NIH-AARP study
MED-1598
Cigarette Smoke Toxins Deposited on Surfaces: Implications for Human Health
Cigarette smoking remains a significant health threat for smokers and nonsmokers alike. Secondhand smoke (SHS) is intrinsically more toxic than directly inhaled smoke. Recently, a new threat has been discovered – Thirdhand smoke (THS) – the accumulation of SHS on surfaces that ages with time, becoming progressively more toxic. THS is a potential health threat to children, spouses of smokers and workers in environments where smoking is or has been allowed. The goal of this study is to investigate the effects of THS on liver, lung, skin healing, and behavior, using an animal model exposed to THS under conditions that mimic exposure of humans. THS-exposed mice show alterations in multiple organ systems and excrete levels of NNAL (a tobacco-specific carcinogen biomarker) similar to those found in children exposed to SHS (and consequently to THS). In liver, THS leads to increased lipid levels and non-alcoholic fatty liver disease, a precursor to cirrhosis and cancer and a potential contributor to cardiovascular disease. In lung, THS stimulates excess collagen production and high levels of inflammatory cytokines, suggesting propensity for fibrosis with implications for inflammation-induced diseases such as chronic obstructive pulmonary disease and asthma. In wounded skin, healing in THS-exposed mice has many characteristics of the poor healing of surgical incisions observed in human smokers. Lastly, behavioral tests show that THS-exposed mice become hyperactive. The latter data, combined with emerging associated behavioral problems in children exposed to SHS/THS, suggest that, with prolonged exposure, they may be at significant risk for developing more severe neurological disorders. These results provide a basis for studies on the toxic effects of THS in humans and inform potential regulatory policies to prevent involuntary exposure to THS.
MED-1599
Exposure to nitrosamines in thirdhand tobacco smoke increases cancer risk in non-smokers.
In addition to passive inhalation, non-smokers, and especially children, are exposed to residual tobacco smoke gases and particles that are deposited to surfaces and dust, known as thirdhand smoke (THS). However, until now the potential cancer risks of this pathway of exposure have been highly uncertain and not considered in public health policy. In this study, we estimate for the first time the potential cancer risk by age group through non-dietary ingestion and dermal exposure to carcinogen N-nitrosamines and tobacco-specific nitrosamines (TSNAs) measured in house dust samples. Using a highly sensitive and selective analytical approach we have determined the presence of nicotine, eight N-nitrosamines and five tobacco-specific nitrosamines in forty-six settled dust samples from homes occupied by both smokers and non-smokers. Using observations of house dust composition, we have estimated the cancer risk by applying the most recent official toxicological information. Calculated cancer risks through exposure to the observed levels of TSNAs at an early life stage (1 to 6years old) exceeded the upper-bound risk recommended by the USEPA in 77% of smokers' and 64% of non-smokers' homes. The maximum risk from exposure to all nitrosamines measured in a smoker occupied home was one excess cancer case per one thousand population exposed. The results presented here highlight the potentially severe long-term consequences of THS exposure, particularly to children, and give strong evidence of its potential health risk and, therefore, they should be considered when developing future environmental and health policies. Copyright © 2014 Elsevier Ltd. All rights reserved.
MED-1600
Beyond celery and starter culture: advances in natural/organic curing processes in the United States.
Over the past 10years there has been ongoing development of curing processes with natural ingredients designed to meet consumer demand and regulatory requirements for natural and organic processed meats. Initially, these processes utilized celery concentrates with a high nitrate content combined with a nitrate-reducing starter culture. Subsequent advances included celery concentrates with the nitrate converted to nitrite by suppliers. Further, as questions developed concerning reduced concentration of preservatives and the microbiological safety of these processed meats, additional advances have resulted in a wide variety of ingredients and processes designed to provide supplementary antimicrobial effects for improved product safety. Copyright © 2012 Elsevier Ltd. All rights reserved.
MED-1601
Survey of naturally and conventionally cured commercial frankfurters, ham, and bacon for physio-chemical characteristics that affect bacterial growth.
Natural and organic food regulations preclude the use of sodium nitrite/nitrate and other antimicrobials for processed meat products. Consequently, processors have begun to use natural nitrate/nitrite sources, such as celery juice/powder, sea salt, and turbinado sugar, to manufacture natural and organic products with cured meat characteristics but without sodium nitrite. The objective of this study was to compare physio-chemical characteristics that affect Clostridium perfringens and Listeria monocytogenes growth in naturally cured and traditionally cured commercial frankfurters, hams, and bacon. Correlations of specific product characteristics to pathogen growth varied between products and pathogens, though water activity, salt concentration, and product composition (moisture, protein and fat) were common intrinsic factors correlated to pathogen growth across products. Other frequently correlated traits were related to curing reactions such as % cured pigment. Residual nitrite and nitrate were significantly correlated to C. perfringens growth but only for the ham products. Copyright © 2012 Elsevier Ltd. All rights reserved.
MED-1602
Dietary intake of nitrate and nitrite and risk of renal cell carcinoma in the NIH-AARP Diet and Health Study
Background: Nitrate and nitrite are present in many foods and are precursors of N-nitroso compounds, known animal carcinogens and potential human carcinogens. We prospectively investigated the association between nitrate and nitrite intake from dietary sources and risk of renal cell carcinoma (RCC) overall and clear cell and papillary histological subtypes in the NIH-AARP Diet and Health Study. Methods: Nitrate and nitrite intakes were estimated from a 124-item food frequency questionnaire. Over a mean follow-up of 9 years, we identified 1816 RCC cases (n=498, clear cell; n=115, papillary cell) among 491 841 participants. Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Individuals in the highest quintile of nitrite intake from animal sources compared with those in the lowest quintile, had an increased risk of total RCC and clear cell subtype (HR=1.28, 95% CI, 1.10–1.49 and HR=1.68, 95% CI, 1.25–2.27, respectively). Nitrite from processed meats and other animal sources were associated with increased clear cell adenocarcinoma risk (HR=1.33, 95% CI, 1.01–1.76 and HR=1.78, 95% CI, 1.34–2.36, respectively). We found no association for nitrite intake from plant sources or nitrate intake overall. Conclusion: Our findings suggest that nitrite from animal sources may increase the risk of RCC, particularly clear cell adenocarcinomas.
MED-1603
Thirdhand cigarette smoke in an experimental chamber: evidence of surface deposition of nicotine, nitrosamines and polycyclic aromatic hydrocarbons...
BACKGROUND: A growing body of evidence shows that secondhand cigarette smoke undergoes numerous chemical changes after it is released into the air: it can adsorb to indoor surfaces, desorb back into the air and undergo chemical changes as it ages. OBJECTIVES: To test the effects of aging on the concentration of polycyclic aromatic hydrocarbons (PAHs), nicotine and tobacco-specific nitrosamines in cigarette smoke. METHODS: We generated sidestream and mainstream cigarette smoke with a smoking machine, diluted it with conditioned filtered air, and passed it through a 6 m(3) flow reactor with air exchange rates that matched normal residential air exchange rates. We tested the effects of 60 min aging on the concentration of 16 PAHs, nicotine, cotinine and tobacco-specific nitrosamines. We also measured sorption and deposition of nicotine, cotinine and tobacco-specific nitrosamines on materials placed within the flow reactor. RESULTS: We observed mass losses of 62% for PAHs, 72%, for nicotine, 79% for N-nitrosonornicotine and 80% for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Extraction of cotton cloth exposed to smoke yielded nicotine and NNK. The ratio of NNK:nicotine on the exposed cloth was 10-fold higher than that in aerosol samples. CONCLUSIONS: Our data suggest that the majority of the PAHs, nicotine, cotinine and tobacco-specific nitrosamines that are released during smoking in homes and public places deposit on room surfaces. These data give an estimate of the potential for accumulation of carcinogens in thirdhand cigarette smoke. Exposure to PAHs and tobacco-specific nitrosamines, through dermal absorption and inhalation of contaminated dust, may contribute to smoking-attributable morbidity and mortality.
MED-1604
Cruciferous vegetables consumption and risk of renal cell carcinoma: a meta-analysis.
Previous cohort and case-control studies on the association between cruciferous vegetables consumption and risk of renal cell carcinoma have illustrated conflicting results so far. To demonstrate the potential association between them, a meta-analysis was performed. Eligible studies were retrieved via both computerized searches and review of references. The summary relative risks (RRs) with 95% confidence interval (CI) for the highest vs. the lowest consumption of cruciferous vegetables were calculated. Heterogeneity and publication bias were also evaluated. Stratified analyses were performed as well. Three cohort and 7 case-control studies were included. A significantly decreased risk with renal cell carcinoma was observed in overall cruciferous vegetables consumption group (RR = 0.73; 95% CI, 0.63-0.83) and subgroup of case-control studies (RR = 0.69; 95% CI, 0.60-0.78), but not in cohort studies (RR = 0.96; 95% CI, 0.71-1.21). No heterogeneity and publication bias were detected across studies. Our findings supported that cruciferous vegetables consumption was related to the decreased risk of renal cell carcinoma. Because of the limited number of studies, further well-designed prospective studies and researches need to be conducted to better clarify the protective effect of cruciferous vegetables on renal cell carcinoma and potential mechanism.
MED-1605
It is time to regulate carcinogenic tobacco-specific nitrosamines in cigarette tobacco
The Family Smoking Prevention and Tobacco Control Act gives the Food and Drug Administration power to regulate tobacco products. This commentary calls for immediate regulation of the carcinogenic tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N’-nitrosonornicotine (NNN) in cigarette tobacco as a logical path to cancer prevention. NNK and NNN, powerful carcinogens in laboratory animals, have been evaluated as “carcinogenic to humans” by the International Agency for Research on Cancer. NNK and NNN are present in the tobacco of virtually all marketed cigarettes; levels in cigarette smoke are directly proportional to the amounts in tobacco. The NNK metabolite NNAL, itself a strong carcinogen, is present in the urine of smokers and non-smokers exposed to secondhand smoke. Some of the highest levels of NNK and NNN are found in U.S. products. It is well established that factors such as choice of tobacco blend, agricultural conditions, and processing methods influence levels of NNK and NNN in cigarette tobacco and cigarette smoke. Therefore, it is time to control these factors and produce cigarettes with 100 ppb or less each of NNK and NNN in tobacco, which would result in an approximate 15-20 fold reduction of these carcinogens in the mainstream smoke of popular cigarettes sold in the United States.
MED-1606
Intake of fiber and fiber-rich plant foods is associated with a lower risk of renal cell carcinoma in a large US cohort
Background: Plant-based and fiber-rich diets high in vegetables, fruit, and whole grains are recommended to prevent cancer and chronic conditions associated with renal cell carcinoma (RCC), such as obesity, hypertension, and diabetes. Diet may play a role in the etiology of RCC directly and/or indirectly. Objective: In a large prospective cohort of US men and women, we comprehensively investigated dietary intake and food sources of fiber in relation to RCC risk. Design: Participants of the NIH-AARP Diet and Health Study (n = 491,841) completed a self-administered questionnaire of demographics, diet, lifestyle, and medical history. Over 9 (mean) years of follow-up we identified 1816 incident cases of RCC. HRs and 95% CIs were estimated within quintiles by using multivariable Cox proportional hazards regression. Results: Total dietary fiber intake was associated with a significant 15–20% lower risk of RCC in the 2 highest quintiles compared with the lowest (P-trend = 0.005). Intakes of legumes, whole grains, and cruciferous vegetables were also associated with a 16–18% reduced risk of RCC. Conversely, refined grain intake was positively associated with RCC risk in a comparison of quintile 5 with quintile 1 (HR: 1.19; 95% CI: 1.02, 1.39; P-trend = 0.04). The inverse association between fiber intake and RCC was consistent among participants who never smoked, had a body mass index [BMI (in kg/m2)] <30, and did not report a history of diabetes or hypertension. Conclusions: Intake of fiber and fiber-rich plant foods was associated with a significantly lower risk of RCC in this large US cohort. This trial was registered at clinicaltrials.gov as NCT00340015.
MED-1607
Long-term dietary sodium, potassium and fluid intake; exploring potential novel risk factors for renal cell cancer in the Netherlands Cohort Study on diet and cancer
Background: As sodium, potassium and fluid intake are related to hypertension, an established risk factor for renal cell cancer (RCC), they may be independent risk factors for RCC. Methods: The Netherlands Cohort Study (NLCS) with case-cohort design included 120 852 participants aged 55–69 years. At baseline, diet and lifestyle were assessed with questionnaires. After 17.3 years of follow-up, 485 RCC cases and 4438 subcohort members were available for analyses. Results: Sodium intake increased RCC risk (P-trend=0.03), whereas fluid and potassium intake did not. For high sodium and low fluid intake, the RCC risk additionally increased (P-interaction=0.02). Conclusion: Sodium intake is a potential risk factor for RCC, particularly if fluid consumption is low.
MED-4476
Determination of total N-nitroso compounds and their precursors in frankfurters, fresh meat, dried salted fish, sauces, tobacco, and tobacco smoke ...
Total N-nitroso compounds (NOC) and NOC precursors (NOCP) were determined in extracts of food and tobacco products. Following Walters' method, NOC were decomposed to NO with refluxing HBr/HCl/HOAc/EtOAc and NO was measured by chemiluminescence. NOC were determined after sulfamic acid treatment to destroy nitrite, and NOCP were determined after treatment with 110 mM nitrite and then sulfamic acid. Analysis without HBr gave results < or =20% of those with HBr. This NOC method was efficient for nitrosamines but not nitrosoureas. The standard nitrosation for determining NOCP gave high yields for readily nitrosated amines, including 1-deoxy-1-fructosylvaline, but not for simple amines, dipeptides, and alkylureas. Mean NOC and NOCP results were (respectively, in micromol/kg of product) 5.5 and 2700 for frankfurters, 0.5 and 660 for fresh meat, 5.8 and 5800 for salted, dried fish, and 660 and 2900 for chewing tobacco (all for aqueous extracts) and 220 and 20000 nmol/cigarette for MeCN extracts of cigarette smoke filter pads.
MED-1621
Coffee, tea, and mortality.
Except for conflicting evidence about coffee and risk of coronary disease, coffee and tea are not linked to major causes of death. Because of widespread use of both beverages and limitations of prior studies, concern persists. Using Cox models (ten covariates) we studied relations in 128,934 persons to 4501 subsequent deaths. Except for slightly increased risk from acute myocardial infarction among heavier (> or = 4 cups/d) coffee users (relative risk versus nondrinkers = 1.4, 95% confidence interval = 1.0 to 1.9, P = 0.07), there was no increased risk of mortality for all deaths (relative risk per cup of coffee per day = 0.99, 95% confidence interval = 0.97 to 1.01; relative risk per cup of tea per day = 0.98, 95% confidence interval = 0.96 to 1.00) or major causes in adjusted analyses. Coffee was related to lower risk of liver cirrhosis death (relative risk per cup of coffee per day = 0.77, 95% confidence interval = 0.67 to 0.89). Use of both beverages was related to a lower risk of suicide, progressively lower at higher coffee intake (relative risk per cup of coffee per day = 0.87, 95% confidence interval = 0.77 to 0.98). We conclude that coffee and tea have no overall relation to mortality risk. If coffee increases coronary risk, this is balanced by an unexplained lower risk of other conditions, notably cirrhosis and suicide.
MED-1622
Coffee, caffeine, and risk of completed suicide: results from 3 prospective cohorts of American adults
Objective To evaluate the association between coffee and caffeine consumption and suicide risk in three large-scale cohorts of U.S. men and women. Methods We accessed data of 43,599 men enrolled in the Health Professionals Follow-up Study (HPFS, 1988–2008), 73,820 women in the Nurses’ Health Study (NHS, 1992–2008), and 91,005 women in the NHS II (1993–2007). Consumption of caffeine, coffee, and decaffeinated coffee, was assessed every four years by validated food-frequency questionnaires. Deaths from suicide were determined by physician review of death certificates. Multivariate adjusted relative risks (RRs) were estimated with Cox proportional hazard models. Cohort specific RRs were pooled using random-effect models. Results We documented 277 deaths from suicide. Compared to those consuming ≤1 cup/week of caffeinated coffee (≤8 oz/237 ml), the pooled multivariate RR (95% confidence interval [CI]) of suicide was 0.55 (0.38–0.78) for those consuming 2–3 cups/day and 0.47 (0.27–0.81) for those consuming ≥4 cups/day (P trend <0.001). The pooled multivariate RR (95% CI) for suicide was 0.75 (0.63–0.90) for each increment of 2 cups/day of caffeinated coffee and 0.77 (0.63–0.93) for each increment of 300 mg/day of caffeine. Conclusions These results from three large cohorts support an association between caffeine consumption and lower risk of suicide.
MED-1623
Possible neurologic effects of aspartame, a widely used food additive.
The artificial sweetener aspartame (L-aspartyl-L-phenylalanyl-methyl ester), is consumed, primarily in beverages, by a very large number of Americans, causing significant elevations in plasma and, probably, brain phenylalanine levels. Anecdotal reports suggest that some people suffer neurologic or behavioral reactions in association with aspartame consumption. Since phenylalanine can be neurotoxic and can affect the synthesis of inhibitory monoamine neurotransmitters, the phenylalanine in aspartame could conceiveably mediate neurologic effects. If mice are given aspartame in doses that elevate plasma phenylalanine levels more than those of tyrosine (which probably occurs after any aspartame dose in humans), the frequency of seizures following the administration of an epileptogenic drug, pentylenetetrazole, is enhanced. This effect is simulated by equimolar phenylalanine and blocked by concurrent administration of valine, which blocks phenylalanine's entry into the brain. Aspartame also potentiates the induction of seizures by inhaled fluorothyl or by electroconvulsive shock. Perhaps regulations concerning the sale of food additives should be modified to require the reporting of adverse reactions and the continuing conduct of mandated safety research.
MED-1624
Direct and indirect cellular effects of aspartame on the brain.
The use of the artificial sweetener, aspartame, has long been contemplated and studied by various researchers, and people are concerned about its negative effects. Aspartame is composed of phenylalanine (50%), aspartic acid (40%) and methanol (10%). Phenylalanine plays an important role in neurotransmitter regulation, whereas aspartic acid is also thought to play a role as an excitatory neurotransmitter in the central nervous system. Glutamate, asparagines and glutamine are formed from their precursor, aspartic acid. Methanol, which forms 10% of the broken down product, is converted in the body to formate, which can either be excreted or can give rise to formaldehyde, diketopiperazine (a carcinogen) and a number of other highly toxic derivatives. Previously, it has been reported that consumption of aspartame could cause neurological and behavioural disturbances in sensitive individuals. Headaches, insomnia and seizures are also some of the neurological effects that have been encountered, and these may be accredited to changes in regional brain concentrations of catecholamines, which include norepinephrine, epinephrine and dopamine. The aim of this study was to discuss the direct and indirect cellular effects of aspartame on the brain, and we propose that excessive aspartame ingestion might be involved in the pathogenesis of certain mental disorders (DSM-IV-TR 2000) and also in compromised learning and emotional functioning.
MED-1625
Sugar substitutes: Health controversy over perceived benefits
Sugar is an inseparable part of the food we consume. But too much sugar is not ideal for our teeth and waistline. There have been some controversial suggestions that excessive sugar may play an important role in certain degenerative diseases. So artificial sweeteners or artificially sweetened products continue to attract consumers. A sugar substitute (artificial sweetener) is a food additive that duplicates the effect of sugar in taste, but usually has less food energy. Besides its benefits, animal studies have convincingly proven that artificial sweeteners cause weight gain, brain tumors, bladder cancer and many other health hazards. Some kind of health related side effects including carcinogenicity are also noted in humans. A large number of studies have been carried out on these substances with conclusions ranging from “safe under all conditions” to “unsafe at any dose”. Scientists are divided in their views on the issue of artificial sweetener safety. In scientific as well as in lay publications, supporting studies are often widely referenced while the opposing results are de-emphasized or dismissed. So this review aims to explore the health controversy over perceived benefits of sugar substitutes.
MED-1626
Adverse reactions to aspartame: double-blind challenge in patients from a vulnerable population.
This study was designed to ascertain whether individuals with mood disorders are particularly vulnerable to adverse effects of aspartame. Although the protocol required the recruitment of 40 patients with unipolar depression and a similar number of individuals without a psychiatric history, the project was halted by the Institutional Review Board after a total of 13 individuals had completed the study because of the severity of reactions within the group of patients with a history of depression. In a crossover design, subjects received aspartame 30 mg/kg/day or placebo for 7 days. Despite the small n, there was a significant difference between aspartame and placebo in number and severity of symptoms for patients with a history of depression, whereas for individuals without such a history there was not. We conclude that individuals with mood disorders are particularly sensitive to this artificial sweetener and its use in this population should be discouraged.
MED-1627
Sweetened Beverages, Coffee, and Tea and Depression Risk among Older US Adults
Sweetened beverages, coffee, and tea are the most consumed non-alcoholic beverages and may have important health consequences. We prospectively evaluated the consumption of various types of beverages assessed in 1995–1996 in relation to self-reported depression diagnosis after 2000 among 263,923 participants of the NIH-AARP Diet and Health Study. Odds ratios (OR) and 95% confidence intervals (CI) were derived from multivariate logistic regressions. The OR (95% CI) comparing ≥4 cans/cups per day with none were 1.30 (95%CI: 1.17–1.44) for soft drinks, 1.38 (1.15–1.65) for fruit drinks, and 0.91 (0.84–0.98) for coffee (all P for trend<0.0001). Null associations were observed for iced-tea and hot tea. In stratified analyses by drinkers of primarily diet versus regular beverages, the ORs were 1.31 (1.16–1.47) for diet versus 1.22 (1.03–1.45) for regular soft drinks, 1.51 (1.18–1.92) for diet versus 1.08 (0.79–1.46) for regular fruit drinks, and 1.25 (1.10–1.41) for diet versus 0.94 (0.83–1.08) for regular sweetened iced-tea. Finally, compared to nondrinkers, drinking coffee or tea without any sweetener was associated with a lower risk for depression, adding artificial sweeteners, but not sugar or honey, was associated with higher risks. Frequent consumption of sweetened beverages, especially diet drinks, may increase depression risk among older adults, whereas coffee consumption may lower the risk.
