Barriers to Heart Disease Prevention
MED-2529
Effect of a very-high-fiber vegetable, fruit, and nut diet on serum lipids and colonic function.
We tested the effects of feeding a diet very high in fiber from fruit and vegetables. The levels fed were those, which had originally inspired the dietary fiber hypothesis related to colon cancer and heart disease prevention and also may have been eaten early in human evolution. Ten healthy volunteers each took 3 metabolic diets of 2 weeks duration. The diets were: high-vegetable, fruit, and nut (very-high-fiber, 55 g/1,000 kcal); starch-based containing cereals and legumes (early agricultural diet); or low-fat (contemporary therapeutic diet). All diets were intended to be weight-maintaining (mean intake, 2,577 kcal/d). Compared with the starch-based and low-fat diets, the high-fiber vegetable diet resulted in the largest reduction in low-density lipoprotein (LDL) cholesterol (33% +/- 4%, P <.001) and the greatest fecal bile acid output (1.13 +/- 0.30 g/d, P =.002), fecal bulk (906 +/- 130 g/d, P <.001), and fecal short-chain fatty acid outputs (78 +/- 13 mmol/d, P <.001). Nevertheless, due to the increase in fecal bulk, the actual concentrations of fecal bile acids were lowest on the vegetable diet (1.2 mg/g wet weight, P =.002). Maximum lipid reductions occurred within 1 week. Urinary mevalonic acid excretion increased (P =.036) on the high-vegetable diet reflecting large fecal steroid losses. We conclude that very high-vegetable fiber intakes reduce risk factors for cardiovascular disease and possibly colon cancer. Vegetable and fruit fibers therefore warrant further detailed investigation. Copyright 2001 by W.B. Saunders Company
MED-2524
Medical nutrition therapy for hypercholesterolemia positively affects patient satisfaction and quality of life outcomes.
Following a heart-healthy diet to lower cholesterol levels is often assumed to be difficult, to be burdensome, and to have a negative impact on quality of life (QOL). The purpose of this study was to evaluate the impact of medical nutrition therapy (MNT) versus usual care (UC) for hypercholesterolemia on patient satisfaction and QOL. Ninety ambulatory care patients (60 men and 30 women), age 28 to 66, were randomly assigned to receive either MNT from dietitians using a National Cholesterol Education Program-based protocol or UC from their physicians. Patients who received MNT reported no difference in QOL related to the taste or enjoyment of food compared with UC patients. However, the MNT group reported initial improvements in QOL related to the convenience and cost of following a low-fat diet when compared with the UC group. The MNT group also reported significant and lasting improvements in perceived QOL related to self-care compared with the UC group. MNT patients were more satisfied with the interaction at visits, knowledge and ability to manage their cholesterol, eating habits, appearance, time spent exercising, and life in general. Moreover, MNT patients did not report any negative impact related to following a low-fat diet in regard to feeling restricted by diet; interference with lifestyle activities; or difficulty planning, purchasing, or preparing meals or eating away from home. Contrary to popular belief there is no apparent reduction but rather an improvement in some measures of QOL and patient satisfaction with MNT for hypercholesterolemia.
MED-2525
A global survey of physicians' perceptions on cholesterol management: the From The Heart study.
AIMS: Guidelines for cardiovascular disease (CVD) prevention cite high levels of low-density lipoprotein cholesterol (LDL-C) as a major risk factor and recommend LDL-C goals for various risk groups. Lifestyle changes are advised as first-line treatment for patients with high cholesterol, and statins are recommended in high-risk patients. The From The Heart study investigated current practice for the diagnosis and treatment of high cholesterol, and attitudes towards management of the condition. METHODS: Physicians were randomly selected from 10 countries, and completed a confidential, semi-structured questionnaire. RESULTS: Of 2790 physicians agreeing to participate, 750 (27%) responded. Physicians rated CVD as the leading cause of death, although physicians (80%) perceived that cancer was the most feared illness among patients. Physicians (71%) believed smoking to be the greatest CVD risk factor, while only 50% thought high cholesterol was the greatest risk. Most physicians (81%) used guidelines to set cholesterol goals, primarily their national guidelines (34%) or the National Cholesterol Education Program Adult Treatment Panel III guidelines (24%). Although only 47% of patients reached and maintained their cholesterol goals, 61% of physicians believed that a sufficient number of patients achieved goals, and 53% did not feel frustrated that they could not always effectively treat patients with CVD. CONCLUSION: Results indicate discrepancies between guideline recommendations and clinical practice. Although physicians appreciate the risk of CVD, the importance of achieving healthy cholesterol levels for CVD prevention does not seem to be widely endorsed. There is a need for improved communication regarding the importance of cholesterol lowering and investigation of initiatives to improve goal achievement among physicians.
MED-2527
Cross-analysis of dietary prescriptions and adherence in 356 hypercholesterolaemic patients.
BACKGROUND: One of the major issues in controlling serum cholesterol through dietetic intervention appears to be the need to improve patient adherence. AIMS: To explore the many questions regarding barriers to, and motivators for, cholesterol-lowering diet adherence. METHODS: We surveyed French general practitioners' dietetic practices for patients with hypercholesterolaemia, and looked at their patients' attitudes towards such an approach. RESULTS: We analysed 234 doctors' personal questionnaires and 356 patient self-survey questionnaires. Patients' reasons for not complying with the prescribed diet included: 'already having satisfactory food habits' (34.7%), 'unwillingness to suffer nutritional deprivation' (33.3%), 'difficulties to conciliate a diet with family life' (27.8%) and 'taking cholesterol-lowering drugs' (22.2%). Despite a generally good understanding by patients of doctors' recommendations, some discrepancies were seen between their respective declarations. While doctors largely thought that patients needed more explanation on why and how a diet can lower cholesterol (and avoid taking drugs), only 39.4% of patients declared needing this kind of information. Other discrepancies were observed concerning barriers to, and motivators for, patient adherence. Moreover, some dietetic rules appeared to be more difficult to comply with than others, e.g. 82.6% patients remembered they should 'eat more fish' but only 51.3% actually did so. Finally, physicians, as well as patients, displayed a lack of confidence in lipid-lowering diet efficiency. CONCLUSION: Improving patient education, especially concerning their perception of risk, as well as increasing the involvement of dieticians, are motivators to explore in order to improve adherence. Copyright © 2012 Elsevier Masson SAS. All rights reserved.
MED-2530
The new pathophysiology of coronary artery disease.
Our understanding of coronary artery disease risk and the atherosclerotic process has changed greatly in recent years. For example, it is now known that angiographically apparent coronary artery plaque is not the major cause of myocardial infarction (MI). Rather, it is unstable, soft plaque that cannot be seen angiographically that is prone to rupture and result in infarction. Also important are changes in vascular reactivity resulting from diet. Cholesterol levels by themselves reveal little about a patient's coronary artery disease risk. Most infarctions occur in patients who have normal total cholesterol levels. At-risk patients can be identified using the ratio of total-to-high-density lipoprotein (HDL) cholesterol levels. The ratio of triglyceride to HDL cholesterol levels is also important. Simple steps to assess patients' risk in practice are outlined. Primary prevention trials demonstrate that coronary artery disease risk can be lowered dramatically with diet and drug therapy.
MED-2528
Improvements in hostility and depression in relation to dietary change and cholesterol lowering. The Family Heart Study.
OBJECTIVE: To describe changes in negative emotions among participants of a cholesterol-lowering study. DESIGN: Cohort study. Quantitative evaluation of changes in negative emotions in relation to diet and plasma cholesterol levels before and after a 5-year dietary intervention program aimed at reducing plasma cholesterol levels. SETTING: Community-dwelling families of the Family Heart Study, Portland, Oregon. PARTICIPANTS: One hundred forty-nine men and 156 women from 233 families (mean age, 37.7 years). MEASUREMENTS: Changes in negative emotions including depression and aggressive hostility as measured by the Hopkins Symptom Checklist (SCL-90). RESULTS: Improvement in overall emotional state was noted for the entire sample. Those who consumed a low-fat, high complex-carbohydrate diet at the end of the study showed significantly greater improvements in depression (P = 0.044; difference in improvement, 2.9 points) and aggressive hostility (P = 0.035; difference in improvement, 3.3 points) as well as a reduction in their plasma cholesterol levels (P = 0.024; difference in improvement, 2.7%) compared with those who ate a high-fat "American diet." CONCLUSIONS: Participation in a cholesterol-lowering program may not be associated with a worsening in emotional state. To the contrary, improvements in diet appear to be associated with reductions in depression and aggressive hostility as well as with lowered plasma cholesterol levels.
MED-2427
Elevated Levels of Cholesterol-Rich Lipid Rafts in Cancer Cells Are Correlated with Apoptosis Sensitivity Induced by Cholesterol-Depleting Agents
Lipid rafts/caveolae are membrane platforms for signaling molecules that regulate various cellular functions, including cell survival. To better understand the role of rafts in tumor progression and therapeutics, we investigated the effect of raft disruption on cell viability and compared raft levels in human cancer cell lines versus their normal counterparts. Here, we report that cholesterol depletion using methyl-β cyclodextrin caused anoikis-like apoptosis, which in A431 cells involved decreased raft levels, Bcl-xL down-regulation, caspase-3 activation, and Akt inactivation regardless of epidermal growth factor receptor activation. Cholesterol repletion replenished rafts on the cell surface and restored Akt activation and cell viability. Moreover, the breast cancer and the prostate cancer cell lines contained more lipid rafts and were more sensitive to cholesterol depletion-induced cell death than their normal counterparts. These results indicate that cancer cells contain increased levels of rafts and suggest a potential use of raft-modulating agents as anti-cancer drugs.
MED-2428
Women and statin use: a women's health advocacy perspective.
This paper is based on a longer report on the benefits, safety and modalities of information representation with regard to women and statin use, situated within the historical context of Women's Health Movement which has advocated for unbiased, appropriate medical research and prescribing for women based on the goals of full-disclosure, informed consent, evidence-based medicine and gender-based analysis. The evidence base for prescribing statins for women, especially for primary prevention is weak, yet Canadian data suggest that half of all prescriptions are for women. Safety meta-analyses do not disaggregate for women; do not consider female vulnerability to statin induced muscle problems, and women-centred concerns such as breast-cancer, miscarriage or birth defects are under-researched. Many trials have not published their non-cardiac serious adverse event data. These factors suggest that the standards of full-disclosure, informed consent, evidence-based prescribing and gender-based analysis are not being met and women should proceed with caution.
MED-2429
Statin use and risk of breast cancer: a meta-analysis of observational studies.
Emerging evidence suggests that statins' may decrease the risk of cancers. However, available evidence on breast cancer is conflicting. We, therefore, examined the association between statin use and risk of breast cancer by conducting a detailed meta-analysis of all observational studies published regarding this subject. PubMed database and bibliographies of retrieved articles were searched for epidemiological studies published up to January 2012, investigating the relationship between statin use and breast cancer. Before meta-analysis, the studies were evaluated for publication bias and heterogeneity. Combined relative risk (RR) and 95 % confidence interval (CI) were calculated using a random-effects model (DerSimonian and Laird method). Subgroup analyses, sensitivity analysis, and cumulative meta-analysis were also performed. A total of 24 (13 cohort and 11 case-control) studies involving more than 2.4 million participants, including 76,759 breast cancer cases contributed to this analysis. We found no evidence of publication bias and evidence of heterogeneity among the studies. Statin use and long-term statin use did not significantly affect breast cancer risk (RR = 0.99, 95 % CI = 0.94, 1.04 and RR = 1.03, 95 % CI = 0.96, 1.11, respectively). When the analysis was stratified into subgroups, there was no evidence that study design substantially influenced the effect estimate. Sensitivity analysis confirmed the stability of our results. Cumulative meta-analysis showed a change in trend of reporting risk of breast cancer from positive to negative in statin users between 1993 and 2011. Our meta-analysis findings do not support the hypothesis that statins' have a protective effect against breast cancer. More randomized clinical trials and observational studies are needed to confirm this association with underlying biological mechanisms in the future.
MED-2430
beta-Sitosterol enhances tamoxifen effectiveness on breast cancer cells by affecting ceramide metabolism.
The objective of this study was to investigate the effects of the dietary phytosterol beta-sitosterol (SIT) and the antiestrogen drug tamoxifen (TAM) on cell growth and ceramide (CER) metabolism in MCF-7 and MDA-MB-231 human breast cancer cells. The MCF-7 and MDA-MB-231 cell lines were studied as models of estrogen receptor positive and estrogen receptor negative breast cancer cells. Growth of both cell lines as determined using the sulforhodamine B assay was inhibited by treatment with 16 microM SIT but only MCF-7 cell growth was inhibited by treatment with 1 microM TAM. The combination of SIT and TAM further inhibited growth in both cell lines, most significantly in MDA-MB-231 cells. CER is a proapoptotic signal and CER levels were increased in both MCF-7 and MDA-MB-231 cells by individual treatment with SIT and TAM and the combined treatment raised cellular CER content even further. SIT and TAM raised CER levels by different means. SIT potently activated de novo CER synthesis in both MCF-7 and MDA-MB-231 cells by stimulating serine palmitoyltransferase activity; whereas TAM promoted CER accumulation in both cell types by inhibiting CER glycosylation. These results suggest that the combination regimen of dietary SIT and TAM chemotherapy may be beneficial in the management of breast cancer patients.
MED-2431
Long-term statin use and risk of ductal and lobular breast cancer among women 55-74 years of age
Background Mechanistic studies largely support the chemopreventive potential of statins. However, results of epidemiologic studies investigating statin use and breast cancer risk have been inconsistent and lacked the ability to evaluate long-term statin use. Materials and Methods We utilized data from a population-based case-control study of breast cancer conducted in the Seattle-Puget Sound region to investigate the relationship between long-term statin use and breast cancer risk. 916 invasive ductal carcinoma (IDC) and 1,068 invasive lobular carcinoma (ILC) cases 55-74 years of age diagnosed between 2000 and 2008 were compared to 902 control women. All participants were interviewed in-person and data on hypercholesterolemia and all episodes of lipid lowering medication use were collected through a structured questionnaire. We assessed the relationship between statin use and IDC and ILC risk using polytomous logistic regression. Results Current users of statins for 10 years or longer had a 1.83-fold increased risk of IDC [95% confidence interval (CI): 1.14-2.93] and a 1.97-fold increased risk of ILC (95% CI: 1.25-3.12) compared to never users of statins. Among women diagnosed with hypercholesterolemia, current users of statins for 10 years or longer had more than double the risk of both IDC [odds ratio (OR): 2.04, 95% CI: 1.17-3.57] and ILC (OR: 2.43, 95% CI: 1.40-4.21) compared to never users. Conclusion In this contemporary population-based case-control study long-term use of statins was associated with increased risks of both IDC and ILC. Impact Additional studies with similarly high frequencies of statin use for various durations are needed to confirm this novel finding.
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-2440
Total Cholesterol and Cancer Risk in a Large Prospective Study in Korea
Purpose To further clarify the relationship between total cholesterol and cancer, which remains unclear. Methods We prospectively examined the association between total cholesterol and site-specific and all-cancer incidence among 1,189,719 Korean adults enrolled in the National Health Insurance Corporation who underwent a standardized biennial medical examination in 1992 to 1995 and were observed for 14 years until cancer diagnosis or death. Results Over follow-up, 53,944 men and 24,475 women were diagnosed with a primary cancer. Compared with levels less than 160 mg/dL, high total cholesterol (≥ 240 mg/dL) was positively associated with prostate cancer (hazard ratio [HR], 1.24; 95% CI, 1.07 to 1.44; P trend = .001) and colon cancer (HR, 1.12; 95% CI, 1.00 to 1.25; P trend = .05) in men and breast cancer in women (HR, 1.17; 95% CI, 1.03 to 1.33; P trend = .03). Higher total cholesterol was associated with a lower incidence of liver cancer (men: HR, 0.42; 95% CI, 0.38 to 0.45; P trend < .001; women: HR, 0.32; 95% CI, 0.27 to 0.39; P trend < .001), stomach cancer (men: HR, 0.87; 95% CI, 0.82 to 0.93; P trend ≤ .001; women: HR, 0.86; 95% CI, 0.77 to 0.97; P trend = .06), and, in men, lung cancer (HR, 0.89; 95% CI, 0.82 to 0.96; P trend < .001). Results for liver cancer were slightly attenuated after additional adjustment for liver enzyme levels and hepatitis B surface antigen status (men: HR, 0.60; P trend < .001; women: HR, 0.46; P trend = .003) and exclusion of the first 10 years of follow-up (men: HR, 0.59; P trend < .001; women: HR, 0.44; P trend < .001). Total cholesterol was inversely associated with all-cancer incidence in both men (HR, 0.84; 95% CI, 0.81 to 0.86; P trend < .001) and women (HR, 0.91; 95% CI, 0.87 to 0.95; P trend < .001), but these associations were attenuated after excluding incident liver cancers (men: HR, 0.95; P trend < .001; women: HR, 0.98; P trend = .32). Conclusion In this large prospective study, we found that total cholesterol was associated with the risk of several different cancers, although these relationships differed markedly by cancer site.
MED-2526
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-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-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-4560
Preventing and arresting coronary atherosclerosis.
