Is Caffeinated Tea Really Dehydrating?
MED-4328
Updates on human papillomavirus and genital warts and counseling messages from the 2010 Sexually Transmitted Diseases Treatment Guidelines.
BACKGROUND: In April 2009, experts on sexually transmitted diseases (STDs) were convened to review updates on STD prevention and treatment in preparation for the revision of the Centers for Disease Control and Prevention (CDC) STD Treatment Guidelines. At this meeting, there was a discussion of important updates on human papillomavirus (HPV), genital warts, and cervical cancer screening. METHODS: Key questions were identified with assistance from an expert panel, and systematic reviews of the literature were conducted searching the English-language literature of the PubMed computerized database (US National Library of Medicine). The available evidence was reviewed, and new information was incorporated in the 2010 CDC STD Treatment Guidelines. RESULTS: Two HPV vaccines are now available, the quadrivalent HPV vaccine and the bivalent HPV vaccine; either vaccine is recommended routinely for girls aged 11 or 12 years. The quadrivalent HPV vaccine may be given to boys and men aged 9-26 years. A new patient-applied treatment option for genital warts, sinecatechins 15% ointment, is available and recommended for treatment of external genital warts. This product is a mixture of active ingredients (catechins) from green tea. Finally, updated counseling guidelines and messages about HPV, genital warts, and cervical cancer are included. CONCLUSIONS: This manuscript highlights updates to the 2010 CDC STD Treatment Guidelines for HPV and genital warts. Important additions to the 2010 STD Treatment Guidelines include information on prophylactic HPV vaccine recommendations, new patient-applied treatment options for genital warts, and counseling messages for patients on HPV, genital warts, cervical cancer screening, and HPV tests.
MED-4329
Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions.
We investigated clinical efficacy of green tea extracts (polyphenon E; poly E and (-)-epigallocatechin-3-gallate [EGCG]) delivered in a form of ointment or capsule in patients with human papilloma virus (HPV) infected cervical lesions. Fifty-one patients with cervical lesions (chronic cervicitis, mild dysplasia, moderate dysplasia and severe dysplasia) were divided into four groups, as compared with 39 untreated patients as a control. Poly E ointment was applied locally to 27 patients twice a week. For oral delivery, a 200 mg of poly E or EGCG capsule was taken orally every day for eight to 12 weeks. In the study, 20 out of 27 patients (74%) under poly E ointment therapy showed a response. Six out of eight patients under poly E ointment plus poly E capsule therapy (75%) showed a response, and three out of six patients (50%) under poly E capsule therapy showed a response. Six out of 10 patients (60%) under EGCG capsule therapy showed a response. Overall, a 69% response rate (35/51) was noted for treatment with green tea extracts, as compared with a 10% response rate (4/39) in untreated controls (P<0.05). Thus, the data collected here demonstrated that green tea extracts in a form of ointment and capsule are effective for treating cervical lesions, suggesting that green tea extracts can be a potential therapy regimen for patients with HPV infected cervical lesions.
MED-4330
Green and black tea in relation to gynecologic cancers
Scope Observational studies have evaluated the relationship between green tea intake and cancers of the ovary and endometrium, but we are not aware of the published studies on green tea intake and risk of human papillomavirus (HPV)-related cancers of the cervix, vagina, or vulva. Methods and results A critical review of the published literature on tea intake and risk of ovarian and endometrial cancers was conducted. In meta-analyses, we report inverse associations for green tea intake and risk of ovarian cancer (odds ratio [OR] = 0.66; 95% confidence interval [CI]: 0.54, 0.80), and for green tea and risk of endometrial cancer (OR = 0.78, 95% CI: 0.62, 0.98). There was no association for black tea and ovarian cancer risk (OR = 0.94, 95% CI: 0.87, 1.02) and a positive association with endometrial cancer risk (OR = 1.20, 95% CI: 1.05, 1.38). We summarized the experimental evidence supporting the antiviral and immunomodulatory activities of green tea catechins, and results from randomized clinical trials that demonstrated green tea catechin efficacy on treatment of cervical lesions and external genital warts. Conclusion Observational data support a protective role of green tea on risk of ovarian and endometrial cancers. Observational data are needed to evaluate whether green tea reduces risk of human papillomavirus-related cancers.
MED-4331
Black tea is not significantly different from water in the maintenance of normal hydration in human subjects: results from a randomised controlled ...
There is a belief that caffeinated drinks, such as tea, may adversely affect hydration. This was investigated in a randomised controlled trial. Healthy resting males (n 21) were recruited from the general population. Following 24 h of abstention from caffeine, alcohol and vigorous physical activity, including a 10 h overnight fast, all men underwent four separate test days in a counter-balanced order with a 5 d washout in between. The test beverages, provided at regular intervals, were 4 × 240 ml black (i.e. regular) tea and 6 × 240 ml black tea, providing 168 or 252 mg of caffeine. The controls were identical amounts of boiled water. The tea was prepared in a standardised way from tea bags and included 20 ml of semi-skimmed milk. All food taken during the 12 h intervention period was controlled, and subjects remained at rest. No other beverages were offered. Blood was sampled at 0, 1, 2, 4, 8 and 12 h, and a 24 h urine sample was collected. Outcome variables were whole blood cell count, Na, K, bicarbonate, total protein, urea, creatinine and osmolality for blood; and total volume, colour, Na, K, creatinine and osmolality for urine. Although data for all twenty-one participants were included in the analysis (mean age 36 years and mean BMI 25·8 kg/m(2)), nineteen men completed all conditions. Statistical analysis, using a factorial ANOVA approach within PROC MIXED, revealed no significant differences between tea and water for any of the mean blood or urine measurements. It was concluded that black tea, in the amounts studied, offered similar hydrating properties to water.
MED-4332
Potent antimutagenic activity of white tea in comparison with green tea in the Salmonella assay.
There is growing interest in the potential health benefits of tea, including the antimutagenic properties. Four varieties of white tea, which represent the least processed form of tea, were shown to have marked antimutagenic activity in the Salmonella assay, particularly in the presence of S9. The most active of these teas, Exotica China white tea, was significantly more effective than Premium green tea (Dragonwell special grade) against 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and four other heterocyclic amine mutagens, namely 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline (4,8-DiMeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). Mechanism studies were performed using rat liver S9 in assays for methoxyresorufin O-demethylase (MROD), a marker for the enzyme cytochrome P4501A2 that activates heterocyclic amines, as well as Salmonella assays with the direct-acting mutagen 2-hydroxyamino-3-methylimidazo[4,5-f]quinoline (N-hydroxy-IQ). White tea at low concentrations in the assay inhibited MROD activity, and attenuated the mutagenic activity of N-hydroxy-IQ in the absence of S9. Nine of the major constituents found in green tea also were detected in white tea, including high levels of epigallocatechin-3-gallate (EGCG) and several other polyphenols. When these major constituents were mixed to produce "artificial" teas, according to their relative levels in white and green teas, the complete tea exhibited higher antimutagenic potency compared with the corresponding artificial tea. The results suggest that the greater inhibitory potency of white versus green tea in the Salmonella assay might be related to the relative levels of the nine major constituents, perhaps acting synergistically with other (minor) constituents, to inhibit mutagen activation as well as "scavenging" the reactive intermediate(s).
MED-4415
Cinnamon and health.
Cinnamon has been used as a spice and as traditional herbal medicine for centuries. The available in vitro and animal in vivo evidence suggests that cinnamon has anti-inflammatory, antimicrobial, antioxidant, antitumor, cardiovascular, cholesterol-lowering, and immunomodulatory effects. In vitro studies have demonstrated that cinnamon may act as an insulin mimetic, to potentiate insulin activity or to stimulate cellular glucose metabolism. Furthermore, animal studies have demonstrated strong hypoglycemic properties. However, there are only very few well-controlled clinical studies, a fact that limits the conclusions that can be made about the potential health benefits of cinnamon for free-living humans. The use of cinnamon as an adjunct to the treatment of type 2 diabetes mellitus is the most promising area, but further research is needed before definitive recommendations can be made.
MED-4416
Cinnamon intake lowers fasting blood glucose: meta-analysis.
Cinnamon, the dry bark and twig of Cinnamomum spp., is a rich botanical source of polyphenolics that has been used for centuries in Chinese medicine and has been shown to affect blood glucose and insulin signaling. Cinnamon's effects on blood glucose have been the subject of many clinical and animal studies; however, the issue of cinnamon intake's effect on fasting blood glucose (FBG) in people with type 2 diabetes and/or prediabetes still remains unclear. A meta-analysis of clinical studies of the effect of cinnamon intake on people with type 2 diabetes and/or prediabetes that included three new clinical trials along with five trials used in previous meta-analyses was done to assess cinnamon's effectiveness in lowering FBG. The eight clinical studies were identified using a literature search (Pub Med and Biosis through May 2010) of randomized, placebo-controlled trials reporting data on cinnamon and/or cinnamon extract and FBG. Comprehensive Meta-Analysis (Biostat Inc., Englewood, NJ, USA) was performed on the identified data for both cinnamon and cinnamon extract intake using a random-effects model that determined the standardized mean difference ([i.e., Change 1(control) - Change 2(cinnamon)] divided by the pooled SD of the post scores). Cinnamon intake, either as whole cinnamon or as cinnamon extract, results in a statistically significant lowering in FBG (-0.49±0.2 mmol/L; n=8, P=.025) and intake of cinnamon extract only also lowered FBG (-0.48 mmol/L±0.17; n=5, P=.008). Thus cinnamon extract and/or cinnamon improves FBG in people with type 2 diabetes or prediabetes.
MED-4417
Glycated haemoglobin and blood pressure-lowering effect of cinnamon in multi-ethnic Type 2 diabetic patients in the UK: a randomized, placebo-contr...