MED-1628
Heavy coffee drinking and the risk of suicide.
Earlier research has implicated coffee drinking as a possible protective factor for suicide. We followed-up 43,166 subjects for the mean 14.6 years, and 213 suicides were committed. Daily coffee drinking had a J-shaped association with the risk of suicide. Using the Cox model we controlled for potential covariates, and found that among heavy coffee drinkers (> or = 8 cups/day) the risk of suicide was 58% higher compared with more moderate drinkers.
MED-5054
The potential toxicity of artificial sweeteners.
Since their discovery, the safety of artificial sweeteners has been controversial. Artificial sweeteners provide the sweetness of sugar without the calories. As public health attention has turned to reversing the obesity epidemic in the United States, more individuals of all ages are choosing to use these products. These choices may be beneficial for those who cannot tolerate sugar in their diets (e.g., diabetics). However, scientists disagree about the relationships between sweeteners and lymphomas, leukemias, cancers of the bladder and brain, chronic fatigue syndrome, Parkinson's disease, Alzheimer's disease, multiple sclerosis, autism, and systemic lupus. Recently these substances have received increased attention due to their effects on glucose regulation. Occupational health nurses need accurate and timely information to counsel individuals regarding the use of these substances. This article provides an overview of types of artificial sweeteners, sweetener history, chemical structure, biological fate, physiological effects, published animal and human studies, and current standards and regulations.
MED-1630
Neurobehavioral effects of aspartame consumption.
Despite its widespread use, the artificial sweetener aspartame remains one of the most controversial food additives, due to mixed evidence on its neurobehavioral effects. Healthy adults who consumed a study-prepared high-aspartame diet (25 mg/kg body weight/day) for 8 days and a low-aspartame diet (10 mg/kg body weight/day) for 8 days, with a 2-week washout between the diets, were examined for within-subject differences in cognition, depression, mood, and headache. Measures included weight of foods consumed containing aspartame, mood and depression scales, and cognitive tests for working memory and spatial orientation. When consuming high-aspartame diets, participants had more irritable mood, exhibited more depression, and performed worse on spatial orientation tests. Aspartame consumption did not influence working memory. Given that the higher intake level tested here was well below the maximum acceptable daily intake level of 40-50 mg/kg body weight/day, careful consideration is warranted when consuming food products that may affect neurobehavioral health. © 2014 Wiley Periodicals, Inc.
MED-1631
Coffee, Caffeine, and Risk of Depression Among Women
Background Caffeine is the world’s most widely used central nervous system stimulant, with about 80% consumed in form of coffee. However, studies that analyzed prospectively the relation of coffee or caffeine consumption and depression risk are scarce. Methods A total of 50,739 U.S. women (mean age=63 years) free from depressive symptoms at baseline (1996) were prospectively followed until 2006. Caffeine and coffee consumption, and other caffeinated and decaffeinated beverages, were obtained from validated questionnaires completed between 1980 through 2002 and computed as cumulative average of consumption with a 2-year latency applied. Clinical depression was defined as reporting both physician-diagnosed depression and antidepressant use. Relative risks of clinical depression were estimate using Cox proportional hazards regression models. Results During 10 years of follow-up (1996–2006), 2,607 incident cases of depression were identified. Compared to women consuming caffeinated coffee less frequently (≤1 cup/wk), multivariate relative risk of depression was 0.85 (95% confidence interval [CI], 0.75 to 0.95) for those consuming 2–3 cups/d and 0.80 (95%CI, 0.64 to 0.99; P trend <0.001) for those consuming ≥4 cups/d. Multivariate relative risk for depression was 0.80 (95%CI, 0.68 to 0.95; P trend=0.02) for women in the highest (≥550 mg/d) vs. lowest (<100 mg/d) of the 5 caffeine consumption categories. Decaffeinated coffee was not associated with depression risk. Conclusions In this large longitudinal study we found that depression risk decreases with increasing caffeinated coffee consumption. Further investigations are needed to confirm this finding and to determine whether usual caffeinated coffee consumption may contribute to depression prevention.
MED-4820
Cancer incidence in British vegetarians
Background: Few prospective studies have examined cancer incidence among vegetarians. Methods: We studied 61 566 British men and women, comprising 32 403 meat eaters, 8562 non-meat eaters who did eat fish (‘fish eaters') and 20 601 vegetarians. After an average follow-up of 12.2 years, there were 3350 incident cancers of which 2204 were among meat eaters, 317 among fish eaters and 829 among vegetarians. Relative risks (RRs) were estimated by Cox regression, stratified by sex and recruitment protocol and adjusted for age, smoking, alcohol, body mass index, physical activity level and, for women only, parity and oral contraceptive use. Results: There was significant heterogeneity in cancer risk between groups for the following four cancer sites: stomach cancer, RRs (compared with meat eaters) of 0.29 (95% CI: 0.07–1.20) in fish eaters and 0.36 (0.16–0.78) in vegetarians, P for heterogeneity=0.007; ovarian cancer, RRs of 0.37 (0.18–0.77) in fish eaters and 0.69 (0.45–1.07) in vegetarians, P for heterogeneity=0.007; bladder cancer, RRs of 0.81 (0.36–1.81) in fish eaters and 0.47 (0.25–0.89) in vegetarians, P for heterogeneity=0.05; and cancers of the lymphatic and haematopoietic tissues, RRs of 0.85 (0.56–1.29) in fish eaters and 0.55 (0.39–0.78) in vegetarians, P for heterogeneity=0.002. The RRs for all malignant neoplasms were 0.82 (0.73–0.93) in fish eaters and 0.88 (0.81–0.96) in vegetarians (P for heterogeneity=0.001). Conclusion: The incidence of some cancers may be lower in fish eaters and vegetarians than in meat eaters.
MED-4821
Diet, Lifestyle, and Acute Myeloid Leukemia in the NIH–AARP Cohort
The relation between diet, lifestyle, and acute myeloid leukemia was assessed in a US cohort of 491,163 persons from the NIH–AARP Diet and Health Study (1995–2003). A total of 338 incident cases of acute myeloid leukemia were ascertained. Multivariate Cox models were utilized to estimate hazard ratios and 95% confidence intervals. Compared with those for never smokers, hazard ratios were 1.29 (95% confidence interval: 0.95, 1.75), 1.79 (95% confidence interval: 1.32, 2.42), 2.42 (95% confidence interval: 1.63, 3.57), and 2.29 (85% confidence interval: 1.38, 3.79) for former smokers who smoked ≤1 or >1 pack/day and for current smokers who smoked ≤1 or >1 pack/day, respectively. Higher meat intake was associated with an increased risk of acute myeloid leukemia (hazard ratio = 1.45, 95% confidence interval: 1.02, 2.07 for the fifth vs. first quintile; P for trend = 0.06); however, there were no clear effects of meat-cooking method or doneness level. Individuals who did not drink coffee appeared to have a higher risk of acute myeloid leukemia than those who drank various quantities of coffee. Neither fruit nor vegetable intake was associated with acute myeloid leukemia. This large prospective study identified smoking and meat intake as risk factors for acute myeloid leukemia.
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-4823
Dietary Fatty Acids and Pancreatic Cancer in the NIH-AARP Diet and Health Study
Background Previous research relating dietary fat, a modifiable risk factor, to pancreatic cancer has been inconclusive. Methods We prospectively analyzed the association between intakes of fat, fat subtypes, and fat food sources and exocrine pancreatic cancer in the National Institutes of Health–AARP Diet and Health Study, a US cohort of 308 736 men and 216 737 women who completed a 124-item food frequency questionnaire in 1995–1996. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models, with adjustment for energy intake, smoking history, body mass index, and diabetes. Statistical tests were two-sided. Results Over an average follow-up of 6.3 years, 865 men and 472 women were diagnosed with exocrine pancreatic cancer (45.0 and 34.5 cases per 100 000 person-years, respectively). After multivariable adjustment and combination of data for men and women, pancreatic cancer risk was directly related to the intakes of total fat (highest vs lowest quintile, 46.8 vs 33.2 cases per 100 000 person-years, HR = 1.23, 95% CI = 1.03 to 1.46; Ptrend  = .03), saturated fat (51.5 vs 33.1 cases per 100 000 person-years, HR = 1.36, 95% CI = 1.14 to 1.62; Ptrend < .001), and monounsaturated fat (46.2 vs 32.9 cases per 100 000 person-years, HR = 1.22, 95% CI = 1.02 to 1.46; Ptrend = .05) but not polyunsaturated fat. The associations were strongest for saturated fat from animal food sources (52.0 vs 32.2 cases per 100 000 person-years, HR = 1.43, 95% CI = 1.20 to 1.70; Ptrend < .001); specifically, intakes from red meat and dairy products were both statistically significantly associated with increased pancreatic cancer risk (HR = 1.27 and 1.19, respectively). Conclusion In this large prospective cohort with a wide range of intakes, dietary fat of animal origin was associated with increased pancreatic cancer risk.
MED-4824
4. Chronic pancreatitis and pancreatic cancer, lifestyle-related diseases.
In Japan, the number of patients with both chronic pancreatitis (CP) and pancreatic cancer (PC) is increasing. A nationwide survey on CP revealed that the total number of patients treated for CP in Japan in 2002 was estimated as 45,200 (95% confidence interval, 35,600-54,700), and 20,137 patients died of PC in 2002. Alcoholic pancreatitis was the most common type of pancreatitis (67.5 %). Cigarette smoking was an independent and significant risk factor for CP. The risks of pancreatic and nonpancreatic cancers increased in the course of CP. While alcohol consumption may increase the risk of PC via CP, smoking was important as a risk factor for both CP and PC. The increasing incidence of PC was closely related to the increasing intake of animal fat. Lifestyle in patients with CP appeared to be the same as that in patients with PC. Environmental factors such as lifestyle in combination with genetic factors may increase the risk for both CP and PC. Therefore, changing and improving lifestyle habits such as drinking, smoking and nutrition may reduce the risks for both CP and PC.
MED-4825
Pancreatic cancer: a review of the evidence on causation.
Pancreatic cancer kills more than 250,000 people each year worldwide and has a poor prognosis. The aim of this article is to critically review the epidemiologic evidence for exposures that may either increase or decrease the risk. A Medline search was performed for epidemiologic studies and reviews published up to April 2007. Consistent evidence of a positive association was found for family history and cigarette smoking. Many studies documented a positive association with diabetes mellitus and chronic pancreatitis, although the etiologic mechanisms are unclear. Other associations were detected, but the results were either inconsistent or from few studies. These included positive associations with red meat, sugar, fat, body mass index, gallstones, and Helicobacter pylori, and protective effects of increasing parity, dietary folate, aspirin, and statins. There was no evidence linking alcohol or coffee consumption with an increased risk of pancreatic cancer. The associations with many exposures need to be clarified from further epidemiologic work in which there is both precise measurement of risk factors, adjustment for potential confounders, and, for dietary studies, information recorded on the method of food preparation and pattern of consumption. Such work is important to reduce the incidence of this fatal disease.
MED-4826
Macronutrients, fatty acids, cholesterol and pancreatic cancer.
A role of diet and nutrition in pancreatic carcinogenesis has been suggested, but the association between selected macronutrients, fatty acids, cholesterol and pancreatic cancer remains controversial. We analysed data from a hospital-based case-control study conducted in Italy between 1991 and 2008, including 326 cases (174 men and 152 women) with incident pancreatic cancer, and 652 controls (348 men and 304 women) frequency-matched to cases by sex, age and study centre. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multiple logistic regression models conditioned on age, sex and study centre, and adjusted for year of interview, education, tobacco smoking, history of diabetes and energy intake. A positive association was found for animal proteins (OR=1.85 for the highest versus the lowest quintile of intake; 95% CI: 1.15-2.96; p for trend=0.039), whereas a negative association was observed for sugars (OR=0.52; 95% CI: 0.31-0.86; p for trend=0.003). Non-significant negative associations emerged for vegetable proteins (OR=0.69) and polyunsaturated fatty acids (OR=0.67). In conclusion, a diet poor in animal proteins and rich in sugars (mainly derived from fruit) appears to have a beneficial effect on pancreatic cancer risk. Copyright (c) 2009 Elsevier Ltd. All rights reserved.
MED-4985
A low-fat vegan diet and a conventional diabetes diet in the treatment of type 2 diabetes: a randomized, controlled, 74-wk clinical trial
Background: Low-fat vegetarian and vegan diets are associated with weight loss, increased insulin sensitivity, and improved cardiovascular health. Objective: We compared the effects of a low-fat vegan diet and conventional diabetes diet recommendations on glycemia, weight, and plasma lipids. Design: Free-living individuals with type 2 diabetes were randomly assigned to a low-fat vegan diet (n = 49) or a diet following 2003 American Diabetes Association guidelines (conventional, n = 50) for 74 wk. Glycated hemoglobin (Hb A1c) and plasma lipids were assessed at weeks 0, 11, 22, 35, 48, 61, and 74. Weight was measured at weeks 0, 22, and 74. Results: Weight loss was significant within each diet group but not significantly different between groups (−4.4 kg in the vegan group and −3.0 kg in the conventional diet group, P = 0.25) and related significantly to Hb A1c changes (r = 0.50, P = 0.001). Hb A1c changes from baseline to 74 wk or last available values were −0.34 and −0.14 for vegan and conventional diets, respectively (P = 0.43). Hb A1c changes from baseline to last available value or last value before any medication adjustment were −0.40 and 0.01 for vegan and conventional diets, respectively (P = 0.03). In analyses before alterations in lipid-lowering medications, total cholesterol decreased by 20.4 and 6.8 mg/dL in the vegan and conventional diet groups, respectively (P = 0.01); LDL cholesterol decreased by 13.5 and 3.4 mg/dL in the vegan and conventional groups, respectively (P = 0.03). Conclusions: Both diets were associated with sustained reductions in weight and plasma lipid concentrations. In an analysis controlling for medication changes, a low-fat vegan diet appeared to improve glycemia and plasma lipids more than did conventional diabetes diet recommendations. Whether the observed differences provide clinical benefit for the macro- or microvascular complications of diabetes remains to be established. This trial was registered at clinicaltrials.gov as NCT00276939.
MED-4983
Meat intake and mortality: a prospective study of over half a million people
Context High intakes of red or processed meat may increase risk of mortality. Objective Determine the relations of red, white and processed meat intakes to risk for total, and cause-specific mortality. Design, Setting, and Participants The NIH-AARP Diet and Health Study cohort of half a million people aged 50-71 years at baseline. Meat intake was estimated from a food frequency questionnaire administered at baseline. Cox proportional hazards regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs) within quintiles of meat intake. The covariates included in the models were: age; education; marital status; family history of cancer (yes/no) (cancer mortality only); race; body mass index; 31-level smoking history; physical activity; energy intake; alcohol intake; vitamin supplement use; fruit consumption; vegetable consumption; and menopausal hormone therapy among women. Main Outcome Measure Total mortality, deaths due to cancer, CVD, accidents, and other causes. Results There were 47,976 male deaths and 23,276 female deaths during 10 years of follow-up. Men and women in the highest versus lowest quintile of red (HR 1.31, 95% CI 1.27-1.35; HR 1.36, 95% CI 1.30-1.43, respectively) and processed meat intake (HR 1.16, 95% CI 1.12-1.20; HR 1.25, 95% 1.20-1.31, respectively) had elevated risks for overall mortality. Regarding cause-specific mortality, men and women had elevated risks for cancer mortality for red (HR 1.22, 95% CI 1.16-1.29; HR 1.20, 95% CI 1.12-1.30, respectively) and processed meats (HR 1.12, 95% CI 1.06-1.19; HR 1.11, 95% CI 1.04-1.19, respectively). Furthermore, CVD risk was elevated for men and women in the highest quintile of red (HR 1.27, 95% CI 1.20-1.35; HR 1.50, 95% CI 1.37-1.65, respectively) and processed meat (HR 1.09, 95% CI 1.03-1.15; HR 1.38, 95% CI 1.26-1.51, respectively). When comparing the highest to the lowest quintile of white meat intake, there was an inverse association for total mortality, and cancer mortality, as well as all other deaths for both men and women. Conclusion Red and processed meat intakes were associated with modest increases in total mortality, cancer mortality and CVD mortality.
MED-1921
Intake of Small-to-Medium-Chain Saturated Fatty Acids Is Associated with Peripheral Leukocyte Telomere Length in Postmenopausal Women
Dietary factors, including dietary fat, may affect the biological aging process, as reflected by the shortening of telomere length (TL), by affecting levels of oxidative stress and inflammatory responses. We examined the direct relations of total and types of dietary fats and fat-rich foods to peripheral leukocyte TL. In 4029 apparently healthy postmenopausal women who participated in the Women’s Health Initiative, intakes of total fat, individual fatty acids, and fat-rich foods were assessed by a questionnaire. TL was measured by quantitative polymerase chain reaction. Intake of short-to-medium-chain saturated fatty acids (SMSFAs; aliphatic tails of ≤12 carbons) was inversely associated with TL. Compared with participants in other quartiles of SMSFA intake, women who were in the highest quartile (median: 1.29% of energy) had shorter TLs [mean: 4.00 kb (95% CI: 3.89, 4.11 kb)], whereas women in the lowest quartile of intake (median: 0.29% of energy) had longer TLs [mean: 4.13 kb (95% CI: 4.03, 4.24 kb); P-trend = 0.046]. Except for lauric acid, all other individual SMSFAs were inversely associated with TL (P < 0.05). In isoenergetic substitution models, the substitution of 1% of energy from SMSFAs with any other energy source was associated with 119 bp longer TLs (95% CI: 21, 216 bp). Intakes of nonskim milk, butter, and whole-milk cheese (major sources of SMSFAs) were all inversely associated with TL. No significant associations were found with long-chain saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids. In conclusion, we found that higher intakes of SMSFAs and SMSFA-rich foods were associated with shorter peripheral leukocyte TL among postmenopausal women. These findings suggest the potential roles of SMSFAs in the rate of biological aging.
MED-4655
Phthalates exposure and attention-deficit/hyperactivity disorder in school-age children.
BACKGROUND: Very few studies have examined the association between attention-deficit/hyperactivity disorder (ADHD) and phthalate exposure in humans. The aim of this study was to investigate the impact of phthalates on symptoms of ADHD in school-age children. METHODS: A cross-sectional examination of urine phthalate concentrations was performed, and scores on measures of ADHD symptoms and neuropsychological dysfunction with regard to attention and impulsivity were obtained from 261 Korean children, age 8-11 years. RESULTS: Mono-2-ethylheyl phthalate (MEHP) and mono-2-ethyl-5-oxohexylphthalate (MEOP) for metabolites of Di-2-ethylhexylphthalate (DEHP) and mono-n-butyl phthalate (MNBP) for metabolites of dibutyl phthalate (DBP) were measured in urine samples. The mean concentrations of MEHP, MEOP, and MNBP were 34.0 microg/dL (SD = 36.3; range: 2.1-386.7), 23.4 microg/dL (SD = 23.0; range: .75-244.8), and 46.7 microg/L (SD = 21.4; range: 13.2-159.3), respectively. After adjustment for covariates, teacher-rated ADHD scores were significantly associated with DEHP metabolites but not with DBP metabolites. We also found significant relationships between the urine concentrations of metabolites for DBP and the number of omission and commission errors in continuous performance tests (CPT) after adjustment for covariates. CONCLUSION: The present study showed a strong positive association between phthalate metabolites in urine and symptoms of ADHD among school-age children.
MED-5088
Mitigation strategies to reduce acrylamide formation in fried potato products.
Potato products contain high amounts of acrylamide, which sometimes exceeds the concentration of 1 mg/L. However, many strategies for acrylamide reduction in potato products are possible. In this work, the different approaches for reducing acrylamide formation have been reviewed, keeping in mind that in the application of strategies for acrylamide formation, the main criteria to be maintained are the overall organoleptic and nutritional qualities of the final product.
MED-4162
Declines in breast cancer after the WHI: apparent impact of hormone therapy.
Large numbers of US women stopped taking hormone therapies (HT), especially estrogen/progestin (EP) formulations, after the Women's Health Initiative trial detected elevated risks of breast cancer in EP users and was halted in July 2002. Recent reports have indicated substantial and significant declines in population-based breast cancer incidence, particularly hormone-sensitive forms, for 2003 and 2004. Are these events linked? This commentary considers the available evidence linking the mass cessation of HT in 2002 to the breast cancer incidence declines of 2003/2004 and quantifies the potential impact of the cessation on the overall burden of breast cancer in the US.
MED-3749
Placebos in clinical practice: comparing attitudes, beliefs, and patterns of use between academic psychiatrists and nonpsychiatrists.