The good news about coronary atherosclerosis is that it takes an awful lot of plaque before symptoms of myocardial ischemia occur. The bad news is that despite the need for large quantities of plaque for symptoms to occur, nevertheless nearly half of us in the United States eventually have the necessary quantity. Atherosclerosis is infrequently hereditary in origin. Most of us get atherosclerosis because we consume too much fat, cholesterol, and calories. The consequence is an elevated ( > 150 mg/dl) serum total cholesterol level, and the higher the number is above 150, the greater is the quantity of plaque deposited in our arteries. If the serum total cholesterol level can be prevented from rising to more than 150 mg/dl, plaques are not laid down; if elevated levels are lowered to 150 mg/dl, further plaque does not form, and parts of those present may vanish. A fruit-vegetarian-starch diet is necessary as a rule to achieve the 150 mg/dl level in most adults. Lipid-lowering drugs are required in the patients with familial hypercholesterolemia and in most patients with atherosclerotic events. The best news about atherosclerosis is that it can be prevented in those without the hereditary form, and it can be arrested by lowering elevated serum total (and LDL) cholesterol to the 150 mg/dl level.
MED-4559
Can a statin neutralize the cardiovascular risk of unhealthy dietary choices?
The cardiovascular risk reduction associated with different statins for the prevention of cardiovascular disease and the cardiovascular risk increase associated with excess dietary intake of fat have been quantified. However, these relative risks have never been directly juxtaposed to determine whether an increase in relative risk by 1 activity could be neutralized by an opposing change in relative risk from a second activity. The investigators compared the increase in relative risk for cardiovascular disease associated with the total fat and trans fat content of fast foods against the relative risk decrease provided by daily statin consumption from a meta-analysis of statins in primary prevention of coronary artery disease (7 randomized controlled trials including 42,848 patients). The risk reduction associated with the daily consumption of most statins, with the exception of pravastatin, is more powerful than the risk increase caused by the daily extra fat intake associated with a 7-oz hamburger (Quarter Pounder) with cheese and a small milkshake. In conclusion, statin therapy can neutralize the cardiovascular risk caused by harmful diet choices. In other spheres of human activity, individuals choosing risky pursuits (motorcycling, smoking, driving) are advised or compelled to use measures to minimize the risk (safety equipment, filters, seatbelts). Likewise, some individuals eat unhealthily. Routine accessibility of statins in establishments providing unhealthy food might be a rational modern means to offset the cardiovascular risk. Fast food outlets already offer free condiments to supplement meals. A free statin-containing accompaniment would offer cardiovascular benefits, opposite to the effects of equally available salt, sugar, and high-fat condiments. Although no substitute for systematic lifestyle improvements, including healthy diet, regular exercise, weight loss, and smoking cessation, complimentary statin packets would add, at little cost, 1 positive choice to a panoply of negative ones.
MED-4598
They think they know but do they? Misalignment of perceptions of lifestyle modification knowledge among health professionals.
OBJECTIVE: The present study aimed to evaluate the knowledge and practices of public-sector primary-care health professionals and final-year students regarding the role of nutrition, physical activity and smoking cessation (lifestyle modification) in the management of chronic diseases of lifestyle within the public health-care sector. DESIGN: A comparative cross-sectional descriptive quantitative study was conducted in thirty primary health-care facilities and four tertiary institutions offering medical and/or nursing programmes in Cape Town in the Western Cape Metropole. Stratified random sampling, based on geographical location, was used to select the health facilities while convenience sampling was used to select students at the tertiary institutions. A validated self-administered knowledge test was used to obtain data from the health professionals. RESULTS: Differential lifestyle modification knowledge exists among both health professionals and students, with less than 10 % achieving the desired scores of 80 % or higher. The majority of health professionals seem to be promoting the theoretical concepts of lifestyle modification but experience difficulty in providing practical advice to patients. Of the health professionals evaluated, doctors appeared to have the best knowledge of lifestyle modification. Lack of time, lack of patient adherence and language barriers were given as the main barriers to providing lifestyle counselling. CONCLUSIONS: The undergraduate curricula of medical and nursing students should include sufficient training on lifestyle modification, particularly practical advice on diet, physical activity and smoking cessation. Health professionals working at primary health-care facilities should be updated by providing lifestyle modification education as part of continuing medical education.
MED-4599
Nutrition Education in U.S. Medical Schools: Latest Update of a National Survey
Purpose To quantify the number of required hours of nutrition education at U.S. medical schools and the types of courses in which the instruction was offered, and to compare these results with results from previous surveys. Method The authors distributed to all 127 accredited U.S. medical schools (that were matriculating students at the time of this study) a two-page online survey devised by the Nutrition in Medicine Project at the University of North Carolina at Chapel Hill. From August 2008 through July 2009, the authors asked their contacts, most of whom were nutrition educators, to report the nutrition contact hours that were required for their medical students and whether those actual hours of nutrition education occurred in a designated nutrition course, within another course, or during clinical rotations. Results Respondents from 109 (86%) of the targeted medical schools completed some part of the survey. Most schools (103/109) required some form of nutrition education. Of the 105 schools answering questions about courses and contact hours, only 26 (25%) required a dedicated nutrition course; in 2004, 32 (30%) of 106 schools did. Overall, medical students received 19.6 contact hours of nutrition instruction during their medical school careers (range: 0–70 hours); the average in 2004 was 22.3 hours. Only 28 (27%) of the 105 schools met the minimum 25 required hours set by the National Academy of Sciences; in 2004, 40 (38%) of 104 schools did so. Conclusions The amount of nutrition education that medical students receive continues to be inadequate.
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-4828
Association between statin-associated myopathy and skeletal muscle damage
Background Many patients taking statins often complain of muscle pain and weakness. The extent to which muscle pain reflects muscle injury is unknown. Methods We obtained biopsy samples from the vastus lateralis muscle of 83 patients. Of the 44 patients with clinically diagnosed statin-associated myopathy, 29 were currently taking a statin, and 15 had discontinued statin therapy before the biopsy (minimal duration of discontinuation 3 weeks). We also included 19 patients who were taking statins and had no myopathy, and 20 patients who had never taken statins and had no myopathy. We classified the muscles as injured if 2% or more of the muscle fibres in a biopsy sample showed damage. Using reverse transcriptase polymerase chain reaction, we evaluated the expression levels of candidate genes potentially related to myocyte injury. Results Muscle injury was observed in 25 (of 44) patients with myopathy and in 1 patient without myopathy. Only 1 patient with structural injury had a circulating level of creatine phosphokinase that was elevated more than 1950 U/L (10× the upper limit of normal). Expression of ryanodine receptor 3 was significantly upregulated in patients with biopsy evidence of structural damage (1.7, standard error of the mean 0.3). Interpretation Persistent myopathy in patients taking statins reflects structural muscle damage. A lack of elevated levels of circulating creatine phosphokinase does not rule out structural muscle injury. Upregulation of the expression of ryanodine receptor 3 is suggestive of an intracellular calcium leak.
MED-4829
Statin therapy, muscle function and falls risk in community-dwelling older adults.
BACKGROUND: Statin therapy can cause myopathy, however it is unclear whether this exacerbates age-related muscle function declines. AIM: To describe differences between statin users and non-users in muscle mass, muscle function and falls risk in a group of community-dwelling older adults. DESIGN: A prospective, population-based cohort study with a mean follow-up of 2.6 years. METHODS: Total 774 older adults [48% female; mean (standard deviation) age = 62 (7) years] were examined at baseline and follow-up. Differences in percentage appendicular lean mass (%ALM), leg strength, leg muscle quality (LMQ; specific force) and falls risk were compared for statin users and non-users. RESULTS: There were 147 (19%) statin users at baseline and 179 (23%) at follow-up. Longitudinal analyses revealed statin use at baseline predicted increased falls risk scores over 2.6 years (0.14, 95% CI 0.01 to 0.27) and a trend towards increased %ALM (0.45%, 95% CI -0.01 to 0.92). Statin users at both time points demonstrated decreased leg strength (-5.02 kg, 95% CI -9.65 to -0.40) and LMQ (-0.30 kg/kg, 95% CI -0.59 to -0.01), and trended towards increased falls risk (0.13, 95% CI -0.01 to 0.26) compared to controls. Finally, statin users at both baseline and follow-up demonstrated decreased leg strength (-16.17 kg, 95% CI -30.19 to -2.15) and LMQ (-1.13 kg/kg, 95% CI -2.02 to -0.24) compared to those who had ceased statin use at follow-up. CONCLUSION: Statin use may exacerbate muscle performance declines and falls risk associated with aging without a concomitant decrease in muscle mass, and this effect may be reversible with cessation.
MED-4830
Statin therapy induces ultrastructural damage in skeletal muscle in patients without myalgia.
Muscle pain and weakness are frequent complaints in patients receiving 3-hydroxymethylglutaryl coenzymeA (HMG CoA) reductase inhibitors (statins). Many patients with myalgia have creatine kinase levels that are either normal or only marginally elevated, and no obvious structural defects have been reported in patients with myalgia only. To investigate further the mechanism that mediates statin-induced skeletal muscle damage, skeletal muscle biopsies from statin-treated and non-statin-treated patients were examined using both electron microscopy and biochemical approaches. The present paper reports clear evidence of skeletal muscle damage in statin-treated patients, despite their being asymptomatic. Though the degree of overall damage is slight, it has a characteristic pattern that includes breakdown of the T-tubular system and subsarcolemmal rupture. These characteristic structural abnormalities observed in the statin-treated patients were reproduced by extraction of cholesterol from skeletal muscle fibres in vitro. These findings support the hypothesis that statin-induced cholesterol lowering per se contributes to myocyte damage and suggest further that it is the specific lipid/protein organization of the skeletal muscle cell itself that renders it particularly vulnerable. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
MED-5277
Effect of fat and carbohydrate consumption on endothelial function.
Consumption of a meal high in monounsaturated fat was associated with acute impairment of endothelial function when compared with a carbohydrate-rich meal. Such a divergent response in endothelial function may be important in the modulation of vascular function in health and disease.
MED-727
Illuminating the 'black box'. A description of 4454 patient visits to 138 family physicians.
BACKGROUND: The content and context of family practice outpatient visits have never been fully described, leaving many aspects of family practice in a "black box," unseen by policymakers and understood only in isolation. This article describes community family practices, physicians, patients, and outpatient visits. METHODS: Practicing family physicians in northeast Ohio were invited to participate in a multimethod study of the content of primary care practice. Research nurses directly observed consecutive patient visits, and collected additional data using medical record reviews, patient and physician questionnaires, billing data, practice environment checklists, and ethnographic fieldnotes. RESULTS: Visits by 4454 patients seeing 138 physicians in 84 practices were observed. Outpatient visits to family physicians encompassed a wide variety of patients, problems, and levels of complexity. The average patient paid 4.3 visits to the practice within the past year. The mean visit duration was 10 minutes. Fifty-eight percent of visits were for acute illness, 24% for chronic illness, and 12% for well care. The most common uses of time were history-taking, planning treatment, physical examination, health education, feedback, family information, chatting, structuring the interaction, and patient questions. CONCLUSIONS: Family practice and patient visits are complex, with competing demands and opportunities to address a wide range of problems of individuals and families over time and at various stages of health and illness. Multimethod research in practice settings can identify ways to enhance the competing opportunities of family practice to improve the health of their patients.
MED-4479
Long-term exposure to sodium nitrite and risk of esophageal carcinoma: a cohort study for 30 years.
The objective of this study is to investigate the risk of esophageal carcinoma in a cohort with long-term occupational exposure to sodium nitrite. The method used was a retrospective cohort study. A small wood screw manufacturer was founded in 1977 and closed down in 2000. In their production process, the sodium nitrite solution was used to serve as anticorrosive and coolant fluid. One hundred sixty workers in turning and milling shops had direct exposure to sodium nitrite through skin, mouth, and airway because of lack of occupational protective knowledge (study group), whereas 255 workers from other workshops without direct contact with sodium nitrite served as control group. The incidence, diagnosis, and treatment of esophageal carcinoma as well as other malignant tumors in these two groups were followed until the end of 2007. The sodium nitrite exposure time in the study group ranged from 16 to 23 years, with an average of 22.1 years. During 30 years of follow-up, there were 11 esophageal carcinomas and 10 other malignant tumors (4 hepatic cell carcinomas, 3 lung cancers, 2 breast cancers, and 1 leukemia) documented in the study group, while no cancer developed in the control group. The risk for esophageal carcinoma was significantly increased in the study group compared with the control group (relative risk = 1.26, 95% confidence interval = 1.08-1.46, chi-square = 116.83, P < 0.001). Long-term exposure to sodium nitrite markedly increases the risk of esophageal carcinoma in human body. © 2010 Copyright the Authors. Journal compilation © 2010, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.
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-4320
Higher bioaccessibility of iron and zinc from food grains in the presence of garlic and onion.
Bioavailability of micronutrients iron and zinc is particularly low from plant foods. Hence there is a need to evolve a food-based strategy to improve the same to combat widespread deficiencies of these minerals in a population dependent on plant foods. Dietary sulfur-containing amino acids have been reported to improve the mineral status of experimental animals. Our objective was to examine whether sulfur compound-rich Allium spices have a similar potential of beneficially modulating the mineral bioavailability. In this context, we examined the influence of exogenously added garlic and onion on the bioaccessibility of iron and zinc from food grains. Two representative cereals and pulses each were studied in both raw and cooked condition employing two levels of garlic (0.25 and 0.5 g/10 g of grain) and onion (1.5 and 3 g/10 g of grain). The enhancing effect of these two spices on iron bioaccessibility was generally evidenced in the case of both the cereals (9.4-65.9% increase) and pulses (9.9-73.3% increase) in both raw and cooked conditions. The two spices similarly enhanced the bioaccessibility of zinc from the food grains, the extent of increase in cereals ranging from 10.4% to 159.4% and in pulses from 9.8% to 49.8%. Thus, both garlic and onion were evidenced here to have a promoting influence on the bioaccessibility of iron and zinc from food grains. This novel information has the potential application in evolving a food-based strategy to improve the bioavailability of trace minerals and hence contributes to the human health benefit.
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-4278
EPIC-Oxford: lifestyle characteristics and nutrient intakes in a cohort of 33 883 meat-eaters and 31 546 non meat-eaters in the UK.
OBJECTIVE: To describe the lifestyle characteristics and nutrient intakes of the Oxford cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN: Cohort of men and women recruited through general practices or by post to include a high proportion of non meat-eaters. Dietary, anthropometric and lifestyle data were collected at baseline and four diet groups were defined. SETTING: United Kingdom. PARTICIPANTS: In total, 65 429 men and women aged 20 to 97 years, comprising 33 883 meat-eaters, 10 110 fish-eaters, 18 840 lacto-ovo vegetarians and 2596 vegans. RESULTS: Nutrient intakes and lifestyle factors differed across the diet groups, with striking differences between meat-eaters and vegans, and fish-eaters and vegetarians usually having intermediate values. Mean fat intake in each diet group was below the UK dietary reference value of 33% of total energy intake. The mean intake of saturated fatty acids in vegans was approximately 5% of energy, less than half the mean intake among meat-eaters (10-11%). Vegans had the highest intakes of fibre, vitamin B1, folate, vitamin C, vitamin E, magnesium and iron, and the lowest intakes of retinol, vitamin B12, vitamin D, calcium and zinc. CONCLUSIONS: The EPIC-Oxford cohort includes 31 546 non meat-eaters and is one of the largest studies of vegetarians in the world. The average nutrient intakes in the whole cohort are close to those currently recommended for good health. Comparisons of the diet groups show wide ranges in the intakes of major nutrients such as saturated fat and dietary fibre. Such variation should increase the ability of the study to detect associations of diet with major cancers and causes of death.
MED-2079
One-month strawberry-rich anthocyanin supplementation ameliorates cardiovascular risk, oxidative stress markers and platelet activation in humans.
Strawberries are an important fruit in the Mediterranean diet because of their high content of essential nutrients and beneficial phytochemicals, which seem to exert beneficial effects in human health. Healthy volunteers were supplemented daily with 500 g of strawberries for 1 month. Plasma lipid profile, circulating and cellular markers of antioxidant status, oxidative stress and platelet function were evaluated at baseline, after 30 days of strawberry consumption and 15 days after the end of the study. A high concentration of vitamin C and anthocyanins was found in the fruits. Strawberry consumption beneficially influenced the lipid profile by significantly reducing total cholesterol, low-density lipoprotein cholesterol and triglycerides levels (-8.78%, -13.72% and -20.80%, respectively; P<.05) compared with baseline period, while high-density lipoprotein cholesterol remained unchanged. Strawberry supplementation also significant decreased serum malondialdehyde, urinary 8-OHdG and isoprostanes levels (-31.40%, -29.67%, -27.90%, respectively; P<.05). All the parameters returned to baseline values after the washout period. A significant increase in plasma total antioxidant capacity measured by both ferric reducing ability of plasma and oxygen radical absorbance capacity assays and vitamin C levels (+24.97%, +41.18%, +41.36%, respectively; P<.05) was observed after strawberry consumption. Moreover, the spontaneous and oxidative hemolysis were significant reduced (-31.7% and -39.03%, respectively; P<.05), compared to the baseline point, which remained stable after the washout period. Finally, strawberry intake significant decrease (P<.05) the number of activated platelets, compared to both baseline and washout values. Strawberries consumption improves plasma lipids profile, biomarkers of antioxidant status, antihemolytic defenses and platelet function in healthy subjects, encouraging further evaluation on a population with higher cardiovascular disease risk. Copyright © 2014 Elsevier Inc. All rights reserved.
MED-3099
The aryl hydrocarbon receptor and its xenobiotic ligands: a fundamental trigger for cardiovascular diseases.