AIMS: To determine the blood glucose lowering effect of cinnamon on HbA1c, blood pressure and lipid profiles in people with type 2 diabetes. METHODS: 58 type 2 diabetic patients (25 males and 33 females), aged 54.9 ± 9.8, treated only with hypoglycemic agents and with an HbA1c more than 7% were randomly assigned to receive either 2g of cinnamon or placebo daily for 12 weeks. RESULTS: After intervention, the mean HbA1c was significantly decreased (P<0.005) in the cinnamon group (8.22% to 7.86%) compared with placebo group (8.55% to 8.68%). Mean systolic and diastolic blood pressures (SBP and DBP) were also significantly reduced (P<0.001) after 12 weeks in the cinnamon group (SBP: 132.6 to 129.2 mmHg and DBP: 85.2 to 80.2 mmHg) compared with the placebo group (SBP: 134.5 to 134.9 mmHg and DBP: 86.8 to 86.1 mmHg). A significant reduction in fasting plasma glucose (FPG), waist circumference and body mass index (BMI) was observed at week 12 compared to baseline in the cinnamon group, however, the changes were not significant when compared to placebo group. There were no significant differences in serum lipid profiles of total cholesterol, triglycerides, HDL and LDL cholesterols neither between nor within the groups. CONCLUSIONS: Intake of 2g of cinnamon for 12 weeks significantly reduces the HbA1c, SBP and DBP among poorly controlled type 2 diabetes patients. Cinnamon supplementation could be considered as an additional dietary supplement option to regulate blood glucose and blood pressure levels along with conventional medications to treat type 2 diabetes mellitus. © 2010 The Authors. Diabetic Medicine © 2010 Diabetes UK.
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-4419
Determination of citrulline in watermelon rind.
Watermelon (Citrullus vulgaris Schrad.) is a natural and rich source of the non-essential amino acid citrulline. Citrulline is used in the nitric oxide system in humans and has potential antioxidant and vasodilatation roles. A method using gas chromatography-mass spectrometry (GC-MS) was developed to separate citrulline from glutamic acid, which co-elute when analyzed by high performance liquid chromatography. Watermelons were analyzed by GC-MS to determine the citrulline content among varieties, types, flesh colors, and tissues. Citrulline content ranged from 3.9 to 28.5 mg/g dry weight (dwt) and was similar between seeded and seedless types (16.6 and 20.3 mg/g dwt, respectively). Red flesh watermelons had slightly less citrulline than the yellow or orange flesh watermelons (7.4, 28.5 and 14.2 mg/g dwt, respectively). Rind contained more citrulline than flesh on a dry weight basis (24.7 and 16.7 mg/g dwt, respectively) but a little less on a fresh weight (fwt) basis (1.3 and 1.9 mg/g fwt, respectively). These results indicate that watermelon rind, an underutilized agricultural waste, offers a source of natural citrulline.
MED-5165
Watermelon consumption increases plasma arginine concentrations in adults.
OBJECTIVE: Watermelon is a rich source of citrulline, an amino acid that can be metabolized to arginine, a conditionally essential amino acid for humans. Arginine is the nitrogenous substrate used in the synthesis of nitric oxide and plays an essential role in cardiovascular and immune functions. No detailed studies have been conducted to evaluate plasma arginine response in humans after long-term feeding of citrulline from natural plant sources. This study investigated if watermelon juice consumption increases fasting concentrations of plasma arginine, ornithine, and citrulline in healthy adult humans. METHODS: Subjects (n = 12-23/treatment) consumed a controlled diet and 0 (control), 780, or 1560 g of watermelon juice per day for 3 wk in a crossover design. The treatments provided 1 and 2 g of citrulline per day. Treatment periods were preceded by washout periods of 2 to 4 wk. RESULTS: Compared with the baseline, fasting plasma arginine concentrations increased 12% after 3 wk of the lower-dose watermelon treatment; arginine and ornithine concentrations increased 22% and 18%, respectively, after 3 wk of the higher-dose watermelon treatment. Fasting citrulline concentrations did not increase relative to the control but remained stable throughout the study. CONCLUSION: The increased fasting plasma concentrations of arginine and ornithine and stable concentrations of plasma citrulline in response to watermelon juice consumption indicated that the citrulline from this plant origin was effectively converted into arginine. These results demonstrate that plasma concentration of arginine can be increased through intake of citrulline from watermelon.
MED-4421
Effects of watermelon supplementation on aortic blood pressure and wave reflection in individuals with prehypertension: a pilot study.
BACKGROUND: Oral L-citrulline is efficiently converted to L-arginine, the precursor for endothelial nitric oxide (NO) synthesis. Oral L-arginine supplementation reduces brachial blood pressure (BP). We evaluated the effects of watermelon supplementation on aortic BP and arterial function in individuals with prehypertension. METHODS: Heart rate (HR), brachial systolic BP (bSBP), brachial pulse pressure (bPP), aortic SBP (aSBP), aortic PP (aPP), augmentation index (AIx), AIx adjusted for HR of 75 beats/min (AIx@75), amplitude of the first (P1) and second (P2) systolic peaks, reflection time (Tr), and carotid-femoral pulse wave velocity (PWV) were evaluated in the supine position in nine subjects (four men/five women, age 54 ± 3 years) with prehypertension (134/77 ± 5/3 mm Hg). Subjects were randomly assigned to 6 weeks of watermelon supplementation (L-citrulline/L arginine, 2.7 g/1.3 g/day) or placebo followed by a 4-week washout period and then crossover. RESULTS: There was a significant treatment effect (change in the value of watermelon minus placebo from baseline to 6 weeks) on bPP (-8 ± 3 mm Hg, P < 0.05), aSBP (-7 ± 2 mm Hg, P < 0.05), aPP (-6 ± 2 mm Hg, P < 0.01), AIx (-6 ± 3%, P < 0.05), AIx@75 (-4 ± 2%, P < 0.05), and P2 (-2 ± 1 mm Hg, P < 0.05). There was no significant treatment effect (P > 0.05) on bSBP, brachial diastolic BP (DBP), aortic DBP, Tr, P1, HR, and carotid-femoral PWV. CONCLUSIONS: This pilot study shows that watermelon supplementation improves aortic hemodynamics through a decrease in the amplitude of the reflected wave in individuals with prehypertension.
MED-4422
Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction.
OBJECTIVES: To test the efficacy and safety of oral L-citrulline supplementation in improving erection hardness in patients with mild erectile dysfunction (ED). L-arginine supplementation improves nitric oxide-mediated vasodilation and endothelial function; however, oral administration has been hampered by extensive presystemic metabolism. In contrast, L-citrulline escapes presystemic metabolism and is converted to L-arginine, thus setting the rationale for oral L-citrulline supplementation as a donor for the L-arginine/nitric oxide pathway of penile erection. METHODS: In the present single-blind study, men with mild ED (erection hardness score of 3) received a placebo for 1 month and L-citrulline, 1.5 g/d, for another month. The erection hardness score, number of intercourses per month, treatment satisfaction, and adverse events were recorded. RESULTS: A total of 24 patients, mean age 56.5 ± 9.8 years, were entered and concluded the study without adverse events. The improvement in the erection hardness score from 3 (mild ED) to 4 (normal erectile function) occurred in 2 (8.3%) of the 24 men when taking placebo and 12 (50%) of the 24 men when taking L-citrulline (P < .01). The mean number of intercourses per month increased from 1.37 ± 0.93 at baseline to 1.53 ± 1.00 at the end of the placebo phase (P = .57) and 2.3 ± 1.37 at the end of the treatment phase (P < .01). All patients reporting an erection hardness score improvement from 3 to 4 reported being very satisfied. CONCLUSIONS: Although less effective than phosphodiesterase type-5 enzyme inhibitors, at least in the short term, L-citrulline supplementation has been proved to be safe and psychologically well accepted by patients. Its role as an alternative treatment for mild to moderate ED, particularly in patients with a psychologically fear of phosphodiesterase type-5 enzyme inhibitors, deserves further research. Copyright Â© 2011 Elsevier Inc. All rights reserved.
MED-4438
Caffeine-Not just a stimulant.
OBJECTIVE: The beneficial effects of human caffeine consumption deserve clarification. METHODS: A detailed literature review was conducted and summarized. RESULTS: A large body of scientific evidence describes the beneficial effects of human caffeine consumption on a number of physiologic systems. CONCLUSION: The consumption of moderate amounts of caffeine 1) increases energy availability, 2) increases daily energy expenditure, 3) decreases fatigue, 4) decreases the sense of effort associated with physical activity, 5) enhances physical performance, 6) enhances motor performance, 7) enhances cognitive performance, 8) increases alertness, wakefulness, and feelings of "energy," 9) decreases mental fatigue, 10) quickens reactions, 11) increases the accuracy of reactions, 12) increases the ability to concentrate and focus attention, 13) enhances short-term memory, 14) increases the ability to solve problems requiring reasoning, 15) increases the ability to make correct decisions, 16) enhances cognitive functioning capabilities and neuromuscular coordination, and 17) in otherwise healthy non-pregnant adults is safe. Copyright © 2010 Elsevier Inc. All rights reserved.
MED-4439
A case of fatal caffeine poisoning.
Caffeine is a natural alkaloid methylxanthine that is found in various plants such as coffee or tea. Symptoms of a severe overdose may present with hypokalemia, hyponatremia, ventricular arrhythmias, hypertension followed by hypotension, respiratory failure, seizures, rhabdomyolysis, ventricular fibrillation and finally circulatory collapse. A 21-year-old woman called for the ambulance herself soon after the ingestion of about 10,000 mg of caffeine. At the arrival of the ambulance, the patient went into cardiac arrest almost immediately. After a total resuscitation period of 34 min including seven counter-shocks and 2 mg epinephrine, the patient was stable enough to be transferred to the hospital. The patient soon went into VF again and received two more counter-shocks and 1 mg epinephrine and finally an intravenous bolus dose of 300 mg amiodarone. The initial arterial blood gas showed pH at 6.47, lactate at 33 mmol/l and potassium level at 2.3 mmol/l. Unfortunately, no blood samples for caffeine analysis were taken. Three days after hospital admission, the patient developed myoclonus, which did not respond to medical treatment. Excessive intake of caffeine may produce arrhythmias and pronounced hypokalemia and ensuing ventricular fibrillation. In case of counter-shock-resistant VF, it can be necessary to give an early loading dose of amiodarone. Furthermore, it may be beneficial to replace the potassium as early as possible. Epinephrine and buffer solutions used during resuscitation may further decrease blood potassium levels and should be administrated cautiously. Epinephrine can be replaced by other vasopressor drugs, such as vasopressin without effects on beta-receptors.