Controversial and ethically tenuous, the use of placebos is central to medicine but even more pivotal to psychosocial therapies. Scholars, researchers, and practitioners largely disagree about the conceptualization of placebos. While different professionals often confound the meanings of placebo effects with placebo responses, physicians continue to prescribe placebos as part of clinical practice. Our study aims to review attitudes and beliefs concerning placebos outside of clinical research. Herein we compare patterns of placebo use reported by academic psychiatrists with those reported by physicians from different specialties across Canadian medical schools. Using a web-based tool, we circulated an online survey to all 17 Canadian medical schools, with a special emphasis on psychiatry departments therein and in university-affiliated teaching hospitals. A variation on earlier efforts, our 5-minute, 21-question survey was anonymous. Among the 606 respondents who completed our online survey, 257 were psychiatrists. Our analysis revealed that psychiatrists prescribed significantly more subtherapeutic doses of medication than physicians in other specialties, although about 20% of both psychiatrists and nonpsychiatrists prescribed placebos regularly as part of routine clinical practice. However, compared with 6% of nonpsychiatrists, only 2% of psychiatrists deemed placebos of no clinical benefit. In addition, more than 60% of psychiatrists either agreed or strongly agreed that placebos had therapeutic effects relative to fewer than 45% of other practitioners. Findings from this pan-Canadian survey suggest that, compared with other physicians, psychiatrists seem to better value the influence placebos wield on the mind and body and maintain more favourable beliefs and attitudes toward placebo phenomena.
MED-5170
Microbiological quality of sushi from sushi bars and retailers.
Sushi is a traditional Japanese food, mostly consisting of rice and raw fish. Fish is considered a healthy food, but as with other animal products, consumption of raw muscle incurs potential health risks such as ingestion of pathogenic bacteria or parasites. In this study, 250 sushi samples were analyzed for their microbiological status and the prevalence of pathogenic bacteria. A comparison was made between frozen sushi from supermarkets and fresh sushi from sushi bars. Aerobic mesophilic bacteria counts differed for sushi from these two sources, with means of 2.7 log CFU/g for frozen sushi and 6.3 log CFU/g for fresh sushi. The prevalence of Escherichia coli and Staphylococcus aureus was higher in the fresh samples. Salmonella was found in four (1.6%) of the sushi samples, and Listeria monocytogenes was found in three (1.2%) of the samples. These results indicate that the microbiological quality of industrially processed sushi is higher than that of freshly prepared sushi. The quality of freshly prepared sushi strongly depends on the skills and habits of the preparation cooks, which may vary.
MED-2999
Western diseases and their emergence related to diet.
Many of the commonest diseases in the economically more developed communities are characteristic of modern Western culture. Evidence is presented suggesting that they represent a failure of adaptation to the dramatic changes in diet that have been associated with the emergence of modern Western culture. Dietary changes aimed at the alleviation and prevention of these diseases are discussed and recommended.
MED-2997
The Etiological Significance of Related Diseases
If disease patterns emerge which show that certain diseases can be related, this is a valuable pointer to a common cause. This article traces the principle of interpreting disease relationships, illustrated by several common conditions of western civilization, for which the common cause is postulated as being removal of fiber from the diet.
MED-4081
Potential dietary links to central sensitization in fibromyalgia: past reports and future directions.
This article reviews the existing literature on fibromyalgia (FM) and diet, discusses the possible role of diet on central sensitization in FM, proposes a novel hypothesis of possible food-related contributors to central sensitization, and makes recommendations for future dietary research directions.
MED-1884
Maintenance of the LDL cholesterol:HDL cholesterol ratio in an elderly population given a dietary cholesterol challenge.
We previously evaluated the responses to dietary cholesterol in children and young adults. In this study, the effects of dietary cholesterol on plasma lipids and LDL atherogenicity were evaluated in 42 elderly subjects (29 postmenopausal women and 13 men > 60 y old). Our exclusion criteria were diabetes, heart disease, and the use of reductase inhibitors. The study followed a randomized crossover design in which subjects were assigned to consume the equivalent of 3 large eggs (EGG) daily or the same amount of a cholesterol-free, fat-free egg substitute (SUB) for a 1-mo period. After a 3-wk washout period, subjects were assigned to the alternate treatment. The concentration of plasma cholesterol after the EGG period varied among subjects. When all subjects were evaluated, there were significant increases in LDL cholesterol (LDL-C) (P < 0.05) and HDL-C (P < 0.001) for both men and women during the EGG period, resulting in no alterations in the LDL-C:HDL-C or the total cholesterol:HDL-C ratios. In addition, the LDL peak diameter was increased during the EGG period for all subjects. In contrast, the measured parameters of LDL oxidation, conjugated diene formation, and LDL lag time did not differ between the EGG and the SUB periods. We conclude from this study that dietary cholesterol provided by eggs does not increase the risk for heart disease in a healthy elderly population.
MED-4602
Manufactured uncertainty: protecting public health in the age of contested science and product defense.
The strategy of "manufacturing uncertainty" has been used with great success by polluters and manufacturers of dangerous products to oppose public health and environmental regulation. This strategy entails questioning the validity of scientific evidence on which the regulation is based. While this approach is most identified with the tobacco industry, it has been used by producers of asbestos, benzene, beryllium, chromium, diesel exhaust, lead, plastics, and other hazardous products to avoid environmental and occupational health regulation. It is also central to the debate on global warming. The approach is now so common that it is unusual for the science not to be challenged by an industry facing regulation. Manufacturing uncertainty has become a business in itself; numerous technical consulting firms provide a service often called "product defense" or "litigation support." As these names imply, the usual objective of these activities is not to generate knowledge to protect public health but to protect a corporation whose products are alleged to have toxic properties. Evidence in the scientific literature of the funding effect--the close correlation between the results of a study desired by a study's funder and the reported results of that study--suggests that the financial interest of a study's sponsors should be taken into account when considering the study's findings. Similarly, the interpretation of data by scientists with financial conflicts should be seen in this light. Manufacturing uncertainty is antithetical to the public health principle that decisions be made using the best evidence currently available.
MED-3396
Oral sildenafil citrate (viagra) for erectile dysfunction: a systematic review and meta-analysis of harms.
OBJECTIVES: To summarize and compare evidence on harms in sildenafil- and placebo-treated men with erectile dysfunction (ED) in a systematic review and meta-analysis. METHODS: Randomized placebo-controlled trials (RCTs) were identified using an electronic search in MEDLINE, EMBASE, PsycINFO, SCOPUS, and Cochrane CENTRAL. The rates of any adverse events (AEs), most commonly reported AEs, withdrawals because of adverse events, and serious adverse events were ascertained and compared between sildenafil and placebo groups. The results of men with ED were stratified by clinical condition(s). Statistical heterogeneity was explored. Meta-analyses based on random-effects model were also performed. RESULTS: A total of 49 RCTs were included. Sildenafil-treated men had a higher risk for all-cause AEs (RR = 1.56, 95% CI: 1.38, 1.76), headache, flushing, dyspepsia, and visual disturbances compared with placebo-treated men. The magnitude of excess risk was greater in fixed- than in flexible-dose trials. The rates of serious adverse events and withdrawals because of adverse events did not differ in sildenafil vs placebo groups. A higher dose of sildenafil corresponded to a greater risk of AEs. The increased risk of harms was observed within and across clinically defined specific groups of patients. CONCLUSIONS: There was a lack of RCTs reporting long-term (>6 months) harms data. In short-term trials, men with ED randomized to sildenafil had an increased risk of all-cause any AEs, headache, flushing, dyspepsia, and visual disturbances. The exploration of different modes of dose optimization of sildenafil may be warranted.
MED-1861
The effectiveness of Hibiscus sabdariffa in the treatment of hypertension: a systematic review.
INTRODUCTION: Hypertension is a common global health problem with significant mortality and morbidity. Hibiscus sabdariffa is a plant known in many countries and is consumed as hot and cold drinks In addition to its use in folk medicine; it has been suggested as treatment for many conditions including hypertension. OBJECTIVES: The objectives of this review were to examine the evidence of effectiveness and safety of hibiscus in the treatment of hypertension. METHODS: We searched several medical databases (MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and the specialized register of the Cochrane Hypertension Group and the general engine Google) to January 2009. We included randomized controlled trials that had examined Hibiscus's effectiveness and safety in the treatment of primary hypertension in adults. Two authors independently selected the trials for the review, extracted the data, and critically appraised the included studies. RESULTS: Four trials, with a total of 390 patients, met our inclusion criteria. Two studies compared Hibiscus sabdariffa to black tea; one study compared it to captopril and one to lisinopril. The studies found that Hibiscus had greater blood pressure reduction than tea but less than the ACE-inhibitors. However, all studies, except one, were short term and of poor quality with a Jadad scoring of <3 and did not meet international standards. CONCLUSION: The four randomized controlled studies identified in this review do not provide reliable evidence to support recommending Hibiscus sabdariffa for the treatment of primary hypertension in adults. Copyright 2009 Elsevier GmbH. All rights reserved.
MED-2351
Specific stimulation of Graves' disease thyrocytes by the natural anti-Gal antibody from normal and autologous serum.
Anti-Gal is a natural Ab abundantly produced in humans. It interacts specifically with the carbohydrate epitope Gal alpha 1-3Gal beta 1-4GlcNAc-R (termed the alpha-galactosyl epitope). This epitope is expressed in large amounts on thyrocytes of nonprimate mammals, but not of humans. We have previously found that binding of anti-Gal to alpha-galactosyl epitopes on porcine thyrocytes results in stimulatory effects similar to those exerted by thyroid-stimulating hormone (thyrotropin). In the present study, we tested the hypothesis that anti-Gal may contribute to Graves' disease (GD) pathogenesis by stimulation of the thyrocytes of patients with this autoimmune disorder. Anti-Gal binding and stimulatory effects were assessed in primary thyrocyte cultures. Anti-Gal specifically bound to GD thyrocytes and induced an increase in cAMP synthesis, 125I uptake, and DNA synthesis in these cells. Furthermore, the stimulatory effects of autologous sera on GD thyrocytes were greatly reduced after specific depletion of anti-Gal from these sera. No binding and no stimulatory effects of anti-Gal were observed, however, with normal human thyrocytes and with thyrocytes from thyrotoxic patients who lack thyroid-stimulating Igs or thyrotropin binding inhibiting Igs. These in vitro stimulatory effects of anti-Gal on GD thyrocytes suggest that this natural Ab may contribute to the in vivo continuous stimulation of thyrocytes in GD patients. The possibility that anti-Gal may stimulate GD thyrocytes via interaction with aberrantly expressed alpha-galactosyl epitopes on the thyroid-stimulating hormone receptor is discussed.
MED-2715
Physical activity energy expenditure has not declined since the 1980s and matches energy expenditures of wild mammals.
OBJECTIVE: Obesity results from protracted energy imbalance. Whether this comprises excessive energy intake, lowered physical activity or both, remains disputed. DESIGN: Physical activity energy expenditure, evaluated in three different ways from daily energy expenditure (DEE) measured using doubly labelled water, was examined for trends over time. Data included subjects in Europe (Maastricht, the Netherlands) and North America extending back to the 1980s. These data were compared with measures from the third world, and measures made on wild terrestrial mammals. RESULTS: Physical activity expenditure in Europe (residual of the regression of DEE on basal energy expenditure (BEE)) has slightly but significantly increased since the 1980s. There was no trend over time in physical activity level (PAL=DEE/BEE), or in the residual variance in DEE once mass, sex and age were accounted for. This latter index of physical activity expenditure also significantly increased over time in North America. DEE of individuals in Europe and North America was not significantly different from individuals measured in the third world. In wild terrestrial mammals, DEE mostly depended on body mass and ambient temperature. Predicted DEE for a 78 kg mammal living at 20 degrees C was 9.2 MJ per day (95% CI: 7.9-12.9 MJ per day), not significantly different from the measured DEE of modern humans (around 10.2-12.6 MJ per day). CONCLUSION: As physical activity expenditure has not declined over the same period that obesity rates have increased dramatically, and daily energy expenditure of modern man is in line with energy expenditure in wild mammals, it is unlikely that decreased expenditure has fuelled the obesity epidemic.
MED-4352
Effects of dietary protein on composition and metabolism of plasma lipoproteins in rabbits.
Changes in the concentration and composition of serum VLDL, LDL, and HDL were studied in rabbits transferred from Chow diets to cholesterol-free, semipurified diets containing casein or isolated soy protein. During the first week on the casein diet, there was a marked increase in LDL-cholesterol and these higher levels were maintained during the subsequent 3 weeks of the study. Similar but less marked changes were obtained with the soy protein diet. When the percent composition of the particles was determined, both VLDL and LDL had a higher proportion of cholesterol. Turnover studies indicated that the FCRs for radiolabelled VLDL and LDL were reduced in casein-fed animals compared to those fed soy protein. The elevated LDL levels in casein-fed rabbits were primarily due to a reduction in receptor-mediated catabolism of LDL-apo B. Receptor-independent removal in the two groups was similar. These studies show that the hypercholesterolemia in casein-fed rabbits, compared to those fed soy protein, is associated with cholesterol enrichment of LDL and impaired receptor-dependent removal of LDL-apo B.
MED-3477
Hesperidin contributes to the vascular protective effects of orange juice: a randomized crossover study in healthy volunteers.
BACKGROUND: Although numerous human studies have shown consistent effects of some polyphenol-rich foods on several intermediate markers for cardiovascular diseases, it is still unknown whether their action could be specifically related to polyphenols. OBJECTIVE: We investigated the effect of orange juice and its major flavonoid, hesperidin, on microvascular reactivity, blood pressure, and cardiovascular risk biomarkers through both postprandial and chronic intervention studies. DESIGN: Twenty-four healthy, overweight men (age 50-65 y) were included in a randomized, controlled, crossover study. Throughout the three 4-wk periods, volunteers daily consumed 500 mL orange juice, 500 mL control drink plus hesperidin (CDH), or 500 mL control drink plus placebo (CDP). All measurements and blood collections were performed in overnight-fasted subjects before and after the 4-wk treatment periods. The postprandial study was conducted at the beginning of each experimental period. RESULTS: Diastolic blood pressure (DBP) was significantly lower after 4 wk consumption of orange juice or CDH than after consumption of CDP (P = 0.02), whereas microvascular endothelium-related reactivity was not significantly affected when measured after an overnight fast. However, both orange juice and CDH ingestion significantly improved postprandial microvascular endothelial reactivity compared with CDP (P < 0.05) when measured at the peak of plasma hesperetin concentration. CONCLUSIONS: In healthy, middle-aged, moderately overweight men, orange juice decreases DBP when regularly consumed and postprandially increases endothelium-dependent microvascular reactivity. Our study suggests that hesperidin could be causally linked to the beneficial effect of orange juice. This trial is registered at clinicaltrials.gov as NCT00983086.
MED-2284
COX-2 inhibitors: a story of greed, deception and death.
In 1999, drug manufacturers introduced a class of NSAIDs called COX-2 inhibitors or coxibs. The drugs were avidly promoted directly to the consumers and became bestsellers from the start. Arthritis sufferers were eager to take medications that eased joint pain with less risk of causing gastrointestinal pain, bleeding and other side-effects. In the year after their introduction, doctors wrote over 100 million prescriptions for celecoxib (Celebrex) and rofecoxib (Vioxx). Celebrex is the sixth best-selling drug, with sales of more than US$ 4 billion since its debut in 1999. Vioxx had sales of US$ 2.6 billion in 2001. However, the coxibs increase the risk of heart attacks and strokes, and their price, in the USA, is obscene. The manufacturers faced a possibly complicit, toothless and bloodless FDA, and used every maneuvering to fleece the patients. We must now reflect on attitudes that we thought only belong to the tobacco industry. Fortunately, safe and active alternatives exist.
MED-4176
Perfluorooctanesulfonate and related fluorochemicals in human blood samples from China.
Perfluorooctanesulfonylfluoride (POSF)-based compounds have been manufactured and used in a variety of industrial applications. These compounds degrade to perfluorooctanesulfonate (PFOS) which is regarded as a persistent end-stage metabolite and is found to accumulate in tissues of humans and wildlife. PFOS, perfluorohexanesulfonate (PFHxS), perfluorooctanoate (PFOA), and perfluorooctanesulfonamide (PFOSA) have been found in human sera from the United States. In this study, concentrations of PFHxS, perfluorobutanesulfonate (PFBS), PFOS, perfluorohexanoic acid (PFHxA), PFOA, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoDA), and PFOSA were measured in 85 samples of whole human blood collected from nine cities (eight provinces) in China, including Shenyang (Liaoning), Beijing (Hebei), Zhengzhou (Henan), Jintan (Jiangsu), Wuhan (Hubei), Zhoushan (Zhejiang), Guiyang (Guizhou), Xiamen (Fujian), and Fuzhou (Fujian). Among the 10 perfluorinated compounds (PFCs) measured, PFOS was the predominant compound. The mean concentration of PFOS was greatest in samples collected from Shenyang (79.2 ng/mL) and least in samples from Jintan (3.72 ng/mL). PFHxS was the next most abundant perfluorochemical in the samples. No age-related differences in the concentrations of PFOA, PFOS, PFOSA, and PFHxS were observed. Gender-related differences were found,with males higher for PFOS and PFHxS, and females higher in PFUnDA. Concentrations of PFHxS were positively correlated with those of PFOS, while concentrations of PFNA, PFDA, and PFUnDA were positively correlated with those of PFOA. There were differences in the concentration profiles (percentage composition) of various PFCs in the samples among the nine cities.
MED-4649
Structural basis for androgen specificity and oestrogen synthesis in human aromatase
Aromatase cytochrome P450 is the only enzyme in vertebrates known to catalyse the biosynthesis of all oestrogens from androgens1–3. Aromatase inhibitors therefore constitute a front-line therapy for oestrogen-dependent breast cancer3,4. In a three-step process, each step requiring 1 mol of O2, 1 mol of NADPH, and coupling with its redox partner cytochrome P450 reductase, aromatase converts androstenedione, testosterone and 16α-hydroxytestosterone to oestrone, 17β-oestradiol and 17β,16α-oestriol, respectively1–3. The first two steps are C19-methyl hydroxylation steps, and the third involves the aromatization of the steroid A-ring, unique to aromatase. Whereas most P450s are not highly substrate selective, it is the hallmark androgenic specificity that sets aromatase apart. The structure of this enzyme of the endoplasmic reticulum membrane has remained unknown for decades, hindering elucidation of the biochemical mechanism. Here we present the crystal structure of human placental aromatase, the only natural mammalian, full-length P450 and P450 in hormone biosynthetic pathways to be crystallized so far. Unlike the active sites of many microsomal P450s that metabolize drugs and xenobiotics, aromatase has an androgen-specific cleft that binds the androstenedione molecule snugly. Hydrophobic and polar residues exquisitely complement the steroid backbone. The locations of catalytically important residues shed light on the reaction mechanism. The relative juxtaposition of the hydrophobic amino-terminal region and the opening to the catalytic cleft shows why membrane anchoring is necessary for the lipophilic substrates to gain access to the active site. The molecular basis for the enzyme’s androgenic specificity and unique catalytic mechanism can be used for developing next-generation aromatase inhibitors.
MED-3308
Third wave of asbestos-related disease from secondary use of asbestos. A case report from industry.
An occupational health survey conducted in a workshop in which asbestos cement was used showed initial atmospheric asbestos levels ranging from 1.9 to 27.5 fibres per millilitre of air. Radiological changes suggestive of asbestos-related pleural disease were found in 2 workers (2.5%), while 3 (3.8%) had borderline features of asbestosis. The survey confirmed that uncontrolled and hazardous use of asbestos continues in industry despite public awareness of its dangers and the Asbestos Regulations of 1987.
MED-3646
Cranberries vs antibiotics to prevent urinary tract infections: a randomized double-blind noninferiority trial in premenopausal women.
BACKGROUND: The increasing prevalence of uropathogens resistant to antimicrobial agents has stimulated interest in cranberries to prevent recurrent urinary tract infections (UTIs). METHODS: In a double-blind, double-dummy noninferiority trial, 221 premenopausal women with recurrent UTIs were randomized to 12-month prophylaxis use of trimethoprim-sulfamethoxazole (TMP-SMX), 480 mg once daily, or cranberry capsules, 500 mg twice daily. Primary end points were the mean number of symptomatic UTIs over 12 months, the proportion of patients with at least 1 symptomatic UTI, the median time to first UTI, and development of antibiotic resistance in indigenous Escherichia coli. RESULTS: After 12 months, the mean number of patients with at least 1 symptomatic UTI was higher in the cranberry than in the TMP-SMX group (4.0 vs 1.8; P = .02), and the proportion of patients with at least 1 symptomatic UTI was higher in the cranberry than in the TMP-SMX group (78.2% vs 71.1%). Median time to the first symptomatic UTI was 4 months for the cranberry and 8 months for the TMP-SMX group. After 1 month, in the cranberry group, 23.7% of fecal and 28.1% of asymptomatic bacteriuria E coli isolates were TMP-SMX resistant, whereas in the TMP-SMX group, 86.3% of fecal and 90.5% of asymptomatic bacteriuria E coli isolates were TMP-SMX resistant. Similarly, we found increased resistance rates for trimethoprim, amoxicillin, and ciprofloxacin in these E coli isolates after 1 month in the TMP-SMX group. After discontinuation of TMP-SMX, resistance reached baseline levels after 3 months. Antibiotic resistance did not increase in the cranberry group. Cranberries and TMP-SMX were equally well tolerated. CONCLUSION: In premenopausal women, TMP-SMX, 480 mg once daily, is more effective than cranberry capsules, 500 mg twice daily, to prevent recurrent UTIs, at the expense of emerging antibiotic resistance. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN50717094.
MED-1521
Effects of peppermint teas on plasma testosterone, follicle-stimulating hormone, and luteinizing hormone levels and testicular tissue in rats.