This review reconsiders a major cause of cardiovascular diseases, tobacco smoking, as the activation of the Aryl hydrocarbon Receptor (AhR), also known as the dioxin receptor, by aryl hydrocarbons from the tar fraction of tobacco in various organs of the cardiovascular domain. This concept sheds new light on well-known albeit controversial epidemiological concepts such as the Mediterranean diet and the French paradox. We also review the discovery that resveratrol, a natural AhR antagonist, may be of interest in the prevention and treatment of cardiovascular diseases.
MED-1104
Multiple myeloma : recent progress in diagnosis and treatment.
Multiple myeloma (MM) has been the most intractable hematological disease for many years. Recently, basic and clinical research has advanced remarkably and a new therapeutic strategy has been established. The introduction of high-dose melphalan with autologous stem-cell transplantation and the availability of molecular-targeted novel agents such as immunomodulatory drugs and proteasome inhibitors have dramatically changed the treatment strategies for MM. Achievement of a high response rate resulted in the extension of overall survival, but further research and the development of more multimodality therapeutic approaches is warranted to cure this disease.
MED-4593
Detection and quantification of methicillin-resistant Staphylococcus aureus (MRSA) clones in retail meat products.
AIMS: The objective of the study was to determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) contamination of retail meat and to determine the level of contamination. METHODS AND RESULTS: Pork (pork chops and ground pork), ground beef and chicken (legs, wings and thighs) were purchased at retail outlets in four Canadian provinces and tested for the presence of methicillin-resistant Staph. aureus using qualitative and quantitative methods. MRSA was isolated from 9.6% of pork, 5.6% of beef and 1.2% of chicken samples (P = 0.0002). Low levels of MRSA were typically present, with 37% below the detection threshold for quantification and <100 CFU g(-1) present in most quantifiable samples. All isolates were classified as Canadian epidemic MRSA-2 (CMRSA-2) by pulsed field gel electrophoresis (PFGE), with two different PFGE subtypes, and were spa type 24/t242. CONCLUSIONS: MRSA contamination of retail meat is not uncommon. While CMRSA-2, a human epidemic clone, has been found in pigs in Canada, the lack of isolation of livestock-associated ST398 was surprising. SIGNIFICANCE AND IMPACT OF THE STUDY: The relevance of MRSA contamination of meat is unclear but investigation is required because of the potential for exposure from food handling. Sources of contamination require investigation because these results suggest that human or animal sources could be involved.
MED-2315
Promiscuous drugs compared to selective drugs (promiscuity can be a virtue)
Background The word selectivity describes a drug's ability to affect a particular cell population in preference to others. As part of the current state of art in the search for new therapeutic agents, the property of selectivity is a mode of action thought to have a high degree of desirability. Consequently there is a growing activity in this area of research. Selectivity is generally a worthy property in a drug because a drug having high selectivity may have a dramatic effect when there is a single agent that can be targeted against the appropriate molecular-driver involved in the pathogenesis of a disease. An example is chronic myeloid leukemia (CML). CML has a specific chromosomal abnormality, the Philadelphia chromosome, that results in a single gene that produces an abnormal protein Discussion There is a burgeoning understanding of the cellular mechanisms that control the etiology and pathogeneses of diseases. This understanding both enables and motivates the development of drugs that induce a specific action in a selected cell population; i.e., a targeted treatment. Consequently, drugs that can target distinct molecular targets involved in pathologic/pathogenetic processes, or signal-transduction pathways, are being developed. However, in most cases, diseases involve multiple abnormalities. A disease may be associated with more than one dysfunctional protein and these may be out-of-balance with each other. Likewise a drug might strongly target a protein that shares a similar active domain with other proteins. A drug may also target pleiotropic cytokines, or other proteins that have multi-physiological functions. In this way multiple normal cellular pathways can be simultaneously influenced. Long term experience with drugs supposedly designed for only a single target, but which unavoidably involve other functional effects, is uncovering the fact that molecular targeting is not medically flawless. Summary We contend that an ideal drug may be one whose efficacy is based not on the inhibition of a single target, but rather on the rebalancing of the several proteins or events, that contribute to the etiology, pathogeneses, and progression of diseases, i.e., in effect a promiscuous drug. Ideally, if this could be done at minimum drug concentration, side effects could be minimized. Corollaries to this argument are that the growing fervor for researching truly selective drugs may be imprudent when considering the totality of responses; and that the expensive screening techniques used to discover these, may be both medically and financially inefficient.
MED-3163
Antioxidants prevent health-promoting effects of physical exercise in humans
Exercise promotes longevity and ameliorates type 2 diabetes mellitus and insulin resistance. However, exercise also increases mitochondrial formation of presumably harmful reactive oxygen species (ROS). Antioxidants are widely used as supplements but whether they affect the health-promoting effects of exercise is unknown. We evaluated the effects of a combination of vitamin C (1000 mg/day) and vitamin E (400 IU/day) on insulin sensitivity as measured by glucose infusion rates (GIR) during a hyperinsulinemic, euglycemic clamp in previously untrained (n = 19) and pretrained (n = 20) healthy young men. Before and after a 4 week intervention of physical exercise, GIR was determined, and muscle biopsies for gene expression analyses as well as plasma samples were obtained to compare changes over baseline and potential influences of vitamins on exercise effects. Exercise increased parameters of insulin sensitivity (GIR and plasma adiponectin) only in the absence of antioxidants in both previously untrained (P < 0.001) and pretrained (P < 0.001) individuals. This was paralleled by increased expression of ROS-sensitive transcriptional regulators of insulin sensitivity and ROS defense capacity, peroxisome-proliferator-activated receptor gamma (PPARγ), and PPARγ coactivators PGC1α and PGC1β only in the absence of antioxidants (P < 0.001 for all). Molecular mediators of endogenous ROS defense (superoxide dismutases 1 and 2; glutathione peroxidase) were also induced by exercise, and this effect too was blocked by antioxidant supplementation. Consistent with the concept of mitohormesis, exercise-induced oxidative stress ameliorates insulin resistance and causes an adaptive response promoting endogenous antioxidant defense capacity. Supplementation with antioxidants may preclude these health-promoting effects of exercise in humans.
MED-4188
Hydro-alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment of mild to moderate depression: a double-blind, randomized pilot tr...
Depressive disorders are very common in clinical practice, with approximately 11.3 of all adults afflicted during any a year. Saffron is the world's most expensive spice and apart from its traditional value as a food additive, recent studies indicate several therapeutic effects for saffron. It is used for depression in Persian traditional medicine. Our objective was to compare the efficacy of hydro-alcoholic extract of Crocus sativus (stigma) with fluoxetine in the treatment of mild to moderate depression in a 6-week double-blind, randomized trial. Forty adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition for major depression based on the structured clinical interview for DSM-IV and with mild to moderate depression participated in the trial. In this double-blind, single-center trial and randomized trial, patients were randomly assigned to receive capsules of saffron 30 mg/day (BD) (Group 1) and capsule of fluoxetine 20 mg/day (BD) (Group 2) for a 6-week study. Saffron at this dose was found to be effective similar to fluoxetine in the treatment of mild to moderate depression (F = 0.13, d.f. = 1, P = 0.71). There were no significant differences in the two groups in terms of observed side effects. The results of this study indicate the efficacy of Crocus sativus in the treatment of mild to moderate depression. A large-scale trial is justified.
MED-970
Diet and risk of diverticular disease in Oxford cohort of European Prospective Investigation into Cancer and Nutrition (EPIC): prospective study of British vegetarians and non-vegetarians
Objective To examine the associations of a vegetarian diet and dietary fibre intake with risk of diverticular disease. Design Prospective cohort study. Setting The EPIC-Oxford study, a cohort of mainly health conscious participants recruited from around the United Kingdom. Participants 47 033 men and women living in England or Scotland of whom 15 459 (33%) reported consuming a vegetarian diet. Main outcome measures Diet group was assessed at baseline; intake of dietary fibre was estimated from a 130 item validated food frequency questionnaire. Cases of diverticular disease were identified through linkage with hospital records and death certificates. Hazard ratios and 95% confidence intervals for the risk of diverticular disease by diet group and fifths of intake of dietary fibre were estimated with multivariate Cox proportional hazards regression models. Results After a mean follow-up time of 11.6 years, there were 812 cases of diverticular disease (806 admissions to hospital and six deaths). After adjustment for confounding variables, vegetarians had a 31% lower risk (relative risk 0.69, 95% confidence interval 0.55 to 0.86) of diverticular disease compared with meat eaters. The cumulative probability of admission to hospital or death from diverticular disease between the ages of 50 and 70 for meat eaters was 4.4% compared with 3.0% for vegetarians. There was also an inverse association with dietary fibre intake; participants in the highest fifth (≥25.5 g/day for women and ≥26.1 g/day for men) had a 41% lower risk (0.59, 0.46 to 0.78; P<0.001 trend) compared with those in the lowest fifth (<14 g/day for both women and men). After mutual adjustment, both a vegetarian diet and a higher intake of fibre were significantly associated with a lower risk of diverticular disease. Conclusions Consuming a vegetarian diet and a high intake of dietary fibre were both associated with a lower risk of admission to hospital or death from diverticular disease.
MED-1358
The acute effects of exercise on mood state.
This paper documents the recent (1976-1995) literature on the acute mood effects associated with participation in single sessions of exercise. Issues regarding experimental design, "ecological validity' and the operational definition of mood are addressed. Results from these studies suggest that both clinical and nonclinical subjects may benefit acutely from even a single bout of exercise. Finally, possible mechanisms and recommendations for future research are discussed.
MED-4704
Lipoid pneumonia presenting as non resolving community acquired pneumonia: a case report
Introduction Lipoid pneumonia is a rare form of pneumonia caused by inhalation or aspiration of fat containing substances like, petroleum jelly, mineral oils, few laxatives etc. It usually presents as insidious onset chronic respiratory illness simulating interstitial lung diseases. Rarely, it may present as an acute respiratory illness, specially, when exposure to fatty substance is acute and/or massive. Radiologically, it may mimic carcinoma, acute or chronic pneumonia, ARDS, or a localized granuloma. Diagnosis of LP requires demonstration of lipid laden macrophages in sputum, bronchoalveolar lavage fluid or fine needle aspiration cytology/biopsy from lung lesion. Treatment of this illness is poorly defined and constitutes supportive therapy and corticosteroids. Case presentation A 20-year old Indian farmer was referred to us with a diagnosis of non resolving community acquired pneumonia. Respiratory examination revealed signs of consolidation. Chest radiograph revealed findings suggestive of bilateral consolidation. Sputum and blood culture were sterile. He was treated with prolonged course of various antibiotics without any significant response. For evaluation of non resolving pneumonia fibreoptic bronchoscopy was done. Bronchoalveolar lavage fluid and biopsy from lung lesion showed lipid laden macrophages. Hence diagnosis of lipoid pneumonia was made. Patient was treated with course of corticosteroids with good response. Literature on this rare entity is discussed. Conclusion Lipoid pneumonia is a rare form of pneumonia which rarely present acutely resembling community acquired pneumonia and requires high degree of suspicion for diagnosis. Its treatment is difficult and poorly defined. However, prolonged corticosteroids may be effective.
MED-3689
Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection.
OBJECTIVES: While fecal microbiota transplantation (FMT) is historically known to be an effective means to treat recurrent Clostridium difficile infection (CDI) refractory to standard antibiotic therapies, the procedure is rarely performed. At least some of the reasons for limited availability are those of practicality, including aesthetic concerns and costs of donor screening. The objective of this study was to overcome these barriers in our clinical FMT program. METHODS: We report clinical experience with 43 consecutive patients who were treated with FMT for recurrent CDI since inception of this program at the University of Minnesota. During this time, we simplified donor identification and screening by moving from patient-identified individual donors to standard volunteer donors. Material preparation shifted from the endoscopy suite to a standardized process in the laboratory, and ultimately to banking frozen processed fecal material that is ready to use when needed. RESULTS: Standardization of material preparation significantly simplified the practical aspects of FMT without loss of apparent efficacy in clearing recurrent CDI. Approximately 30% of the patients had underlying inflammatory bowel disease, and FMT was equally effective in this group. CONCLUSIONS: Several key steps in the standardization of donor material preparation significantly simplified the clinical practice of FMT for recurrent CDI in patients failing antibiotic therapy.
MED-2672
Effects of added connective tissues on the sensory and mechanical properties of restructured beef steaks.
To quantify objectionable levels of connective tissues, restructured beef products were made with 2·5 and 5% added tendon; 5 and 10% added epimysium, gristle, or peri/endomysium; and a control. Initial tenderness (IT), residual connective tissue (CT), and overall texture (OT) were evaluated by a sensory panel. Panelists adversely scored IT, CT, and OT for 2·5 and 5% tendon and CT and OT for 10% epimysium and gristle. CT and OT scores correlated with hydroxyproline content and Lee-Kramer peak shear force for uncooked steaks with added tendon, gristle and epimysium but not peri/endomysium. Acceptable products can be made when raw materials are free of tendons and contain only limited amounts of epimysium. Copyright © 1990. Published by Elsevier Ltd.
MED-1795
Fruit consumption and risk of type 2 diabetes: results from three prospective longitudinal cohort studies
Objective To determine whether individual fruits are differentially associated with risk of type 2 diabetes. Design Prospective longitudinal cohort study. Setting Health professionals in the United States. Participants 66 105 women from the Nurses’ Health Study (1984-2008), 85 104 women from the Nurses’ Health Study II (1991-2009), and 36 173 men from the Health Professionals Follow-up Study (1986-2008) who were free of major chronic diseases at baseline in these studies. Main outcome measure Incident cases of type 2 diabetes, identified through self report and confirmed by supplementary questionnaires. Results During 3 464 641 person years of follow-up, 12 198 participants developed type 2 diabetes. After adjustment for personal, lifestyle, and dietary risk factors of diabetes, the pooled hazard ratio of type 2 diabetes for every three servings/week of total whole fruit consumption was 0.98 (95% confidence interval 0.96 to 0.99). With mutual adjustment of individual fruits, the pooled hazard ratios of type 2 diabetes for every three servings/week were 0.74 (0.66 to 0.83) for blueberries, 0.88 (0.83 to 0.93) for grapes and raisins, 0.89 (0.79 to 1.01) for prunes, 0.93 (0.90 to 0.96) for apples and pears, 0.95 (0.91 to 0.98) for bananas, 0.95 (0.91 to 0.99) for grapefruit, 0.97 (0.92 to 1.02) for peaches, plums, and apricots, 0.99 (0.95 to 1.03) for oranges, 1.03 (0.96 to 1.10) for strawberries, and 1.10 (1.02 to 1.18) for cantaloupe. The pooled hazard ratio for the same increment in fruit juice consumption was 1.08 (1.05 to 1.11). The associations with risk of type 2 diabetes differed significantly among individual fruits (P<0.001 in all cohorts). Conclusion Our findings suggest the presence of heterogeneity in the associations between individual fruit consumption and risk of type 2 diabetes. Greater consumption of specific whole fruits, particularly blueberries, grapes, and apples, is significantly associated with a lower risk of type 2 diabetes, whereas greater consumption of fruit juice is associated with a higher risk.
MED-5015
The intravenous use of coconut water.
Medical resources routinely used for intravenous hydration and resuscitation of critically ill patients may be limited in remote regions of the world. When faced with these shortages, physicians have had to improvise with the available resources, or simply do without. We report the successful use of coconut water as a short-term intravenous hydration fluid for a Solomon Island patient, a laboratory analysis of the local coconuts, and a review of previously documented intravenous coconut use.
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-1351
Conflicts of interest in psychiatry: strategies to cultivate literacy in daily practice.
The relationship between psychiatry and pharmaceutical companies has come under scrutiny during the past decade. Concerns are growing that financial ties of psychiatrists to the pharmaceutical industry may unduly influence professional judgments involving the primary interests of patients. Such conflicts of interest threaten the public trust in psychiatry. The goal of conflict of interest policies is to protect the integrity of professional judgment and to preserve public trust. The disclosure of individual and institutional financial relationships is a critical but limited first step in the process of identifying and responding to conflicts of interest. Conflict of interest policies and procedures can be strengthened by engaged psychiatrists, researchers, institutions, and professional associations in developing policies and consensus standards. Research on conflicts of interest can provide a stronger evidence base for policy design and implementation. Society has traditionally granted the medical profession considerable autonomy and may be willing to continue do so in the case of conflicts of interest. Nevertheless, concern is growing that stronger measures are needed. To avoid undue regulatory burdens, psychiatrists can play a vital role in designing responsible and reasonable conflict of interest policies that reduce the risks of bias and the loss of trust. Psychiatrists and the institutions that carry out research, education, clinical care, and practice guideline development must recognize public concerns about conflicts of interest and take effective measures soon to maintain public trust with a cultural change in the practice of psychiatry, from reactive treatment-seeking for mental illness to proactive advocacy for patients. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.