MED-4471
Lung deposition of fine and ultrafine particles outdoors and indoors during a cooking event and a no activity period.
Some indoor activities increase the number concentration of small particles and, hence, enhance the dose delivered to the lungs. The received particle dose indoors may exceed noticeably the dose from ambient air under routine in-house activities like cooking. In the present work, the internal dose by inhalation of ultrafine and fine particles is assessed, using an appropriate mechanistic model of lung deposition, accommodating aerosol, and inhalation dynamics. The analysis is based on size distribution measurements (10-350 nm) of indoor and outdoor aerosol number concentrations in a typical residence in Athens, Greece. Four different cases are examined, namely, a cooking event, a no activity period indoors and the equivalent time periods outdoors. When the cooking event (frying of bacon-eggs with a gas fire) occurred, the amount of deposited particles deep into the lung of an individual indoors exceeded by up to 10 times the amount received by an individual at the same time period outdoors. The fine particle deposition depends on the level of physical exertion and the hygroscopic properties of the inhaled aerosol. The dose is not found linearly dependant on the indoor/outdoor concentrations during the cooking event, whereas it is during the no activity period. PRACTICAL IMPLICATIONS: The necessity for determining the dose in specific regions of the human lung, as well as the non-linear relationship between aerosol concentration and internal dose makes the application of dosimetry models important. Lung dose of fine and ultrafine particles, during a cooking event, is compared with the dose at no indoor activity and the dose received under outdoor exposure conditions. The dose is expressed in terms of number or surface of deposited particles. This permits to address the dosimetry of very small particles, which are released by many indoor sources but represent a slight fraction of the particulate matter mass. The enhancement of the internal dose resulting from fine and ultrafine particles generated during the cooking event vs. the dose when no indoor source is active is assessed. The results for those cases are also compared with the dose calculated for the measured aerosol outdoors.
MED-4472
N-Nitroso compounds in the diet.
N-Nitroso compounds were known almost 40 years ago to be present in food treated with sodium nitrite, which made fish meal hepatotoxic to animals through formation of nitrosodimethylamine (NDMA). Since that time, N-nitroso compounds have been shown in animal experiments to be the most broadly acting and the most potent group of carcinogens. The key role of nitrite and nitrogen oxides in forming N-nitroso compounds by interaction with secondary and tertiary amino compounds has led to the examination worldwide of foods for the presence of N-nitroso compounds, which have been found almost exclusively in those foods containing nitrite or which have become exposed to nitrogen oxides. Among these are cured meats, especially bacon-and especially when cooked; concentrations of 100 micrograms kg(-1) have been found or, more usually, near 10 micrograms kg(-1). This would correspond to consumption of 1 microgram of NDMA in a 100-g portion. Much higher concentrations of NDMA (but lower ones of other nitrosamines) have been found in Japanese smoked and cured fish (more than 100 micrograms kg(-1)). Beer is one source of NDMA, in which as much as 70 micrograms l(-1) has been reported in some types of German beer, although usual levels are much lower (10 or 5 micrograms l(-1)); this could mean a considerable intake for a heavy beer drinker of several liters per day. Levels of nitrosamines have been declining during the past three decades, concurrent with a lowering of the nitrite used in food and greater control of exposure of malt to nitrogen oxides in beer making. There have been declines of N-nitroso compound concentrations in many foods during the past two decades. The small amounts of nitrosamines in food are nonetheless significant because of the possibility-even likelihood-that humans are more sensitive to these carcinogens than are laboratory rodents. Although it is probable that alkylnitrosamides (which induce brain tumors in rodents) are present in cured meats and other potentially nitrosated products in spite of much searching, there has been only limited indirect evidence of their presence. Copyright 1999 Elsevier Science B.V.
MED-4976
Airborne mutagens produced by frying beef, pork and a soy-based food.
Airborne cooking by-products from frying beef (hamburgers), pork (bacon strips) and soybean-based food (tempeh burgers) were collected, extracted, tested for mutagenicity and chemically analysed. The fumes generated by frying pork and beef were mutagenic, with 4900 and 1300 revertants/g of food cooked, respectively. No mutagenicity was detected in fumes from frying tempeh burgers. Bacon fried to a well-done but non-charred state was eight times more mutagenic in a microsuspension Ames/Salmonella test (TA98 with S-9) than hamburgers and about 350 times more mutagenic than tempeh burgers. Among food samples cooked to a well-done, non-charred state, bacon strips had almost 15-fold more mass (109.5 ng/g) than that of the beef, whereas no heterocyclic amine (HCA) was detected in the fried tempeh burgers. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was the most abundant HCA, followed by 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx). No 2-amino-9H-pyrido[2,3-b]indole (A alpha C) was detected in the food samples fried at about 200 degrees C, although it was present in the collected airborne products. The total amounts of HCAs in the smoke condensates were 3 ng/g from fried bacon, 0.37 ng/g from fried beef and 0.177 ng/g from fried soy-based food. This study indicates that cooks are potentially exposed to relatively high levels of airborne mutagens and carcinogens and that long-term sampling inside restaurants and kitchens may be warranted in order to assess the potential risk of prolonged exposure.
MED-4543
Antitumour effects of Phyllanthus emblica L.: induction of cancer cell apoptosis and inhibition of in vivo tumour promotion and in vitro invasion o...
Phyllanthus emblica Linn. (PE) is a medicinal fruit used in many Asian traditional medicine systems for the treatment of various diseases including cancer. The present study tested the potential anticancer effects of aqueous extract of PE in four ways: (1) against cancer cell lines, (2) in vitro apoptosis, (3) mouse skin tumourigenesis and (4) in vitro invasiveness. The PE extract at 50-100 microg/mL significantly inhibited cell growth of six human cancer cell lines, A549 (lung), HepG2 (liver), HeLa (cervical), MDA-MB-231 (breast), SK-OV3 (ovarian) and SW620 (colorectal). However, the extract was not toxic against MRC5 (normal lung fibroblast). Apoptosis in HeLa cells was also observed as PE extract caused DNA fragmentation and increased activity of caspase-3/7 and caspase-8, but not caspase-9, and up-regulation of the Fas protein indicating a death receptor-mediated mechanism of apoptosis. Treatment of PE extract on mouse skin resulted in over 50% reduction of tumour numbers and volumes in animals treated with DMBA/TPA. Lastly, 25 and 50 microg/mL of PE extract inhibited invasiveness of MDA-MB-231 cells in the in vitro Matrigel invasion assay. These results suggest P. emblica exhibits anticancer activity against selected cancer cells, and warrants further study as a possible chemopreventive and antiinvasive agent. Copyright 2010 John Wiley & Sons, Ltd.
MED-4538
Effect of Amla fruit (Emblica officinalis Gaertn.) on blood glucose and lipid profile of normal subjects and type 2 diabetic patients.
The present study evaluated the anti-hyperglycemic and lipid-lowering properties of Emblica officinalis Gaertn. fruit in normal and diabetic human volunteers. The results indicated a significant decrease (P <  0.05) in fasting and 2-h post-prandial blood glucose levels on the 21st day in both normal and diabetic subjects receiving 1, 2 or 3 g E. officinalis powder per day as compared with their baseline values. Significant (P <  0.05) decreases were also observed in total cholesterol and triglycerides in both normal and diabetic volunteers on day 21 that were given either 2 or 3 g E. officinalis powder per day. However, diabetic volunteers receiving only 3 g E. officinalis powder exhibited a significant (P <  0.05) decrease in total lipids on day 21. Both normal and diabetic volunteers receiving 2 or 3 g E. officinalis powder significantly (P <  0.05) improved high-density lipoprotein-cholesterol and lowered low-density lipoprotein-cholesterol levels.
MED-4539
Natural products as sources of new drugs over the last 25 years.
This review is an updated and expanded version of two prior reviews that were published in this journal in 1997 and 2003. In the case of all approved agents the time frame has been extended to include the 251/2 years from 01/1981 to 06/2006 for all diseases worldwide and from 1950 (earliest so far identified) to 06/2006 for all approved antitumor drugs worldwide. We have continued to utilize our secondary subdivision of a "natural product mimic" or "NM" to join the original primary divisions. From the data presented, the utility of natural products as sources of novel structures, but not necessarily the final drug entity, is still alive and well. Thus, in the area of cancer, over the time frame from around the 1940s to date, of the 155 small molecules, 73% are other than "S" (synthetic), with 47% actually being either natural products or directly derived therefrom. In other areas, the influence of natural product structures is quite marked, with, as expected from prior information, the antiinfective area being dependent on natural products and their structures. Although combinatorial chemistry techniques have succeeded as methods of optimizing structures and have, in fact, been used in the optimization of many recently approved agents, we are able to identify only one de novo combinatorial compound approved as a drug in this 25 plus year time frame. We wish to draw the attention of readers to the rapidly evolving recognition that a significant number of natural product drugs/leads are actually produced by microbes and/or microbial interactions with the "host from whence it was isolated", and therefore we consider that this area of natural product research should be expanded significantly.
MED-4540
Marked variability of monacolin levels in commercial red yeast rice products: buyer beware!
