepared sushi. The quality of freshly prepared sushi strongly depends on the skills and habits of the preparation cooks, which may vary.
MED-1775
Comparison of individual antioxidants of sperm and seminal plasma in fertile and infertile men.
OBJECTIVE: To measure individual antioxidants in sperm and seminal plasma from fertile and infertile men to determine if any particular antioxidant is reduced in infertile men. DESIGN: Semen samples were prepared by a discontinuous Percoll gradient to separate sperm and seminal plasma, and the antioxidant concentrations of each were assessed. Samples also were screened for phorbol ester-induced reactive oxygen species (ROS) activity. SETTING: Departments of Obstetrics and Gynaecology, and Clinical Biochemistry, The Queen's University of Belfast, Northern Ireland. PATIENT(S): Fifty-nine male patients attending our infertility center: 18 men whose wives had ongoing pregnancies from IVF with normozoospermic semen profiles, 20 infertile men with normozoospermic and 21 men with asthenozoospermic semen profiles. MAIN OUTCOME MEASURE(S): Ascorbate, urate, sulphydryl groups, tocopherol and carotenoid concentrations were measured in sperm and seminal plasma from fertile and infertile men. RESULT(S): In seminal plasma, ascorbate contributes almost twice as much as urate and thiol levels are about one third of ascorbate. Ascorbate levels in seminal plasma of asthenozoospermic individuals (+ROS) are significantly reduced. In sperm, thiols contributed most and ascorbate only a fraction of the total. CONCLUSION(S): In seminal plasma, ascorbate, urates, and thiols are the major antioxidants present. In contrast, within sperm, this group is the major contributor. In samples exhibiting ROS activity, ascorbate concentrations in the seminal plasma are significantly reduced.
MED-5099
Nutrient and methyl mercury exposure from consuming fish.
There is controversy about the risks and benefits of consuming fish. Fish consumption provides nutrients, some of which are essential for brain growth and development. All fish, however, contain methyl mercury (MeHg), a known neurotoxicant. The toxic effect of MeHg seems most damaging during brain development, and thus, prenatal exposure is of greatest concern. At present the level of prenatal exposure associated with risk to a child's neurodevelopment is not known. Balancing the rewards and possible risks of fish consumption presents a dilemma to consumers and regulatory authorities. We review the nutrients in fish that are important in brain development and the current evidence of risk from MeHg at exposure levels achieved by consuming fish. We then review the findings from a large prospective cohort study of a population that consumes fish daily, the Seychelles Child Development Study. The MeHg content of the fish consumed in the Seychelles is similar to that of ocean fish available in industrialized countries, so they represent a sentinel population for any risk from fish consumption. In the Seychelles, evaluations of the children through 9 y of age show no consistent pattern of adverse associations with prenatal MeHg exposure. Recent studies in the Seychelles have focused on nutrients in fish that might influence a child's development, including long-chain polyunsaturated fatty acids, iodine, iron, and choline. Preliminary findings from this study suggest that the beneficial influence of nutrients from fish may counter any adverse effects of MeHg on the developing nervous system.
MED-702
The efficacy and safety of liraglutide.
AIM OF THE REVIEW: To systematically analyze the efficacy and safety of liraglutide for the treatment of diabetes mellitus in comparison to other mono- and combination therapies. METHOD: PubMed (any date) and EMBASE (all years) search was conducted with liraglutide as a search term. Phase III clinical trials retrieved by the two databases and resources posted in Drug@FDA website were evaluated with regard to outcomes of efficacy and safety. RESULTS: Eight Phase III clinical studies compared the efficacy and safety of liraglutide to other monotherapies or combinations. Liraglutide as monotherapy in doses of 0.9 mg or above showed a significantly superior reduction in HbA1C compared to monotherapies with glimepiride or glyburide. When liraglutide was used as add-on therapy to glimepiride in doses of 1.2 mg or above, the reduction of HbA1C was greater than that in the combination therapy of glimepiride and rosiglitazone. However, liraglutide as add-on therapy to metformin failed to show benefit over combination of metformin and glimepiride. Triple therapy of using liraglutide in addition to metformin plus either glimepiride or rosiglitazone resulted in additional benefit in HbA1C reduction. Most common adverse events were gastrointestinal disturbance such as nausea, vomit, diarrhea, and constipation. During the eight clinical studies, six cases of pancreatitis and five cases of cancer were reported in liraglutide arm, whereas there was one case of each of pancreatitis in exenatide and glimepiride arms, respectively, and one case of cancer in metformin plus sitagliptin arm. CONCLUSION: Liraglutide is a new therapeutic option to improve glycemic control in patients with type 2 diabetes. However, the present lack of evidence of durability of efficacy and long-term safety appear to limit its utility in the general treatment of type 2 diabetes at this time.
MED-2222
Effect of cocoa/chocolate ingestion on brachial artery flow-mediated dilation and its relevance to cardiovascular health and disease in humans.