MED-2799
Synovial tissue inflammation in early and late osteoarthritis
Objective: To compare selected immunohistological features of inflammation in synovial tissue from patients with early and late osteoarthritis (OA). Methods: Synovial tissue samples were obtained from 10 patients with knee pain, normal radiographs, and arthroscopic manifestations of OA (early OA), and from 15 patients with OA undergoing knee joint arthroplasty (late OA). Conventional immunohistochemical techniques were used to measure microscopic manifestations of inflammation. The inflammatory cell infiltrate, blood vessel formation, and angiogenic factors, NF-κB activation, expression of tumour necrosis factor α (TNFα) and interleukin 1ß (IL1ß), and the presence of cyclo-oxygenase (COX)-1 and COX-2 were quantified. Fibroblast-like synoviocytes (FLS) were isolated from early and late OA tissue samples to compare in vitro production of prostaglandin E2 (PGE2) Results: Synovial tissue from patients with early OA demonstrated significantly greater CD4+ (p = 0.017) and CD68+ (p<0.001) cell infiltration, blood vessel formation (p = 0.01), vascular endothelial growth factor (p = 0.001), and intercellular adhesion molecule-1 expression (p<0.001). Numbers of cells producing TNFα and IL1ß were also significantly greater in early OA (p<0.001). Manifestations of inflammation in early OA were associated with increased expression of the NF-κB1 (p<0.001) and RelA (p = 0.015) subunits, and with increased COX-2 expression (p = 0.04). Cytokine-induced PGE2 production by cultured FLS was similar in both groups. Conclusion: Increased mononuclear cell infiltration and overexpression of mediators of inflammation were seen in early OA, compared with late OA. Isolated FLS were functionally similar in both groups, consistent with microenvironmental differences in the synovial tissue during different phases of OA. These observations may have important therapeutic implications for some patients during the early evolution of OA.
MED-5326
Red meat and colon cancer: should we become vegetarians, or can we make meat safer?
The effect of meat consumption on cancer risk is a controversial issue. However, recent meta-analyses show that high consumers of cured meats and red meat are at increased risk of colorectal cancer. This increase is significant but modest (20-30%). Current WCRF-AICR recommendations are to eat no more than 500 g per week of red meat, and to avoid processed meat. Moreover, our studies show that beef meat and cured pork meat promote colon carcinogenesis in rats. The major promoter in meat is heme iron, via N-nitrosation or fat peroxidation. Dietary additives can suppress the toxic effects of heme iron. For instance, promotion of colon carcinogenesis in rats by cooked, nitrite-treated and oxidized high-heme cured meat was suppressed by dietary calcium and by α-tocopherol, and a study in volunteers supported these protective effects in humans. These additives, and others still under study, could provide an acceptable way to prevent colorectal cancer. Copyright © 2011 Elsevier B.V. All rights reserved.
MED-720
The effect of oral alpha-galactosidase on intestinal gas production and gas-related symptoms.
Bloating, abdominal distention, and flatulence represent very frequent complaints in functional disorders but their pathophysiology and treatment are largely unknown. Patients frequently associate these symptoms with excessive intestinal gas and the reduction of gas production may represent an effective strategy. The aim was to evaluate the effect of alpha-galactosidase administration, in a randomized double-blind placebo-controlled protocol, on intestinal gas production and gas-related symptoms after a challenge test meal in healthy volunteers. Eight healthy volunteers ingested 300 or 1200 GalU of alpha-galactosidase or placebo during a test meal containing 420 g of cooked beans. Breath hydrogen excretion and occurrence of bloating, abdominal pain, discomfort, flatulence, and diarrhea were measured for 8 hr. The administration of 1200 GalU of alpha-galactosidase induced a significant reduction of both breath hydrogen excretion and severity of flatulence. A reduction in severity was apparent for all considered symptoms, but both 300 and 1200 GalU induced a significant reduction in the total symptom score. Alpha-galactosidase reduced gas production following a meal rich in fermentable carbohydrates and may be helpful in patients with gas-related symptoms.
MED-3795
Mastalgia: a review of management.
Mastalgia affects up to two-thirds of women at some time during their reproductive lives. It is usually benign, but thefear of underlying breast cancer is why many women present for evaluation. Mastalgia can be associated with premenstrual syndrome, fibrocystic breast disease, psychologic disturbance and, rarely, breast cancer. Occasionally, extramammary conditions, like Tietzie syndrome, present as mastalgia. A thorough clinical evaluation is required to assess the cause. The majority of women can be reassured after a clinical evaluation. Approximately 15% require pain-relieving therapy. Mechanical breast support; a low-fat, high-carbohydrate diet; and topical nonsteroidal antiinflammatory agents are reasonable first-line treatments. Hormonal agents, such as bromocriptine, tamoxifen and danazol, have all demonstrated efficacy in the treatment of mastalgia. Side effects, however, limit their extensive use. Danazol is the only FDA-approved hormonal treatment and is best used in cyclic form to limit the adverse effects. Lisuride maleate is a new agent recently studied for the treatment of mastalgia. Initial data on this medication are encouraging. Sixty percent of cyclic mastalgia recurs after treatment. Noncyclic mastalgia responds poorly to treatment but resolves spontaneously in up to 50% of cases.
MED-330
Dietary Phosphorus Acutely Impairs Endothelial Function
Excessive dietary phosphorus may increase cardiovascular risk in healthy individuals as well as in patients with chronic kidney disease, but the mechanisms underlying this risk are not completely understood. To determine whether postprandial hyperphosphatemia may promote endothelial dysfunction, we investigated the acute effect of phosphorus loading on endothelial function in vitro and in vivo. Exposing bovine aortic endothelial cells to a phosphorus load increased production of reactive oxygen species, which depended on phosphorus influx via sodium-dependent phosphate transporters, and decreased nitric oxide production via inhibitory phosphorylation of endothelial nitric oxide synthase. Phosphorus loading inhibited endothelium-dependent vasodilation of rat aortic rings. In 11 healthy men, we alternately served meals containing 400 mg or 1200 mg of phosphorus in a double-blind crossover study and measured flow-mediated dilation of the brachial artery before and 2 h after the meals. The high dietary phosphorus load increased serum phosphorus at 2 h and significantly decreased flow-mediated dilation. Flow-mediated dilation correlated inversely with serum phosphorus. Taken together, these findings suggest that endothelial dysfunction mediated by acute postprandial hyperphosphatemia may contribute to the relationship between serum phosphorus level and the risk for cardiovascular morbidity and mortality.
MED-1764
Lipid Concentrations and Semen Quality: The LIFE Study
The decline in sperm count rates over the last 50 years appears to parallel the rising prevalence of obesity. As lipids levels are strongly associated with obesity, high lipids levels or hyperlipidemia may thus play an important role in the decline in fertility in addition to other environmental or lifestyle factors. The objective of this population based cohort study was to evaluate the association between men’s serum lipid concentrations and semen quality parameters among 501 male partners of couples desiring pregnancy and discontinuing contraception. Each participant provided prospectively up to two semen samples (94% of men provided one or more semen samples, and 77% of men provided a second sample approximately one month later). Linear mixed effects models were used to estimate the associations between baseline lipid concentrations and semen quality parameters, adjusted for age, body mass index, and race. We found that higher levels of serum total cholesterol, free cholesterol and phospholipids were associated with a significantly lower percentage of sperm with intact acrosome and smaller sperm head area and perimeter. Our results suggest that lipid concentrations may affect semen parameters, specifically sperm head morphology, highlighting the importance of cholesterol and lipid homeostasis for male fecundity.
MED-1714
Long-term low-protein, low-calorie diet and endurance exercise modulate metabolic factors associated with cancer risk.
BACKGROUND: Western diets, obesity, and sedentary lifestyles are associated with increased cancer risk. The mechanisms responsible for this increased risk, however, are not clear. OBJECTIVE: We hypothesized that long-term low protein, low calorie intake and endurance exercise are associated with low concentrations of plasma growth factors and hormones that are linked to an increased risk of cancer. DESIGN: Plasma growth factors and hormones were evaluated in 21 sedentary subjects, who had been eating a low-protein, low-calorie diet for 4.4 +/- 2.8 y (x +/- SD age: 53.0 +/- 11 y); 21 endurance runners matched by body mass index (BMI; in kg/m2); and 21 age- and sex-matched sedentary subjects eating Western diets. RESULTS: BMI was lower in the low-protein, low-calorie diet (21.3 +/- 3.1) and runner (21.6 +/- 1.6) groups than in the Western diet (26.5 +/- 2.7; P < 0.005) group. Plasma concentrations of insulin, free sex hormones, leptin, and C-reactive protein were lower and sex hormone-binding globulin was higher in the low-protein, low-calorie diet and runner groups than in the sedentary Western diet group (all P < 0.05). Plasma insulin-like growth factor I (IGF-I) and the concentration ratio of IGF-I to IGF binding protein 3 were lower in the low-protein, low-calorie diet group (139 +/- 37 ng/mL and 0.033 +/- 0.01, respectively) than in the runner (177 +/- 37 ng/mL and 0.044 +/- 0.01, respectively) and sedentary Western (201 +/- 42 ng/mL and 0.046 +/- 0.01, respectively) diet groups (P < 0.005). CONCLUSIONS: Exercise training, decreased adiposity, and long-term consumption of a low-protein, low-calorie diet are associated with low plasma growth factors and hormones that are linked to an increased risk of cancer. Low protein intake may have additional protective effects because it is associated with a decrease in circulating IGF-I independent of body fat mass.
MED-1366
Mediterranean diet and public health: personal reflections.
My concern about diet as a public health problem began in the early 1950s in Naples, where we observed very low incidences of coronary heart disease associated with what we later came to call the "good Mediterranean diet." The heart of this diet is mainly vegetarian, and differs from American and northern European diets in that it is much lower in meat and dairy products and uses fruit for dessert. These observations led to our subsequent research in the Seven Countries Study, in which we demonstrated that saturated fat is the major dietary villain. Today, the healthy Mediterranean diet is changing and coronary heart disease is no longer confined to medical textbooks. Our challenge is to persuade children to tell their parents to eat as Mediterraneans do.
MED-3478
Role of hesperetin (a natural flavonoid) and its analogue on apoptosis in HT-29 human colon adenocarcinoma cell line--a comparative study.
Colon cancer is one of the serious health problems in most developed countries and its incidence rate is increasing in India. Hesperetin (HN) (3',5,7-trihydroxy-4'-methoxyflavonone) and hesperetin analogue (HA) were tested for their apoptosis inducing ability. Methyl thiazolyl tetrazolium assay revealed a dose as well as duration-dependent reduction of HT-29 (colon adenocarcinoma) cellular growth in response to HN and HA treatment. At 24 h 70 μM of HN and 32 μM of HA showed 50% reduction of HT-29 cellular growth. Acridine orange/ethidium bromide staining showed apoptotic features of cell death induced by HN and HA. Rhodamine 123 staining showed significant reduction in mitochondrial membrane potential induced by HN and HA. HN and HA induced DNA damage was confirmed by comet tail formation. Lipid peroxidation markers (TBARS) and protein oxidation marker (PCC) were significantly elevated in HN and HA treated groups. Enzymic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) were slightly decreased in their activities compared to control (untreated HT-29 cells). Results of Western blot analysis of apoptosis associated genes revealed an increase in cytochrome C, Bax, cleaved caspase-3 expression and a decrease in Bcl-2 expression. These findings indicate that HN and HA induce apoptosis on HT-29 via Bax dependent mitochondrial pathway involving oxidant/antioxidant imbalance. Copyright Â© 2011 Elsevier Ltd. All rights reserved.
MED-4949
Public Health and Economic Consequences of Methyl Mercury Toxicity to the Developing Brain
Methyl mercury is a developmental neurotoxicant. Exposure results principally from consumption by pregnant women of seafood contaminated by mercury from anthropogenic (70%) and natural (30%) sources. Throughout the 1990s, the U.S. Environmental Protection Agency (EPA) made steady progress in reducing mercury emissions from anthropogenic sources, especially from power plants, which account for 41% of anthropogenic emissions. However, the U.S. EPA recently proposed to slow this progress, citing high costs of pollution abatement. To put into perspective the costs of controlling emissions from American power plants, we have estimated the economic costs of methyl mercury toxicity attributable to mercury from these plants. We used an environmentally attributable fraction model and limited our analysis to the neurodevelopmental impacts—specifically loss of intelligence. Using national blood mercury prevalence data from the Centers for Disease Control and Prevention, we found that between 316,588 and 637,233 children each year have cord blood mercury levels > 5.8 μg/L, a level associated with loss of IQ. The resulting loss of intelligence causes diminished economic productivity that persists over the entire lifetime of these children. This lost productivity is the major cost of methyl mercury toxicity, and it amounts to $8.7 billion annually (range, $2.2–43.8 billion; all costs are in 2000 US$). Of this total, $1.3 billion (range, $0.1–6.5 billion) each year is attributable to mercury emissions from American power plants. This significant toll threatens the economic health and security of the United States and should be considered in the debate on mercury pollution controls.
MED-1281
Scanning the human proteome for calmodulin-binding proteins
The calcium ion (Ca2+) is a ubiquitous second messenger that is crucial for the regulation of a wide variety of cellular processes. The diverse transient signals transduced by Ca2+ are mediated by intracellular Ca2+-binding proteins, also known as Ca2+ sensors. A key obstacle to studying many Ca2+-sensing proteins is the difficulty in identifying the numerous downstream target interactions that respond to Ca2+-induced conformational changes. Among a number of Ca2+ sensors in the eukaryotic cell, calmodulin (CaM) is the most widespread and the best studied. Employing the mRNA display technique, we have scanned the human proteome for CaM-binding proteins and have identified and characterized a large number of both known and previously uncharacterized proteins that interact with CaM in a Ca2+-dependent manner. The interactions of several identified proteins with Ca2+/CaM were confirmed by using pull-down assays and coimmunoprecipitation. Many of the CaM-binding proteins identified belong to protein families such as the DEAD/H box proteins, ribosomal proteins, proteasome 26S subunits, and deubiquitinating enzymes, suggesting the possible involvement of Ca2+/CaM in different signaling pathways. The selection method described herein could be used to identify the binding partners of other calcium sensors on the proteome-wide scale.
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-1983
Transfer of methicillin-resistant Staphylococcus aureus from retail pork products onto food contact surfaces and the potential for consumer exposure.
Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen that has developed resistance to beta-lactam antibiotics and has been isolated at low population numbers in retail meat products. The objectives of this study were to estimate the potential transfer of MRSA from contaminated retail pork products to food contact surfaces and to estimate the potential for human exposure to MRSA by contact with those contaminated surfaces. Pork loins, bacon, and fresh pork sausage were inoculated with a four-strain mixed MRSA culture over a range of populations from approximately 4 to 8 log, vacuum packaged, and stored for 2 weeks at 5°C to simulate normal packaging and distribution. Primary transfer was determined by placing inoculated products on knife blades, cutting boards, and a human skin model (pork skin) for 5 min. Secondary transfer was determined by placing an inoculated product on the contact surface, removing it, and then placing the secondary contact surface on the initial contact surface. A pork skin model was used to simulate transfer to human skin by placing it into contact with the contact surface. The percentages of transfer for primary transfer from the inoculated products to the cutting board ranged from 39 to 49%, while the percentages of transfer to the knife ranged from 17 to 42%. The percentages of transfer from the inoculated products to the pork skin ranged from 26 to 36%. The secondary transfer percentages ranged from 2.2 to 5.2% across all products and contact surfaces. Statistical analysis showed no significant differences in the amounts of transfer between transfer surfaces and across cell concentrations.
MED-2050
The effects of moderate exercise training on natural killer cells and acute upper respiratory tract infections.
A randomly controlled 15-wk exercise training (ET) study (five 45-min sessions/wk, brisk walking at 60% heart rate reserve) with a group of 36 mildly obese, sedentary women was conducted to investigate the relationship between improvement in cardiorespiratory fitness, changes in natural killer (NK) cell number and activity, and acute upper respiratory tract infection (URI) symptomatology. The study was conducted using a 2 (exercise and nonexercise groups) x 3 (baseline, 6-, and 15-wk testing sessions) factorial design, with data analyzed using repeated measures ANOVA. No significant change in NK cell number occurred as a result of ET as measured by the CD16 and Leu-19 monoclonal antibodies. ET did have a significant effect on NK cell activity (E:T 50:1) especially during the initial 6-wk period [F(2.68) = 12.34, p less than 0.001]. Using data from daily logs kept by each subject, the exercise group was found to have significantly fewer URI symptom days/incident than the nonexercise group (3.6 +/- 0.7 vs 7.0 +/- 1.4 days, respectively, p = 0.049). Improvement in cardiorespiratory fitness was correlated significantly with a reduction in URI symptom days/incident (r = 0.37, p = 0.025) and a change in NK cell activity from baseline to six but not 15 wks (r = 0.35, p = 0.036). In summary, moderate ET is associated with elevated NK cell activity after six but not 15 weeks, and reduced URI symptomatology in comparison to a randomized, sedentary control group.
MED-3755
Can deceiving patients be morally acceptable?
Daniel K Sokol argues that on rare occasions benignly deceiving patients can be morally acceptable, and he has devised a decision checklist to help doctors facing such a dilemma
MED-1786
Good semen quality and life expectancy: a cohort study of 43,277 men.
Fertility status may predict later mortality, but no studies have examined the effect of semen quality on subsequent mortality. Men referred to the Copenhagen Sperm Analysis Laboratory by general practitioners and urologists from 1963 to 2001 were, through a unique personal identification number, linked to the Danish central registers that hold information on all cases of cancer, causes of death, and number of children in the Danish population. The men were followed until December 31, 2001, death, or censoring, whichever occurred first, and the total mortality and cause-specific mortality of the cohort were compared with those of all age-standardized Danish men or according to semen characteristics. Among 43,277 men without azospermia referred for infertility problems, mortality decreased as the sperm concentration increased up to a threshold of 40 million/mL. As the percentages of motile and morphologically normal spermatozoa and semen volume increased, mortality decreased in a dose-response manner (P(trend) < 0.05). The decrease in mortality among men with good semen quality was due to a decrease in a wide range of diseases and was found among men both with and without children; therefore, the decrease in mortality could not be attributed solely to lifestyle and/or social factors. Semen quality may therefore be a fundamental biomarker of overall male health.