BACKGROUND: Red yeast rice (RYR) is a widely available dietary supplement used by millions of patients as an alternative therapy for hyperlipidemia. It contains 14 active compounds called monacolins that inhibit hepatic cholesterol synthesis. Although studies have suggested that some formulations of RYR may be effective and safe for lipid lowering, monacolin levels are not standardized among marketed products and are generally not published on labels. We evaluated monacolin levels in 12 commercial RYR formulations and tested for citrinin, a mycotoxin that is nephrotoxic in animals. METHODS: Each formulation of RYR was labeled "600 mg/capsule" of active product. Analyses for monacolins and citrinin were performed between August 2006 and June 2008 using high-performance liquid chromatography with mass spectroscopy-mass spectroscopy detection. Laboratory analyses of RYR products were conducted by ConsumerLab.com, White Plains, New York. RESULTS: There was marked variability in the 12 RYR products in total monacolins (0.31-11.15 mg/capsule), monacolin K (lovastatin) (0.10-10.09 mg/capsule), and monacolin KA (0.00-2.30 mg/capsule). Four products had elevated levels of citrinin. CONCLUSIONS: We found striking variability in monacolin content in 12 proprietary RYR products and the presence of citrinin in one-third of the formulations tested. Although RYR may have potential as an alternative lipid-lowering agent, our findings suggest the need for improved standardization of RYR products and product labeling. Until this occurs, physicians should be cautious in recommending RYR to their patients for the treatment of hyperlipidemia and primary and secondary prevention of cardiovascular disease.
MED-4541
Comparative cardiovascular effects of thiazolidinediones: systematic review and meta-analysis of observational studies
Objective To determine the comparative effects of the thiazolidinediones (rosiglitazone and pioglitazone) on myocardial infarction, congestive heart failure, and mortality in patients with type 2 diabetes. Design Systematic review and meta-analysis of observational studies. Data sources Searches of Medline and Embase in September 2010. Study selection Observational studies that directly compared the risk of cardiovascular outcomes for rosiglitazone and pioglitazone among patients with type 2 diabetes mellitus were included. Data extraction Random effects meta-analysis (inverse variance method) was used to calculate the odds ratios for cardiovascular outcomes with thiazolidinedione use. The I2 statistic was used to assess statistical heterogeneity. Results Cardiovascular outcomes from 16 observational studies (4 case-control studies and 12 retrospective cohort studies), including 810 000 thiazolidinedione users, were evaluated after a detailed review of 189 citations. Compared with pioglitazone, use of rosiglitazone was associated with a statistically significant increase in the odds of myocardial infarction (n=15 studies; odds ratio 1.16, 95% confidence interval 1.07 to 1.24; P<0.001; I2=46%), congestive heart failure (n=8; 1.22, 1.14 to 1.31; P<0.001; I2=37%), and death (n=8; 1.14, 1.09 to 1.20; P<0.001; I2=0%). Numbers needed to treat to harm (NNH), depending on the population at risk, suggest 170 excess myocardial infarctions, 649 excess cases of heart failure, and 431 excess deaths for every 100 000 patients who receive rosiglitazone rather than pioglitazone. Conclusion Among patients with type 2 diabetes, use of rosiglitazone is associated with significantly higher odds of congestive heart failure, myocardial infarction, and death relative to pioglitazone in real world settings.
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-4671
Saffron in the treatment of patients with mild to moderate Alzheimer's disease: a 16-week, randomized and placebo-controlled trial.
WHAT IS KNOWN: Herbal medicines have been used in the treatment of behavioural and psychological symptoms of dementia but with variable response. Crocus sativus (saffron) may inhibit the aggregation and deposition of amyloid β in the human brain and may therefore be useful in Alzheimer's disease (AD). OBJECTIVE: The goal of this study was to assess the efficacy of saffron in the treatment of mild to moderate AD. METHODS: Forty-six patients with probable AD were screened for a 16-week, double-blind study of parallel groups of patients with mild to moderate AD. The psychometric measures, which included AD assessment scale-cognitive subscale (ADAS-cog), and clinical dementia rating scale-sums of boxes, were performed to monitor the global cognitive and clinical profiles of the patients. Patients were randomly assigned to receive capsule saffron 30 mg/day (15 mg twice per day) (Group A) or capsule placebo (two capsules per day) for a 16-week study. RESULTS: After 16 weeks, saffron produced a significantly better outcome on cognitive function than placebo (ADAS-cog: F=4·12, d.f.=1, P=0·04; CDR: F=4·12, d.f.=1, P=0·04). There were no significant differences in the two groups in terms of observed adverse events. WHAT IS NEW AND CONCLUSION: This double-blind, placebo-controlled study suggests that at least in the short-term, saffron is both safe and effective in mild to moderate AD. Larger confirmatory randomized controlled trials are called for. Copyright © 2010 The Authors. JCPT © 2010 Blackwell Publishing Ltd.
MED-4775
Green tea consumption and mortality among Japanese elderly people: the prospective Shizuoka elderly cohort.
PURPOSE: To investigate the association between green tea consumption and mortality from all causes, cancer, and cardiovascular disease (CVD) among elderly people. METHODS: In a population-based, prospective cohort study, a total of 14,001 elderly residents (aged 65-84 years), randomly chosen from all 74 municipalities in Shizuoka, Japan, completed questionnaires that included items about frequency of green tea consumption. They were followed for up to 6 years, from December 1999 to March 2006. Consequently, 12,251 subjects were analyzed to estimate the hazard ratios (HRs) for all-cause mortality, cancer, and CVD. RESULTS: Among 64,002 person-years, 1,224 deaths were identified (follow-up rate, 71.6%). The multivariate HRs and 95% confidence intervals (CIs) for CVD mortality compared those who consumed seven or more cups per day with those who consumed less than one cup per day, were 0.24 (0.14-0.40), 0.30 (0.15-0.61), and 0.18 (0.08-0.40) for total participants, men, and women, respectively. Although green tea consumption was not inversely associated with cancer mortality, green tea consumption and colorectal cancer mortality were inversely associated with a moderate dose-response relationship. CONCLUSIONS: Green tea consumption is associated with reduced mortality from all causes and CVD. This study also suggests that green tea could have protective effects against colorectal cancer.
MED-4867
Evaluation of the genotoxicity of stevioside and steviol using six in vitro and one in vivo mutagenicity assays.
Stevioside, a constituent of Stevia rebaudiana, is commonly used as a non-caloric sugar substitute in Japan. The genetic toxicities of stevioside and its aglycone, steviol, were examined with seven mutagenicity tests using bacteria (reverse mutation assay, forward mutation assay, umu test and rec assay), cultured mammalian cells (chromosomal aberration test and gene mutation assay) and mice (micronucleus test). Stevioside was not mutagenic in any of the assays examined. The aglycone, steviol, however, produced dose-related positive responses in some mutagenicity tests, i.e. the forward mutation assay using Salmonella typhimurium TM677, the chromosomal aberration test using Chinese hamster lung fibroblast cell line (CHL) and the gene mutation assay using CHL. Metabolic activation systems containing 9000 g supernatant fraction (S9) of liver homogenates prepared from polychlorinated biphenyl or phenobarbital plus 5,6-benzoflavone-pretreated rats were required for mutagenesis and clastogenesis. Steviol was weakly positive in the umu test using S.typhimurium TA1535/pSK1002 either with or without the metabolic activation system. Steviol, even in the presence of the S9 activation system, was negative in other assays, i.e. the reverse mutation assays using S.typhimurium TA97, TA98, TA100, TA102, TA104, TA1535, TA1537 and Escherichia coli WP2 uvrA/pKM101 and the rec-assay using Bacillus subtilis. Steviol was negative in the mouse micronucleus test. The genotoxic risk of steviol to humans is discussed.
MED-4868
Stevia (Stevia rebaudiana) a bio-sweetener: a review.
Studies revealed that Stevia has been used throughout the world since ancient times for various purposes; for example, as a sweetener and a medicine. We conducted a systematic literature review to summarize and quantify the past and current evidence for Stevia. We searched relevant papers up to 2007 in various databases. As we know that the leaves of Stevia plants have functional and sensory properties superior to those of many other high-potency sweeteners, Stevia is likely to become a major source of high-potency sweetener for the growing natural food market in the future. Although Stevia can be helpful to anyone, there are certain groups who are more likely to benefit from its remarkable sweetening potential. These include diabetic patients, those interested in decreasing caloric intake, and children. Stevia is a small perennial shrub that has been used for centuries as a bio-sweetener and for other medicinal uses such as to lower blood sugar. Its white crystalline compound (stevioside) is the natural herbal sweetener with no calories and is over 100-300 times sweeter than table sugar.
MED-4869
Evaluation of certain food additives.
This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives, including flavouring agents, with a view to recommending acceptable daily intakes (ADIs) and to preparing specifications for identity and purity. The first part of the report contains a general discussion of the principles governing the toxicological evaluation and assessment of intake of food additives (in particular, flavouring agents). A summary follows of the Committee's evaluations of technical, toxicological and intake data for certain food additives (asparaginase from Aspergillus niger expressed in A. niger, calcium lignosulfonate (40-65), ethyl lauroyl arginate, paprika extract, phospholipase C expressed in Pichia pastoris, phytosterols, phytostanols and their esters, polydimethylsiloxane, steviol glycosides and sulfites [assessment of dietary exposure]) and 10 groups of related flavouring agents (aliphatic branched-chain saturated and unsaturated alcohols, aldehydes, acids and related esters; aliphatic linear alpha,beta-unsaturated aldehydes, acids and related alcohols, acetals and esters; aliphatic secondary alcohols, ketones and related esters; alkoxy-substituted allylbenzenes present in foods and essential oils and used as flavouring agents; esters of aliphatic acyclic primary alcohols with aliphatic linear saturated carboxylic acids; furan-substituted aliphatic hydrocarbons, alcohols, aldehydes, ketones, carboxylic acids and related esters, sulfides, disulfides and ethers; miscellaneous nitrogen-containing substances; monocyclic and bicyclic secondary alcohols, ketones and related esters; hydroxy- and alkoxy-substituted benzyl derivatives; and substances structurally related to menthol). Specifications for the following food additives were revised: canthaxanthin; carob bean gum and carob bean gum (clarified); chlorophyllin copper complexes, sodium and potassium salts; Fast Green FCF; guar gum and guar gum (clarified); iron oxides; isomalt; monomagnesium phosphate; Patent Blue V; Sunset Yellow FCF; and trisodium diphosphate. Re-evaluation of flavouring agents for which estimated intake was based on anticipated poundage data was carried out for 2-isopropyl- N,2,3-trimethylbutyramide (No. 1595) and L-monomenthyl glutarate (No. 1414). Annexed to the report are tables summarizing the Committee's recommendations for intakes and toxicological evaluations of the food additives considered.