OBJECTIVES: To justify the effects of Mentha piperita labiatae and Mentha spicata labiatae herbal teas on plasma total testosterone, luteinizing hormone, and follicle-stimulating hormone levels and testicular histologic features. We performed this study because of major complaints in our area from men about the adverse effects of these herbs on male reproductive function. METHODS: The experimental study included 48 male Wistar albino rats (body weight 200 to 250 g). The rats were randomized into four groups of 12 rats each. The control group was given commercial drinking water, and the experimental groups were given 20 g/L M. piperita tea, 20 g/L M. spicata tea, or 40 g/L M. spicata tea. RESULTS: The follicle-stimulating hormone and luteinizing hormone levels had increased and total testosterone levels had decreased in the experimental groups compared with the control group; the differences were statistically significant. Also, the Johnsen testicular biopsy scores were significantly different statistically between the experimental groups and the control group. Although the mean seminiferous tubular diameter of the experimental groups was relatively greater than in the control group, the difference was not statistically significant. The only effects of M. piperita on testicular tissue was segmental maturation arrest in the seminiferous tubules; however, the effects of M. spicata extended from maturation arrest to diffuse germ cell aplasia in relation to the dose. CONCLUSIONS: Despite the beneficial effects of M. piperita and M. spicata in digestion, we should also be aware of the toxic effects when the herbs are not used in the recommended fashion or at the recommended dose.
MED-4629
Vegetarian diet for patients with rheumatoid arthritis: can the clinical effects be explained by the psychological characteristics of the patients?
In a controlled, single blind clinical trial we have demonstrated recently a beneficial effect of fasting and vegetarian diet in RA. In the present study we compared 53 patients who participated in this clinical trial with 71 other RA patients with regard to some psychological parameters. The patients who participated in the clinical trial differed significantly from other RA patients. Firstly, they had a higher internal score and a lower chance score on the Multi-dimensional Health Locus of Control Scale (MHLCS). Secondly, their belief in the effect of ordinary medical treatment, evaluated by a 10-cm visual analogue scale, was lower, and their belief in the effect of 'alternative', unconventional forms of treatment was higher. Of the patients who were randomized to a vegetarian diet, there was no significant difference between diet responders and diet non-responders with regard to the MHLCS scores. But, diet responders had a significantly lower belief in the effect of ordinary medical treatment compared with diet non-responders. The psychological distress imposed on the patients by changing from an omnivorous diet to a vegetarian diet was monitored during the clinical trial by means of the General Health Questionnaire. Throughout the clinical trial, this variable favoured the vegetarians compared with the omnivorous and the diet responders vs the diet non-responders. We conclude, firstly, that patients with certain psychological characteristics were selected to the clinical trial; secondly, that the MHLCS scores could not explain the clinical improvement, but it may have been influenced by the patients' beliefs in ordinary and 'alternative' forms of treatment; and thirdly, that dietary treatment decreased psychological distress.
MED-4750
Assessment of endogenous androgen levels in meat, liver and testis of Iranian native cross-breed male sheep and bull by gas chromatography-mass spe...
Androgenic steroids always exist in different animal tissues at trace level, with significant numbers of interfering compounds, which makes their determination difficult. To solve some of the problems in quantification of the natural steroids in those tissues, a new GC-MS method was developed in this study. By using a surrogate analyte approach, which was developed in the authors' previous studies, and extensive sample preparation procedure, which successfully eliminates many of the interfering compounds and resulting in a cleaner extract, accuracy, precision, sensitivity and selectivity of the method for the determination of steroids in complex matrices such as meat, liver and testis were improved. By aid of this method, the levels of androgens in different tissues of Iranian native cross-breed bulls and male sheep were determined. According to the results obtained in the present study, although the androgenic profile (contents and ratios of precursors and metabolites to the main hormones) is similar between the same tissues of both animals, the total androgenic content of each tissue is higher in the bull than the same tissue in male sheep. In addition, in both animals higher amount of androgens were found in liver in comparison with meat and testis.
MED-5356
Rye whole grain and bran intake compared with refined wheat decreases urinary C-peptide, plasma insulin, and prostate specific antigen in men with ...
Rye whole grain and bran intake has shown beneficial effects on prostate cancer progression in animal models, including lower tumor take rates, smaller tumor volumes, and reduced prostate specific antigen (PSA) concentrations. A human pilot study showed increased apoptosis after consumption of rye bran bread. In this study, we investigated the effect of high intake of rye whole grain and bran on prostate cancer progression as assessed by PSA concentration in men diagnosed with prostate cancer. Seventeen participants were provided with 485 g rye whole grain and bran products (RP) or refined wheat products with added cellulose (WP), corresponding to ~50% of daily energy intake, in a randomized controlled, crossover design. Blood samples were taken from fasting men before and after 2, 4, and 6 wk of treatment and 24-h urine samples were collected before the first intervention period and after treatment. Plasma total PSA concentrations were lower after treatment with RP compared with WP, with a mean treatment effect of -14% (P = 0.04). Additionally, fasting plasma insulin and 24-h urinary C-peptide excretion were lower after treatment with RP compared with WP (P < 0.01 and P = 0.01, respectively). Daily excretion of 5 lignans was higher after the RP treatment than after the WP treatment (P < 0.001). We conclude that whole grain and bran from rye resulted in significantly lower plasma PSA compared with a cellulose-supplemented refined wheat diet in patients with prostate cancer. The effect may be related to inhibition of prostate cancer progression caused by decreased exposure to insulin, as indicated by plasma insulin and urinary C-peptide excretion.
MED-3946
Antioxidant capacity and other bioactivities of the freeze-dried Amazonian palm berry, Euterpe oleraceae mart. (acai).
The fruit of Euterpe oleraceae, commonly known as acai, has been demonstrated to exhibit significantly high antioxidant capacity in vitro, especially for superoxide and peroxyl scavenging, and, therefore, may have possible health benefits. In this study, the antioxidant capacities of freeze-dried acai fruit pulp/skin powder (OptiAcai) were evaluated by different assays with various free radical sources. It was found to have exceptional activity against superoxide in the superoxide scavenging (SOD) assay, the highest of any food reported to date against the peroxyl radical as measured by the oxygen radical absorbance capacity assay with fluorescein as the fluorescent probe (ORACFL), and mild activity against both the peroxynitrite and hydroxyl radical by the peroxynitrite averting capacity (NORAC) and hydroxyl radical averting capacity (HORAC) assays, respectively. The SOD of acai was 1614 units/g, an extremely high scavenging capacity for O2*-, by far the highest of any fruit or vegetable tested to date. Total phenolics were also tested as comparison. In the total antioxidant (TAO) assay, antioxidants in acai were differentiated into "slow-acting" and "fast-acting" components. An assay measuring inhibition of reactive oxygen species (ROS) formation in freshly purified human neutrophils showed that antioxidants in acai are able to enter human cells in a fully functional form and to perform an oxygen quenching function at very low doses. Furthermore, other bioactivities related to anti-inflammation and immune functions were also investigated. Acai was found to be a potential cyclooxygenase (COX)-1 and COX-2 inhibitor. It also showed a weak effect on lipopolysaccharide (LPS)-induced nitric oxide but no effect on either lymphocyte proliferation and phagocytic capacity.
MED-2067
Sulforaphane as a promising molecule for fighting cancer.
A number of natural compounds with inhibitory effects on tumorigenesis have been identified from our diet. Several studies have documented the cancer-preventive activity of a significant number of isothiocyanates (ITCs), the majority of which occur in plants, especially in Cruciferous vegetables. The most characterized ITC is sulforaphane (SFN). SFN has received a great deal of attention because of its ability to simultaneously modulate multiple cellular targets involved in cancer development, including: (i) DNA protection by modulating carcinogen-metabolizing enzymes and blocking the action of mutagens; (ii) inhibition of cell proliferation and induction of apoptosis, thereby retarding or eliminating clonal expansion of initiated, transformed, and/or neoplastic cells; (iii) inhibition of neoangiogenesis, progression of benign tumors to malignant tumors, and metastasis formation. SFN is therefore able to prevent, delay, or reverse preneoplastic lesions, as well as to act on cancer cells as a therapeutic agent. Taking into account this evidence and its favorable toxicological profile, SFN can be viewed as a conceptually promising agent in cancer prevention and/or therapy.
MED-3987
Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis
Background: Currently, there is a lack of clarity in the literature as to whether there is a definitive difference between the effects of vitamins D2 and D3 in the raising of serum 25-hydroxyvitamin D [25(OH)D]. Objective: The objective of this article was to report a systematic review and meta-analysis of randomized controlled trials (RCTs) that have directly compared the effects of vitamin D2 and vitamin D3 on serum 25(OH)D concentrations in humans. Design: The ISI Web of Knowledge (January 1966 to July 2011) database was searched electronically for all relevant studies in adults that directly compared vitamin D3 with vitamin D2. The Cochrane Clinical Trials Registry, International Standard Randomized Controlled Trials Number register, and clinicaltrials.gov were also searched for any unpublished trials. Results: A meta-analysis of RCTs indicated that supplementation with vitamin D3 had a significant and positive effect in the raising of serum 25(OH)D concentrations compared with the effect of vitamin D2 (P = 0.001). When the frequency of dosage administration was compared, there was a significant response for vitamin D3 when given as a bolus dose (P = 0.0002) compared with administration of vitamin D2, but the effect was lost with daily supplementation. Conclusions: This meta-analysis indicates that vitamin D3 is more efficacious at raising serum 25(OH)D concentrations than is vitamin D2, and thus vitamin D3 could potentially become the preferred choice for supplementation. However, additional research is required to examine the metabolic pathways involved in oral and intramuscular administration of vitamin D and the effects across age, sex, and ethnicity, which this review was unable to verify.
MED-3431
A Population-Based, Longitudinal Study of Erectile Dysfunction and Future Coronary Artery Disease
OBJECTIVE: To assess the association between erectile dysfunction (ED) and the long-term risk of coronary artery disease (CAD) and the role of age as a modifier of this association. PARTICIPANTS AND METHODS: From January 1, 1996, to December 31, 2005, we biennially screened a random sample of 1402 community-dwelling men with regular sexual partners and without known CAD for the presence of ED. Incidence densities of CAD were calculated after age stratification and adjusted for potential confounders by time-dependent Cox proportional hazards models. RESULTS: The prevalence of ED was 2% for men aged 40 to 49 years, 6% for men aged 50 to 59 years, 17% for men aged 60 to 69 years, and 39% for men aged 70 years or older. The CAD incidence densities per 1000 person-years for men without ED in each age group were 0.94 (40-49 years), 5.09 (50-59 years), 10.72 (60-69 years), and 23.30 (≥70 years). For men with ED, the incidence densities of CAD for each age group were 48.52 (40-49 years), 27.15 (50-59 years), 23.97 (60-69 years), and 29.63 (≥70 years). CONCLUSION: ED and CAD may be differing manifestations of a common underlying vascular pathology. When ED occurs in a younger man, it is associated with a marked increase in the risk of future cardiac events, whereas in older men, ED appears to be of little prognostic importance. Young men with ED may be ideal candidates for cardiovascular risk factor screening and medical intervention.
MED-3459
Whole-Body Vibration and the Prevention and Treatment of Delayed-Onset Muscle Soreness
Context: Numerous recovery strategies have been used in an attempt to minimize the symptoms of delayed-onset muscle soreness (DOMS). Whole-body vibration (WBV) has been suggested as a viable warm-up for athletes. However, scientific evidence to support the protective effects of WBV training (WBVT) on muscle damage is lacking. Objective: To investigate the acute effect of WBVT applied before eccentric exercise in the prevention of DOMS. Design: Randomized controlled trial. Setting: University laboratory. Patients or Other Participants: A total of 32 healthy, untrained volunteers were randomly assigned to either the WBVT (n  =  15) or control (n  =  17) group. Intervention(s): Volunteers performed 6 sets of 10 maximal isokinetic (60°/s) eccentric contractions of the dominant-limb knee extensors on a dynamometer. In the WBVT group, the training was applied using a vibratory platform (35 Hz, 5 mm peak to peak) with 100° of knee flexion for 60 seconds before eccentric exercise. No vibration was applied in the control group. Main Outcome Measure(s): Muscle soreness, thigh circumference, and pressure pain threshold were recorded at baseline and at 1, 2, 3, 4, 7, and 14 days postexercise. Maximal voluntary isometric and isokinetic knee extensor strength were assessed at baseline, immediately after exercise, and at 1, 2, 7, and 14 days postexercise. Serum creatine kinase was measured at baseline and at 1, 2, and 7 days postexercise. Results: The WBVT group showed a reduction in DOMS symptoms in the form of less maximal isometric and isokinetic voluntary strength loss, lower creatine kinase levels, and less pressure pain threshold and muscle soreness (P < .05) compared with the control group. However, no effect on thigh circumference was evident (P < .05). Conclusions: Administered before eccentric exercise, WBVT may reduce DOMS via muscle function improvement. Further investigation should be undertaken to ascertain the effectiveness of WBVT in attenuating DOMS in athletes.
MED-4942
Association of polychlorinated biphenyls with hypertension in the 1999-2002 National Health and Nutrition Examination Survey.
The association of 11 polychlorinated biphenyls (PCBs) with hypertension was investigated using the National Health and Nutrition Examination Survey (NHANES), 1999-2002. The unweighted number of participants assessed for hypertension ranged from 2074 to 2556 depending on the chemical(s) being analyzed. In unadjusted logistic regressions all 11 PCBs were associated with hypertension. After adjustment for age, gender, race, smoking status, body mass index, exercise, total cholesterol, and family history of coronary heart disease, seven of the 11 PCBs (PCBs 126, 74, 118, 99, 138/158, 170, and 187) were significantly associated with hypertension. The strongest adjusted associations with hypertension were found for dioxin-like PCBs 126 and 118. PCB 126>59.1 pg/g lipid adjusted had an odds ratio of 2.45 (95% CI 1.48-4.04) compared to PCB 126<or=26.1 pg/g lipid adjusted. PCB 118>27.5 ng/g lipid adjusted had an odds ratio of 2.30 (95% CI 1.29-4.08) compared to PCB 118<or=12.5 ng/g lipid adjusted. Moreover, participants with one or more elevated PCBs had an odds ratio of 1.84 (95% CI 1.25-2.70) compared to no PCBs elevated in an adjusted logistic regression. The prevalence of one or more elevated PCBs was 22.76% or 32 million of 142 million persons >or=20 years old in the non-institutionalized US population. We hypothesize that association of seven PCBs with hypertension indicates elevated PCBs are a risk factor for hypertension. What clinicians can do, given the results of this study, is limited unless the appropriate laboratory methods can be made more widely available for testing patients.
MED-5018
American Academy of Pediatrics recommendations on the Effects of Early Nutritional Interventions on the Development of Atopic Disease
Purpose of review This article reviews the AAP’s statement on early nutritional interventions on the development of atopic disease in infants and children. Recent findings Recent findings suggest that restriction of maternal diet during pregnancy and lactation does not play a major role in the development of allergic disease. In high risk infants exclusive breastfeeding for at least 4 months prevents or delays atopic dermatitis, cow milk allergy, and wheezing early in life. There is evidence that supplementing breastfeeding with a hydrolyzed formula protects against atopic disease, especially atopic dermatitis in at risk infants. Finally there is little evidence that delaying the introduction of complimentary foods beyond 4 to 6 months of age has any protective effect against allergy. There is insufficient data that any dietary intervention beyond 4 to 6 months of age has any protective effect against developing atopic disease. Summary In high risk infants there is evidence for exclusive breastfeeding for at least 4 months and delaying of complimentary foods until 4 to 6 months prevents the development of allergy. There is some evidence that supplementing hydrolyzed formulas in high risk infants may delay or prevent allergic disease. There is no convincing evidence that maternal manipulation of diet during pregnancy or lactation, use of soy products, or infant dietary restrictions beyond 4 to 6 months has any effect on the development of atopic disease.
MED-3399
Pistachio diet improves erectile function parameters and serum lipid profiles in patients with erectile dysfunction.
We investigated the effects of Antep pistachio on International Index of Erectile Function (IIEF) scores, penile color Doppler ultrasound (PCDU) parameters and serum lipid levels in patients with ED. A total of 17 married male patients with ED for at least 12 months were included in this prospective study. Patients were put on a 100 g pistachio nuts diet for 3 weeks. IIEF and PCDU were evaluated before and after the pistachio diet. In addition, plasma total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride were measured before and after dietary modifications from all subjects. Mean IIEF-15 score was 36 ± 7.5 before the diet and 54.2 ± 4.9 after the diet (P=0.001). Similarly, an increase in all five domains of IIEF was observed after the diet (P<0.05). Mean peak systolic velocity values before and after the pistachio diet were 35.5 ± 15.2 and 43.3 ± 12.4 cm s(-1), respectively (P=0.018). After the pistachio diet, TC and LDL levels decreased significantly, whereas HDL level increased (P=0.008, 0.007 and 0.001, respectively). We demonstrated that a pistachio diet improved IIEF scores and PCDU parameters without any associated side effects in patients with ED. Furthermore, the lipid parameters showed statistically significant improvements after this diet.
MED-3656
A Longitudinal Study of Vaginal Douching and Bacterial Vaginosis—A Marginal Structural Modeling Analysis
The etiology of bacterial vaginosis is unknown, and there are no long-term therapies for preventing this frequently recurring condition. Vaginal douching has been reported to be associated with bacterial vaginosis in observational studies. However, this association may be due to confounding by indication—that is, confounding by women douching in response to vaginal symptoms associated with bacterial vaginosis. The authors used marginal structural modeling to estimate the causal effect of douching on bacterial vaginosis risk while controlling for this confounding effect. In 1999–2002, nonpregnant women (n = 3,620) were recruited into a prospective study when they visited one of 12 public health clinics in Birmingham, Alabama, for routine care. Participants were assessed quarterly for 1 year. Bacterial vaginosis was based on a Nugent's Gram stain score of 7 or higher. Thirty-two percent of participants douched in every study interval, and 43.0% never douched. Of the 12,349 study visits, 40.2% were classified as involving bacterial vaginosis. The relative risk for regular douching as compared with no douching was 1.21 (95% confidence interval: 1.08, 1.38). These findings indicate that douching confers increased risk of disruption of vaginal flora. In the absence of a large randomized trial, these findings provide the best evidence to date for a risk of bacterial vaginosis associated with douching.
MED-1733
Rhabdomyolysis from an intramuscular injection of glyphosate-surfactant herbicide.
INTRODUCTION: Glyphosate-surfactant herbicide (GlySH) is widely used as a non-selective herbicide. Most intoxicated cases are from ingestion, inhalation, and skin exposure. Intramuscular injection of GlySH has never been reported. We present a case of GlySH intoxication via intramuscular injection. CASE REPORT: A 42-year-old woman came to the emergency department complaining of painful swelling of left upper limb for 12 h. She had performed an intramuscular injection of 6 mL of GlySH over the lateral aspect of the left elbow 15 h previously. Physical examination disclosed painful swelling over left distal arm, elbow, and forearm with three needle punctures. CT scan revealed ill-defined areas of heterogeneous high density with marked swelling at subcutaneous tissue over posterior aspect of the elbow. DISCUSSION: The mechanism of toxicity of GlySH is complicated and surfactant was thought to play an important role in GlySH intoxication. Intramuscular GlySH poisoning is different from oral GlySH intoxication. Care should be taken when monitoring acute rhabdomyolysis and compartment syndrome, which may develop rapidly and contribute to the surfactant component of glyphosate formulation.
MED-1020
Pan retinal photocoagulation for proliferative diabetic retinopathy: pattern scan laser versus argon laser.
PURPOSE OF REVIEW: Diabetic retinopathy is the leading cause of visual impairment in working-age adults worldwide. Pan retinal photocoagulation (PRP) has provided an effective treatment to decrease the risk of severe vision loss in patients with proliferative diabetic retinopathy for the past four decades. Pattern scan laser (PASCAL) was developed to minimize the side effects of PRP. The purpose of this review is to discuss the differences between the traditional argon laser and the PASCAL. RECENT FINDINGS: PASCAL can achieve comparable results with the conventional argon PRP in the treatment of patients with diabetic retinopathy. The PASCAL delivery system creates well aligned arrays of retinal lesions in a shorter period. PASCAL provides amore comfortable profile when compared to the argon laser. SUMMARY: The PASCAL is now being substituted for the conventional argon laser for PRP in many clinics. Ophthalmologists should keep in mind that adjusting the PASCAL settings (including the duration, number, and size of laser burns) might become necessary to maintain regression and eliminate recurrence of neovascularization in patients with proliferative diabetic retinopathy. Further studies are needed to determine the parameters for optimal safety and efficacy on the PASCAL.
MED-2178
Blood Harmane, Blood Lead, and Severity of Hand Tremor: Evidence of Additive Effects
Background Tremor is a widespread phenomenon in human populations. Environmental factors are likely to play an etiological role. Harmane (1-methyl-9H-pyrido[3,4-β]indole) is a potent tremor-producing β-carboline alkaloid. Lead is another tremor-producing neurotoxicant. The effects of harmane and lead with respect to tremor have been studied in isolation. Objectives We tested the hypothesis that tremor would be particularly severe among individuals who had high blood concentrations of both of these toxicants. Methods Blood concentrations of harmane and lead were each quantified in 257 individuals (106 essential tremor cases and 151 controls) enrolled in an environmental epidemiological study. Total tremor score (range = 0 – 36) was a clinical measure of tremor severity. Results The total tremor score ranged from 0 – 36, indicating that a full spectrum of tremor severities was captured in our sample. Blood harmane concentration correlated with total tremor score (p = 0.007), as did blood lead concentration (p = 0.045). The total tremor score was lowest in participants with both low blood harmane and lead concentrations (8.4 ± 8.2), intermediate in participants with high concentrations of either toxicant (10.5 ± 9.8), and highest in participants with high concentrations of both toxicants (13.7 ± 10.4)(p = 0.01). Conclusions Blood harmane and lead concentrations separately correlated with total tremor scores. Participants with high blood concentrations of both toxicants had the highest tremor scores, suggesting an additive effect of these toxicants on tremor severity. Given the very high population prevalence of tremor disorders, identifying environmental determinants is important for primary disease prevention.