MED-1130
Changes of faecal flora in rheumatoid arthritis during fasting and one-year vegetarian diet.
The beneficial effect of a 1-yr vegetarian diet in RA has recently been demonstrated in a clinical trial. We have analysed stool samples of the 53 RA patients by using direct stool sample gas-liquid chromatography of bacterial cellular fatty acids. Based on repeated clinical assessments disease improvement indices were constructed for the patients. At each time point during the intervention period the patients in the diet group were then assigned either to a group with a high improvement index (HI) or a group with a low improvement index (LI). Significant alteration in the intestinal flora was observed when the patients changed from omnivorous to vegan diet. There was also a significant difference between the periods with vegan and lactovegetarian diets. The faecal flora from patients with HI and LI differed significantly from each other at 1 and 13 months during the diet. This finding of an association between intestinal flora and disease activity may have implications for our understanding of how diet can affect RA.
MED-1876
Consumption of whole grain reduces risk of deteriorating glucose tolerance, including progression to prediabetes.
BACKGROUND: High whole-grain intake has been reportedly associated with reduced risk of developing type 2 diabetes (T2D), which is an effect possibly subject to genetic effect modification. Confirmation in prospective studies and investigations on the impact on prediabetes is needed. OBJECTIVES: In a prospective population-based study, we investigated whether a higher intake of whole grain protects against the development of prediabetes and T2D and tested for modulation by polymorphisms of the TCF7L2 gene. DESIGN: We examined the 8-10-y incidence of prediabetes (impaired glucose tolerance, impaired fasting glucose, or the combination of both) and T2D in relation to the intake of whole grain. Baseline data were available for 3180 women and 2297 men aged 35-56 y. RESULTS: A higher intake of whole grain (>59.1 compared with <30.6 g/d) was associated with a 34% lower risk to deteriorate in glucose tolerance (to prediabetes or T2D; women and men combined). The association remained after adjustments for age, family history of diabetes, BMI, physical activity, smoking, education, and blood pressure (OR: 0.78; 95% CI: 0.63, 0.96). Risk reduction was significant in men (OR: 0.65; 95% CI: 0.49, 0.85) but not in women. Associations were significant for prediabetes per se (all, OR: 0.73; 95% CI: 0.56, 0.94; men, OR: 0.57; 95% CI: 0.40, 0.80). The intake of whole grain correlated inversely with insulin resistance (HOMA-IR). The impact of whole-grain intake was undetectable in men who harbored diabetogenic polymorphisms of the TCF7L2 gene. CONCLUSIONS: A higher intake of whole grain is associated with decreased risk of deteriorating glucose tolerance including progression from normal glucose tolerance to prediabetes by mechanisms likely tied to effects on insulin sensitivity. Effect modifications by TCF7L2 genetic polymorphisms are supported.
MED-875
Inhibition of bacterial quorum sensing by vanilla extract.
AIMS: The purpose of this study was to search for a novel quorum sensing inhibitor and analyse its inhibitory activity. METHODS AND RESULTS: Quorum sensing inhibition was monitored using the Tn-5 mutant, Chromobacterium violaceum CV026. Vanilla beans (Vanilla planifolia Andrews) were extracted using 75% (v/v) aqueous methanol and added to C. violaceum CV026 cultures. Inhibitory activity was measured by quantifying violacein production using a spectrophotometer. The results have revealed that vanilla extract significantly reduced violacein production in a concentration-dependent manner, indicating inhibition of quorum sensing. CONCLUSIONS: Vanilla, a widely used spice and flavour, can inhibit bacterial quorum sensing. SIGNIFICANCE AND IMPACT OF THE STUDY: The results suggest that the intake of vanilla-containing food materials might promote human health by inhibiting quorum sensing and preventing bacterial pathogenesis. Further studies are required to isolate specific substances from vanilla extract acting as quorum sensing inhibitors.
MED-1289
A mechanism for slow release of biomagnified cyanobacterial neurotoxins and neurodegenerative disease in Guam
As root symbionts of cycad trees, cyanobacteria of the genus Nostoc produce β-methylamino-l-alanine (BMAA), a neurotoxic nonprotein amino acid. The biomagnification of BMAA through the Guam ecosystem fits a classic triangle of increasing concentrations of toxic compounds up the food chain. However, because BMAA is polar and nonlipophilic, a mechanism for its biomagnification through increasing trophic levels has been unclear. We report that BMAA occurs not only as a free amino acid in the Guam ecosystem but also can be released from a bound form by acid hydrolysis. After first removing free amino acids from tissue samples of various trophic levels (cyanobacteria, root symbioses, cycad seeds, cycad flour, flying foxes eaten by the Chamorro people, and brain tissues of Chamorros who died from amyotrophic lateral sclerosis/Parkinsonism dementia complex), we then hydrolyzed the remaining fraction and found BMAA concentrations increased 10- to 240-fold. This bound form of BMAA may function as an endogenous neurotoxic reservoir, accumulating and being transported between trophic levels and subsequently being released during digestion and protein metabolism. Within brain tissues, the endogenous neurotoxic reservoir can slowly release free BMAA, thereby causing incipient and recurrent neurological damage over years or even decades, which may explain the observed long latency period for neurological disease onset among the Chamorro people. The presence of BMAA in brain tissues from Canadian patients who died of Alzheimer's disease suggests that exposure to cyanobacterial neurotoxins occurs outside of Guam.
MED-3910
Effect of Consumption of Dried California Mission Figs on Lipid Concentrations
Background Figs are a rich source of soluble fiber. We evaluated the effect of consuming dried California Mission figs on serum lipids in hyperlipidemic adults. Methods In a crossover trial men and women aged 30–75 years with elevated low-density lipoprotein cholesterol (100–189 mg/dl) were randomized to add dried California Mission figs (120 g/day) to their usual diet for 5 weeks or eat their usual diet for 5 weeks, then crossed over to the other condition for another 5 weeks. Six 24-hour dietary recalls were obtained. Results Low- and high-density lipoprotein cholesterol and triglyceride concentrations did not differ between usual and figs-added diets (Bonferroni-corrected p > 0.017), while total cholesterol tended to increase with fig consumption (p = 0.02). Total cholesterol increased in participants (n = 41) randomized to usual followed by figs-added diet (p = 0.01), but remained unchanged in subjects (n = 42) who started with figs-added followed by usual diet (p = 0.4). During the figs-added diet, soluble fiber intake was 12.6 ± 3.7 versus 8.2 ± 4.1 g/day in the usual diet (p < 0.0001). Sugar intake increased from 23.4 ± 6.5 to 32.2 ± 6.3% of kcal in the figs-added diet (p < 0.0001). Body weight did not change (p = 0.08). Conclusions Daily consumption of figs did not reduce low-density lipoprotein cholesterol. Triglyceride concentrations were not significantly changed despite an increase in sugar intake.
MED-1651
Body weight status and cardiovascular risk factors in adults by frequency of candy consumption
Background Limited information is available regarding the impact of candy consumption on health. The purpose of this study was to investigate associations between typical frequency of candy consumption and body weight status and select cardiovascular risk factors among adults in the United States. Methods Using data collected in the 2003–2006 National Health and Nutrition Examination Surveys (NHANES), adults were categorized as infrequent (≤ 3 eating occasions [EO]/month), moderate (> 3 EO/month and ≤ 3.5 EO/week), or frequent (> 3.5 EO/week) candy consumers based on the combined frequency of chocolate and other candy consumption over the previous 12 months. Weight and adiposity status were analyzed using logistic regression models, and blood pressure, lipids, and insulin sensitivity were analyzed using linear regression models. Models were adjusted for age, sex and race/ethnicity, and also for additional covariates with potential associations with the outcomes. Appropriate statistical weights were used to yield results generalizable to the US population. Results Frequency of candy consumption was not associated with the risk of obesity, overweight/obesity, elevated waist circumference, elevated skinfold thickness, blood pressure, low density lipoprotein (LDL) or high density lipoprotein (HDL) cholesterol, triglycerides, or insulin resistance. Increased frequency of candy consumption was associated with higher energy intakes and higher energy adjusted intakes of carbohydrates, total sugars and added sugars, total fat, saturated fatty acids and monounsaturated fatty acids (p < 0.05), and lower adjusted intakes of protein and cholesterol (p < 0.001). Conclusions Increased frequency of candy consumption among adults in the United States was not associated with objective measures of adiposity or select cardiovascular risk factors, despite associated dietary differences. Given the cross-sectional study design, however, it cannot be concluded that candy consumption does not cause obesity or untoward levels of cardiovascular risk markers. The lack of an association between frequency of candy consumption and cardiovascular risk factors could be due to reduced intake of candy among the overweight due to dieting or a health professional’s recommendations. Additionally, it is important to note that the analysis was based on frequency of candy consumption and not amount of candy consumed. Longitudinal studies are needed to confirm the lack of associations between frequency of candy consumption and cardiovascular risk factors.
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-4589
Flavonoid permeability across an in situ model of the blood-brain barrier.
Understanding mechanisms associated with flavonoid neuroprotection is complicated by the lack of information on their ability to enter the CNS. This study examined naringenin and quercetin permeability across the blood-brain barrier (BBB), using in vitro (ECV304/C6 coculture) and in situ (rat) models. We report measurable permeabilities (P(app)) for both flavonoids across the in vitro BBB model, consistent with their lipophilicity. Both flavonoids showed measurable in situ BBB permeability. The rates of uptake (K(in)) into the right cerebral hemisphere were 0.145 and 0.019 ml min(-1) g(-1) for naringenin and quercetin, respectively. Quercetin K(in) was comparable to that of colchicine (0.006 ml min(-1) g(-1)), a substrate for P-glycoprotein (P-gp). Preadministration of the P-gp inhibitor PSC833 or GF120918 (10 mg/kg body wt) significantly increased colchicine K(in), but only GF120918 (able to inhibit breast cancer resistance protein, BCRP) affected K(in) for quercetin. Naringenin K(in) was not affected. The influence of efflux transporters on flavonoid permeability at the BBB was further studied using MDCK-MDR1 and immortalized rat brain endothelial cells (RBE4). Colchicine, quercetin, and naringenin all showed measurable accumulation (distribution volume, V(d) (microl/mg protein)) in both cell types. The V(d) for colchicine increased significantly in both cell lines following coincubation with either PSC833 (25 microM) or GF120918 (25 microM). Both inhibitors also caused an increase in naringenin V(d); by contrast only GF120918 coincubation significantly increased quercetin V(d). In conclusion, the results demonstrate that flavonoids are able to traverse the BBB in vivo. However, the permeability of certain flavonoids in vivo is influenced by their lipophilicity and interactions with efflux transporters.
MED-3850
Excretion, isolation and structure of a new phenolic constituent of female urine.
The regular occurrence of a peak due to an unidentified substance (X) in the gas chromatographic traces obtained from phenolic extracts of urine from human pregnant and non-pregnant females has been reported. The biphasic excretion of X with maxima in the luteal phase of the ovulatory cycle and relatively high levels in the first trimester of pregnancy were noteworthy and suggested that the substance may have a biological significance. Close similarities between the excretory pattern, the chemical and chromatographic properties of X and of those of the known phenolic steroids suggested initially that this compound was steroidal in nature. The same, or a similar, substance seems to be excreted in the vervet monkey (Cercopithecus aethiops pygerythrus). We now report the excretory pattern of X in more detail, the isolation of the pure compound from pooled pregnancy urine and the chemical structure. The structure determined by mass spectrometry, IR spectroscopy and NMR spectrometry is: trans-(+/-)-3,4-bis[(3-hydroxyphenyl)methyl]dihydro-2-(3H)-furanone (HPMF) and was confirmed by synthesis.
MED-3227
The impact of dietary protein on calcium absorption and kinetic measures of bone turnover in women.
Although high-protein diets induce hypercalciuria in humans, the source of the additional urinary calcium remains unclear. One hypothesis is that the high endogenous acid load of a high-protein diet is partially buffered by bone, leading to increased skeletal resorption and hypercalciuria. We used dual stable calcium isotopes to quantify the effect of a high-protein diet on calcium kinetics in women. The study consisted of 2 wk of a lead-in, well-balanced diet followed by 10 d of an experimental diet containing either moderate (1.0 g/kg) or high (2.1 g/kg) protein. Thirteen healthy women received both levels of protein in random order. Intestinal calcium absorption increased during the high-protein diet in comparison with the moderate (26.2 +/- 1.9% vs. 18.5 +/- 1.6%, P < 0.0001, mean +/- sem) as did urinary calcium (5.23 +/- 0.37 vs. 3.57 +/- 0.35 mmol/d, P < 0.0001, mean +/- sem). The high-protein diet caused a significant reduction in the fraction of urinary calcium of bone origin and a nonsignificant trend toward a reduction in the rate of bone turnover. There were no protein-induced effects on net bone balance. These data directly demonstrate that, at least in the short term, high-protein diets are not detrimental to bone.
MED-5045
Suppressive Effects of Selected Food Phytochemicals on CD74 Expression in NCI-N87 Gastric Carcinoma Cells
Helicobacter pylori (H. pylori) is one of the most widespread human pathogens, and plays major roles in chronic gastritis and gastric cancer. CD74 of gastric epithelial cells has recently been identified as an adhesion molecule to urease in H. pylori. In this study, we found that CD74 is highly expressed in a constitutive manner in NCI-N87 human gastric carcinoma cells at both the protein and mRNA levels as compared with Hs738St./Int fetal gastric cells. Subsequently, a novel cell-based ELISA able to rapidly screen the suppressive agents of CD74 expression was established. NCI-N87 cells were treated separately with 25 different food phytochemicals (4–100 µM) for 48 h and subjected to our novel assay. From those results, a citrus coumarin, bergamottin, was indicated to be the most promising compound with an LC50/IC50 value greater than 7.1, followed by luteolin (>5.4), nobiletin (>5.3), and quercetin (>5.1). Our findings suggest that these CD74 suppressants are unique candidates for preventing H. pylori adhesion and subsequent infection with reasonable action mechanisms.
MED-1888
Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk
BACKGROUND Recent studies in animals have shown a mechanistic link between intestinal microbial metabolism of the choline moiety in dietary phosphatidylcholine (lecithin) and coronary artery disease through the production of a proatherosclerotic metabolite, trimethylamine-N-oxide (TMAO). We investigated the relationship among intestinal microbiota-dependent metabolism of dietary phosphatidylcholine, TMAO levels, and adverse cardiovascular events in humans. METHODS We quantified plasma and urinary levels of TMAO and plasma choline and betaine levels by means of liquid chromatography and online tandem mass spectrometry after a phosphatidylcholine challenge (ingestion of two hard-boiled eggs and deuterium [d9]-labeled phosphatidylcholine) in healthy participants before and after the suppression of intestinal microbiota with oral broad-spectrum antibiotics. We further examined the relationship between fasting plasma levels of TMAO and incident major adverse cardiovascular events (death, myocardial infarction, or stroke) during 3 years of follow-up in 4007 patients undergoing elective coronary angiography. RESULTS Time-dependent increases in levels of both TMAO and its d9 isotopologue, as well as other choline metabolites, were detected after the phosphatidylcholine challenge. Plasma levels of TMAO were markedly suppressed after the administration of antibiotics and then reappeared after withdrawal of antibiotics. Increased plasma levels of TMAO were associated with an increased risk of a major adverse cardiovascular event (hazard ratio for highest vs. lowest TMAO quartile, 2.54; 95% confidence interval, 1.96 to 3.28; P<0.001). An elevated TMAO level predicted an increased risk of major adverse cardiovascular events after adjustment for traditional risk factors (P<0.001), as well as in lower-risk subgroups. CONCLUSIONS The production of TMAO from dietary phosphatidylcholine is dependent on metabolism by the intestinal microbiota. Increased TMAO levels are associated with an increased risk of incident major adverse cardiovascular events. (Funded by the National Institutes of Health and others.)
MED-3551
Modulation of angiogenesis by dietary phytoconstituents in the prevention and intervention of breast cancer.
Breast cancer is the leading cause of cancer-related deaths for women in the United States and the rest of the world. About 8% of women develop breast cancer during the course of their lives. Dietary habits are closely associated with both the risk and progression of breast cancer. Dietary agents have accumulated increasing importance with regards to the prevention and treatment of breast cancer. One such manner by which these compounds can target breast cancer development and progression is through interference with the angiogenic pathways. Angiogenesis is an intricate process that involves the development of new capillaries from previously existing blood vessels. Disruption of this pathway, therefore, provides a novel and effective avenue for therapeutic intervention of breast cancer. Various phytochemicals found in the diet kill breast cancer cells in vitro and prevent as well as suppress breast cancer progression in various preclinical animal models. This review examines the value of dietary phytoconstituents in the prevention and treatment of breast cancer through modulation of the intricate and complex process of angiogenesis. In addition, the potential benefits, challenges, and future directions of research on anti-angiogenic dietary phytochemicals in the prevention and intervention of breast cancer are also addressed. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
MED-1661
Lumbar disc degeneration: correlation with age, sex, and spine level in 600 autopsy specimens.