Prospective studies indicate that high intake of dietary flavanols, such as those contained in cocoa/chocolate, are associated with reduced rates of cardiovascular-related morbidity and mortality in humans. Numerous mechanisms may underlie these associations such as favorable effects of flavanols on blood pressure, platelet aggregation, thrombosis, inflammation, and the vascular endothelium. The brachial artery flow-mediated dilation (FMD) technique has emerged as a robust method to quantify endothelial function in humans. Collectively, the preponderance of evidence indicates that FMD is a powerful surrogate measure for firm cardiovascular endpoints, such as cardiovascular-related mortality, in humans. Thus, literally thousands of studies have utilized this technique to document group differences in FMD, as well as to assess the effects of various interventions on FMD. In regards to the latter, numerous studies indicate that both acute and chronic ingestion of cocoa/chocolate increases FMD in humans. Increases in FMD after cocoa/chocolate ingestion appear to be dose-dependent such that greater increases in FMD are observed after ingestion of larger quantities. The mechanisms underlying these responses are likely diverse, however most data suggest an effect of increased nitric oxide bioavailability. Thus, positive vascular effects of cocoa/chocolate on the endothelium may underlie (i.e., be linked mechanistically to) reductions in cardiovascular risk in humans. Copyright © 2012 Elsevier Inc. All rights reserved.
MED-4556
Tolerable upper intake levels for trans fat, saturated fat, and cholesterol.
Tolerable upper intake levels (ULs) set by the Institute of Medicine (IOM) are important, in part because they are used for estimating the percentage of the population at potential risk of adverse effects from excessive nutrient intake. The IOM did not set ULs for trans fat, saturated fat, and cholesterol because any intake level above 0% of energy increased LDL cholesterol concentration and these three food components are unavoidable in ordinary diets. The purpose of the analysis presented in this review was to evaluate clinical trial and prospective observational data that were not previously considered for setting a UL with the aim of determining whether the current UL model could be used for saturated fat, trans fat, and cholesterol. The results of this analysis confirm the limitations of the risk assessment model for setting ULs because of its inability to identify a UL for food components, such as cholesterol, that lack an intake threshold associated with increased chronic disease risk. © 2011 International Life Sciences Institute.
MED-3806
Toxicology of nutmeg abuse.
BACKGROUND: Unpleasant and frightening side effects associated with the abuse of nutmeg occasionally generate emergency department referrals. We report a young patient's first-time experience with nutmeg and review the mechanisms of its toxicity. CASE REPORT: A 13-year-old female ingested 15-24 g of nutmeg over a 3-hour period and smoked and shared 2 joints of marijuana. To facilitate ingestion, the nutmeg was put into 00-000 gelatin capsules. Bizarre behavior and visual, auditory, and tactile hallucinations developed. She also experienced nausea, gagging, hot/cold sensations, and blurred vision followed by numbness, double, and "triple" vision, headache, and drowsiness. Nystagmus, muscle weakness, and ataxia were present. Her vital signs and laboratory tests were normal. She received 50 g of activated charcoal and except for complaints of dizziness and visual changes, her 2-day admission was uneventful. The central nervous system activity of nutmeg is often postulated to result from biotransformation of its chemical components to amphetamine-like compounds, but this has not been proven. Nutmeg contains several compounds with structural similarities to substances with known central nervous system neuromodulatory activity.
MED-2926
In vitro investigation of the potential immunomodulatory and anti-cancer activities of black pepper (Piper nigrum) and cardamom (Elettaria cardamom...
Although the immunomodulatory effects of many herbs have been extensively studied, research related to possible immunomodulatory effects of various spices is relatively scarce. Here, the potential immunomodulatory effects of black pepper and cardamom are investigated. Our data show that black pepper and cardamom aqueous extracts significantly enhance splenocyte proliferation in a dose-dependent, synergistic fashion. Enzyme-linked immunosorbent assay experiments reveal that black pepper and cardamom significantly enhance and suppress, respectively, T helper (Th)1 cytokine release by splenocytes. Conversely, Th2 cytokine release by splenocytes is significantly suppressed and enhanced by black pepper and cardamom, respectively. Experimental evidence suggests that black pepper and cardamom extracts exert pro-inflammatory and anti-inflammatory roles, respectively. Consistently, nitric oxide production by macrophages is significantly augmented and reduced by black pepper and cardamom, respectively. Remarkably, it is evident that black pepper and cardamom extracts significantly enhance the cytotoxic activity of natural killer cells, indicating their potential anti-cancer effects. Our findings strongly suggest that black pepper and cardamom exert immunomodulatory roles and antitumor activities, and hence they manifest themselves as natural agents that can promote the maintenance of a healthy immune system. We anticipate that black pepper and cardamom constituents can be used as potential therapeutic tools to regulate inflammatory responses and prevent/attenuate carcinogenesis.
MED-5216
Prevalence of Vitamin A Deficiency in South Asia: Causes, Outcomes, and Possible Remedies
Vitamin A deficiency (VAD) has been recognized as a public-health issue in developing countries. Economic constraints, sociocultural limitations, insufficient dietary intake, and poor absorption leading to depleted vitamin A stores in the body have been regarded as potential determinants of the prevalence of VAD in South Asian developing countries. VAD is exacerbated by lack of education, poor sanitation, absence of new legislation and enforcement of existing food laws, and week monitoring and surveillance system. Several recent estimates confirmed higher morbidly and mortality rate among children and pregnant and non-pregnant women of childbearing age. Xerophthalmia is the leading cause of preventable childhood blindness with its earliest manifestations as night blindness and Bitot's spots, followed by blinding keratomalacia, all of which are the ocular manifestations of VAD. Children need additional vitamin A because they do not consume enough in their normal diet. There are three general ways for improving vitamin A status: supplementation, fortification, and dietary diversification. These approaches have not solved the problem in South Asian countries to the desired extent because of poor governmental support and supervision of vitamin A supplementation twice a year. An extensive review of the extant literature was carried out, and the data under various sections were identified by using a computerized bibliographic search via PubMed, Web of Science, and Google Scholar. All abstracts and full-text articles were examined, and the most relevant articles were selected for screening and inclusion in this review. Conclusively, high prevalence of VAD in South Asian developing countries leads to increased morbidity and mortality among infants, children, and pregnant women. Therefore, stern efforts are needed to address this issue of public-health significance at local and international level in lower- and middle-income countries of South Asia.