MED-3502
Review of harmful gastrointestinal effects of carrageenan in animal experiments.
In this article I review the association between exposure to carrageenan and the occurrence of colonic ulcerations and gastrointestinal neoplasms in animal models. Although the International Agency for Research on Cancer in 1982 identified sufficient evidence for the carcinogenicity of degraded carrageenan in animals to regard it as posing a carcinogenic risk to humans, carrageenan is still used widely as a thickener, stabilizer, and texturizer in a variety of processed foods prevalent in the Western diet. I reviewed experimental data pertaining to carrageenan's effects with particular attention to the occurrence of ulcerations and neoplasms in association with exposure to carrageenan. In addition, I reviewed from established sources mechanisms for production of degraded carrageenan from undegraded or native carrageenan and data with regard to carrageenan intake. Review of these data demonstrated that exposure to undegraded as well as to degraded carrageenan was associated with the occurrence of intestinal ulcerations and neoplasms. This association may be attributed to contamination of undegraded carrageenan by components of low molecular weight, spontaneous metabolism of undegraded carrageenan by acid hydrolysis under conditions of normal digestion, or the interactions with intestinal bacteria. Although in 1972, the U.S. Food and Drug Administration considered restricting dietary carrageenan to an average molecular weight > 100,000, this resolution did not prevail, and no subsequent regulation has restricted use. Because of the acknowledged carcinogenic properties of degraded carrageenan in animal models and the cancer-promoting effects of undegraded carrageenan in experimental models, the widespread use of carrageenan in the Western diet should be reconsidered.
MED-1688
Effects of tomato extract on platelet function: a double-blinded crossover study in healthy humans.
BACKGROUND: Aqueous extracts from tomatoes display a range of antiplatelet activities in vitro. We previously showed that the active components also alter ex vivo platelet function in persons with a high response to ADP agonist. OBJECTIVE: The objective was to evaluate the suitability of a tomato extract for use as a dietary supplement to prevent platelet activation. DESIGN: A randomized, double-blinded, placebo-controlled crossover study was conducted in 90 healthy human subjects selected for normal platelet function. Changes from baseline hemostatic function were measured 3 h after consumption of extract-enriched or control supplements. RESULTS: Significant reductions in ex vivo platelet aggregation induced by ADP and collagen were observed 3 h after supplementation with doses of tomato extract equivalent to 6 (6TE) and 2 (2TE) tomatoes [3 micromol ADP/L: 6TE (high dose), -21.3%; 2TE (low dose), -12.7%; P < 0.001; 7.5 micromol ADP/L: 6TE, -7.8%, 2TE, -7.6%; P < 0.001; 3 mg collagen/L: 6TE, -17.5%; 2TE, -14.6%; P = 0.007]. No significant effects were observed for control supplements. A dose response to tomato extract was found at low levels of platelet stimulation. Inhibition of platelet function was greatest in a subgroup with the highest plasma homocysteine (P < 0.05) and C-reactive protein concentrations (P < 0.001). CONCLUSION: As a functional food or dietary supplement, tomato extract may have a role in primary prevention of cardiovascular disease by reducing platelet activation, which could contribute to a reduction in thrombotic events.
MED-5283
Chocolate/cocoa and human health: a review.
Chocolate/cocoa has been known for its good taste and proposed health effects for centuries. Earlier, chocolate used to be criticised for its fat content and its consumption was a sin rather than a remedy, associated with acne, caries, obesity, high blood pressure, coronary artery disease and diabetes. Therefore, many physicians tended to warn patients about the potential health hazards of consuming large amounts of chocolate. However, the recent discovery of biologically active phenolic compounds in cocoa has changed this perception and stimulated research on its effects in ageing, oxidative stress, blood pressure regulation, and atherosclerosis. Today, chocolate is lauded for its tremendous antioxidant potential. However, in many studies, contradictory results and concerns about methodological issues have made it hard for health professionals and the public to understand the available evidence on chocolate's effects on health. The purpose of this review is to interpret research done in the last decade on the benefits and risks of chocolate consumption.
MED-2372
Egg consumption and endothelial function: a randomized controlled crossover trial.
BACKGROUND: Because of egg cholesterol content, reduction in egg consumption is generally recommended to reduce risk of cardiovascular disease. Recently, however, evidence has been accumulating to suggest that dietary cholesterol is less relevant to cardiovascular risk than dietary saturated fat. This randomized controlled crossover trial was conducted to determine the effects of egg ingestion on endothelial function, a reliable index of cardiovascular risk. METHODS: Forty-nine healthy adults (mean age 56 years, 40% females) underwent a baseline brachial artery reactivity study (BARS), and were assigned to two eggs or oats daily for 6 weeks in random sequence with a 4-week washout. A BARS was done at the end of each treatment phase, measuring flow-mediated vasodilation (FMD) in the brachial artery using a high-frequency ultrasound. RESULTS: FMD was stable in both egg and oat groups, and between-treatment differences were not significant (egg -0.96%, oatmeal -0.79%; p value >0.05). Six weeks of egg ingestion had no effect on total cholesterol (baseline: 203.8 mg/dl; post-treatment: 205.3) or LDL (baseline: 124.8 mg/dl; post-treatment: 129.1). In contrast, 6 weeks of oats lowered total cholesterol (to 194 mg/dl; p = 0.0017) and LDL (to 116.6 mg/dl; p = 0.012). There were no differences in body mass index (BMI), triglyceride, HDL or SBP levels between egg and oat treatment assignments. CONCLUSION: Short-term egg consumption does not adversely affect endothelial function in healthy adults, supporting the view that dietary cholesterol may be less detrimental to cardiovascular health than previously thought.
MED-1554
Reduced or modified dietary fat for preventing cardiovascular disease.
BACKGROUND: Reduction or modification of dietary fat can improve total cholesterol levels, but may also have a variety of effects, both positive and negative, on other cardiovascular risk factors. OBJECTIVES: The aim of this systematic review was to assess the effect of reduction or modification of dietary fats on total and cardiovascular mortality and cardiovascular morbidity over at least 6 months, using all available randomized clinical trials. SEARCH STRATEGY: The Cochrane Library, MEDLINE, EMBASE, CAB s, CVRCT registry and related Cochrane Groups' trial registers were searched through spring 1998, SIGLE to January 1999. Trials known to experts in the field and biographies were included through May 1999. SELECTION CRITERIA: Trials fulfilled the following criteria: 1) randomized with appropriate control group, 2) intention to reduce or modify fat or cholesterol intake (excluding exclusively omega-3 fat interventions), 3) not multi factorial, 4) healthy adult humans, 5) intervention at least six months, 6) mortality or cardiovascular morbidity data available. Inclusion decisions were duplicated, disagreement resolved by discussion or a third party. DATA COLLECTION AND ANALYSIS: Rate data were extracted by two independent reviewers and meta-analysis performed using random effects methodology. Meta-regression and funnel plots were used. MAIN RESULTS: Twenty seven studies were included (40 intervention arms, 30,901 person-years). There was no significant effect on total mortality (rate ratio 0.98, 95% CI 0.86 to 1.12), a trend towards protection form cardiovascular mortality (rate ratio 0.91, 95% CI 0.77 to 1.07), and significant protection from cardiovascular events (rate ratio 0.84, 95% CI 0.72 to 0.99). The latter became non-significant on sensitivity analysis. Trials where participants were involved for more than 2 years showed significant reductions in the rate of cardiovascular events and a suggestion of protection from total mortality. The degree of protection from cardiovascular events appeared similar in high and low risk groups, but was statistically significant only in the former. REVIEWER'S CONCLUSIONS: The findings are suggestive of a small but potentially important reduction in cardiovascular risk in trials longer than two years. Lifestyle advice to all those at high risk of cardiovascular disease (especially where statins are unavailable or rationed), and to lower risk population groups, should continue to include permanent reduction of dietary saturated fat and partial replacement by unsaturates.
MED-4305
Macronutrient intake, plasma large neutral amino acids and mood during weight-reducing diets.
Influence of diet composition on mood during weight-reducing diets was studied in healthy young women of normal weight. A broad range of macronutrient intake was achieved by means of divergent dietary instructions for the composition of a 1,000 kcal per day diet adhered to for six weeks. Global mood during the last three weeks of the diet was significantly better in the "vegetarian" than in the "mixed" diet group. During this time a significant correlation was observed between relative carbohydrate intake and global mood (r = -0.74; p less than 0.01) and between the ratio of plasma tryptophan to other large neutral amino acids (a predictor of tryptophan flow into brain) and global mood (r = -0.52; p less than 0.05). Results suggest that group differences are related to differences in carbohydrate intake. It is hypothesized that impairment of central serotonergic function due to reduced tryptophan availability can prompt mood deterioration in situations of relatively low carbohydrate intake.
MED-692
The effectiveness and safety of ginger for pregnancy-induced nausea and vomiting: a systematic review.
BACKGROUND: Ginger has been used throughout the world as a therapeutic agent for centuries. The herb is increasingly used in Western society also, with one of the most common indications being pregnancy-induced nausea and vomiting (PNV). OBJECTIVES: To examine the evidence for the safety and effectiveness of ginger for PNV. METHODS: Randomised controlled trials (RCTs) of ginger and PNV were sourced from CINAHL, the Cochrane library, MEDLINE and TRIP. The methodological quality of RCTs was assessed using the Critical Appraisal Skills Programme (CASP) tool. RESULTS: Four RCTs met the inclusion criteria. All trials found orally administered ginger to be significantly more effective than placebo in reducing the frequency of vomiting and intensity of nausea. Adverse events were generally mild and infrequent. CONCLUSION: The best available evidence suggests that ginger is a safe and effective treatment for PNV. However, there remains uncertainty regarding the maximum safe dosage of ginger, appropriate duration of treatment, consequences of over-dosage, and potential drug-herb interactions; all of which are important areas for future research. Copyright © 2012 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.
MED-3595
Heavy Metals and Couple Fecundity, the LIFE Study
The effect of heavy metals at environmentally relevant concentrations on couple fecundity has received limited study despite ubiquitous exposure. In 2005–2009, couples (n=501) desiring pregnancy and discontinuing contraception were recruited and asked to complete interviews and to provide blood specimens for the quantification of cadmium (μg/L), lead (μg/dL) and mercury (μg/L) using inductively coupled plasma-mass spectrometry. Couples completed daily journals on lifestyle and intercourse along with menstruation and pregnancy testing for women. Couples were followed for 12 months or until pregnant. Fecundability odds ratios (FORs) and 95% confidence intervals (CIs) were estimated adjusting for age, body mass index, cotinine, and serum lipids in relation to female then male exposures. FORs <1 denote a longer time to pregnancy. In adjusted models, reduced FORs were observed for both female cadmium (0.78; 95% CI 0.63–0.97) and male lead (0.85; 95% CI 0.73–0.98) concentrations. When jointly modeling couples’ exposures, only male lead concentration significantly reduced the FOR (0.82; 95% CI 0.68, 0.97), though the FOR remained <1 for female cadmium (0.80; 95% CI 0.64, 1.00). This prospective couple based cohort with longitudinal capture of time to pregnancy is suggestive of cadmium and lead’s reproductive toxicity at environmentally relevant concentrations.
MED-4638
Bowel movement and constipation frequencies and the risk of colorectal cancer among men in the Netherlands Cohort Study on Diet and Cancer.
The authors investigated the associations between bowel movement and constipation frequencies and colorectal cancer (CRC) endpoints among men in the Netherlands Cohort Study on Diet and Cancer (n = 58,279) and explored whether dietary fiber intake may modify associations. After 13.3 years (1986-1999), 1,207 CRC cases and 1,753 subcohort members were available for case-cohort analyses. Multivariate analyses showed a significantly increased hazard ratio for CRC overall and rectal cancer in men who reported having a bowel movement 1-2 times per day (second-highest category) as compared with once a day (CRC: hazard ratio (HR) = 1.29, 95% confidence interval (CI): 1.09, 1.53 (P(trend) < 0.001); rectal cancer: HR = 1.50, 95% CI: 1.15, 1.95 (P(trend) = 0.001)). Hazard ratios for CRC overall and rectal cancer were significantly decreased and lowest in men who reported suffering from constipation sometimes or more often versus never (CRC: HR = 0.76, 95% CI: 0.58, 0.98 (P(trend) = 0.02); rectal cancer: HR = 0.57, 95% CI: 0.35, 0.90 (P(trend) = 0.01)). No trends in the associations with proximal or distal colon cancer risk were observed. Interactions with dietary fiber intake were not significant. In this study, frequent bowel movements were associated with an increased risk of rectal cancer in men, and constipation was associated with a decreased risk.
MED-3022
The many faces of methylmercury poisoning.
Methylmercury (MM) is a very potent neurotoxic agent. Its role in polluting the environment is well documented. A vast amount of study over the past several decades has finally provided insight into many aspects of its effect. Exposure to MM may be through ingestion of poisoned fish or inadvertent misuse of grain treated with the poison as a fungicide. Major epidemics have occurred in Japan (Fetal Minamata disease), Iraq, Pakistan, Guatemala, and Ghana. Sporadic incidences have occurred in the United States and Canada. There is no effective antidote to counteract the effect of MM on the central nervous system, although the information documented should provide hope for more effective therapy in acute cases.
MED-4198
Insect food for astronauts: gas exchange in silkworms fed on mulberry and lettuce and the nutritional value of these insects for human consumption ...
In this study, silkworm moth (Bombyx mori L.) larvae were regarded as an animal protein source for astronauts in the bioregenerative life support system during long-term deep space exploration in the future. They were fed with mulberry and stem lettuce leaves during the first three instars and the last two instars, respectively. In addition, this kind of environmental approach, which utilised inedible biomass of plants to produce animal protein of high quality, can likewise be applied terrestrially to provide food for people living in extreme environments and/or impoverished agro-ecosystems, such as in polar regions, isolated military bases, ships, submarines, etc. Respiration characteristics of the larvae during development under two main physiological conditions, namely eating and not-eating of leaves, were studied. Nutrient compositions of silkworm powder (SP), ground and freeze-dried silkworms on the 3rd day of the 5th instar larvae, including protein, fat, vitamins, minerals and fatty acids, were measured using international standard methods. Silkworms' respiration rates, measured when larvae were eating mulberry leaves, were higher than those of similar larvae that hadn't eaten such leaves. There was a significant difference between silkworms fed on mulberry leaves and those fed on stem lettuce in the 4th and 5th instars (P<0.01). Amounts of CO2 exhaled by the silkworms under the two physiological regimes differed from each other (P<0.01). There was also a significant difference between the amount of O2 inhaled when the insects were under the two physiological statuses (P<0.01). Moreover, silkworms' respiration quotient under the eating regime was larger than when under the not-eating regime. The SP was found to be rich in protein and amino acids in total; 12 essential vitamins, nine minerals and twelve fatty acids were detected. Moreover, 359 kcal could be generated per 100 gram of SP (dry weight).
MED-4798
Efficacy of cleaning products for C difficile
OBJECTIVE To review the evidence for the efficacy of products used for environmental or hand cleaning on the rates of Clostridium difficile–associated diarrhea (CDAD). QUALITY OF EVIDENCE MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews were searched for articles pertinent to the efficacy of cleaning products against C difficile or studies with outcomes related to rates of CDAD. Evidence was level II. MAIN MESSAGE Minimizing the incidence of CDAD in geriatric rehabilitation units is essential to achieving the goals of increasing patient function and independence for discharge into the community. Attention to environmental control of C difficile and its spores by health care workers and patient visitors is an important secondary prevention strategy. CONCLUSION Chlorine-releasing agents are more effective than detergents for killing spores produced by C difficile. No level I evidence is available to determine if the use of chlorine-releasing agents has an effect on rates of CDAD. Hand-washing is currently the recommended strategy for reducing transmission of C difficile. Alcohol gels do not inactivate C difficile spores; however, increased use of alcohol hand gel has not been associated with higher rates of CDAD. Résumé OBJECTIF Examiner les preuves indiquant que les produits utilisés pour nettoyer l’environnement et les mains sont efficaces pour réduire le taux de diarrhée due au Clostridium difficile (DDCD). QUALITÉ DES PREUVES On a consulté MEDLINE, EMBASE et la Cochrane Database of Systematic Reviews en retenant les articles portant sur l’efficacité des agents de nettoyage contre le C difficile ou les études traitant de questions liées aux taux de DDCD. Les preuves étaient de niveau II. PRINCIPAL MESSAGE La réduction de l’incidence de la DDCD dans les unités de réadaptation gériatrique est une condition essentielle pour accroître l’état fonctionnel et l’indépendance des patients qui retournent dans la communauté. Pour les intervenants et pour les visiteurs des patients, le contrôle du C difficile et de ses spores dans l’environnement est primordial comme stratégie de prévention secondaire. Les agents qui libèrent du chlore sont plus efficaces que les détergents pour tuer les spores du C difficile. Il n’existe pas de preuves de niveau I indiquant que l’utilisation d’agents libérant du chlore influence les taux de DDCD. Le lavage des mains est la stratégie présentement recommandée pour réduire la transmission du C difficile. Les gels d’alcool n’inactivent pas les spores du C difficile; toutefois, une utilisation accrue de gels d’alcool n’a pas entraîné d’augmentation du taux de DDCD.
MED-4418
Toxicology and risk assessment of coumarin: focus on human data.
Coumarin is a secondary phytochemical with hepatotoxic and carcinogenic properties. For the carcinogenic effect, a genotoxic mechanism was considered possible, but was discounted by the European Food Safety Authority in 2004 based on new evidence. This allowed the derivation of a tolerable daily intake (TDI) for the first time, and a value of 0.1 mg/kg body weight was arrived at based on animal hepatotoxicity data. However, clinical data on hepatotoxicity from patients treated with coumarin as medicinal drug is also available. This data revealed a subgroup of the human population being more susceptible for the hepatotoxic effect than the animal species investigated. The cause of the high susceptibility is currently unknown; possible mechanisms are discussed. Using the human data, a TDI of 0.1 mg/kg body weight was derived, confirming that of the European Food Safety Authority. Nutritional exposure may be considerably, and is mainly due to use of cassia cinnamon, which is a popular spice especially, used for cookies and sweet dishes. To estimate exposure to coumarin during the Christmas season in Germany, a telephone survey was performed with more than 1000 randomly selected persons. Heavy consumers of cassia cinnamon may reach a daily coumarin intake corresponding to the TDI.
MED-862
Traditionally living populations in East Africa have a mean serum 25-hydroxyvitamin D concentration of 115 nmol/l.
Cutaneous synthesis of vitamin D by exposure to UVB is the principal source of vitamin D in the human body. Our current clothing habits and reduced time spent outdoors put us at risk of many insufficiency-related diseases that are associated with calcaemic and non-calcaemic functions of vitamin D. Populations with traditional lifestyles having lifelong, year-round exposure to tropical sunlight might provide us with information on optimal vitamin D status from an evolutionary perspective. We measured the sum of serum 25-hydroxyvitamin D₂ and D₃ (25(OH)D) concentrations of thirty-five pastoral Maasai (34 (SD 10) years, 43 % male) and twenty-five Hadzabe hunter-gatherers (35 (SD 12) years, 84 % male) living in Tanzania. They have skin type VI, have a moderate degree of clothing, spend the major part of the day outdoors, but avoid direct exposure to sunlight when possible. Their 25(OH)D concentrations were measured by liquid chromatography-MS/MS. The mean serum 25(OH)D concentrations of Maasai and Hadzabe were 119 (range 58-167) and 109 (range 71-171) nmol/l, respectively. These concentrations were not related to age, sex or BMI. People with traditional lifestyles, living in the cradle of mankind, have a mean circulating 25(OH)D concentration of 115 nmol/l. Whether this concentration is optimal under the conditions of the current Western lifestyle is uncertain, and should as a possible target be investigated with concomitant appreciation of other important factors in Ca homeostasis that we have changed since the agricultural revolution.
MED-1390
Olive oil intake and risk of cardiovascular disease and mortality in the PREDIMED Study
Background It is unknown whether individuals at high cardiovascular risk sustain a benefit in cardiovascular disease from increased olive oil consumption. The aim was to assess the association between total olive oil intake, its varieties (extra virgin and common olive oil) and the risk of cardiovascular disease and mortality in a Mediterranean population at high cardiovascular risk. Methods We included 7,216 men and women at high cardiovascular risk, aged 55 to 80 years, from the PREvención con DIeta MEDiterránea (PREDIMED) study, a multicenter, randomized, controlled, clinical trial. Participants were randomized to one of three interventions: Mediterranean Diets supplemented with nuts or extra-virgin olive oil, or a control low-fat diet. The present analysis was conducted as an observational prospective cohort study. The median follow-up was 4.8 years. Cardiovascular disease (stroke, myocardial infarction and cardiovascular death) and mortality were ascertained by medical records and National Death Index. Olive oil consumption was evaluated with validated food frequency questionnaires. Multivariate Cox proportional hazards and generalized estimating equations were used to assess the association between baseline and yearly repeated measurements of olive oil intake, cardiovascular disease and mortality. Results During follow-up, 277 cardiovascular events and 323 deaths occurred. Participants in the highest energy-adjusted tertile of baseline total olive oil and extra-virgin olive oil consumption had 35% (HR: 0.65; 95% CI: 0.47 to 0.89) and 39% (HR: 0.61; 95% CI: 0.44 to 0.85) cardiovascular disease risk reduction, respectively, compared to the reference. Higher baseline total olive oil consumption was associated with 48% (HR: 0.52; 95% CI: 0.29 to 0.93) reduced risk of cardiovascular mortality. For each 10 g/d increase in extra-virgin olive oil consumption, cardiovascular disease and mortality risk decreased by 10% and 7%, respectively. No significant associations were found for cancer and all-cause mortality. The associations between cardiovascular events and extra virgin olive oil intake were significant in the Mediterranean diet intervention groups and not in the control group. Conclusions Olive oil consumption, specifically the extra-virgin variety, is associated with reduced risks of cardiovascular disease and mortality in individuals at high cardiovascular risk. Trial registration This study was registered at controlled-trials.com (http://www.controlled-trials.com/ISRCTN35739639). International Standard Randomized Controlled Trial Number (ISRCTN): 35739639. Registration date: 5 October 2005.