Using data from 16 published reports, the authors correlated macroscopic disc degeneration grades with age, sex, and spine level in 600 lumbar intervertebral discs from 273 cadavers (ages: 0-96 years). Male discs were more degenerated than female discs at most ages; significantly so in the second, fifth, sixth, and seventh decades. On average, L4-L5 and L3-L4 level discs showed more degeneration than discs at other lumbar levels. These macroscopic findings corroborate radiographic data from epidemiologic studies. The calculations suggest that higher mechanical stress, perhaps combined with longer nutritional pathways, may be responsible for the earlier degeneration of male discs.
MED-1990
Intensive versus conventional glucose control in critically ill patients.
BACKGROUND: The optimal target range for blood glucose in critically ill patients remains unclear. METHODS: Within 24 hours after admission to an intensive care unit (ICU), adults who were expected to require treatment in the ICU on 3 or more consecutive days were randomly assigned to undergo either intensive glucose control, with a target blood glucose range of 81 to 108 mg per deciliter (4.5 to 6.0 mmol per liter), or conventional glucose control, with a target of 180 mg or less per deciliter (10.0 mmol or less per liter). We defined the primary end point as death from any cause within 90 days after randomization. RESULTS: Of the 6104 patients who underwent randomization, 3054 were assigned to undergo intensive control and 3050 to undergo conventional control; data with regard to the primary outcome at day 90 were available for 3010 and 3012 patients, respectively. The two groups had similar characteristics at baseline. A total of 829 patients (27.5%) in the intensive-control group and 751 (24.9%) in the conventional-control group died (odds ratio for intensive control, 1.14; 95% confidence interval, 1.02 to 1.28; P=0.02). The treatment effect did not differ significantly between operative (surgical) patients and nonoperative (medical) patients (odds ratio for death in the intensive-control group, 1.31 and 1.07, respectively; P=0.10). Severe hypoglycemia (blood glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was reported in 206 of 3016 patients (6.8%) in the intensive-control group and 15 of 3014 (0.5%) in the conventional-control group (P<0.001). There was no significant difference between the two treatment groups in the median number of days in the ICU (P=0.84) or hospital (P=0.86) or the median number of days of mechanical ventilation (P=0.56) or renal-replacement therapy (P=0.39). CONCLUSIONS: In this large, international, randomized trial, we found that intensive glucose control increased mortality among adults in the ICU: a blood glucose target of 180 mg or less per deciliter resulted in lower mortality than did a target of 81 to 108 mg per deciliter. (ClinicalTrials.gov number, NCT00220987.) 2009 Massachusetts Medical Society
MED-3848
Meta-analyses of lignans and enterolignans in relation to breast cancer risk.
BACKGROUND: Epidemiologic studies that examined whether lignans, the most important class of phytoestrogens in the Western diet, protect against breast cancer have yielded inconsistent results. OBJECTIVE: In this study, we conducted meta-analyses on the association between lignans and breast cancer risk. DESIGN: We performed a systematic MEDLINE search to identify epidemiologic studies published between 1997 and August 2009. We calculated pooled risk estimates (REs) for total lignan exposure, dietary lignan intake, enterolignan exposure, and blood or urine concentrations of enterolactone and according to menopausal and estrogen receptor (ER) status of tumors. RESULTS: We included 21 studies (11 prospective cohort studies and 10 case-control studies) in the meta-analyses. Lignan exposure was not associated with an overall breast cancer risk (RE: 0.92; 95% CI: 0.81, 1.02; P for heterogeneity = 0.004). However, in postmenopausal women, high lignan intake was associated with a significant reduced risk of breast cancer (13 studies; RE: 0.86; 95% CI: 0.78, 0.94; P for heterogeneity = 0.32). Breast cancer risk was also inversely associated with enterolignan exposure (4 studies; RE: 0.84; 95% CI: 0.71, 0.97) but not with blood or urine enterolactone concentrations. The associations were not significantly different between ER-status subgroups (6 studies). CONCLUSIONS: High lignan exposure may be associated with a reduced breast cancer risk in postmenopausal women. Additional work is warranted to clarify the association between lignan exposure and breast cancer risk.
MED-3667
Genotoxicity of lavender oil, linalyl acetate, and linalool on human lymphocytes in vitro.
The potential genotoxicity of lavender essential oil and its major components, linalool, and linalyl acetate, was evaluated in vitro by the micronucleus test on peripheral human lymphocytes. In the range of non-toxic concentrations (0.5-100 μg/ml), linalyl acetate increased the frequency of micronuclei significantly and in concentration-dependent manner; lavender oil did so only at the highest concentration tested, whereas linalool was devoid of genotoxicity. None of the tested substances led to an increase in nucleoplasmic bridges or nuclear buds frequency. These findings suggest that the mutagenic activity of lavender oil can be related to the presence of linalyl acetate, which seems to have a profile of an aneugenic agent. Copyright © 2010 Wiley-Liss, Inc.
MED-3199
Potential risks resulting from fruit/vegetable-drug interactions: effects on drug-metabolizing enzymes and drug transporters.
It has been well established that complex mixtures of phytochemicals in fruits and vegetables can be beneficial for human health. Moreover, it is becoming increasingly apparent that phytochemicals can influence the pharmacological activity of drugs by modifying their absorption characteristics through interactions with drug transporters as well as drug-metabolizing enzyme systems. Such effects are more likely to occur in the intestine and liver, where high concentrations of phytochemicals may occur. Alterations in cytochrome P450 and other enzyme activities may influence the fate of drugs subject to extensive first-pass metabolism. Although numerous studies of nutrient-drug interactions have been published and systematic reviews and meta-analyses of these studies are available, no generalizations on the effect of nutrient-drug interactions on drug bioavailability are currently available. Several publications have highlighted the unintended consequences of the combined use of nutrients and drugs. Many phytochemicals have been shown to have pharmacokinetic interactions with drugs. The present review is limited to commonly consumed fruits and vegetables with significant beneficial effects as nutrients and components in folk medicine. Here, we discuss the phytochemistry and pharmacokinetic interactions of the following fruit and vegetables: grapefruit, orange, tangerine, grapes, cranberry, pomegranate, mango, guava, black raspberry, black mulberry, apple, broccoli, cauliflower, watercress, spinach, tomato, carrot, and avocado. We conclude that our knowledge of the potential risk of nutrient-drug interactions is still limited. Therefore, efforts to elucidate potential risks resulting from food-drug interactions should be intensified in order to prevent undesired and harmful clinical consequences. © 2011 Institute of Food Technologists®
MED-1428
Optimal low-density lipoprotein is 50 to 70 mg/dl: lower is better and physiologically normal.
The normal low-density lipoprotein (LDL) cholesterol range is 50 to 70 mg/dl for native hunter-gatherers, healthy human neonates, free-living primates, and other wild mammals (all of whom do not develop atherosclerosis). Randomized trial data suggest atherosclerosis progression and coronary heart disease events are minimized when LDL is lowered to <70 mg/dl. No major safety concerns have surfaced in studies that lowered LDL to this range of 50 to 70 mg/dl. The current guidelines setting the target LDL at 100 to 115 mg/dl may lead to substantial undertreatment in high-risk individuals.
MED-3166
The effect of acute pre-exercise dark chocolate consumption on plasma antioxidant status, oxidative stress and immunoendocrine responses to prolong...
PURPOSE: Acute antioxidant supplementation may modulate oxidative stress and some immune perturbations that typically occur following prolonged exercise. The aims of the present study were to examine the effects of acutely consuming dark chocolate (high polyphenol content) on plasma antioxidant capacity, markers of oxidative stress and immunoendocrine responses to prolonged exercise. METHODS: Fourteen healthy men cycled for 2.5 h at ~60% maximal oxygen uptake 2 h after consuming 100 g dark chocolate (DC), an isomacronutrient control bar (CC) or neither (BL) in a randomised-counterbalanced design. RESULTS: DC enhanced pre-exercise antioxidant status (P = 0.003) and reduced by trend (P = 0.088) 1 h post-exercise plasma free [F₂-isoprostane] compared with CC (also, [F₂-isoprostane] increased post-exercise in CC and BL but not DC trials). Plasma insulin concentration was significantly higher pre-exercise (P = 0.012) and 1 h post-exercise (P = 0.026) in the DC compared with the CC trial. There was a better maintenance of plasma glucose concentration on the DC trial (2-way ANOVA trial × time interaction P = 0.001), which decreased post-exercise in all trials but was significantly higher 1 h post-exercise (P = 0.039) in the DC trial. There were no between trial differences in the temporal responses (trial × time interactions all P > 0.05) of hypothalamic-pituitary-adrenal axis stress hormones, plasma interleukin-6, the magnitude of leukocytosis and neutrophilia and changes in neutrophil function. CONCLUSION: Acute DC consumption may affect insulin, glucose, antioxidant status and oxidative stress responses, but has minimal effects on immunoendocrine responses, to prolonged exercise.
MED-2901
The Association between Glaucoma Prevalence and Supplementation with the Oxidants Calcium and Iron
Purpose. To investigate the relationship between supplementary consumption of the oxidants calcium and iron and the prevalence of glaucoma. Methods. This cross-sectional study included 3833 participants in the National Health and Nutrition Examination Survey (NHANES) for 2007 and 2008, ≥40 years of age, who reported a presence or absence of glaucoma. Participants were interviewed regarding the use of dietary supplements and antacids during the preceding 30-day period. Data pertaining to the supplementary intake of calcium and iron was aggregated and divided into quintiles. Information regarding the presence or absence of glaucoma and demographics, comorbidities, and health-related behavior was obtained via interview. Results. Participants who consumed ≥800 mg/d of supplementary calcium or ≥18 mg/d of supplementary iron had significantly higher odds of having been diagnosed with glaucoma than did those who had not consumed supplementary calcium or iron, after adjustment for potential confounders (odds ratio [OR] 2.44, 95% confidence interval [CI] 1.25–4.76 for calcium; OR 3.80, 95% CI 1.79–8.06 for iron). Concurrent consumption of both calcium and iron above these levels was associated with still greater odds of having been diagnosed with glaucoma (OR 7.24, 95% CI 2.42–21.62). A clear dose–response relationship between quintiles of supplementary calcium or iron intake and glaucoma prevalence was not found. Conclusions. These results suggest that there may be a threshold intake of iron and calcium above which there is an increased risk of development of glaucoma. Prospective longitudinal studies are needed, to assess whether oxidant intake is a risk factor for development and progression of glaucoma.
MED-3151
Baker's yeast β-glucan supplementation increases monocytes and cytokines post-exercise: implications for infection risk?
Strenuous aerobic exercise is known to weaken the immune system, and while many nutritional supplements have been proposed to boost post-exercise immunity, few are known to be effective. The purpose of the present study was to evaluate whether 10 d of supplementation with a defined source of baker's yeast β-glucan (BG, Wellmune WGP®) could minimise post-exercise immunosuppression. Recreationally active men and women (n 60) completed two 10 d trial conditions using a cross-over design with a 7 d washout period: placebo (rice flour) and baker's yeast BG (250 mg/d of β-1,3/1,6-glucans derived from Saccharomyces cerevisiae) before a bout of cycling (49 ± 6 min) in a hot (38 ± 2°C), humid (45 ± 2 % relative humidity) environment. Blood was collected at baseline (before supplement), pre- (PRE), post- (POST) and 2 h (2H) post-exercise. Total and subset monocyte concentration was measured by four-colour flow cytometry. Plasma cytokine levels and lipopolysaccharide (LPS)-stimulated cytokine production were measured using separate multiplex assays. Total (CD14⁺) and pro-inflammatory monocyte concentrations (CD14⁺/CD16⁺) were significantly greater at POST and 2H (P<0·05) with BG supplementation. BG supplementation boosted LPS-stimulated production of IL-2, IL-4, IL-5 and interferon-γ (IFN-γ) at PRE and POST (P<0·05). Plasma IL-4, IL-5 and IFN-γ concentrations were greater at 2H following BG supplementation. It appears that 10 d of supplementation with BG increased the potential of blood leucocytes for the production of IL-2, IL-4, IL-5 and IFN-γ. The key findings of the present study demonstrate that BG may have potential to alter immunity following a strenuous exercise session.
MED-852
Fiber intake and the risk of oral, pharyngeal and esophageal cancer.
The relation between various types of fiber and oral, pharyngeal and esophageal cancer was investigated using data from a case-control study conducted between 1992 and 1997 in Italy. Cases were 271 hospital patients with incident, histologically confirmed oral cancer, 327 with pharyngeal cancer and 304 with esophageal cancer. Controls were 1,950 subjects admitted to the same network of hospitals as the cases for acute, nonneoplastic diseases. Cases and controls were interviewed during their hospital stay using a validated food frequency questionnaire. Odds ratios (OR) were computed after allowance for age, sex, and other potential confounding factors, including alcohol, tobacco consumption, and energy intake. The ORs for the highest vs. the lowest quintile of intake of oral, pharyngeal and esophageal cancer combined were 0.40 for total (Englyst) fiber, 0.37 for soluble fiber, 0.52 for cellulose, 0.48 for insoluble non cellulose polysaccharide, 0.33 for total insoluble fiber and 0.38 for lignin. The inverse relation were similar for vegetable fiber (OR = 0.51), fruit fiber (OR = 0.60) and grain fiber (OR = 0.56), and were somewhat stronger for oral and pharyngeal cancer than for esophageal cancer. The ORs were similar for the two sexes and strata of age, education, alcohol and tobacco consumption, and total non-alcohol energy intake. Our study indicates that fiber intake may have a protective role on oral, pharyngeal and esophageal cancer.
MED-4871
Monosodium glutamate 'allergy': menace or myth?
Monosodium glutamate (MSG) is a salt form of a non-essential amino acid commonly used as a food additive for its unique flavour enhancing qualities. Since the first description of the 'Monosodium glutamate symptom complex', originally described in 1968 as the 'Chinese restaurant syndrome', a number of anecdotal reports and small clinical studies of variable quality have attributed a variety of symptoms to the dietary ingestion of MSG. Descriptions of MSG-induced asthma, urticaria, angio-oedema, and rhinitis have prompted some to suggest that MSG should be an aetiologic consideration in patients presenting with these conditions. This review prevents a critical review of the available literature related to the possible role of MSG in the so-called 'Chinese restaurant syndrome' and in eliciting asthmatic bronchospasm, urticaria, angio-oedema, and rhinitis. Despite concerns raised by early reports, decades of research have failed to demonstrate a clear and consistent relationship between MSG ingestion and the development of these conditions.
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-1433
Dietary Advanced Glycation End Products and Aging
Advanced glycation end products (AGEs) are a heterogeneous, complex group of compounds that are formed when reducing sugar reacts in a non-enzymatic way with amino acids in proteins and other macromolecules. This occurs both exogenously (in food) and endogenously (in humans) with greater concentrations found in older adults. While higher AGEs occur in both healthy older adults and those with chronic diseases, research is progressing to both quantify AGEs in food and in people, and to identify mechanisms that would explain why some human tissues are damaged, and others are not. In the last twenty years, there has been increased evidence that AGEs could be implicated in the development of chronic degenerative diseases of aging, such as cardiovascular disease, Alzheimer’s disease and with complications of diabetes mellitus. Results of several studies in animal models and humans show that the restriction of dietary AGEs has positive effects on wound healing, insulin resistance and cardiovascular diseases. Recently, the effect of restriction in AGEs intake has been reported to increase the lifespan in animal models. This paper will summarize the work that has been published for both food AGEs and in vivo AGEs and their relation with aging, as well as provide suggestions for future research.
MED-4652
Ductal carcinoma in situ: terminology, classification, and natural history.
Ductal carcinoma in situ (DCIS) refers to breast epithelial cells that have become "cancerous" but still reside in their normal place in the ducts and lobules. In this setting, cancerous means that there is an abnormal increase in the growth of the epithelial cells, which accumulate within and greatly expand the ducts and lobules. DCIS is a nonlethal type of cancer because it stays in its normal place. However, DCIS is very important because it is the immediate precursor of invasive breast cancers, which are potentially lethal. This article provides a general overview of DCIS, including historical perspective, methods of classification, current perspective, and future goals.
MED-5182
Dietary fibre and risk of breast cancer in the UK Women's Cohort Study.
BACKGROUND: Reports of relationships between dietary fibre intake and breast cancer have been inconsistent. Previous cohort studies have been limited by a narrow range of intakes. METHODS: Women who developed invasive breast cancer, 350 post-menopausally and 257 pre-menopausally, during 240,959 person-years of follow-up in the UK Women's Cohort Study (UKWCS) were studied. This cohort has 35,792 subjects with a wide range of exposure to dietary fibre with intakes of total fibre in the lowest quintile of <20 g/day up to >30 g/day in the top quintile. Fibre and breast cancer relationships were explored using Cox regression modelling adjusted for measurement error. Effects of fibre, adjusting for confounders were examined for pre- and post-menopausal women separately. RESULTS: In pre-menopausal, but not post-menopausal women a statistically significant inverse relationship was found between total fibre intake and risk of breast cancer (P for trend = 0.01). The top quintile of fibre intake was associated with a hazard ratio of 0.48 [95% confidence interval (CI) 0.24-0.96] compared with the lowest quintile. Pre-menopausally, fibre from cereals was inversely associated with risk of breast cancer (P for trend = 0.05) and fibre from fruit had a borderline inverse relationship (P for trend = 0.09). A further model including dietary folate strengthened the significance of the inverse relationship between total fibre and pre-menopausal breast cancer. CONCLUSIONS: These findings suggest that in pre-menopausal women, total fibre is protective against breast cancer; in particular, fibre from cereals and possibly fruit.