MED-3205
Prospective study of the association between grapefruit intake and risk of breast cancer in the European Prospective Investigation into Cancer and ...
Grapefruit inhibits cytochrome P450 3A4 and may affect estrogen metabolism. In the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined the relationships of grapefruit intake with risk of breast cancer and with serum sex hormone levels. 114,504 women with information on dietary intake of grapefruit and on reproductive and lifestyle risk factors were followed for a median 9.5 years and 3,747 incident breast cancers were identified. Fifty-nine percent of women reported eating grapefruit, 4% ate > or = 60 g/day. Cox proportional hazard models were used to estimate the hazard ratio (HR) for breast cancer according to grapefruit intake, adjusting for study centre, reproductive factors, body mass index, energy intake, and alcohol intake. Grapefruit intake was not related to the risk of breast cancer: compared with women who ate no grapefruit, women with the highest intake of > or =60 g/day had a HR of 0.93 (95% CI 0.77-1.13), p for linear trend = 0.5. There was no relationship between grapefruit intake and breast cancer risk among premenopausal women, all postmenopausal women, or postmenopausal women categorized by hormone replacement therapy use (all p>0.05). There was no association between grapefruit intake and estradiol or estrone among postmenopausal women. In this study, we found no evidence of an association between grapefruit intake and risk of breast cancer.
MED-4654
Sexual selection and genital anatomy of male primates.
Correlations between mating system and various aspects of genital anatomy suggest a strong influence of sexual selection on genital morphology. We test the generality of the influence by examining whether primate taxa in which there might be enhanced sexual selection (those with multi-male mating systems) possess, as expected, relatively more spinous penises than do taxa with other mating systems. As most prosimians, but few anthropoids (monkeys and apes), possess penile spines, and because the predominant mating systems of the two taxa differ, taxonomic constraints are taken into account. Sexual selection apparently does not act on penile spines in the same manner as on other aspects of genital anatomy: spinosity is not greatest in multi-male taxa of either prosimians or anthropoids. In some taxa, spines might stimulate reproductive readiness and synchrony in situations in which the sexes live apart and do not have other means of communicating reproductive state (dispersed social systems and 'stolen' extra-pair copulations), but problems exist with the hypothesis, as they do with the idea that spines are involved with scent marking. It seems that either penile spines have several functions, or penile spinosity in primates, and other orders, remains to be explained.
MED-2009
Nutritional quality and health benefits of chickpea (Cicer arietinum L.): a review.
Chickpea (Cicer arietinum L.) is an important pulse crop grown and consumed all over the world, especially in the Afro-Asian countries. It is a good source of carbohydrates and protein, and protein quality is considered to be better than other pulses. Chickpea has significant amounts of all the essential amino acids except sulphur-containing amino acids, which can be complemented by adding cereals to the daily diet. Starch is the major storage carbohydrate followed by dietary fibre, oligosaccharides and simple sugars such as glucose and sucrose. Although lipids are present in low amounts, chickpea is rich in nutritionally important unsaturated fatty acids such as linoleic and oleic acids. β-Sitosterol, campesterol and stigmasterol are important sterols present in chickpea oil. Ca, Mg, P and, especially, K are also present in chickpea seeds. Chickpea is a good source of important vitamins such as riboflavin, niacin, thiamin, folate and the vitamin A precursor β-carotene. As with other pulses, chickpea seeds also contain anti-nutritional factors which can be reduced or eliminated by different cooking techniques. Chickpea has several potential health benefits, and, in combination with other pulses and cereals, it could have beneficial effects on some of the important human diseases such as CVD, type 2 diabetes, digestive diseases and some cancers. Overall, chickpea is an important pulse crop with a diverse array of potential nutritional and health benefits.
MED-4315
Differences in metal content of the heart muscle in death from ischemic heart disease.
In a group of patients dying suddenly from ischemic heart disease, the uninfarcted heart muscle contained significantly lower concentrations of magnesium, iron, and potassium and a significantly higher concentration of calcium than the heart muscle from a group of normal controls and a group of patients dying more than three months after a coronary thrombosis. The late death group had significantly lower concentrations of manganese and copper than the normal group, and a slight decrease in magnesium concentration which was probably significant. There was no significant difference in the sodium concentration between the three groups. The results are discussed in relation to the increased death rate from ischemic heart disease in areas with soft drinking water, and possible dietary deficiencies in mineral salts.
MED-3921
Consumption of Hibiscus sabdariffa L. aqueous extract and its impact on systemic antioxidant potential in healthy subjects.
BACKGROUND: To evaluate health benefits attributed to Hibiscus sabdariffa L. a randomized, open-label, two-way crossover study was undertaken to compare the impact of an aqueous H. sabdariffa L. extract (HSE) on the systemic antioxidant potential (AOP; assayed by ferric reducing antioxidant power (FRAP)) with a reference treatment (water) in eight healthy volunteers. The biokinetic variables were the areas under the curve (AUC) of plasma FRAP, ascorbic acid and urate that are above the pre-dose concentration, and the amounts excreted into urine within 24 h (Ae(0-24) ) of antioxidants as assayed by FRAP, ascorbic acid, uric acid, malondialdehyde (biomarker for oxidative stress), and hippuric acid (metabolite and potential biomarker for total polyphenol intake). RESULTS: HSE caused significantly higher plasma AUC of FRAP, an increase in Ae(0-24) of FRAP, ascorbic acid and hippuric acid, whereas malondialdehyde excretion was reduced. Furthermore, the main hibiscus anthocyanins as well as one glucuronide conjugate could be quantified in the volunteers' urine (0.02% of the administered dose). CONCLUSION: The aqueous HSE investigated in this study enhanced the systemic AOP and reduced the oxidative stress in humans. Furthermore, the increased urinary hippuric acid excretion after HSE consumption indicates a high biotransformation of the ingested HSE polyphenols, most likely caused by the colonic microbiota. Copyright © 2012 Society of Chemical Industry.