MED-3386
Bronchiolitis obliterans organizing pneumonia (BOOP) after thoracic radiotherapy for breast carcinoma
Common complications of thoracic radiotherapy include esophagitis and radiation pneumonitis. However, it is important to be aware of uncommon post-radiotherapy complications such as bronchiolitis obliterans organizing pneumonia (BOOP). We report on two patients with carcinoma of the breast who developed an interstitial lung disease consistent with BOOP. BOOP responds to treatment with corticosteroids and the prognosis is generally good despite of the need for long-term administration of corticosteroids as relapses can occur during tapering of steroids. This report provides guidelines for the evaluation and treatment of patients with pulmonary infiltrates after radiotherapy.
MED-3610
Effects of Melissa officinalis L. on oxidative status and DNA damage in subjects exposed to long-term low-dose ionizing radiation.
The aim of this study was to determine the capability of Melissa officinalis L. (Lemon balm) infusion on improvement of oxidative stress status in radiology staff that were exposed to persistent low-dose radiation during work. The study was a before-after clinical trial performed on 55 radiology staff. They were asked to drink Lemon balm infusion which was prepared like a tea bag twice daily (1.5 g/100 mL) for 30 days. In the plasma, lipid peroxidation, DNA damage, catalase, superoxide dismutase, myeloperoxidase, and glutathione peroxidase activity were measured before and after using Lemon balm infusion.Use of Lemon balm infusion in radiology unit workers resulted in a significant improvement in plasma levels of catalase, superoxide dismutase, and glutathione peroxidase and a marked reduction in plasma DNA damage, myeloperoxidase, and lipid peroxidation. It is concluded that infusion of Lemon balm markedly improve oxidative stress condition and DNA damage in radiology staff when used as a dietary supplement for radiation protection.
MED-4863
Phenolic substance characterization and chemical and cell-based antioxidant activities of 11 lentils grown in the northern United States.
Chemical and cellular antioxidant activities and phenolic profiles of 11 lentil cultivars grown in the cool northern parts of the United States were investigated. Individual phenolic compounds, including phenolic acids, flavan-3-ols, flavones, and anthocyanins, were further quantitatively investigated by HPLC. Cellular antioxidant activities (CAA) and peroxyl radical scavenging capacity (PRSC) were evaluated by fluorescence microplate reader. Cultivar Morton exhibited the highest individual flavan-3-ols (catechin and epicatechin) and total flavonoids, as well as the highest antioxidant properties (PRSC and CAA) among all lentils tested. Five phenolic acids of the benzoic types and their derivates (gallic, protocatechuic, 2,3,4-trihydroxybenzoic, p-hydroxybenzoic acid, and protocatechualdehyde) and four phenolic acids of the cinnamic type (chlorogenic, p-coumaric, m-coumaric, and sinapic acid) were detected in all lentil cultivars. Two flavan-3-ols [(+)-catechin and (-)-epicatechin] and one flavone (luteolin) were detected in all lentil cultivars. Among all phenolic compounds detected, sinapic acid was the predominant phenolic acid, and (+)-catechin and (-)-epicatechin were the predominant flavonoids. These results showed that different phenotype lentils possessed considerable variations in their individual phenolic compounds, as well as chemical and cellular antioxidant activities. Caffeic acid, catechin, epicatechin, and total flavonoids significantly (p < 0.05) correlated with peroxyl radical scavenging assay. Cellular antioxidant assay significantly correlated with chemical antioxidant assay ORAC. The results from this study could be very interesting for breeding programs to improve lentils for use as functional foods.
MED-5331
Influencing public nutrition for non-communicable disease prevention: from community intervention to national programme--experiences from Finland.
A global health transition is currently underway. The burden of non-communicable diseases (NCDs) is increasing rapidly in the developing world, very much as a result of changes in lifestyles. In addition to changes in tobacco use and physical activity, major changes are taking place in diets, contributing greatly to the growing epidemic of NCD. Thus, a huge global public health challenge is how to influence the trends in diet and nutrition for effective global NCD prevention. The health transition took place rapidly in Finland after World War II and mortality from cardiovascular disease (CVD) was exceptionally high. The North Karelia Project was launched in 1972 as a community-based, and later as a national, programme to influence diet and other lifestyles that are crucial in the prevention of CVD. The intervention had a strong theory base and it employed comprehensive strategies. Broad community organisation and the strong participation of people were the key elements. Evaluation has shown how the diet (particularly fat consumption) has changed and how these changes have led to a major reduction in population serum cholesterol and blood pressure levels. It has also shown how ischaemic heart disease mortality in a working-age population has declined by 73% in North Karelia and by 65% in the whole country from 1971 to 1995. Although Finland is an industrialised country, North Karelia was rural, of rather low socio-economic level and with many social problems in the 1970s and 1980s. The project was based on low-cost intervention activities, where people's participation and community organisations played a key role. Comprehensive interventions in the community were eventually supported by national activities--from expert guidelines and media activities to industry collaboration and policy. Similar principles for nutrition intervention programmes could be used in developing countries, obviously tailored to the local conditions. This paper discusses the experiences of the North Karelia Project in the light of needs from the less-industrialised countries and makes some general recommendations.
MED-4257
A Systematic Review of Body Fat Distribution and Mortality in Older People
We conducted a systematic review investigating body fat distribution in older adults and its association with morbidity and mortality. Our search yielded 2,702 citations. Following three levels of screening, 25 studies were selected to evaluate the association between body fat distribution and comorbidity, and 17 studies were used in the mortality analysis. Most of the selected studies in our analyses used anthropometric measures, e.g., body mass index (BMI), waist circumference, and waist-hip ratio; relatively few studies used direct measures, such as body fat/lean mass, and percentage body fat. Studies reported inconsistent findings regarding the strongest predictor(s) of morbidity and mortality. However, the majority of studies suggested that BMI per se was not the most appropriate predictor of morbidity and mortality in the elderly because of its inability to discern or detect age-related body fat redistribution. In addition, studies using BMI found that the optimal BMI range for the lowest mortality in the elderly was overweight (25 kg/m2 ≤ BMI < 30 kg/m2) or mildly obese (30 kg/m2 ≤ BMI < 35 kg/m2). Our findings suggest that the current clinical guidelines, recommending that overweight and obesity are major risk factors for increased morbidity and mortality are not applicable to this population. Therefore, the central message of this review is to admonish the government to establish new guidelines specifically for this population, using a combination of body fat distribution measurements, and to certify that these guidelines will not be applied to inappropriate populations.
MED-3771
What is the cell hydration status of healthy children in the USA? Preliminary data on urine osmolality and water intake.
OBJECTIVE: Hyperosmotic stress on cells limits many aspects of cell function, metabolism and health. International data suggest that schoolchildren may be at risk of hyperosmotic stress on cells because of suboptimal water intake. The present study explored the cell hydration status of two samples of children in the USA. DESIGN: Cross-sectional study describing the urine osmolality (an index of hyperosmotic cell shrinkage) and water intake of convenience samples from Los Angeles (LA) and New York City (NYC). SETTING: Each participant collected a urine sample at an outpatient clinic on the way to school on a weekday morning in spring 2009. Each was instructed to wake, eat, drink and do as usual before school, and complete a dietary record form describing the type and amounts of all foods and beverages consumed after waking, before giving the sample. SUBJECTS: The children (9-11 years) in LA (n 337) and NYC (n 211) considered themselves healthy enough to go to school on the day they gave the urine sample. RESULTS: Elevated urine osmolality (>800 mmol/kg) was observed in 63 % and 66 % of participants in LA and NYC, respectively. In multivariable-adjusted logistic regression models, elevated urine osmolality was associated with not reporting intake of drinking water in the morning (LA: OR = 2·1, 95 % CI 1·2, 3·5; NYC: OR = 1·8, 95 % CI 1·0, 3·5). Although over 90 % of both samples had breakfast before giving the urine sample, 75 % did not drink water. CONCLUSIONS: Research is warranted to confirm these results and pursue their potential health implications.
MED-2594
Nut intake and adiposity: meta-analysis of clinical trials.
BACKGROUND: Epidemiologic studies have shown an inverse association between the frequency of nut consumption and body mass index (BMI) and risk of obesity. However, clinical trials that evaluated nut consumption on adiposity have been scarce and inconclusive. OBJECTIVE: We performed a systematic review and meta-analysis of published, randomized nut-feeding trials to estimate the effect of nut consumption on adiposity measures. DESIGN: MEDLINE and the Cochrane Central Register of Controlled Trials databases were searched for relevant clinical trials of nut intake that provided outcomes of body weight, BMI (in kg/m(2)), or waist-circumference measures and were published before December 2012. There were no language restrictions. Two investigators independently selected and reviewed eligible studies. The weighted mean difference (WMD) between nut or control diets was estimated by using a random-effects meta-analysis with 95% CIs. RESULTS: Thirty-three clinical trials met our inclusion criteria. Pooled results indicated a nonsignificant effect on body weight (WMD: -0.47 kg; 95% CI: -1.17, 0.22 kg; I(2) = 7%), BMI (WMD: -0.40 kg/m(2); 95% CI: -0.97, 0.17 kg/m(2); I(2) = 49%), or waist circumference (WMD: -1.25 cm; 95% CI: -2.82, 0.31 cm; I(2) = 28%) of diets including nuts compared with control diets. These findings were remarkably robust in the sensitivity analysis. No publication bias was shown. CONCLUSION: Compared with control diets, diets enriched with nuts did not increase body weight, body mass index, or waist circumference in controlled clinical trials.
MED-3833
Reduction in Ki-67 in Benign Breast Tissue of High Risk Women with the Lignan Secoisolariciresinol Diglycoside (SDG)
Preclinical and correlative studies suggest reduced breast cancer with higher lignan intake or blood levels. We conducted a pilot study of modulation of risk biomarkers for breast cancer in premenopausal women after administration of the plant lignan secoisolariciresinol given as the diglycoside (SDG). Eligibility criteria included regular menstrual cycles, no oral contraceptives, a greater than 3-fold increase in 5 year risk, and baseline Ki-67 ≥2% in areas of hyperplasia in breast tissue sampled by random periareolar fine needle aspiration (RPFNA) during the follicular phase of the menstrual cycle. SDG 50 mg daily was given for 12 months, followed by repeat RPFNA. The primary endpoint was change in Ki-67. Secondary endpoints included change in cytomorphology, mammographic breast density, serum bioavailable estradiol, and testosterone IGF-I and IGFBP-3, and plasma lignan levels. Forty-five of 49 eligible women completed the study with excellent compliance (median = 96%) and few serious side effects (4% grade 3). Median plasma enterolactone increased ~ 9-fold, and total lignans 16 fold. Thirty-six (80%) of the 45 evaluable subjects demonstrated a decrease in Ki-67, from a median of 4% (range 2–16.8 %) to 2% (range 0–15.2%) (p<0.001 by Wilcoxon signed rank test). A decrease from baseline in the proportion of women with atypical cytology (p=0.035) was also observed. Based on favorable risk biomarker modulation and lack of adverse events, we are initiating a randomized trial of SDG vs. placebo in premenopausal women.
MED-4865
Evaluation of the cyto- and genotoxic activity of yerba mate (Ilex paraguariensis) in human lymphocytes in vitro.
Despite its antioxidant capacity and well-known health benefits, yerba mate tea (Ilex paraguariensis) has been shown to possess some genotoxic and mutagenic activities and to increase incidence of some types of cancer. The aim of this study was to estimate the cyto- and genotoxicity of mate tea in human peripheral lymphocytes in vitro. We found that yerba mate extract induced a concentration-dependent, statistically significant increase in the level of apoptotic and necrotic cells and a decrease in the nuclear division index (NDI). Mate-exposed lymphocytes had a reduced transcriptional rDNA activity, which may be due to the stress conditions, and showed an elevated production of micronuclei. The FISH technique revealed the appearance of an acrocentric signal in mate-induced micronuclei, which suggests that under these conditions yerba mate extract may display aneugenic activity. Since caffeine is one of the most abundant compounds found in the dry mass of mate, we conducted additional experiments with caffeine alone. We showed that caffeine used at the same concentrations manifests a more potent cyto- and genotoxic effect that may account, at least in part, for the disadvantageous effects observed for yerba mate extract.
MED-2773
The experience of Japan as a clue to the etiology of testicular and prostatic cancers.
In Japan dramatic lifestyle changes occurred after World War 2. To examine the experience of Japan as a clue to the etiology, trends in the mortality rates of testicular and prostatic cancers from 1947 to 1998 were related to changes in dietary practices. The male population born before 1945 had a peak in death from testicular cancer in their thirties or forties, whereas those born after 1946 had a peak in their twenties. The death rate of prostatic cancer increased 25-fold almost linearly after the war. The intake of milk, meat, and eggs increased 20-, 9-, and 7-fold, respectively, after the war. In connection with the development and growth of testicular and prostatic cancers in Japan, particular attention should be paid to milk, because the increase in its consumption in this country is a recent occurrence and because milk contains considerable amounts of estrogens plus saturated fats.
MED-4106
Potassium intake, stroke, and cardiovascular disease a meta-analysis of prospective studies.
OBJECTIVES: The objective of this study was to assess the relation between the level of habitual potassium intake and the incidence of cardiovascular disease (CVD). BACKGROUND: Prospective cohort studies have evaluated the relationship between habitual potassium intake and incidence of vascular disease, but their results have not been not entirely consistent. METHODS: We performed a systematic search for prospective studies published, without language restrictions (1966 to December 2009). Criteria for inclusion were prospective adult population study, assessment of baseline potassium intake, assessment of vascular events as outcome, and follow-up of at least 4 years. For each study, relative risks (RRs) and 95% confidence intervals (CIs) were extracted and pooled using a random-effect model, weighted for the inverse of the variance. Heterogeneity, publication bias, subgroup, and meta-regression analyses were performed. RESULTS: Eleven studies were identified, providing 15 cohort samples that included 247,510 male and female participants (follow-up 5 to 19 years), 7,066 strokes, 3,058 coronary heart disease (CHD) events, and 2,497 total CVD events. Potassium intake was assessed by 24-h dietary recall (n = 2), food frequency questionnaire (n = 6), or 24-h urinary excretion (n = 3). In the pooled analysis, a 1.64-g (42 mmol) per day higher potassium intake was associated with a 21% lower risk of stroke (RR: 0.79; 95% CI: 0.68 to 0.90; p = 0.0007), with a trend toward lower risk of CHD and total CVD that attained statistical significance after the exclusion of a single cohort, based on sensitivity analysis (RR: 0.93; 95% CI: 0.87 to 0.99; p = 0.03 and RR: 0.74; 95% CI: 0.60 to 0.91; p = 0.0037). CONCLUSIONS: Higher dietary potassium intake is associated with lower rates of stroke and might also reduce the risk of CHD and total CVD. These results support recommendations for higher consumption of potassium-rich foods to prevent vascular diseases. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
MED-1010
Treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis.
BACKGROUND: Sexual dysfunction (SD) is an important underestimated adverse effect of antidepressant drugs. Patients, in fact, if not directly questioned, tend to scarcely report them. The aim of the present meta-analysis was to quantify SD caused by antidepressants on the basis of studies where sexual functioning was purposely investigated through direct inquiry and specific questionnaires. METHODS: A literature search was conducted using MEDLINE, ISI Web of Knowledge, and references of selected articles. Selected studies performed on patients without previous SD were entered in the Cochrane Collaboration Review Manager (RevMan version 4.2). Our primary outcome measure was the rate of total treatment-emergent SD. Our secondary outcome measures were the rates of treatment-emergent desire, arousal, and orgasm dysfunction. RESULTS: Our analyses indicated a significantly higher rate of total and specific treatment-emergent SD and specific phases of dysfunction compared with placebo for the following drugs in decreasing order of impact: sertraline, venlafaxine, citalopram, paroxetine, fluoxetine, imipramine, phenelzine, duloxetine, escitalopram, and fluvoxamine, with SD ranging from 25.8% to 80.3% of patients. No significant difference with placebo was found for the following antidepressants: agomelatine, amineptine, bupropion, moclobemide, mirtazapine, and nefazodone. DISCUSSION: Treatment-emergent SD caused by antidepressants is a considerable issue with a large variation across compounds. Some assumptions, such as the inclusion of open-label studies or differences in scales used to assess SD, could reduce the significance of our findings. However, treatment-emergent SD is a frequent adverse effect that should be considered in clinical activity for the choice of the prescribed drug.
MED-2091
Comparison of the effectiveness of 0.5% tea, 2% neem and 0.2% chlorhexidine mouthwashes on oral health: a randomized control trial.
BACKGROUND: The aim of this study was to evaluate and compare the effectiveness of 0.5% tea, 2% neem, and 0.2% chlorhexidine mouthwashes on oral health. MATERIALS AND METHODS: A randomized blinded controlled trial with 30 healthy human volunteers of age group 18-25 years was carried out. The subjects were randomly assigned to 3 groups i.e., group A - 0.2% chlorhexidine gluconate (bench mark control), Group B - 2% neem, and group C - 0.5% tea of 10 subjects per group. Plaque accumulation and gingival condition were recorded using plaque index and gingival index. Oral hygiene was assessed by simplified oral hygiene index (OHIS). Salivary pH was assessed by indikrom pH strips. Plaque, gingival, and simplified OHI scores as well as salivary pH were recorded at baseline, immediately after 1 st rinse, after 1 week, 2 nd week, and 3 rd week. The 3 rd week was skipped for group A. RESULTS: Mean plaque and gingival scores were reduced over the 3 week trial period for experimental and control groups. Anti-plaque effectiveness was observed in all groups and the highest being in group C (P < 0.05). Neem and tea showed comparative effectiveness on gingiva better than chlorhexidine (P < 0.05). The salivary pH rise was sustained and significant in Group B and C compared to Group A. Oral hygiene improvement was better appreciated in Group B and Group C. CONCLUSION: The effectiveness of 0.5% tea was more compared to 2% neem and 0.2% chlorhexidine mouth rinse.
MED-1037
A brief journey into medical care and disease in ancient Egypt.
Ancient Egypt was one of the greatest civilizations to have arisen, becoming the cradle of scientific enquiry and social development over 3 millennia; undoubtedly its knowledge of medicine has been vastly underestimated. Few artefacts survive which describe the medical organization, but from the extent of the diseases afflicting that ancient populus there would have been much to study. Evidence from papyri, tomb bas reliefs and the writings of historians of antiquity tell of an intense interest in the sciences, humanities and medicine born of an educated society which had overcome the superstitions of its nomadic ancestors.
MED-2171
β-Carboline Alkaloids and Essential Tremor: Exploring the Environmental Determinants of One of the Most Prevalent Neurological Diseases
Essential tremor (ET) is among the most prevalent neurological diseases, yet its etiology is not well understood. Susceptibility genotypes undoubtedly underlie many ET cases, although no genes have been identified thus far. Environmental factors are also likely to contribute to the etiology of ET. Harmane (1-methyl-9H-pyrido[3,4-β]indole) is a potent, tremor-producing β-carboline alkaloid, and emerging literature has provided initial links between this neurotoxin and ET. In this report, we review this literature. Two studies, both in New York, have demonstrated higher blood harmane levels in ET cases than controls and, in one study, especially high levels in familial ET cases. Replication studies of populations outside of New York and studies of brain harmane levels in ET have yet to be undertaken. A small number of studies have explored several of the biological correlates of exposure to harmane in ET patients. Studies of the mechanisms of this putative elevation of harmane in ET have explored the role of increased dietary consumption, finding weak evidence of increased exogenous intake in male ET cases, and other studies have found initial evidence that the elevated harmane in ET might be due to a hereditarily reduced capacity to metabolize harmane to harmine (7-methoxy-1-methyl-9H-pyrido[3,4-β]-indole). Studies of harmane and its possible association with ET have been intriguing. Additional studies are needed to establish more definitively whether these toxic exposures are associated with ET and are of etiological importance.
MED-4097
Green Tea and Breast Cancer
The identification of modifiable lifestyle factors that could reduce the risk of breast cancer is a research priority. Despite the enormous chemo preventive potential of green tea and compelling evidence from animal studies, its role in breast cancer development in humans is still unclear. Part of the uncertainty is related to the relatively small number of epidemiological studies on green tea and breast cancer and that the overall results from case-control studies and prospective cohort studies are discordant. In addition, the mechanisms by which green tea intake may influence risk of breast cancer in humans remains not well studied. We review the human studies that have evaluated the relationship between green tea intake and four biomarkers (sex steroid hormones, mammographic density, insulin-like growth factor, adiponectin) that are believed to be important in breast cancer development. Results from these biomarker studies are also inconclusive. Limitations of human studies and areas of further investigations are discussed.