MED-2130
Deconvoluting mTOR biology
In metazoans, TOR is an essential protein that functions as a master regulator of cellular growth and proliferation. Over the past decade, there has been an explosion of information about this critical master kinase, ranging from the composition of the TOR protein complex to its ability to act as an integrator of numerous extracellular signals. Unfortunately, this plethora of information has also raised numerous questions regarding TOR function. Currently, the prevailing view is that mammalian TOR (mTOR) exists in at least two molecular complexes, mTORC1 and mTORC2, which are largely defined by the presence of either RAPTOR or RICTOR. However, additional co-factors have been identified for each complex, and their importance in mediating mTOR signals has been incompletely elucidated. Similarly, there are differences in mTOR function that reflect the tissue of origin. In this review, we present an alternative view to mTOR complex formation and function, which envisions mTOR regulation and signal propagation as a reflection of cell type- and basal state-dependent conditions. The re-interpretation of mTOR biology in this framework may facilitate the design of therapies most likely to effectively inhibit this central regulator of cell behavior.
MED-1210
Comparing indices of diet quality with chronic disease mortality risk in postmenopausal women in the Women's Health Initiative Observational Study:...
Poor diet quality is thought to be a leading risk factor for years of life lost. We examined how scores on 4 commonly used diet quality indices-the Healthy Eating Index 2010 (HEI), the Alternative Healthy Eating Index 2010 (AHEI), the Alternate Mediterranean Diet (aMED), and the Dietary Approaches to Stop Hypertension (DASH)-are related to the risks of death from all causes, cardiovascular disease (CVD), and cancer among postmenopausal women. Our prospective cohort study included 63,805 participants in the Women's Health Initiative Observational Study (from 1993-2010) who completed a food frequency questionnaire at enrollment. Cox proportional hazards models were fit using person-years as the underlying time metric. We estimated multivariate hazard ratios and 95% confidence intervals for death associated with increasing quintiles of diet quality index scores. During 12.9 years of follow-up, 5,692 deaths occurred, including 1,483 from CVD and 2,384 from cancer. Across indices and after adjustment for multiple covariates, having better diet quality (as assessed by HEI, AHEI, aMED, and DASH scores) was associated with statistically significant 18%-26% lower all-cause and CVD mortality risk. Higher HEI, aMED, and DASH (but not AHEI) scores were associated with a statistically significant 20%-23% lower risk of cancer death. These results suggest that postmenopausal women consuming a diet in line with a priori diet quality indices have a lower risk of death from chronic disease. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.
MED-4713
A case of Kombucha tea toxicity.
INTRODUCTION: Kombucha "mushroom'' tea is touted to have medicinal properties. Here, we present a case of hyperthermia, lactic acidosis, and acute renal failure within 15 hours of Kombucha tea ingestion. CASE PRESENTATION: A 22 year old male, newly diagnosed with HIV, became short of breath and febrile to 103.0F, within twelve hours of Kombucha tea ingestion. He subsequently became combative and confused, requiring sedation and intubation for airway control. Laboratories revealed a lactate of 12.9 mmol/L, and serum creatinine of 2.1 mg/dL. DISCUSSION: Kombucha tea is black tea fermented in a yeast-bacteria medium. Several case reports exist of serious, and sometimes fatal, hepatic dysfunction and lactic acidosis within close proximity to ingestion. CONCLUSION: While Kombucha tea is considered a healthy elixir, the limited evidence currently available raises considerable concern that it may pose serious health risks. Consumption of this tea should be discouraged, as it may be associated with life-threatening lactic acidosis.
MED-1502
The longer-term impacts of Western diet on human cognition and the brain.
Animal work over the last three decades has generated a convincing body of evidence that a Western diet - one high in saturated fat and refined carbohydrates (HFS diet) - can damage various brain systems. In this review we examine whether there is evidence for this in humans, using converging lines of evidence from neuropsychological, epidemiological and neuroimaging data. Using the animal research as the organizing principal, we examined evidence for dietary induced impairments in frontal, limbic and hippocampal systems, and with their associated functions in learning, memory, cognition and hedonics. Evidence for the role of HFS diet in attention deficit disorder and in neurodegenerative conditions was also examined. While human research data is still at an early stage, there is evidence of an association between HFS diet and impaired cognitive function. Based upon the animal data, and a growing understanding of how HFS diets can disrupt brain function, we further suggest that there is a causal link running from HFS diet to impaired brain function in humans, and that HFS diets also contribute to the development of neurodegenerative conditions. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.
MED-5228
Phytochemicals and their impact on adipose tissue inflammation and diabetes.
Type 2 diabetes mellitus is an inflammatory disease and the mechanisms that underlie this disease, although still incompletely understood, take place in the adipose tissue of obese subjects. Concurrently, the prevalence of obesity caused by Western diet's excessive energy intake and the lack of exercise escalates, and is believed to be causative for the chronic inflammatory state in adipose tissue. Overnutrition itself as an overload of energy may induce the adipocytes to secrete chemokines activating and attracting immune cells to adipose tissue. But also inflammation-mediating food ingredients like saturated fatty acids are believed to directly initiate the inflammatory cascade. In addition, hypoxia in adipose tissue as a direct consequence of obesity, and its effect on gene expression in adipocytes and surrounding cells in fat tissue of obese subjects appears to play a central role in this inflammatory response too. In contrast, revisiting diet all over the world, there are also some natural food products and beverages which are associated with curative effects on human health. Several natural compounds known as spices such as curcumin, capsaicin, and gingerol, or secondary plant metabolites catechin, resveratrol, genistein, and quercetin have been reported to provide an improved health status to their consumers, especially with regard to diabetes, and therefore have been investigated for their anti-inflammatory effect. In this review, we will give an overview about these phytochemicals and their role to interfere with inflammatory cascades in adipose tissue and their potential for fighting against inflammatory diseases like diabetes as investigated in vivo. Copyright © 2012 Elsevier Inc. All rights reserved.
MED-4861
Fruit and vegetable intake and overall cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).
BACKGROUND: It is widely believed that cancer can be prevented by high intake of fruits and vegetables. However, inconsistent results from many studies have not been able to conclusively establish an inverse association between fruit and vegetable intake and overall cancer risk. METHODS: We conducted a prospective analysis of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to assess relationships between intake of total fruits, total vegetables, and total fruits and vegetables combined and cancer risk during 1992-2000. Detailed information on the dietary habit and lifestyle variables of the cohort was obtained. Cancer incidence and mortality data were ascertained, and hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression models. Analyses were also conducted for cancers associated with tobacco and alcohol after stratification for tobacco smoking and alcohol drinking. RESULTS: Of the initial 142 605 men and 335 873 women included in the study, 9604 men and 21 000 women were identified with cancer after a median follow-up of 8.7 years. The crude cancer incidence rates were 7.9 per 1000 person-years in men and 7.1 per 1000 person-years in women. Associations between reduced cancer risk and increased intake of total fruits and vegetables combined and total vegetables for the entire cohort were similar (200 g/d increased intake of fruits and vegetables combined, HR = 0.97, 95% CI = 0.96 to 0.99; 100 g/d increased intake of total vegetables, HR = 0.98, 95% CI = 0.97 to 0.99); intake of fruits showed a weaker inverse association (100 g/d increased intake of total fruits, HR = 0.99, 95% CI = 0.98 to 1.00). The reduced risk of cancer associated with high vegetable intake was restricted to women (HR = 0.98, 95% CI = 0.97 to 0.99). Stratification by alcohol intake suggested a stronger reduction in risk in heavy drinkers and was confined to cancers caused by smoking and alcohol. CONCLUSIONS: A very small inverse association between intake of total fruits and vegetables and cancer risk was observed in this study. Given the small magnitude of the observed associations, caution should be applied in their interpretation.
MED-5177
Pilot evaluation of flaxseed for the management of hot flashes.
The objective of this study was to evaluate, in a phase 2 pilot study, tolerability and the effect of 6 weeks of flaxseed therapy on hot flash scores in women not wishing to receive estrogen therapy. Eligibility included 14 hot flashes per week for at least 1 month. In the baseline week, participants took no study medication and documented the characteristics of their hot flashes. Thereafter, crushed flaxseed was administered at 40 g daily. Participants provided weekly toxicity reports and health-related quality of life information. The primary end point was a change in hot flash score prospectively reported in a daily hot flash diary. Thirty women were enrolled between June 17 and November 8, 2005. The mean decrease in hot flash scores after flaxseed therapy was 57% (median decrease 62%). The mean reduction in daily hot flash frequency was 50% (median reduction 50%), from 7.3 hot flashes to 3.6. Fourteen of the 28 participants (50%) experienced mild or moderate abdominal distention. Eight participants (29%) experienced mild diarrhea, one experienced flatulence, and six (21%) withdrew because of toxicities. This study suggests that dietary therapy decreases hot flash activity in women not taking estrogen therapy. This reduction is greater than what would be expected with placebo.
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-861
Associations of whole-blood fatty acids and dietary intakes with prostate cancer in Jamaica.
OBJECTIVE: To investigate the association of whole-blood fatty acids and reported intakes of fats with risk of prostate cancer (PCa). DESIGN: Case-control study of 209 men 40-80 years old with newly diagnosed, histologically confirmed prostate cancer and 226 cancer-free men attending the same urology clinics. Whole-blood fatty acid composition (mol%) was measured by gas chromatography and diet assessed by food frequency questionnaire. RESULTS: High whole-blood oleic acid composition (tertile 3 vs. tertile 1: OR, 0.37; CI, 0.14-0.0.98) and moderate palmitic acid proportions (tertile 2: OR, 0.29; CI, 0.12-0.70) (tertile 3: OR, 0.53; CI, 0.19-1.54) were inversely related to risk of PCa, whereas men with high linolenic acid proportions were at increased likelihood of PCa (tertile 3 vs. tertile 1: OR, 2.06; 1.29-3.27). Blood myristic, stearic and palmitoleic acids were not associated with PCa. Higher intakes of dietary MUFA were inversely related to prostate cancer (tertile 3 vs. tertile 1: OR, 0.39; CI 0.16-0.92). The principal source of dietary MUFA was avocado intake. Dietary intakes of other fats were not associated with PCa. CONCLUSIONS: Whole-blood and dietary MUFA reduced the risk of prostate cancer. The association may be related to avocado intakes. High blood linolenic acid was directly related to prostate cancer. These associations warrant further investigation.
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-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-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-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-4312
Post-epidemic eosinophilia myalgia syndrome associated with L-Tryptophan
Eosinophilia–myalgia syndrome (EMS) is characterized by subacute onset of myalgias and peripheral eosinophilia, followed by chronic neuropathy and skin induration. An epidemic of EMS in 1989 was linked to L-tryptophan consumption originating from a single source. Following the Food and Drug Administration (FDA) ban on the sale of L-tryptophan, the incidence of EMS declined rapidly. Moreover, no new cases have been published since the FDA ban was lifted in 2005. We report the clinical, histopathological and immunogenetic features of a new case of L-tryptophan-associated EMS along with evidence of activated transforming growth factor-ß and interleukin-4 signaling in the lesional skin.
MED-5272
Chronic effects of a high-fat diet enriched with virgin olive oil and a low-fat diet enriched with alpha-linolenic acid on postprandial endothelial...
Traditional cardiovascular risk factors are associated with endothelial dysfunction. The vascular endothelium plays a key role in local vascular tone regulation and can be modulated by dietary fat. We propose to determine the chronic effect of three diets with different fat compositions on postprandial endothelial function and inflammatory biomarkers. Twenty healthy men followed three 4-week diets in a randomised cross-over design: a Western diet, rich in saturated fat (22% SFA, 12% MUFA and 0.4% alpha-linolenic acid (ALA), all fractions are % of energy); a Mediterranean diet, rich in MUFA ( < 10 % SFA, 24 % MUFA and 0.4% ALA); a low-fat diet enriched in ALA ( < 10% SFA, 12% MUFA and 2% ALA). At the end of each dietary period all subjects underwent a postprandial study. Plasma concentrations of lipid parameters, soluble intercellular cell-adhesion molecule-1, soluble vascular cell-adhesion molecule-1 (sVCAM-1), nitrates and nitrites (NOx) and endothelial function studied by laser Doppler were examined at 0, 2, 4, 6 and 8 h. The endothelium-dependent vasodilatory response was greater 4 h after the ingestion of the MUFA-rich diet than after the SFA or ALA low-fat diets (P = 0.031). The 4 h postprandial plasma sVCAM-1 levels were lower after the MUFA meals than after the ALA low-fat diet (P = 0.043). The bioavailability of NOx was higher following the MUFA diet than after the SFA and ALA low-fat diets (P = 0.027). We found no differences in the other parameters measured. Chronic ingestion of a Mediterranean diet avoids the postprandial deterioration of endothelial function associated with Westernised diets in healthy individuals.
MED-1128
Rheumatoid arthritis is linked to Proteus--the evidence.
Rheumatoid arthritis (RA) is a chronic inflammatory arthritic and potentially disabling condition, mainly affecting women of middle age and having characteristic clinical features. Various microbial agents were implicated in the causation of RA. Extensive literature based on the results of various genetic, microbiological, molecular, and immunological studies carried out by independent research groups supports the role of Proteus mirabilis bacteria in the etiopathogenesis of RA. New diagnostic markers and criteria and the use of a novel therapeutic protocol in the form of antibiotic and dietary measures are suggested to be used together with current treatments in the management of RA. Prospective longitudinal studies with the use of antimicrobial measures in patients with RA are required to establish the therapeutic benefit of this microbe-disease association.
MED-3274
Olfactory detection of human bladder cancer by dogs: proof of principle study
Objective To determine whether dogs can be trained to identify people with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. Design Experimental, “proof of principle” study in which six dogs were trained to discriminate between urine from patients with bladder cancer and urine from diseased and healthy controls and then evaluated in tests requiring the selection of one bladder cancer urine sample from six controls. Participants 36 male and female patients (age range 48-90 years) presenting with new or recurrent transitional cell carcinoma of the bladder (27 samples used for training; 9 used for formal testing); 108 male and female controls (diseased and healthy, age range 18-85 years—54 samples used in training; 54 used for testing). Main outcome measure Mean proportion of successes per dog achieved during evaluation, compared with an expected value of 1 in 7 (14%). Results Taken as a group, the dogs correctly selected urine from patients with bladder cancer on 22 out of 54 occasions. This gave a mean success rate of 41% (95% confidence intervals 23% to 58% under assumptions of normality, 26% to 52% using bootstrap methods), compared with 14% expected by chance alone. Multivariate analysis suggested that the dogs' capacity to recognise a characteristic bladder cancer odour was independent of other chemical aspects of the urine detectable by urinalysis. Conclusions Dogs can be trained to distinguish patients with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. This suggests that tumour related volatile compounds are present in urine, imparting a characteristic odour signature distinct from those associated with secondary effects of the tumour, such as bleeding, inflammation, and infection.
MED-901
Cow's milk allergy is associated with recurrent otitis media during childhood.
To determine whether cow's milk allergy (CMA) in infancy is associated with recurrent otitis media (ROM) or other chronic ear infections, we conducted a cohort study by enrolling 56 milk-allergic and 204 control schoolchildren. We also studied the association between ear problems and different atopic manifestations. A higher proportion of children with CMA had had ROM. defined as at least 15 acute otitis media episodes by the age of 10 years (27%, vs 12%, p = 0.009), and had undergone adenoidectomy and or tympanostomy compared with the controls (48%, vs 28%, p = 0.005). However, this was only true of the children who had developed respiratory atopy. Asthma and/or allergic rhinitis, but not atopic dermatitis, posed a significant risk for ROM, while all the three atopic manifestations enhanced the risk for secretory otitis media. Positive skin prick tests with food, but not with inhaled allergens, tended to be associated with ear problems. In conclusion, we found that children with CMA in infancy, even when properly treated, had experienced significantly more ROM, the risk associating with concomitant development of respiratory atopy.
MED-4184
High concentrations of polybrominated diphenylethers (PBDEs) in breast adipose tissue of California women.
We measured major PBDEs and PCBs in breast adipose tissues of California women participating in a breast cancer study in the late 1990s. Samples were analyzed using gas chromatography with electron impact ionization and tandem mass spectrometry detection. The congener profile observed was: BDE47>BDE99>BDE153>BDE100>BDE154 and PCB153>PCB180>PCB138>PCB118. Whereas high correlations were observed within each chemical class, very weak correlations appeared between classes, pointing to different exposure pathways. Weak negative associations were observed for PBDE congeners and age. Our PBDE data are among the highest reported, exceeding data from the National Health and Nutrition Examination Survey and consistent with the high use of PBDEs in California. These data may be helpful in establishing a baseline for PBDE body burdens to gauge changes over time as a result of restrictions in the use of PBDE formulations. Copyright © 2010 Elsevier Ltd. All rights reserved.
MED-1732
Glyphosate induces human breast cancer cells growth via estrogen receptors.