MED-4877
Increased telomerase activity and comprehensive lifestyle changes: a pilot study.
BACKGROUND: Telomeres are protective DNA-protein complexes at the end of linear chromosomes that promote chromosomal stability. Telomere shortness in human beings is emerging as a prognostic marker of disease risk, progression, and premature mortality in many types of cancer, including breast, prostate, colorectal, bladder, head and neck, lung, and renal cell. Telomere shortening is counteracted by the cellular enzyme telomerase. Lifestyle factors known to promote cancer and cardiovascular disease might also adversely affect telomerase function. However, previous studies have not addressed whether improvements in nutrition and lifestyle are associated with increases in telomerase activity. We aimed to assess whether 3 months of intensive lifestyle changes increased telomerase activity in peripheral blood mononuclear cells (PBMC). METHODS: 30 men with biopsy-diagnosed low-risk prostate cancer were asked to make comprehensive lifestyle changes. The primary endpoint was telomerase enzymatic activity per viable cell, measured at baseline and after 3 months. 24 patients had sufficient PBMCs needed for longitudinal analysis. This study is registered on the ClinicalTrials.gov website, number NCT00739791. FINDINGS: PBMC telomerase activity expressed as natural logarithms increased from 2.00 (SD 0.44) to 2.22 (SD 0.49; p=0.031). Raw values of telomerase increased from 8.05 (SD 3.50) standard arbitrary units to 10.38 (SD 6.01) standard arbitrary units. The increases in telomerase activity were significantly associated with decreases in low-density lipoprotein (LDL) cholesterol (r=-0.36, p=0.041) and decreases in psychological distress (r=-0.35, p=0.047). INTERPRETATION: Comprehensive lifestyle changes significantly increase telomerase activity and consequently telomere maintenance capacity in human immune-system cells. Given this finding and the pilot nature of this study, we report these increases in telomerase activity as a significant association rather than inferring causation. Larger randomised controlled trials are warranted to confirm the findings of this study.
MED-4878
Dietary patterns, food groups, and telomere length in the Multi-Ethnic Study of Atherosclerosis (MESA)
Background Telomere length reflects biological aging and may be influenced by environmental factors, including those that affect inflammatory processes. Objective With data from 840 white, black, and Hispanic adults from the Multi-Ethnic Study of Atherosclerosis, we studied cross-sectional associations between telomere length and dietary patterns and foods and beverages that were associated with markers of inflammation. Design Leukocyte telomere length was measured by quantitative polymerase chain reaction. Length was calculated as the amount of telomeric DNA (T) divided by the amount of a single-copy control DNA (S) (T/S ratio). Intake of whole grains, fruit and vegetables, low-fat dairy, nuts or seeds, nonfried fish, coffee, refined grains, fried foods, red meat, processed meat, and sugar-sweetened soda were computed with responses to a 120-item food-frequency questionnaire completed at baseline. Scores on 2 previously defined empirical dietary patterns were also computed for each participant. Results After adjustment for age, other demographics, lifestyle factors, and intakes of other foods or beverages, only processed meat intake was associated with telomere length. For every 1 serving/d greater intake of processed meat, the T/S ratio was 0.07 smaller (β ± SE: −0.07 ± 0.03, P = 0.006). Categorical analysis showed that participants consuming ≥1 serving of processed meat each week had 0.017 smaller T/S ratios than did nonconsumers. Other foods or beverages and the 2 dietary patterns were not associated with telomere length. Conclusions Processed meat intake showed an expected inverse association with telomere length, but other diet features did not show their expected associations.
MED-4879
Estimating age of humans based on telomere shortening.
To estimate age using DNA based on telomere shortening, we determined the terminal restriction fragment (TRF) length, as telomere length, using Southern blot analysis of peripheral human blood and blood stains. All blood stains had been stored at room temperature for 5 months. The average TRF length clearly showed a tendency to shortening with aging. The formula for age estimation was based on a correlation between average TRF length and age of the subjects. The estimated age calculated from TRF length widely depends on environmental and genetic factors. However, as long as the DNA is well preserved, use of our method is feasible regardless of age of the subject and can give a rough estimation of age of subjects in forensic samples that carry no morphological information. Copyright 2002 Elsevier Science Ireland Ltd.
MED-4886
Clinical events in prostate cancer lifestyle trial: results from two years of follow-up.
OBJECTIVES: Previous research has demonstrated that patients with prostate cancer participating in the Prostate Cancer Lifestyle Trial had a reduction in prostate-specific antigen (PSA) levels, inhibition of LNCaP cell growth, and fewer prostate cancer-related clinical events at the end of 1 year compared with controls. The aim of this study was to examine the clinical events in this trial during a 2-year period. METHODS: The Prostate Cancer Lifestyle Trial was a 1-year randomized controlled clinical trial of 93 patients with early-stage prostate cancer (Gleason score <7, PSA 4-10 ng/mL) undergoing active surveillance. The patients in the experimental arm were encouraged to adopt a low-fat, plant-based diet, to exercise and practice stress management, and to attend group support sessions. The control patients received the usual care. RESULTS: By 2 years of follow-up, 13 of 49 (27%) control patients and 2 of 43 (5%) experimental patients had undergone conventional prostate cancer treatment (radical prostatectomy, radiotherapy, or androgen deprivation, P < .05). No differences were found between the groups in other clinical events (eg, cardiac), and no deaths occurred. Three of the treated control patients but none of the treated experimental patients had a PSA level of >or=10 ng/mL, and 1 treated control patient but no treated experimental patients had a PSA velocity of >2 ng/mL/y before treatment. No significant differences were found between the untreated experimental and untreated control patients in PSA change or velocity at the end of 2 years. CONCLUSIONS: Patients with early-stage prostate cancer choosing active surveillance might be able to avoid or delay conventional treatment for at least 2 years by making changes in their diet and lifestyle.
MED-4887
Angina pectoris and atherosclerotic risk factors in the multisite cardiac lifestyle intervention program.
Cardiovascular symptom relief is a major indicator for revascularization procedures. To examine the effects of intensive lifestyle modification on symptom relief, we investigated changes in angina pectoris, coronary risk factors, quality of life, and lifestyle behaviors in patients with stable coronary artery disease enrolled in the multisite cardiac lifestyle intervention program, an ongoing health insurance-covered lifestyle intervention conducted at 22 sites in the united states. Patients with coronary artery disease (nonsmokers; 757 men, 395 women; mean age 61 years) were asked to make changes in diet (10% calories from fat, plant based), engage in moderate exercise (3 hours/week), and practice stress management (1 hour/day). At baseline, 108 patients (43% women) reported mild angina and 174 patients (37% women) reported limiting angina. By 12 weeks, 74% of these patients were angina free, and an additional 9% moved from limiting to mild angina. This improvement in angina was significant for patients with mild and limiting angina at baseline regardless of gender (p <0.01). Significant improvements in cardiac risk factors, quality of life, and lifestyle behaviors were observed, and patients with angina who became angina free by 12 weeks showed the greatest improvements in exercise capacity, depression, and health-related quality of life (p <0.05). In conclusion, the observed improvements in angina in patients making intensive lifestyle changes could drastically reduce their need for revascularization procedures.
MED-4888
Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention
Epidemiological and prospective studies indicate that comprehensive lifestyle changes may modify the progression of prostate cancer. However, the molecular mechanisms by which improvements in diet and lifestyle might affect the prostate microenvironment are poorly understood. We conducted a pilot study to examine changes in prostate gene expression in a unique population of men with low-risk prostate cancer who declined immediate surgery, hormonal therapy, or radiation and participated in an intensive nutrition and lifestyle intervention while undergoing careful surveillance for tumor progression. Consistent with previous studies, significant improvements in weight, abdominal obesity, blood pressure, and lipid profile were observed (all P < 0.05), and surveillance of low-risk patients was safe. Gene expression profiles were obtained from 30 participants, pairing RNA samples from control prostate needle biopsy taken before intervention to RNA from the same patient's 3-month postintervention biopsy. Quantitative real-time PCR was used to validate array observations for selected transcripts. Two-class paired analysis of global gene expression using significance analysis of microarrays detected 48 up-regulated and 453 down-regulated transcripts after the intervention. Pathway analysis identified significant modulation of biological processes that have critical roles in tumorigenesis, including protein metabolism and modification, intracellular protein traffic, and protein phosphorylation (all P < 0.05). Intensive nutrition and lifestyle changes may modulate gene expression in the prostate. Understanding the prostate molecular response to comprehensive lifestyle changes may strengthen efforts to develop effective prevention and treatment. Larger clinical trials are warranted to confirm the results of this pilot study.
MED-5337
Intensive lifestyle changes may affect the progression of prostate cancer.