MED-3975
Cost-effectiveness of gargling for the prevention of upper respiratory tract infections
Background In Japan, gargling is a generally accepted way of preventing upper respiratory tract infection (URTI). The effectiveness of gargling for preventing URTI has been shown in a randomized controlled trial that compared incidences of URTI between gargling and control groups. From the perspective of the third-party payer, gargling is dominant due to the fact that the costs of gargling are borne by the participant. However, the cost-effectiveness of gargling from a societal perspective should be considered. In this study, economic evaluation alongside a randomized controlled trial was performed to evaluate the cost-effectiveness of gargling for preventing URTI from a societal perspective. Methods Among participants in the gargling trial, 122 water-gargling and 130 control subjects were involved in the economic analysis. Sixty-day cumulative follow-up costs and effectiveness measured by quality-adjusted life days (QALD) were compared between groups on an intention-to-treat basis. Incremental cost-effectiveness ratio (ICER) was converted to dollars per quality-adjusted life years (QALY). The 95% confidence interval (95%CI) and probability of gargling being cost-effective were estimated by bootstrapping. Results After 60 days, QALD was increased by 0.43 and costs were $37.1 higher in the gargling group than in the control group. ICER of the gargling group was $31,800/QALY (95%CI, $1,900–$248,100). Although this resembles many acceptable forms of medical intervention, including URTI preventive measures such as influenza vaccination, the broad confidence interval indicates uncertainty surrounding our results. In addition, one-way sensitivity analysis also indicated that careful evaluation is required for the cost of gargling and the utility of moderate URTI. The major limitation of this study was that this trial was conducted in winter, at a time when URTI is prevalent. Care must be taken when applying the results to a season when URTI is not prevalent, since the ICER will increase due to decreases in incidence. Conclusion This study suggests gargling as a cost-effective preventive strategy for URTI that is acceptable from perspectives of both the third-party payer and society.
MED-4231
Onion and garlic intake and the odds of benign prostatic hyperplasia.
OBJECTIVE: To analyze the relationship between onion and garlic intake and benign prostatic hyperplasia (BPH), using data from a multicenter case-control study conducted in Italy. METHODS: A multicenter case-control study of 1369 patients with BPH and 1451 controls, admitted to the same hospitals for a wide spectrum of acute, non-neoplastic conditions, was conducted in Italy between 1991 and 2002. Information was collected by trained interviewers using a validated and reproducible food frequency questionnaire. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were obtained after allowance for recognized confounding factors and energy intake. RESULTS: Compared with nonusers, the multivariate ORs for the highest category of onion and garlic intake were 0.41 (95% CI 0.24 to 0.72) and 0.72 (95% CI 0.57 to 0.91), respectively. The combined OR for frequent users versus nonusers of both onion and garlic was 0.65 (95% CI 0.49 to 0.86). The inverse relationships were consistent across age strata. CONCLUSIONS: This uniquely large data set from European populations showed an inverse association between allium vegetable consumption and BPH.
MED-3817
Dietary polyamine intake and risk of colorectal adenomatous polyps
Background: Putrescine, spermidine, and spermine are the polyamines required for human cell growth. The inhibition of ornithine decarboxylase (ODC), which is the rate-limiting enzyme of polyamine biosynthesis, decreases tumor growth and the development of colorectal adenomas. A database was developed to estimate dietary polyamine exposure and relate exposure to health outcomes. Objective: We hypothesized that high polyamine intake would increase risk of colorectal adenoma and that the allelic variation at ODC G>A +316 would modify the association. Design: Polyamine exposure was estimated in subjects pooled (n = 1164) from the control arms of 2 randomized trials for colorectal adenoma prevention [Wheat Bran Fiber low-fiber diet arm (n = 585) and Ursodeoxycholic Acid placebo arm (n = 579)] by using baseline food-frequency questionnaire data. All subjects had to have a diagnosis of colorectal adenoma to be eligible for the trial. Results: A dietary intake of polyamines above the median amount in the study population was associated with 39% increased risk of colorectal adenoma at follow-up (adjusted OR: 1.39; 95% CI: 1.06, 1.83) in the pooled sample. In addition, younger participants (OR: 1.94; 95% CI: 1.23, 3.08), women (OR: 2.43; 95% CI: 1.48, 4.00), and ODC GG genotype carriers (OR: 1.59; 95% CI: 1.00, 2.53) had significantly increased odds of colorectal adenoma if they consumed above-median polyamine amounts. Conclusions: This study showed a role for dietary polyamines in colorectal adenoma risk. Corroboration of these findings would confirm a previously unrecognized, modifiable dietary risk factor for colorectal adenoma.
MED-3701
Anti-aromatase chemicals in red wine.
Estrogen synthesized in situ plays a more important role in breast cancer cell proliferation than does circulating estrogen. Aromatase is the enzyme that converts androgen to estrogen and is expressed at a higher level in breast cancer tissue than in surrounding noncancer tissue. A promising route of chemoprevention against breast cancer may be through the suppression of in situ estrogen formation using aromatase inhibitors. A diet high in fruits and vegetables may reduce the incidence of breast cancer, because they contain phytochemicals that can act as aromatase inhibitors. In our previous studies, we found that grapes and wine contain potent phytochemicals that can inhibit aromatase. We show that red wine was more effective than white wine in suppressing aromatase activity. Interestingly, our results from white wine studies suggest a weak inductive effect of alcohol on aromatase activity. On the other hand, the potent effect of anti-aromatase chemicals in red wine overcomes the weak inductive effect of alcohol in wine. Several purification procedures were performed on whole red wine to separate active aromatase inhibitors from non-active compounds. These techniques included liquid-liquid extraction, silica gel chromatography, various solid phase extraction (SPE) columns, and high performance liquid chromatography. An active Pinot Noir red wine SPE C18 column fraction (20% acetonitrile:water) was more effective than complete Pinot Noir wine in suppressing aromatase assay. This red wine extract was further analyzed in a transgenic mouse model in which aromatase was over-expressed in mammary tissue. Our gavaged red wine extract completely abrogated aromatase-induced hyperplasia and other neoplastic changes in mammary tissue. These results suggest that red wine or red wine extract may be a chemopreventive diet supplement for postmenopausal women who have a high risk of breast cancer. Further research is underway to purify and characterize the active compounds in red wine that are responsible for the inhibition of aromatase.
MED-2469
An anthroposophic lifestyle and intestinal microflora in infancy.
The intestinal flora is considered to have an impact on the development of the immune system. In the anthroposophic lifestyle, a diet comprising vegetables spontaneously fermented by lactobacilli, and a restrictive use of antibiotics, anti-pyretics and vaccinations, is typical. The aim of this study was to assess the gut flora in infants in relation to certain lifestyle characteristics associated with anthroposophy. Sixty-nine children < 2 years of age with an anthroposophic lifestyle, and 59 infants of a similar age with a traditional lifestyle, were clinically examined and questionnaire replies assessed. Fecal samples were analyzed by bacterial enumeration, bacterial typing through biochemical fingerprinting and by measuring microflora-associated characteristics (MACs). The numbers of colony-forming units (CFU)/g of feces were significantly higher for enterococci and lactic acid bacteria in children who had never been exposed to antibiotics (5.5 x 107 vs. 2.1 x 107; p < 0.001 and 10 x 107 vs. 4.1 x 107; p < 0.01, respectively). Furthermore, the number of enterococci was significantly higher in breastfed and vegetarian infants (p < 0.01). The diversity (Simpson's diversity index) of lactobacilli, as determined by biochemical fingerprinting, was higher in infants born at home than in those born in hospital (p < 0.01). Several MACs were related to specific lifestyle features, and infants with an anthroposophic lifestyle had a higher proportion of acetic acid and a lower proportion of propionic acid in their stool as compared to the control children. In conclusion, lifestyle factors related to the anthroposophic way of life influenced the composition of the gut flora in the infants. These differences may contribute to the lower prevalence of atopic disease previously observed in children in anthroposophic families.
MED-3546
Elevated monoamine oxidase a levels in the brain: an explanation for the monoamine imbalance of major depression.
CONTEXT: The monoamine theory of depression proposes that monoamine levels are lowered, but there is no explanation for how monoamine loss occurs. Monoamine oxidase A (MAO-A) is an enzyme that metabolizes monoamines, such as serotonin, norepinephrine, and dopamine. OBJECTIVE: To determine whether MAO-A levels in the brain are elevated during untreated depression. SETTING: Tertiary care psychiatric hospital. PATIENTS: Seventeen healthy and 17 depressed individuals with major depressive disorder that met entry criteria were recruited from the care of general practitioners and psychiatrists. All study participants were otherwise healthy and nonsmoking. Depressed individuals had been medication free for at least 5 months. MAIN OUTCOME MEASURE: Harmine labeled with carbon 11, a radioligand selective for MAO-A and positron emission tomography, was used to measure MAO-A DVS (specific distribution volume), an index of MAO-A density, in different brain regions (prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex, caudate, putamen, thalamus, anterior temporal cortex, midbrain, hippocampus, and parahippocampus). RESULTS: The MAO-A DVS was highly significantly elevated in every brain region assessed (t test; P=.001 to 3x10(-7)). The MAO-A DVS was elevated on average by 34% (2 SDs) throughout the brain during major depression. CONCLUSIONS: The sizable magnitude of this finding and the absence of other compelling explanations for monoamine loss during major depressive episodes led to the conclusion that elevated MAO-A density is the primary monoamine-lowering process during major depression.
MED-2476
Diet, infection and wheezy illness: lessons from adults.
An increase in asthma and atopic disease has been recorded in many countries where society has become more prosperous. We have investigated two possible explanations: a reduction in childhood infections and a change in diet. In a cohort of people followed up since 1964, originally selected as a random sample of primary school children, we have investigated the relevance of family size and the common childhood infectious diseases to development of eczema, hay fever and asthma. Although membership of a large family reduced risks of hay fever and eczema (but not asthma), this was not explained by the infections the child had suffered. Indeed, the more infections the child had had, the greater the likelihood of asthma, although measles gave a modest measure of protection. We have investigated dietary factors in two separate studies. In the first, we have shown the risks of bronchial hyper-reactivity are increased seven-fold among those with the lowest intake of vitamin C, while the lowest intake of saturated fats gave a 10-fold protection. In the second, we have shown that the risk of adult-onset wheezy illness is increased five-fold by the lowest intake of vitamin E and doubled by the lowest intake of vitamin C. These results were supported by direct measurements of the vitamins and triglycerides in plasma. We have proposed that changes in the diet of pregnant women may have reflected those observed in the population as a whole and that these may have resulted in the birth of cohorts of children predisposed to atopy and asthma. The direct test of this is to study the diet and nutritional status of a large cohort of pregnant women and to follow their offspring forward. This is our current research.
MED-3890
Detection of a Common and Persistent tet(L)-Carrying Plasmid in Chicken-Waste-Impacted Farm Soil
The connection between farm-generated animal waste and the dissemination of antibiotic resistance in soil microbial communities, via mobile genetic elements, remains obscure. In this study, electromagnetic induction (EMI) surveying of a broiler chicken farm assisted soil sampling from a chicken-waste-impacted site and a marginally affected site. Consistent with the EMI survey, a disparity existed between the two sites with regard to soil pH, tetracycline resistance (Tcr) levels among culturable soil bacteria, and the incidence and prevalence of several tet and erm genes in the soils. No significant difference was observed in these aspects between the marginally affected site and several sites in a relatively pristine regional forest. When the farm was in operation, tet(L), tet(M), tet(O), erm(A), erm(B), and erm(C) genes were detected in the waste-affected soil. Two years after all waste was removed from the farm, tet(L), tet(M), tet(O), and erm(C) genes were still detected. The abundances of tet(L), tet(O), and erm(B) were measured using quantitative PCR, and the copy numbers of each were normalized to eubacterial 16S rRNA gene copy numbers. tet(L) was the most prevalent gene, whereas tet(O) was the most persistent, although all declined over the 2-year period. A mobilizable plasmid carrying tet(L) was identified in seven of 14 Tcr soil isolates. The plasmid's hosts were identified as species of Bhargavaea, Sporosarcina, and Bacillus. The plasmid's mobilization (mob) gene was quantified to estimate its prevalence in the soil, and the ratio of tet(L) to mob was shown to have changed from 34:1 to 1:1 over the 2-year sampling period.
MED-4689
The total antioxidant content of more than 3100 foods, beverages, spices, herbs and supplements used worldwide
Background A plant-based diet protects against chronic oxidative stress-related diseases. Dietary plants contain variable chemical families and amounts of antioxidants. It has been hypothesized that plant antioxidants may contribute to the beneficial health effects of dietary plants. Our objective was to develop a comprehensive food database consisting of the total antioxidant content of typical foods as well as other dietary items such as traditional medicine plants, herbs and spices and dietary supplements. This database is intended for use in a wide range of nutritional research, from in vitro and cell and animal studies, to clinical trials and nutritional epidemiological studies. Methods We procured samples from countries worldwide and assayed the samples for their total antioxidant content using a modified version of the FRAP assay. Results and sample information (such as country of origin, product and/or brand name) were registered for each individual food sample and constitute the Antioxidant Food Table. Results The results demonstrate that there are several thousand-fold differences in antioxidant content of foods. Spices, herbs and supplements include the most antioxidant rich products in our study, some exceptionally high. Berries, fruits, nuts, chocolate, vegetables and products thereof constitute common foods and beverages with high antioxidant values. Conclusions This database is to our best knowledge the most comprehensive Antioxidant Food Database published and it shows that plant-based foods introduce significantly more antioxidants into human diet than non-plant foods. Because of the large variations observed between otherwise comparable food samples the study emphasizes the importance of using a comprehensive database combined with a detailed system for food registration in clinical and epidemiological studies. The present antioxidant database is therefore an essential research tool to further elucidate the potential health effects of phytochemical antioxidants in diet.
MED-1236
Pathogenesis of type 2 diabetes: tracing the reverse route from cure to cause.
The metabolic abnormalities of type 2 diabetes can be reversed reproducibly by bariatric surgery. By quantifying the major pathophysiological abnormalities in insulin secretion and insulin action after surgery, the sequence of events leading to restoration of normal metabolism can be defined. Liver fat levels fall within days and normal hepatic insulin sensitivity is restored. Simultaneously, plasma glucose levels return towards normal. Insulin sensitivity of muscle remains abnormal, at least over the weeks and months after bariatric surgery. The effect of the surgery is explicable solely in terms of energy restriction. By combining this information with prospective observation of the changes immediately preceding the onset of type 2 diabetes, a clear picture emerges. Insulin resistance in muscle, caused by inherited and environmental factors, facilitates the development of fatty liver during positive energy balance. Once established, the increased insulin secretion required to maintain plasma glucose levels will further increase liver fat deposition. Fatty liver causes resistance to insulin suppression of hepatic glucose output as well as raised plasma triacylglycerol. Exposure of beta cells to increased levels of fatty acids, derived from circulating and locally deposited triacylglycerol, suppresses glucose-mediated insulin secretion. This is reversible initially, but eventually becomes permanent. The essential time sequence of the pathogenesis of type 2 diabetes is now evident. Muscle insulin resistance determines the rate at which fatty liver progresses, and ectopic fat deposition in liver and islet underlies the related dynamic defects of hepatic insulin resistance and beta cell dysfunction. These defects are capable of dramatic reversal under hypoenergetic feeding conditions, completely in early diabetes and to a worthwhile extent in more established disease.
MED-5061
Humans have antibodies reactive with Bovine leukemia virus.
Bovine leukemia virus (BLV) is an oncogenic retrovirus that commonly infects cattle and causes B cell leukosis in 1-5% of infected cattle. BLV-infected cells are present in marketed beef and dairy products. In the decade after the discovery of BLV in 1969, studies using agar gel immunodiffusion and complement fixation assays failed to find antibodies to BLV in human sera. This led to the prevailing opinion that exposure of humans to BLV and/or the potential for infection are not significant and therefore the virus is not a public health hazard. We reexamined this issue using more sensitive immunological techniques available today. Using immunoblotting to test the sera of 257 humans for antibodies of four isotypes (IgG1, IgM, IgA, and IgG4) to the BLV capsid antigen (p24), we detected at least one antibody isotype reactive with BLV in 74% of the human sera tested. The specificity of the reactivity was strongly suggested by competition studies and by ruling out cross-reacting antibodies to other chronic human viruses. Our results suggest that antibodies reactive with the BLV capsid antigen may serve as a biomarker for exposure to BLV and this exposure may be widespread. The results do not necessarily mean that humans are actually infected with BLV; the antibodies could be a response to heat-denatured BLV antigens consumed in food. They do, however, suggest that further studies in this area could be important.
MED-2270
Gastrointestinal safety of NSAIDs and over-the-counter analgesics.
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used. It is well recognised that they may adversely cause damage throughout the gastrointestinal tract and aggravate pre-existing disease. Their side effects on the upper gastrointestinal tract can be assessed by various means; each study type has different clinical connotations. Short-term use (less than 14 days) demonstrates dose-dependent damage of prescribed NSAIDs; the damage is proportional to the acidity of the drugs and not seen with Cyclooxygenase-2 (COX-2) selective inhibitors that have a pKa over 7.0. There have not been any serious outcomes, such as bleeding or perforation in these studies, and Helicobacter pylori (HP) plays no role in this damage. Long-term (3 months or more) endoscopy studies in patients show ulcer rates from 15%-35% with the various NSAIDs, but serious outcomes are exceedingly rare. Epidemiological studies show an association between NSAID intake and serious events. Ibuprofen is consistently at the lower end of toxicity rankings, whereas ketorolac and azapropazone are the worst. The risk of bleeding is increased with advancing age, presence of HP, previous history of bleeding, anticoagulant use, etc. The mega-trials show that COX-2 selective agents halve the bleeding episodes, but NSAID-induced gastric bleeding is very rare usually, less than 1 in 200 subjects taking them for a year. Seventy percent of patients develop NSAID-enteropathy, which is associated with intestinal blood and protein loss and rarely strictures. Over-the-counter (OTC) use of ibuprofen and diclofenac is associated with symptomatic gastrointestinal side effects comparable with placebo. Ibuprofen is shown to be remarkably well tolerated at OTC doses in a number of studies. There are recent studies to suggest that OTC NSAIDs should be taken on a fasting stomach, not with food as commonly advocated. © 2012 Blackwell Publishing Ltd.
MED-4933
Polybrominated diphenyl ethers (PBDEs) in farmed and wild salmon marketed in the Northeastern United States.
Recently, we reported on the analysis of polychlorinated biphenyls (PCBs) and chlorinated pesticides in farmed Atlantic salmon (Salmo salar) from Maine, eastern Canada, and Norway, and wild Alaskan Chinook salmon (Oncorhynchus tshawytscha). In this paper, we extend the analysis to polybrominated diphenyl ethers (PBDEs) in these samples. Total PBDE concentrations in the farmed salmon (0.4-1.4ng/g, wet weight, ww) were not significantly different from those in the wild Alaskan Chinook samples (0.4-1.2ng/g, ww), nor were significant differences found among regions. However, significant intra-regional variations in concentrations of total PBDEs and tetra-BDE 47 were observed in the salmon from the Canadian farms (p<0.01). Congener profiles were dominated by BDE-47, followed by the penta-BDEs 99 and 100. PBDE concentrations in the Canadian samples were lower than those reported two years earlier. Removal of skin resulted in no overall reduction in PBDE concentrations in our farmed salmon, and in some cases, PBDE concentrations were higher in skin-off samples. PBDEs were correlated with lipids only in the skinned samples, suggesting that there is greater accumulation and retention of PBDEs in muscle lipids than in skin-associated fat. In skin-on samples, modest correlations were observed between concentrations of PBDEs and PCBs (R(2)=0.47) and mono-ortho PCBs (R(2)=0.50), whereas PBDEs were not correlated with non-ortho PCBs.
MED-5225
Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with Type 2 diabetes
Aims The aim of this study was to compare the effects of calorie-restricted vegetarian and conventional diabetic diets alone and in combination with exercise on insulin resistance, visceral fat and oxidative stress markers in subjects with Type 2 diabetes. Methods A 24-week, randomized, open, parallel design was used. Seventy-four patients with Type 2 diabetes were randomly assigned to either the experimental group (n = 37), which received a vegetarian diet, or the control group (n = 37), which received a conventional diabetic diet. Both diets were isocaloric, calorie restricted (-500 kcal/day). All meals during the study were provided. The second 12 weeks of the diet were combined with aerobic exercise. Participants were examined at baseline, 12 weeks and 24 weeks. Primary outcomes were: insulin sensitivity measured by hyperinsulinaemic isoglycaemic clamp; volume of visceral and subcutaneous fat measured by magnetic resonance imaging; and oxidative stress measured by thiobarbituric acid reactive substances. Analyses were by intention to treat. Results Forty-three per cent of participants in the experimental group and 5% of participants in the control group reduced diabetes medication (P < 0.001). Body weight decreased more in the experimental group than in the control group [–6.2 kg (95% CI –6.6 to –5.3) vs. –3.2 kg (95% CI –3.7 to –2.5); interaction group × time P = 0.001]. An increase in insulin sensitivity was significantly greater in the experimental group than in the control group [30% (95% CI 24.5–39) vs. 20% (95% CI 14–25), P = 0.04]. A reduction in both visceral and subcutaneous fat was greater in the experimental group than in the control group (P = 0.007 and P = 0.02, respectively). Plasma adiponectin increased (P = 0.02) and leptin decreased (P = 0.02) in the experimental group, with no change in the control group. Vitamin C, superoxide dismutase and reduced glutathione increased in the experimental group (P = 0.002, P < 0.001 and P = 0.02, respectively). Differences between groups were greater after the addition of exercise training. Changes in insulin sensitivity and enzymatic oxidative stress markers correlated with changes in visceral fat. Conclusions A calorie-restricted vegetarian diet had greater capacity to improve insulin sensitivity compared with a conventional diabetic diet over 24 weeks. The greater loss of visceral fat and improvements in plasma concentrations of adipokines and oxidative stress markers with this diet may be responsible for the reduction of insulin resistance. The addition of exercise training further augmented the improved outcomes with the vegetarian diet.