MED-692
The effectiveness and safety of ginger for pregnancy-induced nausea and vomiting: a systematic review.
BACKGROUND: Ginger has been used throughout the world as a therapeutic agent for centuries. The herb is increasingly used in Western society also, with one of the most common indications being pregnancy-induced nausea and vomiting (PNV). OBJECTIVES: To examine the evidence for the safety and effectiveness of ginger for PNV. METHODS: Randomised controlled trials (RCTs) of ginger and PNV were sourced from CINAHL, the Cochrane library, MEDLINE and TRIP. The methodological quality of RCTs was assessed using the Critical Appraisal Skills Programme (CASP) tool. RESULTS: Four RCTs met the inclusion criteria. All trials found orally administered ginger to be significantly more effective than placebo in reducing the frequency of vomiting and intensity of nausea. Adverse events were generally mild and infrequent. CONCLUSION: The best available evidence suggests that ginger is a safe and effective treatment for PNV. However, there remains uncertainty regarding the maximum safe dosage of ginger, appropriate duration of treatment, consequences of over-dosage, and potential drug-herb interactions; all of which are important areas for future research. Copyright © 2012 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.
MED-3782
Egg, red meat, and poultry intake and risk of lethal prostate cancer in the prostate specific antigen-era: incidence and survival
Red and processed meat may increase risk of advanced prostate cancer. Data on post-diagnostic diet and prostate cancer are sparse, but post-diagnostic intake of poultry with skin and eggs may increase risk of disease progression. Therefore, we prospectively examined total, unprocessed, and processed red meat, poultry, and eggs in relation to risk of lethal prostate cancer (e.g. men without cancer at baseline who developed distant organ metastases or died from prostate cancer during follow-up) among 27, 607 men followed from 1994–2008. We also performed a case-only survival analysis to examine post-diagnostic consumption of these foods and risk of lethal prostate cancer among the 3,127 men initially diagnosed with non-metastatic prostate cancer during follow-up. In the incidence analysis, we observed 199 events during 306,715 person-years. Men who consumed 2.5 or more eggs per week had an 81% increased risk of lethal prostate cancer compared to men who consumed less than 0.5 eggs per week (HR: 1.81; 95% confidence interval (CI): 1.13, 2.89; p-trend: 0.01). In the case-only survival analysis, we observed 123 events during 19,354 person-years. There were suggestive, but not statistically significant, positive associations between post-diagnostic poultry (HR ≥3.5 vs. <1.5 servings per week: 1.69; 95%CI: 0.96, 2.99; p-trend: 0.07) and post-diagnostic processed red meat (HR ≥3 vs. <0.5 servings per week: 1.45; 95%CI: 0.73, 2.87; p-trend: 0.08) and risk of progression of localized prostate cancer to lethal disease. In conclusion, consumption of eggs may increase risk of developing a lethal-form of prostate cancer among healthy men.
MED-4461
Sulforaphane potentiates oxaliplatin-induced cell growth inhibition in colorectal cancer cells via induction of different modes of cell death.
The objective of this study was to investigate, whether the plant-derived isothiocyanate Sulforaphane (SFN) enhances the antitumor activities of the chemotherapeutic agent oxaliplatin (Ox) in a cell culture model of colorectal cancer. Caco-2 cells were cultured under standard conditions and treated with increasing concentrations of SFN [1-20 μM] and/or Ox [100 nM-10 μM]. For co-incubation, cells were pre-treated with SFN for 24 h. Cell growth was determined by BrdU incorporation. Drug interactions were assessed using the combination-index method (CI) (Cl < 1 indicates synergism). Apoptotic events were characterized by different ELISA techniques. Protein levels were examined by Western blot analysis. Annexin V- and propidium iodide (PI) staining followed by FACS analysis was used to differentiate between apoptotic and necrotic events. SFN and Ox alone inhibited cell growth of Caco-2 cells in a dose-dependent manner, an effect, which could be synergistically enhanced, when cells were incubated with the combination of both agents. Co-treated cells further displayed distinctive morphological changes that occurred during the apoptotic process, such as cell surface exposure of phosphatidylserine, membrane blebbing as well as the occurence of cytoplasmic histone-associated DNA fragments. Further observations thereby pointed toward simultaneous activation of both extrinsic and intrinsic apoptotic pathways. With increasing concentrations and treatment duration, a shift from apoptotic to necrotic cell death could be observed. In conclusion, the data suggest that the isothiocyanate SFN sensitizes colon cancer cells to Ox-induced cell growth inhibition via induction of different modes of cell death.