PURPOSE: Men with prostate cancer are often advised to make changes in diet and lifestyle, although the impact of these changes has not been well documented. Therefore, we evaluated the effects of comprehensive lifestyle changes on prostate specific antigen (PSA), treatment trends and serum stimulated LNCaP cell growth in men with early, biopsy proven prostate cancer after 1 year. MATERIALS AND METHODS: Patient recruitment was limited to men who had chosen not to undergo any conventional treatment, which provided an unusual opportunity to have a nonintervention randomized control group to avoid the confounding effects of interventions such as radiation, surgery or androgen deprivation therapy. A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were randomly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group. RESULTS: None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and/or progression of disease on magnetic resonance imaging. PSA decreased 4% in the experimental group but increased 6% in the control group (p = 0.016). The growth of LNCaP prostate cancer cells (American Type Culture Collection, Manassas, Virginia) was inhibited almost 8 times more by serum from the experimental than from the control group (70% vs 9%, p <0.001). Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle. CONCLUSIONS: Intensive lifestyle changes may affect the progression of early, low grade prostate cancer in men. Further studies and longer term followup are warranted.
MED-4890
Effect of diet and exercise intervention on the growth of prostate epithelial cells.
Epidemiological studies suggest a positive association between nutrient intake, hyperinsulinemia and risk of Benign prostatic hyperplasis (BPH). This study tests the hypothesis that a low-fat, high-fiber diet and daily exercise would lower serum insulin and reduce the growth of serum-stimulated primary prostate epithelial cells in culture. Serum samples were obtained from eight overweight men before and after the Pritikin residential, 2-week diet and exercise intervention and from seven men who were long-term followers of the low-fat, high-fiber diet and regular exercise lifestyle. The serum was used to stimulate primary prostate epithelial cells in culture. Growth was measured after 48 and 96 h and apoptosis after 96 h. At 48 h there was no significant difference in growth within the Pre, 2-week or Long-Term groups. At 96 h growth was significantly reduced in the 2-week (13%) and in the Long-Term (14%) groups compared to the Pre data. At 96 h, apoptosis was not significantly different among the three groups. Fasting insulin was reduced by 30% in the 2-week group and by 52% in the Long-Term group compared to the Pre data. Testosterone was unchanged in the 2-week group. The results of this study indicate that a low-fat, high-fiber diet and daily exercise lowers insulin and reduces growth of prostate primary epithelial cells and suggests that lifestyle may be an important factor in the development or progression of BPH. Future prospective trials should address the effects of this lifestyle modification on BPH symptomatology and progression.
MED-4891
Epidemiology of Sudden Cardiac Death: Clinical and Research Implications
The current annual incidence of sudden cardiac death in the US is likely to be in the range of 180–250,000 per year. Coinciding with the decreased mortality from coronary artery disease, there is evidence pointing toward a significant decrease in rates of sudden cardiac death in the US during the second half of the twentieth century. However the alarming rise in prevalence of obesity and diabetes in the first decade of the new millennium both in the US and worldwide, would indicate that this favorable trend is unlikely to persist. We are likely to witness a resurgence of coronary artery disease and heart failure, as a result of which sudden cardiac death will have to be confronted as a shared and indiscriminate, worldwide public health problem. There is also increasing recognition of the fact that discovery of meaningful and relevant risk stratification and prevention methodologies will require careful prospective community-wide analyses, with access to large archives of DNA, serum and tissue that link with well-phenotyped databases. The purpose of this review is to summarize current knowledge of sudden cardiac death epidemiology. We will discuss the significance and strengths of community-wide evaluations of sudden cardiac death, summarize recent observations from such studies, and finally highlight specific potential predictors that warrant further evaluation as determinants of sudden cardiac death in the general population.
MED-5046
Common tea formulations modulate in vitro digestive recovery of green tea catechins.
Epidemiological evidence suggests a role for tea catechins in reduction of chronic disease risk. However, stability of catechins under digestive conditions is poorly understood. The objective of this study was to characterize the effect of common food additives on digestive recovery of tea catechins. Green tea water extracts were formulated in beverages providing 4.5, 18, 23, and 3.5 mg per 100 mL epicatechin (EC), epigallocatechin (EGC), epigallocatechin-gallate (EGCG), and epicatechin-gallate (ECG), respectively. Common commercial beverage additives; citric acid (CA), BHT, EDTA, ascorbic acid (AA), milk (bovine, soy, and rice), and citrus juice (orange, grapefruit, lemon, and lime) were formulated into finished tea beverages at incremental dosages. Samples were then subjected to in vitro digestion simulating gastric and small intestinal conditions with pre- and post-digestion catechin profiles assessed by HPLC. Catechin stability in green tea was poor with <20% total catechins remaining post-digestion. EGC and EGCG were most sensitive with less, not double equals 10% recovery. Teas formulated with 50% bovine, soy, and rice milk increased total catechin recovery significantly to 52, 55, and 69% respectively. Including 30 mg AA in 250 mL of tea beverage significantly (p<0.05) increased catechin recovery of EGC, EGCG, EC, and ECG to 74, 54, 82, and 45% respectively. Juice preparation resulted in the highest recovery of any formulation for EGC (81-98%), EGCG (56-76%), EC (86-95%), and ECG (30-55%). These data provide evidence that tea consumption practices and formulation factors likely impact catechin digestive recovery and may result in diverse physiological profiles.
MED-5047
The Association between Concentrations of Green Tea and Blood Glucose Levels
Our objective was to examine whether habitual green tea consumption is associated with blood glucose levels and other biomarkers of glucose metabolism. We conducted a cross-sectional study of 35 male volunteers, 23–63 years old and residing in Shizuoka Prefecture in Japan. Biochemical data were measured and we conducted a questionnaire survey on health, lifestyle, and nutrition, as well as frequency of consumption and concentrations (1%, 2%, and 3%) of green tea. Men who consumed a 3% concentration of green tea showed lower mean values of fasting blood glucose and fructosamine than those who consumed a 1% concentration. Fasting blood glucose levels were found to be significantly associated with green tea concentration (β = −0.14, p = 0.03). However, green tea consumption frequency showed no significant differences in mean levels of blood glucose, fructosamine and hemoglobin A1c. In conclusion, our findings suggest that the consumption of green tea at a high concentration has the potential to reduce blood glucose levels.
MED-5048
Effect of green tea and (-)-epigallocatechin gallate on ethanol-induced toxicity in HepG2 cells.
Despite the continuing reports supporting the hepatoprotective effects of green tea against ethanol intoxication, there remain controversies regarding the active compound(s) and molecular mechanism. These issues were addressed in the present study using cultured HepG2 cells exposed to a lethal dose of ethanol. Gamma-glutamyl transferase (GGT) was chosen as a marker of ethanol toxicity because it is widely used in clinics. When the cells were treated with ethanol at various concentrations, there was a dose-dependent increase of GGT activity in the culture media and loss of cell viability. Pretreatment of the cells with green tea extract attenuated the changes significantly. Among the green tea constituents, (-)-epigallocatechin gallate (EGCG) attenuated the ethanol cytotoxicity effectively, whereas L-theanine and caffeine had no effects. The ethanol cytotoxicity was also attenuated by alcohol dehydrogenase inhibitor 4-methyl pyrazol and GGT inhibitor acivicin as well as by thiol modulators such as S-adenosyl-L-methionine, N-acetyl-L-cysteine and glutathione. EGCG failed to prevent the intracellular glutathione loss caused by ethanol, but it appeared to be a strong GGT inhibitor. Therefore the cytoprotective effects of green tea could be attributed to the inhibition of GGT activity by EGCG. This study suggests that GGT inhibitors including EGCG may provide a novel strategy for attenuating ethanol-induced liver damage.
MED-5049
Association between soy and green tea (Camellia sinensis) diminishes hypercholesterolemia and increases total plasma antioxidant potential in dysli...
OBJECTIVE: To evaluate the hypolipemic and antioxidant effects of soy and green tea alone and/or in association in dyslipidemic subjects. METHODS: One hundred dyslipidemic individuals were allocated into four groups. The soy group ingested 50 g of soy (kinako) daily, and the green tea group ingested 3 g of green tea in 500 mL of water per day. A third group ingested 50 g of soy and 3 g of green tea daily, and the control group had a hypocholesterolemic diet. Evaluations were performed at baseline and after 45 and 90 d. Plasma levels of total cholesterol, high-density lipoprotein, and triacylglycerols were evaluated by automated methods. Low-density lipoprotein (LDL) cholesterol was calculated using the Friedewald equation. LDL was isolated by ultracentrifugation. Total plasma antioxidant capacity and plasma levels of total lipid hydroperoxides and those linked to LDL were evaluated by chemiluminescence. The results were expressed as median values and their 25th to 75th percentiles, with a 5% level of significance. RESULTS: No significant difference occurred in LDL, high-density lipoprotein cholesterol, and triacylglycerol levels across groups. However, a statistically significant difference in total cholesterol occurred within the soy/green tea group 45 and 90 d after intervention. No statistically significant difference occurred in plasma levels of lipid hydroperoxides or those linked to LDL in any of the groups studied. All the groups that used soy and/or green tea presented increased total plasma antioxidant potential. CONCLUSION: Soy and green tea, alone or in combination, increased the total antioxidant potential of hypercholesterolemic patients, whereas only the combination decreased total cholesterol levels.
MED-5050
L-theanine, a natural constituent in tea, and its effect on mental state.
Tea is the most widely consumed beverage in the world after water. Tea is known to be a rich source of flavonoid antioxidants. However tea also contains a unique amino acid, L-theanine that may modulate aspects of brain function in humans. Evidence from human electroencephalograph (EEG) studies show that it has a direct effect on the brain (Juneja et al. Trends in Food Science & Tech 1999;10;199-204). L-theanine significantly increases activity in the alpha frequency band which indicates that it relaxes the mind without inducing drowsiness. However, this effect has only been established at higher doses than that typically found in a cup of black tea (approximately 20mg). The aim of the current research was to establish this effect at more realistic dietary levels. EEG was measured in healthy, young participants at baseline and 45, 60, 75, 90 and 105 minutes after ingestion of 50mg L-theanine (n=16) or placebo (n=19). Participants were resting with their eyes closed during EEG recording. There was a greater increase in alpha activity across time in the L-theanine condition (relative to placebo (p+0.05). A second study replicated this effect in participants engaged in passive activity. These data indicate that L-theanine, at realistic dietary levels, has a significant effect on the general state of mental alertness or arousal. Furthermore, alpha activity is known to play an important role in critical aspects of attention, and further research is therefore focussed on understanding the effect of L-theanine on attentional processes.