MED-4864
Comparative flavonoids contents of selected herbs and associations of their radical scavenging activity with antiproliferative actions in V79-4 cells.
To elucidate the health benefit of herbal teas on the cytotoxicity induced by H(2)O(2) in V79-4 cells, herbal extracts and its flavonoids were tested using lactate dehydrogenase release and determining intracellular reactive oxygen species generation and antioxidant activity with superoxide radical scavenging assay. Significant decrease in cell viability was observed on V79-4 cells treated with H(2)O(2) (1 mM), while herbal extracts and its flavonoids including catechin and epigallocatechin gallate prevented the LDH release from H(2)O(2) cytotoxicity. Total catechin contents of green tea (65.6 mg/g of dry matter) were significantly higher than other herbal teas (35.8 to 1.2 mg/g of DM). The relative concentration of the 4 major tea catechins ranked EGCG > EGC > EC > C. Green tea exhibited the lowest IC(50) values (2 g fresh herb/100 mL) of superoxide radical scavenging activity among the tested herbal tea, which indicates powerful antioxidant activity in O(2)(*-) radicals scavenging, followed by black tea, dandelion, hawthorn, rose hip, chamomile.
MED-2982
Surgical management of bisphosphonate-related osteonecrosis of the jaw in oncologic patients: a challenging problem.
AIM: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious oral complication of supportive cancer therapy and the best method of treatment is still unclear. The purpose of this article is to analyze the type of treatment and outcome in a large patient cohort with BRONJ. PATIENTS AND METHODS: A total of 142 patients suffering from BRONJ at different sites were studied. All patients had been treated with intravenous bisphosphonates for various oncological disease. A descriptive analysis of all relevant patient data was performed with particular emphasis on surgical outcome. RESULTS: The mandible was affected in 58% of the patients. All but two patients had previous invasive dental procedures. The mean duration of bisphosphonate treatment was 37.1 months. A total of 86% of the patients were treated surgically, including sequestrectomies and mandibular resections. Soft-tissue reconstruction was achieved by local closure, myofascial flap using the mylohyoid muscle, and a vascularized fasciocutaneous flap in one patient. No bony reconstruction was performed. CONCLUSION: Surgical treatment of BRONJ remains challenging. There is only limited evidence that oncologic patients with BRONJ are candidates for vascularized bone reconstruction.
MED-2986
Effect of phytic acid on the absorption, distribution, and endogenous excretion of zinc in rats.
Zinc metabolism in male rats was studied by combining nutritional balance methods with an analysis of 65Zn kinetics. The rats, two groups of 84 each, were fed zinc-adequate diets (33 ppm Zn) with either 0 (basal) or 2% phytic acid added as sodium phytate. A fourth-order exponential function described the time-course of 65Zn in plasma, and compartmental models were developed accordingly. Plasma zinc exchanged more rapidly with zinc in liver and kidneys than it did with zinc in testes, skeletal muscle, or bone. Total body zinc content (2.6 mg/100 g live body weight) measured chemically was about 9 times higher than estimates of exchangeable zinc in the body. Whole-body retention of 65Zn was higher and endogenous fecal zinc excretion was lower in rats fed phytate than in those fed the basal diet; these responses to phytate may reflect a homeostatic adjustment to decreased absorption of zinc. Respective values for apparent absorption and true absorption of zinc were 13 and 32% of zinc intake in rats fed phytate, and 19 and 46% of zinc intake in rats fed the basal diet. When whole grains or mature seeds constitute a major portion of the diet, the phytate: zinc molar ratio may approach that (60:1) used in our study. Whether or not phytic acid occurring naturally in foods affects zinc metabolism to the same extent as sodium phytate can not be determined from our study.
MED-3892
Application of Bayesian Techniques to Model the Burden of Human Salmonellosis Attributable to U.S. Food Commodities at the Point of Processing: Adaptation of a Danish Model
Mathematical models that estimate the proportion of foodborne illnesses attributable to food commodities at specific points in the food chain may be useful to risk managers and policy makers to formulate public health goals, prioritize interventions, and document the effectiveness of mitigations aimed at reducing illness. Using human surveillance data on laboratory-confirmed Salmonella infections from the Centers for Disease Control and Prevention and Salmonella testing data from U.S. Department of Agriculture Food Safety and Inspection Service's regulatory programs, we developed a point-of-processing foodborne illness attribution model by adapting the Hald Salmonella Bayesian source attribution model. Key model outputs include estimates of the relative proportions of domestically acquired sporadic human Salmonella infections resulting from contamination of raw meat, poultry, and egg products processed in the United States from 1998 through 2003. The current model estimates the relative contribution of chicken (48%), ground beef (28%), turkey (17%), egg products (6%), intact beef (1%), and pork (<1%) across 109 Salmonella serotypes found in food commodities at point of processing. While interpretation of the attribution estimates is constrained by data inputs, the adapted model shows promise and may serve as a basis for a common approach to attribution of human salmonellosis and food safety decision-making in more than one country.
MED-3900
Dried fruit consumption is associated with improved diet quality and reduced obesity in US adults: National Health and Nutrition Examination Survey...
Epidemiological studies examining potential associations between dried fruit consumption, diet quality, and weight status are lacking. The goal of this study was to examine the association of dried fruit consumption with nutrient intake, diet quality, and anthropometric indicators of overweight/obesity. A secondary analysis of dietary and anthropometric data collected from adult (19+ years) participants (n = 13 292) of the 1999-2004 National Health and Nutrition Examination Survey was conducted. Dried fruit consumers were defined as those consuming amounts ⅛ cup-equivalent fruit per day or more and identified using 24-hour recalls. Diet quality was measured using the Healthy Eating Index 2005. Covariate-adjusted means, SEs, prevalence rates, and odds ratios were determined to conduct statistical tests for differences between dried fruit consumers and nonconsumers. Seven percent of the population consumed dried fruit. Mean differences (P < .01) between consumers and nonconsumers in adult shortfall nutrients were dietary fiber (+6.6 g/d); vitamins A (+173 μg retinol activity equivalent per day), E (+1.5 mg α-tocopherol per day), C (+20 mg/d), and K (+20 mg/d); calcium (+103 mg/d); phosphorus (+126 mg/d); magnesium (+72 mg/d); and potassium (+432 mg/d). Dried fruit consumers had improved MyPyramid food intake, including lower solid fats/alcohol/added sugars intake, and a higher solid fats/alcohol/added sugars score (11.1 ± 0.2 vs 8.2 ± 0.1) than nonconsumers. The total Healthy Eating Index 2005 score was significantly higher (P < .01) in consumers (59.3 ± 0.5) than nonconsumers (49.4 ± 0.3). Covariate-adjusted weight (78.2 ± 0.6 vs 80.7 ± 0.3 kg), body mass index (27.1 ± 0.2 vs 28.1 ± 0.2), and waist circumference (94.0 ± 0.5 vs 96.5 ± 0.2 cm) were lower (P < .01) in consumers than nonconsumers, respectively. Dried fruit consumption was associated with improved nutrient intakes, a higher overall diet quality score, and lower body weight/adiposity measures. Copyright © 2011 Elsevier Inc. All rights reserved.
MED-4883
[Flatufonia--or the musical anus].
The art of the musical anus is reviewed in the light of its most prominent performers and of anorectal physiological aspects related to this specific musical performance.
MED-3023
Relationship between the prenatal exposure to low-level of mercury and the size of a newborn's cerebellum.
Exposure to methylmercury at any stage of central nervous system development could induce alterations and result in severe congenital abnormalities. Total mercury level in maternal hair during pregnancy correlates well with blood levels of methylmercury and with total mercury levels in fetal brain. A prospective study has been conducted and a total of 137 childbearing women living at the coastal region with term, normal pregnancies were included and their newborns evaluated by ultrasonography. Mothers and their newborns are divided in two groups according to their hair mercury levels; examined group with high body levels of mercury (≥ 1 μg/g) and control group with low body levels of mercury (<1 μg/g). Neurosonographic examination was conducted to all newborns. Two dimensions of cerebellum in the sagital-medial plane have been measured: maximum height and width starting from the roof of the fourth chamber. Majority of mothers had hair mercury levels lower than 1 μg/g (N = 107). Mean value was 0.88 μg/g (SD 1.24), ranging from 0.02 to 8.71 μg/g. There was no significant difference between the two groups when it comes to the width of cerebellum (Mann-Whitney test: Z = 1471; p = 0.141). However, comparison related to the length of cerebellum shows statistically significant smaller cerebellum in newborns whose mother had hair mercury levels higher than 1 μg/g (Mann-Whitney test: Z = 2329; p = 0.019). Our results lead to a conclusion that prenatal exposure to, what we consider to be, low-levels of methylmercury does influence fetal brain development detected as decreased size of newborn's cerebellum. From a clinical point of view, a question related to the influence of prenatal low-level methylmercury exposure on fetal neurodevelopment remains open. Our further objectives are to direct the research towards performing detailed neuropshychological tests on children at the age of 18 months. Such tests could indicate the presence of subtle neurological or neuropsychological deficits. Copyright © 2010 Elsevier Ltd. All rights reserved.
MED-2069
Sulforaphane can protect lens cells against oxidative stress: implications for cataract prevention.
PURPOSE: Protecting the lens against oxidative stress is of great importance in delaying the onset of cataract. Isothiocyanates, such as sulforaphane (SFN), are proposed to provide cytoprotection against oxidative stress. We therefore tested the ability of SFN to perform this role in lens cells and establish its ability to delay the onset of cataract. METHODS: The human lens epithelial cell line FHL124 and whole porcine lens culture systems were used. The ApoTox-Glo Triplex Assay was used to assess FHL124 cell survival, cytotoxicity, and apoptosis. The MTS assay was used to assess cell populations. To determine levels of DNA strand breaks, the alkaline comet assay was performed and quantified. Lactate dehydrogenase levels in the medium were evaluated to reflect cell damage/death. To assess level of gene expression, an Illumina whole-genome HT-12 v4 beadchip was used. Protein expression was determined by Western blot and immunocytochemistry. RESULTS: Exposures of 30 μM H2O2 to FHL124 cells caused a reduction in cell viability and increased cytotoxicity/apoptosis; these effects were significantly inhibited by 24-hour pretreatment with 1 μM SFN. In addition, 1 μM SFN significantly reduced H2O2-induced DNA strand breaks. When applied to cultured porcine lenses, SFN protected against H2O2-induced opacification. Illumina whole-genome HT-12 v4 beadchip microarray data revealed eight genes upregulated following 24-hour exposure to 1- and 2-μM SFN, which included NQO1 and TXNRD1. This pattern was confirmed at the protein level. Nrf2 translocated to the nucleus in response to 0.5- to 2.0-μM SFN exposure CONCLUSIONS: The dietary component SFN demonstrates an ability to protect human lens cells against oxidative stress and thus could potentially delay the onset of cataract.
MED-3675
A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome
Chronic fatigue syndrome (CFS) is complex illness of unknown etiology. Among the broad range of symptoms, many patients report disturbances in the emotional realm, the most frequent of which is anxiety. Research shows that patients with CFS and other so-called functional somatic disorders have alterations in the intestinal microbial flora. Emerging studies have suggested that pathogenic and non-pathogenic gut bacteria might influence mood-related symptoms and even behavior in animals and humans. In this pilot study, 39 CFS patients were randomized to receive either 24 billion colony forming units of Lactobacillus casei strain Shirota (LcS) or a placebo daily for two months. Patients provided stool samples and completed the Beck Depression and Beck Anxiety Inventories before and after the intervention. We found a significant rise in both Lactobacillus and Bifidobacteria in those taking the LcS, and there was also a significant decrease in anxiety symptoms among those taking the probiotic vs controls (p = 0.01). These results lend further support to the presence of a gut-brain interface, one that may be mediated by microbes that reside or pass through the intestinal tract.
MED-1690
Effects of antiplatelet components of tomato extract on platelet function in vitro and ex vivo: a time-course cannulation study in healthy humans.
BACKGROUND: Natural antithrombotic agents that influence platelet function are of potential interest for primary prevention of cardiovascular disease. Previous reports showed that tomato extracts inhibit platelet aggregation in vitro, but little is known of the active components, their mode of action, or their efficacy in vivo. OBJECTIVE: The objectives of the study were to examine the antiplatelet activity of specific tomato components by in vitro experimentation and to establish their ex vivo efficacy in healthy humans. DESIGN: The mechanisms of action of antiplatelet components isolated from tomato extracts were examined in vitro. A 7-h time-course study was carried out in cannulated human subjects (n = 23) to determine the ex vivo efficacy of a supplement drink containing tomato extract and the onset and duration of antiplatelet effects. RESULTS: The inhibition of ADP-, collagen-, thrombin-, and arachidonate-mediated platelet aggregation by tomato extract components appears to be linked to the inhibition of glycoprotein IIb/IIIa and platelet secretory mechanisms. We found a significant inhibition of baseline platelet function, from 2.9 +/- 1.4% (optimal ADP concentrations; P = 0.03) to 20.0 +/- 4.9% (suboptimal ADP concentrations; P < 0.001), 3 h after supplementation with a dose of tomato extract equivalent to 6 tomatoes. The observed effects persisted for >12 h. Coagulation variables were not affected. CONCLUSIONS: The ingestion of tomato components with in vitro antiplatelet activity significantly affects ex vivo platelet function. The reported cardioprotective effects of tomatoes are potentially linked to a modulation of platelet function.
MED-1924
Saturated fatty acid metabolism is key link between cell division, cancer, and senescence in cellular and whole organism aging
Cellular senescence is an in vivo and in vitro phenomenon, accompanied by physiological changes including cessation of division and disturbances of organelle structure and function. Review of the literature was undertaken to determine whether there is evidence that whole organism aging and cell senescence share a common initiation pathway. In vivo aged cells of different lineages, including aged T lymphocytes, show high expression of the INK4A-p16 gene. In cell culture when telomeres are shortened past a key length or state, the Arf/Ink gene system (p16/p14 humans, p16/p19 mice) switches on and activates p53, which suppresses further cell division. The p53 gene is a key tumor suppressor and its deletion or mutation allows cancerous growth. The switching on of p53 also causes changes in fatty acid metabolism, especially down-regulation of both fatty acid synthase and stearoyl-CoA (delta-9) desaturase. The co-suppression of these genes together with enhanced uptake of extracellular fatty acids, leads to raised levels of cellular palmitate and induction of either apoptosis or senescence. In senescent cells, the fatty acid composition of the cellular membranes alters and leads to changes in both structure and function of organelles, especially mitochondria. Animal models of accelerated aging exhibit repression of stearoyl-CoA desaturase activity while anti-aging calorie restriction stimulates the same enzyme system. It is concluded that aging in cells and whole organisms share a common initiation pathway and that cellular senescence is protective against cancer. Healthy longevity is likely to be most enhanced by factors that actively suppress excessive cell division.
MED-973
What is a high fiber diet?
There is no recognized definition of what constitutes a high fiber diet. Intakes of dietary fiber in different populations internationally vary widely from less than 20 g to more than 80 g per day. The types of foods contributing fiber also vary; in some countries cereals contribute the most fiber, in others leafy or root vegetables predominate. Vegetables have the highest fiber content per Kcal, and in most populations with fiber intakes over 50 g, vegetables contribute over 50% of total fiber intake. In rural Uganda, where the fiber hypothesis was first developed by Burkitt and Trowell, vegetables contribute over 90% of fiber intake. An experimental diet, the "Simian" diet, has been developed to mimic as closely as possible using human foods, the diet consumed by our simian ancestors the great apes. It is also similar to the Ugandan diet in containing large amounts of vegetables and 50 g fiber/1000 Kcal. Though nutritionally adequate, this diet is very bulky and not a suitable model for general recommendations. Dietary guidelines are that fat intake should be < 30% of energy, with a fiber intake of 20-35 g/d. These recommendations are inconsistent with a high fiber diet because, for people consuming more than about 2400 Kcal, low fiber choices for fruits and grains must be selected to keep dietary fiber intake within the range of 20-35 g. In a 30% fat, 1800 Kcal omnivorous diet, selection of wholemeal bread and whole fruit, results in a fiber intake over 35 g/d, and for and 1800 Kcal vegetarian diet, with substitution of modest amounts of peanut butter and beans for meats, dietary fiber intake goes up to 45 g/d. Thus, if it is desirable to promote the use of unrefined foods, the recommended dietary fiber intake should be a minimum of 15-20 g/1000 Kcal.
MED-1041
Gastroenterology in ancient Egypt.
Physicians in ancient Egypt devoted their care to disorders of individual organs. Notable among the specialties was gastroenterology, a subject matter that occupied a major portion of the surviving medical papyri. Although they did not name diseases as we know them, Pharaonic physicians described a host of gastroenterological symptoms for which an extensive array of therapeutics was prescribed. Their clinical accounts indicated an impressive knowledge of gastric and anorectal conditions. In their thinking on disease mechanism, the circulating materia peccans absorbed from feces represented a major cause of medical symptoms and disorders. This served as the rationale for the popular practice of self-purgation with enemas.
MED-3671
Investigating the role of perceived stress on bacterial flora activity and salivary cortisol secretion: a possible mechanism underlying susceptibil...
This study examined the impact of academic stress on salivary cortisol concentrations and lactic acid bacteria activity. Whole, unstimulated saliva samples and faecal samples were collected from 23 healthy undergraduate students (23.0+/-6.8 years; range 18-44) over two 1-week periods: during the beginning of semester (low-stress baseline condition) and during the first week of exams (high-stress condition). Students also completed a series of questionnaires measuring perceived levels of stress, gastrointestinal symptoms, and nutritional intake. Significant findings indicated that faecal lactic acid bacterial levels were lower during the high-stress condition. Paralleling this, students rated perceived levels of stress as being greater during the exam period compared to the baseline condition. The findings from this study have provided further insight into the link between stress and gastrointestinal flora activity in humans.
MED-1479
BEYOND THE PALEOLITHIC PRESCRIPTION: INCORPORATING DIVERSITY AND FLEXIBILITY IN THE STUDY OF HUMAN DIET EVOLUTION
Evolutionary paradigms of human health and nutrition center on the evolutionary discordance or “mismatch” model whereby human bodies, reflecting adaptations established in the Paleolithic era, are ill-suited to modern industrialized diets resulting in rapidly increasing rates of chronic metabolic disease. Whereas this model remains useful, we argue that its utility in explaining the evolution of human dietary tendencies is limited. The assumption that human diets are mismatched to our evolved biology implies that they are instinctual or genetically determined and rooted in the Paleolithic. We review current research indicating that human eating habits are primarily learned through behavioral, social and physiological mechanisms starting in utero and extending throughout the life course. Those adaptations that appear to be strongly genetic likely reflect Neolithic, rather than Paleolithic, adaptations and are significantly influenced by human niche-constructing behavior. Incorporating a broader understanding of the evolved mechanisms by which humans learn and imprint eating habits and the reciprocal effects of those habits on physiology would provide useful tools for structuring more lasting nutrition interventions.
MED-1140
Organic food: buying more safety or just peace of mind? A critical review of the literature.
Consumer concern over the quality and safety of conventional food has intensified in recent years, and primarily drives the increasing demand for organically grown food, which is perceived as healthier and safer. Relevant scientific evidence, however, is scarce, while anecdotal reports abound. Although there is an urgent need for information related to health benefits and/or hazards of food products of both origins, generalized conclusions remain tentative in the absence of adequate comparative data. Organic fruits and vegetables can be expected to contain fewer agrochemical residues than conventionally grown alternatives; yet, the significance of this difference is questionable, inasmuch as actual levels of contamination in both types of food are generally well below acceptable limits. Also, some leafy, root, and tuber organic vegetables appear to have lower nitrate content compared with conventional ones, but whether or not dietary nitrate indeed constitutes a threat to human health is a matter of debate. On the other hand, no differences can be identified for environmental contaminants (e.g. cadmium and other heavy metals), which are likely to be present in food from both origins. With respect to other food hazards, such as endogenous plant toxins, biological pesticides and pathogenic microorganisms, available evidence is extremely limited preventing generalized statements. Also, results for mycotoxin contamination in cereal crops are variable and inconclusive; hence, no clear picture emerges. It is difficult, therefore, to weigh the risks, but what should be made clear is that 'organic' does not automatically equal 'safe.' Additional studies in this area of research are warranted. At our present state of knowledge, other factors rather than safety aspects seem to speak in favor of organic food.
MED-3107
IELs: enforcing law and order in the court of the intestinal epithelium.
The intestinal intraepithelial lymphocytes (IELs) are mostly T cells dispersed as single cells within the epithelial cell layer that surrounds the intestinal lumen. IELs are, therefore, strategically located at the interface between the antigen-rich outside world and the sterile core of the body. The intestine of higher vertebrates has further evolved to harbor numerous commensal bacteria that carry out important functions for the host, and while defensive immunity can effectively protect against the invasion of pathogens, similar immune reactions against food-derived antigens or harmless colonizing bacteria can result in unnecessary and sometimes damaging immune responses. Probably as a result of this unique dilemma imposed by the gut environment, multiple subsets of IEL have differentiated, which all display characteristics of 'activated yet resting' immune cells. Despite this common feature, IELs are heterogeneous with regard to their phenotype, ontogeny, and function. In this review, we discuss the different subtypes of IELs and highlight the distinct pathways they took that led to their unique differentiation into highly specialized effector memory T cells, which provide the most effective immune protection yet in a strictly regulated fashion to preserve the integrity and vital functions of the intestinal mucosal epithelium.