MED-2391
Perfluorinated Compounds, Polychlorinated Biphenyls, and Organochlorine Pesticide Contamination in Composite Food Samples from Dallas, Texas, USA
Objectives The objective of this article is to extend our previous studies of persistent organic pollutant (POP) contamination of U.S. food by measuring perfluorinated compounds (PFCs), organochlorine pesticides, and polychlorinated biphenyls (PCBs) in composite food samples. This study is part of a larger study reported in two articles, the other of which reports levels of polybrominated diphenyl ethers and hexabromocyclododecane brominated flame retardants in these composite foods [Schecter et al. 2010. Polybrominated diphenyl ethers (PBDEs) and hexabromocyclodecane (HBCD) in composite U.S. food samples, Environ Health Perspect 118:357–362]. Methods In this study we measured concentrations of 32 organochlorine pesticides, 7 PCBs, and 11 PFCs in composite samples of 31 different types of food (310 individual food samples) purchased from supermarkets in Dallas, Texas (USA), in 2009. Dietary intake of these chemicals was calculated for an average American. Results Contamination varied greatly among chemical and food types. The highest level of pesticide contamination was from the dichlorodiphenyltrichloroethane (DDT) metabolite p,p′- dichlorodiphenyldichloroethylene, which ranged from 0.028 ng/g wet weight (ww) in whole milk yogurt to 2.3 ng/g ww in catfish fillets. We found PCB congeners (28, 52, 101, 118, 138, 153, and 180) primarily in fish, with highest levels in salmon (PCB-153, 1.2 ng/g ww; PCB-138, 0.93 ng/g ww). For PFCs, we detected perfluorooctanoic acid (PFOA) in 17 of 31 samples, ranging from 0.07 ng/g in potatoes to 1.80 ng/g in olive oil. In terms of dietary intake, DDT and DDT metabolites, endosulfans, aldrin, PCBs, and PFOA were consumed at the highest levels. Conclusion Despite product bans, we found POPs in U.S. food, and mixtures of these chemicals are consumed by the American public at varying levels. This suggests the need to expand testing of food for chemical contaminants.
MED-3105
Starting at the beginning: new perspectives on the biology of mucosal T cells.
The gastrointestinal tract is the central organ for uptake of fluids and nutrients, and at the same time it forms the main protective barrier between the sterile environment of the body and the outside world. In mammals, the intestine has further evolved to harbor a vast load of commensal bacteria that have important functions for the host. Discrimination by the host defense system of nonself from self can prevent invasion of pathogens, but equivalent responses to dietary or colonizing bacteria can lead to devastating consequences for the organism. This dilemma imposed by the gut environment has probably contributed significantly to the evolutionary drive that has led to sophisticated mechanisms and diversification of the immune system to allow for protection while maintaining the integrity of the mucosal barrier. The immense expansion and specialization of the immune system is particularly mirrored in the phylogeny, ontogeny, organization, and regulation of the adaptive intraepithelial lymphocytes, or IEL, which are key players in the unique intestinal defense mechanisms that have evolved in mammals.
MED-1614
Insulin sensitivity in Chinese ovo-lactovegetarians compared with omnivores.
AIM: To compare the insulin sensitivity indices between Chinese vegetarians and omnivores. METHODS: The study included 36 healthy volunteers (vegetarian, n=19; omnivore, n=17) who had normal fasting plasma glucose levels. Each participant completed an insulin suppression test. We compared steady-state plasma glucose (SSPG), fasting insulin, the homeostasis model assessment for insulin sensitivity (HOMA-IR and HOMA %S) and beta-cell function (HOMA %beta) between the groups. We also tested the correlation of SSPG with years on a vegetarian diet. RESULTS: The omnivore subjects were younger than the vegetarians (55.7+/-3.7 vs 58.6+/-3.6 year of age, P=0.022). There was no difference between the two groups in sex, blood pressure, renal function tests and lipid profiles. The omnivores had higher serum uric acid levels than vegetarians (5.25+/-0.84 vs 4.54+/-0.75 mg/dl, P=0.011). The results of the indices were different between omnivores and vegetarians (SSPG (mean+/-s.d.) 105.4+/-10.2 vs 80.3+/-11.3 mg/dl, P<0.001; fasting insulin, 4.06+/-0.77 vs 3.02+/-1.19 microU/ml, P=0.004; HOMA-IR, 6.75+/-1.31 vs 4.78+/-2.07, P=0.002; HOMA %S, 159.2+/-31.7 vs 264.3+/-171.7%, P=0.018) except insulin secretion index, HOMA %beta (65.6+/-18.0 vs 58.6+/-14.8%, P=0.208). We found a clear linear relation between years on a vegetarian diet and SSPG (r=-0.541, P=0.017). CONCLUSIONS: The vegetarians were more insulin sensitive than the omnivore counterparts. The degree of insulin sensitivity appeared to be correlated with years on a vegetarian diet.
MED-754
Effect of a dietary portfolio of cholesterol-lowering foods given at 2 levels of intensity of dietary advice on serum lipids in hyperlipidemia: a r...