MED-5052
Can green tea do that? A literature review of the clinical evidence.
OBJECTIVE: Habitual green tea consumption has long been associated with health benefits including chemoprevention and cardiovascular protection. This non-systematic literature review presents the clinical evidence to date. METHOD: A literature review of peer-reviewed articles on observational and interventional studies was conducted to include green tea, its extract or its purified polyphenol (-)-epigallocatechin-3-gallate (EGCG). Electronic databases searched included PubMed (1966-2009) and the Cochrane Library (Issue 4, 2008). RESULTS: Observational studies are inconclusive on the benefits of habitual consumption of green tea in the prevention of most cancers. However, there are trends towards prevention in breast and prostate cancers. Interventional studies have demonstrated reduction in relapses following surgical resection in colorectal adenomas and increased survival rates in epithelial ovarian cancer. Observational studies indicate that green tea may provide protection against hypertension and reduce the risk for stroke, and interventional studies are providing biochemical and physiological evidence. CONCLUSION: Although the overall clinical evidence is inconclusive, habitual green tea consumption may be providing some level of chemoprevention in prostate and breast cancer. Green tea may also attenuate the risk factors association with the development of atherosclerosis thus reducing the incidence of cardiovascular events and stoke.
MED-5058
Sucrose and behavioral problems.
Various mechanisms by which sucrose could influence behavior are reviewed. Firstly there is food intolerance. There are dozens of foods to which an adverse reaction has been demonstrated, although a reaction to sucrose is less frequent than many other foods. A second possible mechanism is hypoglycemia. There is evidence that a tendency to develop low blood glucose levels, but higher than those that can be described clinically as hypoglycemic, is associated with irritability and violence. However, sucrose is not the predominant cause of swings in blood glucose levels. Thirdly, the role of sucrose intake on micro-nutrient status has been considered as studies have found that micro-nutrient supplementation decreased anti-social behavior. Micro-nutrient intake is more closely associated with the total energy rather than sucrose intake; typically the amount of sucrose in the diet does not lead to micro-nutrient deficiency. In fact meta-analysis of well designed studies that have examined the impact of sucrose on the behavior of children produced no evidence that it has an adverse influence.
MED-5064
Consumption of Brussels sprouts protects peripheral human lymphocytes against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and oxidative ...
To find out if the cancer protective effects of Brussels sprouts seen in epidemiological studies are due to protection against DNA-damage, an intervention trial was conducted in which the impact of vegetable consumption on DNA-stability was monitored in lymphocytes with the comet assay. After consumption of the sprouts (300 g/p/d, n = 8), a reduction of DNA-migration (97%) induced by the heterocyclic aromatic amine 2-amino-1-methyl-6-phenyl-imidazo-[4,5-b]pyridine (PhIP) was observed whereas no effect was seen with 3-amino-1-methyl-5H-pyrido[4,3-b]-indole (Trp-P-2). This effect protection may be due to inhibition of sulfotransferase 1A1, which plays a key role in the activation of PhIP. In addition, a decrease of the endogenous formation of oxidized bases was observed and DNA-damage caused by hydrogen peroxide was significantly (39%) lower after the intervention. These effects could not be explained by induction of antioxidant enzymes glutathione peroxidase and superoxide dismutase, but in vitro experiments indicate that sprouts contain compounds, which act as direct scavengers of reactive oxygen species. Serum vitamin C levels were increased by 37% after sprout consumption but no correlations were seen between prevention of DNA-damage and individual alterations of the vitamin levels. Our study shows for the first time that sprout consumption leads to inhibition of sulfotransferases in humans and to protection against PhIP and oxidative DNA-damage.
MED-5065
Anthocyanin-rich grape extract blocks breast cell DNA damage.
Anthocyanins, belonging to the flavonoid family of phytochemicals, have received attention as agents that may have potential in preventing chronic diseases such as cardiovascular diseases and certain cancers. In the present study, an anthocyanin-rich extract from Concord grapes [referred to as Concord grape extract (CGE)] and the anthocyanin delphinidin were evaluated for their capacity to inhibit DNA adduct formation due to the environmental carcinogen benzo[a]pyrene (BP) in MCF-10F cells, a noncancerous, immortalized human breast epithelial cell line. CGE at 10 and 20 microg/mL and delphinidin at 0.6 microM concentrations significantly inhibited BP-DNA adduct formation. This was associated with a significant increase in activities of the phase II detoxification enzymes glutathione S-transferase and NAD(P)H:quinone reductase 1. In addition, these grape components also suppressed reactive oxygen species (ROS) formation, but did not induce antioxidant response element-dependent transcription. Taken together, these data suggest that CGE and a component grape anthocyanin have breast cancer chemopreventive potential due in part to their capacity to block carcinogen-DNA adduct formation, modulate activities of carcinogen-metabolizing enzymes, and suppress ROS in these noncancerous human breast cells.
MED-5176
Effects of dietary flaxseed lignan extract on symptoms of benign prostatic hyperplasia.
A flaxseed lignan extract containing 33% secoisolariciresinol diglucoside (SDG) was evaluated for its ability to alleviate lower urinary tract symptoms (LUTS) in 87 subjects with benign prostatic hyperplasia (BPH). A randomized, double-blind, placebo-controlled clinical trial with repeated measurements was conducted over a 4-month period using treatment dosages of 0 (placebo), 300, or 600 mg/day SDG. After 4 months of treatment, 78 of the 87 subjects completed the study. For the 0, 300, and 600 mg/day SDG groups, respectively, the International Prostate Symptom Score (IPSS) decreased -3.67 +/- 1.56, -7.33 +/- 1.18, and -6.88 +/- 1.43 (mean +/- SE, P = .100, < .001, and < .001 compared to baseline), the Quality of Life score (QOL score) improved by -0.71 +/- 0.23, -1.48 +/- 0.24, and -1.75 +/- 0.25 (mean +/- SE, P = .163 and .012 compared to placebo and P = .103, < .001, and < .001 compared to baseline), and the number of subjects whose LUTS grade changed from "moderate/severe" to "mild" increased by three, six, and 10 (P = .188, .032, and .012 compared to baseline). Maximum urinary flows insignificantly increased 0.43 +/- 1.57, 1.86 +/- 1.08, and 2.7 +/- 1.93 mL/second (mean +/- SE, no statistical significance reached), and postvoiding urine volume decreased insignificantly by -29.4 +/- 20.46, -19.2 +/- 16.91, and -55.62 +/- 36.45 mL (mean +/- SE, no statistical significance reached). Plasma concentrations of secoisolariciresinol (SECO), enterodiol (ED), and enterolactone (EL) were significantly raised after the supplementation. The observed decreases in IPSS and QOL score were correlated with the concentrations of plasma total lignans, SECO, ED, and EL. In conclusion, dietary flaxseed lignan extract appreciably improves LUTS in BPH subjects, and the therapeutic efficacy appeared comparable to that of commonly used intervention agents of alpha1A-adrenoceptor blockers and 5alpha-reductase inhibitors.
MED-5177
Pilot evaluation of flaxseed for the management of hot flashes.
The objective of this study was to evaluate, in a phase 2 pilot study, tolerability and the effect of 6 weeks of flaxseed therapy on hot flash scores in women not wishing to receive estrogen therapy. Eligibility included 14 hot flashes per week for at least 1 month. In the baseline week, participants took no study medication and documented the characteristics of their hot flashes. Thereafter, crushed flaxseed was administered at 40 g daily. Participants provided weekly toxicity reports and health-related quality of life information. The primary end point was a change in hot flash score prospectively reported in a daily hot flash diary. Thirty women were enrolled between June 17 and November 8, 2005. The mean decrease in hot flash scores after flaxseed therapy was 57% (median decrease 62%). The mean reduction in daily hot flash frequency was 50% (median reduction 50%), from 7.3 hot flashes to 3.6. Fourteen of the 28 participants (50%) experienced mild or moderate abdominal distention. Eight participants (29%) experienced mild diarrhea, one experienced flatulence, and six (21%) withdrew because of toxicities. This study suggests that dietary therapy decreases hot flash activity in women not taking estrogen therapy. This reduction is greater than what would be expected with placebo.
MED-5178
Dietary flaxseed lignan extract lowers plasma cholesterol and glucose concentrations in hypercholesterolaemic subjects.
Lignans, derived from flaxseed, are phyto-oestrogens being increasingly studied for their health benefits. An 8-week, randomised, double-blind, placebo-controlled study was conducted in fifty-five hypercholesterolaemic subjects, using treatments of 0 (placebo), 300 or 600 mg/d of dietary secoisolariciresinol diglucoside (SDG) from flaxseed extract to determine the effect on plasma lipids and fasting glucose levels. Significant treatment effects were achieved (P < 0.05 to < 0.001) for the decrease of total cholesterol (TC), LDL-cholesterol (LDL-C) and glucose concentrations, as well as their percentage decrease from baseline. At weeks 6 and 8 in the 600 mg SDG group, the decreases of TC and LDL-C concentrations were in the range from 22.0 to 24.38 % respectively (all P < 0.005 compared with placebo). For the 300 mg SDG group, only significant differences from baseline were observed for decreases of TC and LDL-C. A substantial effect on lowering concentrations of fasting plasma glucose was also noted in the 600 mg SDG group at weeks 6 and 8, especially in the subjects with baseline glucose concentrations > or = 5.83 mmol/l (lowered 25.56 and 24.96 %; P = 0.015 and P = 0.012 compared with placebo, respectively). Plasma concentrations of secoisolariciresinol (SECO), enterodiol (ED) and enterolactone were all significantly raised in the groups supplemented with flaxseed lignan. The observed cholesterol-lowering values were correlated with the concentrations of plasma SECO and ED (r 0.128-0.302; P < 0.05 to < 0.001). In conclusion, dietary flaxseed lignan extract decreased plasma cholesterol and glucose concentrations in a dose-dependent manner.