Glyphosate is an active ingredient of the most widely used herbicide and it is believed to be less toxic than other pesticides. However, several recent studies showed its potential adverse health effects to humans as it may be an endocrine disruptor. This study focuses on the effects of pure glyphosate on estrogen receptors (ERs) mediated transcriptional activity and their expressions. Glyphosate exerted proliferative effects only in human hormone-dependent breast cancer, T47D cells, but not in hormone-independent breast cancer, MDA-MB231 cells, at 10⁻¹² to 10⁻⁶M in estrogen withdrawal condition. The proliferative concentrations of glyphosate that induced the activation of estrogen response element (ERE) transcription activity were 5-13 fold of control in T47D-KBluc cells and this activation was inhibited by an estrogen antagonist, ICI 182780, indicating that the estrogenic activity of glyphosate was mediated via ERs. Furthermore, glyphosate also altered both ERα and β expression. These results indicated that low and environmentally relevant concentrations of glyphosate possessed estrogenic activity. Glyphosate-based herbicides are widely used for soybean cultivation, and our results also found that there was an additive estrogenic effect between glyphosate and genistein, a phytoestrogen in soybeans. However, these additive effects of glyphosate contamination in soybeans need further animal study. Copyright © 2013 Elsevier Ltd. All rights reserved.
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-719
Flatulence--causes, relation to diet and remedies.
In addition to causing embarrassment and unease, flatulence is linked to a variety of symptoms, some of which may be distressing. This review describes the origins of intestinal gas, its composition and methods which have been developed for its analysis. Emphasis is placed upon the effects of legumes in the diet in producing excessive intestinal gas and, particularly, on the role of raffinose-type oligosaccharides, containing alpha-galactosidic groupings. Suggestions for overcoming the problem are presented, including drug treatment, enzyme treatment, food processing and plant breeding. It is emphasised that removal of all raffinose-oligosaccharides from beans does not remove the problem of flatulence in animals and man; the compounds responsible--though assumed to be polysaccharides (or polysaccharide-derived oligomers formed by processing or cooking)--have yet to be characterised.
MED-3659
Results of patch testing with lavender oil in Japan.
We report the annual results of patch testing with lavender oil for a 9-year period from 1990 to 1998 in Japan. Using Finn Chambers and Scanpor tape, we performed 2-day closed patch testing with lavender oil 20% pet. on the upper back of each patient suspected of having cosmetic contact dermatitis. We compared the frequency of positive patch tests to lavender oil each year with those to other fragrances. We diagnosed contact allergy when patch test reactions were + or <+ at 1 day after removal. The positivity rate of lavender oil was 3.7% (0-13.9%) during the 9-year period from 1990 to 1998. The positivity rate of lavender oil increased suddenly in 1997. Recently, in Japan, there has been a trend for aromatherapy using lavender oil. With this trend, placing dried lavender flowers in pillows, drawers, cabinets, or rooms has become a new fashion. We asked patients who showed a positive reaction to lavender oil about their use of dried lavender flowers. We confirmed the use of dried lavender flowers in 5 cases out of 11 positive cases in 1997 and 8 out of 15 positive cases in 1998. We concluded that the increase in patch test positivity rates to lavender oil in 1997 and 1998 was due to the above fashion, rather than due to fragrances in cosmetic products.
MED-5312
Capsinoids and related food ingredients activating brown fat thermogenesis and reducing body fat in humans.
PURPOSE OF REVIEW: Capsaicin and its nonpungent analog (capsinoids) are known to be food ingredients that increase energy expenditure and decrease body fat. This article reviews the role of brown adipose tissue (BAT) for the thermogenic effect of these compounds in humans and proposes the possibility of some other antiobesity food ingredients. RECENT FINDINGS: A single oral ingestion of capsinoids increases energy expenditure in human individuals with metabolically active BAT, but not those without it, indicating that capsinoids activate BAT and thereby increase energy expenditure. This finding gave a rational explanation for discrepant results of the effects of capsinoids in the previous studies. Human BAT may be largely composed of inducible 'beige' adipocytes more than typical brown adipocytes because its gene expression patterns are similar to beige cells isolated from murine white fat depots. In fact, preadipocytes isolated from supraclavicular fat deposits - where BAT is often detected - are capable of differentiating into brown-like adipocytes in vitro, providing evidence of inducible brown adipogenesis in adult humans. SUMMARY: As human BAT may be inducible, a prolonged ingestion of capsinoids would recruit active BAT and thereby increase energy expenditure and decrease body fat. In addition to capsinoids, there are numerous food ingredients that are expected to activate BAT and so be useful for the prevention of obesity in daily life.
MED-2224
Dark chocolate improves coronary vasomotion and reduces platelet reactivity.
BACKGROUND: Dark chocolate has potent antioxidant properties. Coronary atherosclerosis is promoted by impaired endothelial function and increased platelet activation. Traditional risk factors, high oxidative stress, and reduced antioxidant defenses play a crucial role in the pathogenesis of atherosclerosis, particularly in transplanted hearts. Thus, flavonoid-rich dark chocolate holds the potential to have a beneficial impact on graft atherosclerosis. METHODS AND RESULTS: We assessed the effect of flavonoid-rich dark chocolate compared with cocoa-free control chocolate on coronary vascular and platelet function in 22 heart transplant recipients in a double-blind, randomized study. Coronary vasomotion was assessed with quantitative coronary angiography and cold pressor testing before and 2 hours after ingestion of 40 g of dark (70% cocoa) chocolate or control chocolate, respectively. Two hours after ingestion of flavonoid-rich dark chocolate, coronary artery diameter was increased significantly (from 2.36+/-0.51 to 2.51+/-0.59 mm, P<0.01), whereas it remained unchanged after control chocolate. Endothelium-dependent coronary vasomotion improved significantly after dark chocolate (4.5+/-11.4% versus -4.3+/-11.7% in the placebo group, P=0.01). Platelet adhesion decreased from 4.9+/-1.1% to 3.8+/-0.8% (P=0.04) in the dark chocolate group but remained unchanged in the control group. CONCLUSIONS: Dark chocolate induces coronary vasodilation, improves coronary vascular function, and decreases platelet adhesion 2 hours after consumption. These immediate beneficial effects were paralleled by a significant reduction of serum oxidative stress and were positively correlated with changes in serum epicatechin concentration.
MED-4548
Common Household Chemicals and the Allergy Risks in Pre-School Age Children
Background The risk of indoor exposure to volatile organic compounds (VOCs) on allergic airway diseases in children remains unknown. Objective We examined the residential concentrations of VOCs, emitted from building materials, paints, furniture, and other lifestyle practices and the risks of multiple allergic diseases as well as the IgE-sensitization in pre-school age children in Sweden. Methods In a case-control investigation (198 case children with asthma and allergy and 202 healthy controls), air samples were collected in the room where the child slept. The air samples were analyzed for the levels of eight classes of VOCs. Results A natural-log unit of summed propylene glycol and glycol ethers (PGEs) in bedroom air (equal to interquartile range, or 3.43 – 15.65 µg/m3) was associated with 1.5-fold greater likelihood of being a case (95% CI, 1.1 – 2.1), 1.5-fold greater likelihood of asthma (95% CI, 1.0 – 2.3), 2.8-fold greater likelihood of rhinitis (95% CI, 1.6 – 4.7), and 1.6-fold greater likelihood of eczema (95% CI, 1.1 – 2.3), accounting for gender, secondhand smoke, allergies in both parents, wet cleaning with chemical agents, construction period of the building, limonene, cat and dog allergens, butyl benzyl phthalate (BBzP), and di(2-ethylhexyl)phthalate (DEHP). When the analysis was restricted to the cases, the same unit concentration was associated with 1.8-fold greater likelihood of IgE-sensitization (95% CI, 1.1 – 2.8) compared to the non-IgE sensitized cases. No similar associations were found for the other classes of VOCs. Conclusion We propose a novel hypothesis that PGEs in indoor air exacerbate and/or induce the multiple allergic symptoms, asthma, rhinitis and eczema, as well as IgE sensitization respectively.
MED-4093
Serum uric acid level as an independent risk factor for all-cause, cardiovascular, and ischemic stroke mortality: a Chinese cohort study.
OBJECTIVE: The association between hyperuricemia and cardiovascular events has been documented in high-risk groups, but is still undetermined in general populations, especially Chinese. This study assessed the temporal association between serum uric acid level, hyperuricemia, and cardiovascular mortality. METHODS: A prospective cohort study of 41,879 men and 48,514 women ages > or = 35 years was conducted using data from the MJ Health Screening Centers in Taiwan. Mortality from all causes, total cardiovascular disease (CVD), ischemic stroke, congestive heart failure, hypertensive disease, and coronary heart disease were compared according to increasing serum uric acid levels. RESULTS: A total of 1,151 (21.2%) events of 5,427 total deaths were ascribed to CVD (mean followup 8.2 years). Hazard ratios (HRs) for hyperuricemia (serum uric acid level >7 mg/dl) were estimated with Cox regression model after adjusting for age, sex, body mass index, cholesterol, triglycerides, diabetes, hypertension, heavy cigarette smoking, and frequent alcohol consumption. In all patients, HRs were 1.16 (P < 0.001) for all-cause mortality, 1.39 (P < 0.001) for total CVD, and 1.35 (P = 0.02) for ischemic stroke. In subgroup analysis, the HRs for cardiovascular risk remained significant in patients with hypertension (1.44, P < 0.001) and in patients with diabetes (1.64, P < 0.001). In addition, in a low metabolic risk subgroup, the HRs for all-cause mortality and total cardiovascular morbidity were 1.24 (P = 0.02) and 1.48 (P = 0.16), respectively. CONCLUSION: Hyperuricemia was an independent risk factor of mortality from all causes, total CVD, and ischemic stroke in the Taiwanese general population, in high-risk groups, and potentially in low-risk groups.
MED-1035
How trustworthy are bowel histories? Comparison of recalled and recorded information.
One hundred and fifty hospital outpatients were questioned about their bowel habits and then asked to record these in diary booklets for two weeks. Overall, recalled and recorded figures for frequency of defecation agreed fairly closely, but in 16% of patients there was a discrepancy of three or more bowel actions per week. This was usually an exaggeration of the difference from the norm of one a day. Patients were bad at predicting episodes of changed bowel frequency. These findings cast doubt on the value of population surveys of bowel habit based solely on questionnaires. They also suggest that the irritable bowel syndrome might be correctly diagnosed more often if patients were routinely asked to record their bowel actions.
MED-4136
Vital signs: incidence and trends of infection with pathogens transmitted commonly through food--foodborne diseases active surveillance network, 10...
BACKGROUND: In the United States, contaminated food causes approximately 1,000 reported disease outbreaks and an estimated 48 million illnesses, 128,000 METHODS: The Foodborne Diseases Active Surveillance Network (FoodNet) conducts surveillance among 15% of the U.S. population for laboratory-confirmed infections with nine pathogens transmitted commonly through food. Overall and pathogen-specific changes in incidence were estimated from 1996-1998 to 2010 and from 2006-2008 to 2010.hospitalizations, and 3,000 deaths annually. This report summarizes 2010 surveillance data and describes trends since 1996. RESULTS: A total of 19,089 infections, 4,247 hospitalizations, and 68 deaths were reported from FoodNet sites in 2010. Salmonella infection was the most common infection reported (17.6 illnesses per 100,000 persons) and was associated with the largest number of hospitalizations (2,290) and deaths (29); no significant change in incidence of Salmonella infection has occurred since the start of surveillance during 1996-1998. Shiga toxin-producing Escherichia coli (STEC) O157 infection caused 0.9 illnesses per 100,000. Compared with 1996-1998, overall incidence of infection with six key pathogens in 2010 was 23% lower, and pathogen-specific incidence was lower for Campylobacter, Listeria, STEC O157, Shigella, and Yersinia infection but higher for Vibrio infection. Compared with a more recent period, 2006--2008, incidence in 2010 was lower for STEC O157 and Shigella infection but higher for Vibrio infection. CONCLUSIONS: The incidence of STEC O157 infection has declined to reach the 2010 national health objective target of ≥1 case per 100,000. This success, as well as marked declines since 1996-1998 in overall incidence of six key foodborne infections, demonstrates the feasibility of preventing foodborne illnesses. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Salmonella infection should be targeted because it has not declined significantly in more than a decade, and other data indicate that it is one of the most common foodborne infections, resulting in an estimated $365 million in direct medical costs annually. The prevention measures that reduced STEC O157 infection need to be applied more broadly to reduce Salmonella and other infections. Effective measures from farm to table include preventing contamination of meat during slaughter and of all foods, including produce, during processing and preparation; cooking meat thoroughly; vigorously detecting and investigating outbreaks; and recalling contaminated food.
MED-1747
Is there a legacy of the U.S. Public Health Syphilis Study at Tuskegee in HIV/AIDS-related beliefs among heterosexual African-Americans and Latinos?
Knowledge of the US Public Health Syphilis Study at Tuskegee is sometime cited as a principal reason for the relatively low participation rates seen among racial/ethnic minorities, particularly African Americans, in biomedical research. However, only a few studies have actually explored this possibility. We use data from a random digit dial telephone survey of 510 African-Americans and 253 Latinos, age 18 to 45 years, to investigate associations between knowledge of the USPHS Syphilis Study at Tuskegee and endorsement of HIV/AIDS conspiracy theories. All respondents were drawn from an area of low-income, predominantly race-segregated inner city households in Los Angeles. Results indicate that African Americans were significantly more likely than Latinos to endorse HIV/AIDS conspiracy theories. Further, African Americans were more aware of the USPHS Syphilis Study at Tuskegee (SST). Nevertheless, 72% of African Americans and 94% of Latinos reported that they have never heard of the Syphilis Study at Tuskegee. Further, while awareness of the Syphilis Study at Tuskegee was a significant predictor of endorsing HIV/AIDS conspiracy theories, results suggest that other factors may be more important in accounting for low biomedical and behavioral study participation rates.
MED-4822
Sweets, sweetened beverages, and risk of pancreatic cancer in a large population-based case–control study
Objective We examined the associations between sweets, sweetened and unsweetened beverages, and sugars and pancreatic cancer risk. Methods We conducted a population-based case–control study (532 cases, 1,701 controls) and used multivariate logistic regression models to calculate odds ratios (OR) and 95% confidence intervals (CI). Because associations were often different by sex, we present results for men and women combined and separately. Results Among men, greater intakes of total and specific sweets were associated with pancreatic cancer risk (total sweets: OR = 1.9, 95% CI: 1.0, 3.6; sweet condiments: OR = 1.9, 95% CI: 1.2, 3.1; chocolate candy: OR = 2.4, 95% CI: 1.1, 5.0; other mixed candy bars: OR = 3.3, 95% CI: 1.5, 7.3 for 1 + servings/day versus none/rarely). Sweets were not consistently associated with risk among women. Sweetened beverages were not associated with increased pancreatic cancer risk. In contrast, low-calorie soft drinks were associated with increased risk among men only; while other low-/non-caloric beverages (e.g., coffee, tea, and water) were unassociated with risk. Of the three sugars assessed (lactose, fructose, and sucrose), only the milk sugar lactose was associated with pancreatic cancer risk (OR = 2.0, 95% CI: 1.5, 2.7 comparing extreme quartiles). Conclusion These results provide limited support for the hypothesis that sweets or sugars increase pancreatic cancer risk.
MED-3508
Gastrointestinal infections and the development of irritable bowel syndrome.
PURPOSE OF REVIEW: Approximately 10% of the millions of persons with functional gastrointestinal disorders (FGDs) including irritable bowel syndrome (IBS) had their illness onset following an acute bout of infectious diarrhea and are referred to as having postinfectious (PI) FGD or PI-IBS. Recent studies have helped to identify the pathogenesis and natural history of these disorders. RECENT FINDINGS: Groups of patients with acute diarrhea or dysentery (passage of grossly bloody stools) are being followed for development of PI-IBS. Persistent mucosal inflammation, air trapping in the gut, and alteration of intestinal motility contribute to the disease symptoms in genetically susceptible persons. The prognosis of postinfectious forms of IBS is more favorable compared with people with idiopathic forms of the disorder. SUMMARY: With full characterization of postdiarrhea forms of FGDs, we should be able to define the mechanisms of disease early in the course of chronic illness and to better understand the more common idiopathic forms of the disease. We are likely to identify specific alteration of gut pathophysiology in postinfectious FGDs and to then classify them not as a poorly characterized group of functional disorders but as specific gastrointestinal disorders.
MED-5353
Cancer risks in second-generation immigrants to Sweden.
We used the nationwide Swedish Family-Cancer Database to analyze cancer risks in Sweden-born descendants of immigrants from European and North American countries. Our study included close to 600,000 0-66-year-old descendants of an immigrant father or mother. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for 17 cancer sites using native Swedes as a reference. All cancer was marginally below the Swedish incidence in offspring of immigrant origin. Decreased SIRs were observed for breast cancer among Norwegian descendants, melanoma among descendants of Hungarian fathers and ovarian and bladder cancer among descendents of Finnish mothers, all consistent with the difference in cancer incidence between Swedes and the indigenous populations. Cervical cancer was increased in daughters of Danish men, whereas thyroid cancer and non-Hodgkin's lymphoma were in excess in offspring of parents of Yugoslav and Asian descent. Even these results agreed with the high incidence rates in parents compared to Swedes, except that for non-Hodgkin's lymphoma other explanations are needed; these may be related to immune malfunction. Comparison of the results between the first- and the second-generation immigrants suggest that the first 2 decades of life are important in setting the pattern for cancer development in subsequent life. Birth in Sweden sets the Swedish pattern for cancer incidence, irrespective of the nationality of descent, while entering Sweden in the 20s is already too late to influence the environmentally imprinted program for the cancer destiny. Copyright 2002 Wiley-Liss, Inc.