CONTEXT: Combining foods with recognized cholesterol-lowering properties (dietary portfolio) has proven highly effective in lowering serum cholesterol under metabolically controlled conditions. OBJECTIVE: To assess the effect of a dietary portfolio administered at 2 levels of intensity on percentage change in low-density lipoprotein cholesterol (LDL-C) among participants following self-selected diets. DESIGN, SETTING, AND PARTICIPANTS: A parallel-design study of 351 participants with hyperlipidemia from 4 participating academic centers across Canada (Quebec City, Toronto, Winnipeg, and Vancouver) randomized between June 25, 2007, and February 19, 2009, to 1 of 3 treatments lasting 6 months. INTERVENTION: Participants received dietary advice for 6 months on either a low-saturated fat therapeutic diet (control) or a dietary portfolio, for which counseling was delivered at different frequencies, that emphasized dietary incorporation of plant sterols, soy protein, viscous fibers, and nuts. Routine dietary portfolio involved 2 clinic visits over 6 months and intensive dietary portfolio involved 7 clinic visits over 6 months. MAIN OUTCOME MEASURES: Percentage change in serum LDL-C. RESULTS: In the modified intention-to-treat analysis of 345 participants, the overall attrition rate was not significantly different between treatments (18% for intensive dietary portfolio, 23% for routine dietary portfolio, and 26% for control; Fisher exact test, P = .33). The LDL-C reductions from an overall mean of 171 mg/dL (95% confidence interval [CI], 168-174 mg/dL) were -13.8% (95% CI, -17.2% to -10.3%; P < .001) or -26 mg/dL (95% CI, -31 to -21 mg/dL; P < .001) for the intensive dietary portfolio; -13.1% (95% CI, -16.7% to -9.5%; P < .001) or -24 mg/dL (95% CI, -30 to -19 mg/dL; P < .001) for the routine dietary portfolio; and -3.0% (95% CI, -6.1% to 0.1%; P = .06) or -8 mg/dL (95% CI, -13 to -3 mg/dL; P = .002) for the control diet. Percentage LDL-C reductions for each dietary portfolio were significantly more than the control diet (P < .001, respectively). The 2 dietary portfolio interventions did not differ significantly (P = .66). Among participants randomized to one of the dietary portfolio interventions, percentage reduction in LDL-C on the dietary portfolio was associated with dietary adherence (r = -0.34, n = 157, P < .001). CONCLUSION: Use of a dietary portfolio compared with the low-saturated fat dietary advice resulted in greater LDL-C lowering during 6 months of follow-up. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00438425.
MED-1679
Healthy lifestyle factors in the primary prevention of coronary heart disease among men: benefits among users and nonusers of lipid-lowering and an...
BACKGROUND: Healthy lifestyle choices such as eating a prudent diet, exercising regularly, managing weight, and not smoking may substantially reduce coronary heart disease (CHD) risk by improving lipids, blood pressure, and other risk factors. The burden of CHD that could be avoided through adherence to these modifiable lifestyle factors has not been assessed among middle-aged and older US men, specifically men taking medications for hypertension or hypercholesterolemia. METHODS AND RESULTS: We prospectively monitored 42 847 men in the Health Professionals Follow-up Study, 40 to 75 years of age and free of disease in 1986. Lifestyle factors were updated through self-reported questionnaires. Low risk was defined as (1) absence of smoking, (2) body mass index <25 kg/m2, (3) moderate-to-vigorous activity > or = 30 min/d, (4) moderate alcohol consumption (5 to 30 g/d), and (5) the top 40% of the distribution for a healthy diet score. Over 16 years, we documented 2183 incident cases of CHD (nonfatal myocardial infarction and fatal CHD). In multivariate-adjusted Cox proportional hazards models, men who were at low risk for 5 lifestyle factors had a lower risk of CHD (relative risk: 0.13; 95% confidence interval [CI]: 0.09, 0.19) compared with men who were at low risk for no lifestyle factors. Sixty-two percent (95% CI: 49%, 74%) of coronary events in this cohort may have been prevented with better adherence to these 5 healthy lifestyle practices. Among men taking medication for hypertension or hypercholesterolemia, 57% (95% CI: 32%, 79%) of all coronary events may have been prevented with a low-risk lifestyle. Compared with men who did not make lifestyle changes during follow-up, those who adopted > or = 2 additional low-risk lifestyle factors had a 27% (95% CI: 7%, 43%) lower risk of CHD. CONCLUSIONS: A majority of CHD events among US men may be preventable through adherence to healthy lifestyle practices, even among those taking medications for hypertension or hypercholesterolemia.
MED-2616
The significance of azo-reduction in the mutagenesis and carcinogenesis of azo dyes.
Azo dyes are widely used in textile, printing, cosmetic, drug and food-processing industries. They are also used extensively in laboratories as either biological stains or pH indicators. The extent of such use is related to the degree of industrialization. Since intestinal cancer is more common in highly industrialized countries, a possible connection may exist between the increase in the number of cancer cases and the use of azo dyes. Azo dyes can be reduced to aromatic amines by the intestinal microflora. The mutagenicity of a number of azo dyes is reviewed in this paper. They include Trypan Blue, Ponceau 3R, Pinceau 2R, Methyl Red, Methyl Yellow, Methyl Orange, Lithol Red, Orange I, Orange II, 4-Phenylazo-Naphthylamine, Sudan I, Sudan IV, Acid Alizarin Violet N, Fast Garnet GBC, Allura Red, Ponceau SX, Sunset Yellow, Tartrazine, Citrus Red No. 2, Orange B, Yellow AB, Carmoisine, Mercury Orange, Ponceau S, Versatint Blue, Phenylazophenol, Evan's Blue and their degraded aromatic amines. The significance of azo reduction in the mutagenesis and carcinogenesis of azo dyes is discussed.
MED-3473
Orange juice improved lipid profile and blood lactate of overweight middle-aged women subjected to aerobic training.
OBJECTIVE: This study investigated how consumption of orange juice associated with aerobic training affected serum lipids and physical characteristics of overweight, middle-aged women. METHODS: The experimental group consisted of 13 women who consumed 500 mL/d of orange juice and did 1h aerobic training 3 times a week for 3 months. The control group consisted of another 13 women who did the same aerobic training program but did not consume orange juice. RESULTS: At the end of the experiment, the control group lost an average of 15% of fat mass (P<0.05) and 2.5% of weight (P<0.05), whereas the experimental group lost 11% of fat mass and 1.2% of weight (P<0.05). Consumption of orange juice by the experimental group was associated with increased dietary intake of vitamin C and folate by 126% and 61% respectively. Serum LDL-C decreased 15% (P<0.05) and HDL-C increased 18% (P<0.05) in the experimental group, but no significant change was observed in the control group. Both groups improved the anaerobic threshold by 20% (P<0.05), but blood lactate concentration decreased 27% in the experimental group compared to the 17% control group, suggesting that experimental group has less muscle fatigue and better response to training. CONCLUSIONS: The consumption of 500 mL/d of orange juice associated with aerobic training in overweight women decreased cardiovascular disease risk by reducing LDL-C levels and increasing HDL-C levels. This association also decreased blood lactate concentration and increased anaerobic threshold, showing some improvement in the physical performance. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
MED-4369
Interventions for nausea and vomiting in early pregnancy
Background Nausea, retching and vomiting are very commonly experienced by women in early pregnancy. There are considerable physical and psychological effects on women who experience these symptoms. This is an update of a review of interventions for nausea and vomiting in early pregnancy previously published in 2003. Objectives To assess the effectiveness and safety of all interventions for nausea, vomiting and retching in early pregnancy, up to 20 weeks’ gestation. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (28 May 2010). Selection criteria All randomised controlled trials of any intervention for nausea, vomiting and retching in early pregnancy. We excluded trials of interventions for hyperemesis gravidarum which are covered by another review. We also excluded quasi-randomised trials and trials using a crossover design. Data collection and analysis Four review authors, in pairs, reviewed the eligibility of trials and independently evaluated the risk of bias and extracted the data for included trials. Main results Twenty-seven trials, with 4041 women, met the inclusion criteria. These trials covered many interventions, including acupressure, acustimulation, acupuncture, ginger, vitamin B6 and several antiemetic drugs. We identified no studies of dietary or other lifestyle interventions. Evidence regarding the effectiveness of P6 acupressure, auricular (ear) acupressure and acustimulation of the P6 point was limited. Acupuncture (P6 or traditional) showed no significant benefit to women in pregnancy. The use of ginger products may be helpful to women, but the evidence of effectiveness was limited and not consistent. There was only limited evidence from trials to support the use of pharmacological agents including vitamin B6, and anti-emetic drugs to relieve mild or moderate nausea and vomiting. There was little information on maternal and fetal adverse outcomes and on psychological, social or economic outcomes. We were unable to pool findings from studies for most outcomes due to heterogeneity in study participants, interventions, comparison groups, and outcomes measured or reported. The methodological quality of the included studies was mixed. Authors’ conclusions Given the high prevalence of nausea and vomiting in early pregnancy, health professionals need to provide clear guidance to women, based on systematically reviewed evidence. There is a lack of high-quality evidence to support that advice. The difficulties in interpreting the results of the studies included in this review highlight the need for specific, consistent and clearly justified outcomes and approaches to measurement in research studies.
MED-4944
Studies of fish consumption as source of methylmercury should consider fish-meal-fed farmed fish and other animal foods.
The co-occurrence of fish MeHg and omega-3 fatty acids in wild species can indeed be optimized by choosing certain species. Farmed finfish and shellfish that are fed fish-meal, however, can bioconcentrate both MeHg (in muscle) and organohalogen pollutants passed on in the fat components [Dorea, J.G., 2006. Fish meal in animal feed and human exposure to persistent bioaccumulative and toxic substances. J. Food Prot. 69, 2777-2785); when fish-meal is used to feed farm animals it may offer the worst of both worlds: saturated fat (with organohalogen pollutants) and MeHg. It is time to address the dietary sources of Hg derived from animals raised on fish-meal that may contribute to increase tissue Hg concentrations.
MED-1831
Children's daily exposure to polychlorinated biphenyls from dietary supplements containing fish oils.
In children, omega-3 polyunsaturated fatty acids (PUFAs) may elicit a suite of health benefits including enhancement of cognitive development. Subsequently, dietary supplements containing omega-3 PUFAs have become increasingly popular. Often, the largest source of beneficial PUFAs in these supplements is fish oil, which may contain significant levels of contaminants such as polychlorinated biphenyls (PCBs). The objectives of this study were to evaluate congener-specific PCB concentrations in 13 over-the-counter children's dietary supplements containing fish oils/powders and assess potential PCB exposures through ingestion of these products on a daily basis. Every supplement analysed contained PCBs, with a mean concentration of 9 ± 8 ng PCBs/g supplement. When following serving size suggestions, mean daily exposure values ranged from 2.5 to 50.3 ng PCBs/day. Daily exposures for children's supplements were significantly lower than those previously reported for adult supplements and may be explained, in part, by the variability in the amount of fish oil (and PUFA content) in a serving size. Based on this study, factors such as fish oil purification methods (e.g., molecular distillation) and the trophic level of the fish species used to make the fish oil cannot be used as indicators of PCB levels within children's supplements. Fish supplements may decrease or increase daily PCB exposure compared with ingestion of fresh fish. However, eating fish high in omega-3 PUFAs and low in PCBs may reduce PCB exposure compared with daily supplementation with fish oils for some products studied.
MED-5219
The antiaging approach for the treatment of dry eye.
Dry eye is one of the most common eye disorders affecting millions of people. It causes ocular irritation or discomfort, and decreases functional vision, causing a dramatic deterioration in the quality of life. Although new treatments such as the P2Y2 agonist or cyclosporine eye drops have been developed and a certain level of patient satisfaction can now be obtained, no fundamental treatment has been developed. Currently, there is no therapy available to recover lacrimal function to its normal status. Recent progress in the understanding of aging has laid the foundations for a new way of thinking about intervention of the aging process. Because dry eye is accelerated by aging, a useful approach for the prevention or treatment of dry eye may be to interfere with the aging process. In the scientific community, there is a global consensus that calorie restriction can extend the life span of various kinds of animals, establishing an intervention to aging. Another important hypothesis believed to be involved in aging is the free radical theory. According to these theories, the aging process may be managed by controlling levels of calories or reactive oxygen species. In this review, these 2 important aging theories, calorie restriction and free radical aging, are examined, and we discuss how to apply these theories to the prevention and treatment of dry eye.
MED-2923
Death receptor ligands in tumors.
Activation of apoptosis via death receptors is a tightly regulated event, and the death pathway itself is open to interference on the part of soluble or membrane-bound decoy receptors. The aggregation state of the death-inducing ligand is a crucial factor, particularly when these molecules are used as recombinant drugs against tumors. Whether tumors are sensitive to such ligands is determined by both the net abundance of death receptors versus decoy receptors and the balance between intracellular apoptotic and antiapoptotic mechanisms. This means that in vivo elimination of tumor cells by effector arms such as T lymphocytes, natural killer cells, macrophages, and dendritic cells is dependent on both the function of activated lymphoid cells and the genetic properties of tumor cells. Death receptor ligands, however, may be a double-edged sword. When expressed on cytotoxic T lymphocytes, natural killer cells, monocytes, and dendritic cells, they induce the apoptosis of many tumor cells, whereas their expression on tumor cells induces the apoptosis of killer cells. The in vivo result is influenced by the number of infiltrating cells, their state of activation, the cytokine repertoire in the tumor microenvironment, and the ability of the tumor to produce soluble factors inhibiting their cytolytic functions.
MED-3691
Probiotics, prebiotics infant formula use in preterm or low birth weight infants: a systematic review
Background Previous reviews (2005 to 2009) on preterm infants given probiotics or prebiotics with breast milk or mixed feeds focused on prevention of Necrotizing Enterocolitis, sepsis and diarrhea. This review assessed if probiotics, prebiotics led to improved growth and clinical outcomes in formula fed preterm infants. Methods Cochrane methodology was followed using randomized controlled trials (RCTs) which compared preterm formula containing probiotic(s) or prebiotic(s) to conventional preterm formula in preterm infants. The mean difference (MD) and corresponding 95% confidence intervals (CI) were reported for continuous outcomes, risk ratio (RR) and corresponding 95% CI for dichotomous outcomes. Heterogeneity was assessed by visual inspection of forest plots and a chi2 test. An I2 test assessed inconsistencies across studies. I2> 50% represented substantial heterogeneity. Results Four probiotics studies (N=212), 4 prebiotics studies (N=126) were included. Probiotics: There were no significant differences in weight gain (MD 1.96, 95% CI: -2.64 to 6.56, 2 studies, n=34) or in maximal enteral feed (MD 35.20, 95% CI: -7.61 to 78.02, 2 studies, n=34), number of stools per day increased significantly in probiotic group (MD 1.60, 95% CI: 1.20 to 2.00, 1 study, n=20). Prebiotics: Galacto-oligosaccharide / Fructo-oligosaccharide (GOS/FOS) yielded no significant difference in weight gain (MD 0.04, 95% CI: -2.65 to 2.73, 2 studies, n=50), GOS/FOS yielded no significant differences in length gain (MD 0.01, 95% CI: -0.03 to 0.04, 2 studies, n=50). There were no significant differences in head growth (MD −0.01, 95% CI: -0.02 to 0.00, 2 studies, n=76) or age at full enteral feed (MD −0.79, 95% CI: -2.20 to 0.61, 2 studies, n=86). Stool frequency increased significantly in prebiotic group (MD 0.80, 95% CI: 0.48 to 1.1, 2 studies, n=86). GOS/FOS and FOS yielded higher bifidobacteria counts in prebiotics group (MD 2.10, 95% CI: 0.96 to 3.24, n=27) and (MD 0.48, 95% CI: 0.28 to 0.68, n=56). Conclusions There is not enough evidence to state that supplementation with probiotics or prebiotics results in improved growth and clinical outcomes in exclusively formula fed preterm infants.
MED-2656
Effects of intestinal microflora and the environment on the development of asthma and allergy.
The aim of previous research into the causes of allergic diseases, including asthma was mostly to identify potential risk factors in the environment. No major risk factors have been identified, however. Over the past 10 years, focus has, therefore, more been directed towards protective factors that could enhance the development of tolerance to allergens which were previously encountered early in life, but are now lost in modern affluent societies. In particular, the role of childhood infections has been discussed, but so far these studies have not been conclusive. Recent epidemiological studies and experimental research suggest that the microbial environment and exposure to microbial products in infancy modifies immune responses and enhances the development of tolerance to ubiquitous allergens. The intestinal microflora may play a particular role in this respect, as it is the major external driving force in the maturation of the immune system after birth, and animal experiments have shown it to be a prerequisite for normal development of oral tolerance. Recent studies have shown differences in the composition of the microflora between healthy and allergic infants in countries with a high and low prevalence of allergies and between healthy and allergic infants within such countries. These differences are apparent within the first week of life and thus precede clinical symptoms. The use of live microorganisms that might be beneficial to health has a long tradition and the safety is well documented. Very recently, several prospective intervention studies, modifying the gut flora from birth have yielded encouraging results and may suggest a new mode of primary prevention of allergy in the future.