MED-5179
Dietary supplementation with flaxseed oil lowers blood pressure in dyslipidaemic patients.
OBJECTIVE: Alpha-linolenic acid (ALA) is the natural precursor of the cardioprotective long-chain n-3 fatty acids. Available data indicate a possible beneficial effect of ALA on cardiovascular disease (CVD), but the response of various CVD risk factors to increased ALA intake is not well characterized. The purpose of the present study was to examine the effect of increased ALA intake on blood pressure in man. DESIGN, SETTING, SUBJECTS AND INTERVENTIONS: We used a prospective, two-group, parallel-arm design to examine the effect of a 12-week dietary supplementation with flaxseed oil, rich in ALA (8 g/day), on blood pressure in middle-aged dyslipidaemic men (n=59). The diet of the control group was supplemented with safflower oil, containing the equivalent n-6 fatty acid (11 g/day linoleic acid (LA); n=28). Arterial blood pressure was measured at the beginning and at the end of the dietary intervention period. RESULTS: Supplementation with ALA resulted in significantly lower systolic and diastolic blood pressure levels compared with LA (P=0.016 and P=0.011, respectively, from analysis of variance (ANOVA) for repeated measures). CONCLUSIONS: We observed a hypotensive effect of ALA, which may constitute another mechanism accounting in part for the apparent cardioprotective effect of this n-3 fatty acid.
MED-5184
Dietary lignan intakes and risk of breast cancer by tumor estrogen receptor status.
We examined the association of dietary lignan intake with estrogen receptor negative (ER-) and ER positive (ER+) breast cancer risk in a breast cancer case-control study. Among premenopausal women only, there was a reduced risk of ER- breast cancer for those in the highest compared to the lowest quartile of lignan intake suggesting that the observed negative association of lignans with breast cancer may be limited to ER- tumors.
MED-1858
Influence of drinking patterns of carbonated beverages on dental erosion.
As a hard tissue dental disease, dental erosion has a multifactorial etiology. The majority of dental erosion that originates from extrinsic sources is the result of dietary intake, particularly acidic beverages. Several preventive means have been proposed to minimize the damage to the dentition, including a reduction in the consumption of causative beverages and the adoption of a specific method of drinking, utilizing a straw instead of a cup. This article presents two cases involving the clinical and radiographic features of erosion lesions associated with chronic and excessive intake of acidic carbonated beverages. These examples embody how drinking patterns influence the formation of erosion lesions in various anatomic locations within the dentition. The clinical and radiographic evidence presented in this report cautions against the use of nonspecific terms, such as "cup versus straw," and instead suggests implementing a more precise description of the suggested method. In view of the extensive damage inflicted by the chronic, excessive intake of carbonated beverages, preventive measures are considered to be the only effective course of management. This article offers illustrative examples of erosion lesions associated with long-term excessive intake of carbonated beverages. The influence of the drinking method--that is, a straw positioned into the labial vestibule versus a cup--on the anatomic location of the erosion lesions will be demonstrated through clinical and radiographic evidence.
MED-4354
Scientific and technical factors affecting the setting of Salmonella criteria for raw poultry: a global perspective.
Concerns about foodborne salmonellosis have led many countries to introduce microbiological criteria for certain food products. If such criteria are not well-grounded in science, they could be an unjustified obstacle to trade. Raw poultry products are an important part of the global food market. Import and export ambiguities and regulatory confusion resulting from different Salmonella requirements were the impetus for convening an international group of scientific experts from 16 countries to discuss the scientific and technical issues that affect the setting of a microbiological criterion for Salmonella contamination of raw chicken. A particular concern for the group was the use of criteria implying a zero tolerance for Salmonella and suggesting complete absence of the pathogen. The notion can be interpreted differently by various stakeholders and was considered inappropriate because there is neither an effective means of eliminating Salmonella from raw poultry nor any practical method for verifying its absence. Therefore, it may be more useful at present to set food safety metrics that involve reductions in hazard levels. Such terms as "zero tolerance" or "absence of a microbe" in relation to raw poultry should be avoided unless defined and explained by international agreement. Risk assessment provides a more meaningful approach than a zero tolerance philosophy, and new metrics, such as performance objectives that are linked to human health outcomes, should be utilized throughout the food chain to help define risk and identify ways to reduce adverse effects on public health.
MED-2886
Goji berry effects on macular characteristics and plasma antioxidant levels.
PURPOSE: Goji berry (Lycium barbarum L.) is purported to benefit vision because of its high antioxidant (especially zeaxanthin) content, although this effect has not been demonstrated in high-quality human studies. The purpose of this study was to evaluate the effects of daily supplementation with a proprietary milk-based formulation of goji berry, Lacto-Wolfberry (LWB), on macular characteristics and plasma zeaxanthin and antioxidant capacity levels in elderly subjects. METHODS: This was a double-masked, randomized, placebo-controlled trial in healthy elderly subjects (range, 65 to 70 years) receiving 13.7 g/d of LWB (n = 75) or placebo (n = 75) for 90 days. Subjects underwent direct ophthalmic examination to assess pigmentation and soft drusen count in the macula and a blood draw to measure plasma zeaxanthin level and total antioxidant capacity. RESULTS: The placebo group demonstrated hypopigmentation and soft drusen accumulation in the macula, whereas the LWB group remained stable. Both plasma zeaxanthin level and antioxidant capacity increased significantly in the LWB group, by 26% and 57%, respectively, but did not change in the placebo group. No product-related adverse events were reported in either group. CONCLUSIONS: Overall, daily dietary supplementation with goji berry for 90 days increases plasma zeaxanthin and antioxidant levels as well as protects from hypopigmentation and soft drusen accumulation in the macula of elderly subjects. However, the mechanism of action is unclear, given the lack of relationship between change in plasma zeaxanthin and change in macular characteristics.
MED-2707
Ambient odor of orange in a dental office reduces anxiety and improves mood in female patients.
Essential oils have been used as remedies for a long time in different cultures across the world. However, scientific proof of such application is scarce. We included 72 patients between the ages of 22 and 57 while waiting for dental treatment in our study. The participants were assigned to either a control group (14 men, 23 women) or to an odor group (18 men and 17 women). Ambient odor of orange was diffused in the waiting room through an electrical dispenser in the odor group whereas in the control group no odor was in the air. We assessed by means of self-report demographic and cognitive variables, trait and state anxiety, and current pain, mood, alertness, and calmness. In this study, we report that exposure to ambient odor of orange has a relaxant effect. Specifically, compared to the controls, women who were exposed to orange odor had a lower level of state anxiety, a more positive mood, and a higher level of calmness. Our data support the previous notion of sedative properties of the natural essential oil of orange (Citrus sinensis).
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-5222
Pharmaceutical and herbal products that may contribute to dry eyes.
BACKGROUND: Symptomatic dryness of the eyes is a most common blepharoplasty complication. The authors reviewed the medications and herbal products that may potentiate this complication. METHODS: The MEDLINE and PubMed databases were searched for the years 1991 to 2011. Search terms included "dry eye syndrome," "keratitis sicca," "keratoconjunctivitis sicca," "ocular side effects," "herbal supplements," "herbals and dry eye," "dry eye risk factors," "etiology of dry eye," "drugs side effects," "drugs and dry eye," "dietary supplements," "ocular toxicity," and "tear film." References from herbal product reviews and eligible medication reports were searched for additional articles. A manual search was also conducted based on citations in the published literature. RESULTS: Of 232 articles found to be related to dry eye syndrome and possible risk factors, 196 were excluded because they did not discuss medications or herbal products as risk factors in dry eye syndrome. Thirty-six articles that examined the pathophysiology and risk factors of dry eye were included. Nine books were reviewed that contained some information regarding the association of medications and herbal products with dry eye. These agents were then categorized based on mechanism of action and usage. Medications listed include antihistamines, decongestants, antidepressants, anticonvulsants, antipsychotics, antiparkinson drugs, beta-blockers, and hormone replacement therapy. The three main herbal products that contribute to dry eye are niacin, echinacea, and kava. There was a strong association between anticholinergic alkaloids and dry eye. CONCLUSION: This study identifies the medications and herbal products that should be considered when a patient undergoes blepharoplasty and complains of symptoms associated with dryness of the eyes.
MED-4390
Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers.
The medicinal properties of curcumin obtained from Curcuma longa L. cannot be utilised because of poor bioavailability due to its rapid metabolism in the liver and intestinal wall. In this study, the effect of combining piperine, a known inhibitor of hepatic and intestinal glucuronidation, was evaluated on the bioavailability of curcumin in rats and healthy human volunteers. When curcumin was given alone, in the dose 2 g/kg to rats, moderate serum concentrations were achieved over a period of 4 h. Concomitant administration of piperine 20 mg/kg increased the serum concentration of curcumin for a short period of 1-2 h post drug. Time to maximum was significantly increased (P < 0.02) while elimination half life and clearance significantly decreased (P < 0.02), and the bioavailability was increased by 154%. On the other hand in humans after a dose of 2 g curcumin alone, serum levels were either undetectable or very low. Concomitant administration of piperine 20 mg produced much higher concentrations from 0.25 to 1 h post drug (P < 0.01 at 0.25 and 0.5 h; P < 0.001 at 1 h), the increase in bioavailability was 2000%. The study shows that in the dosages used, piperine enhances the serum concentration, extent of absorption and bioavailability of curcumin in both rats and humans with no adverse effects.
MED-2770
The experience of Japan as a clue to the etiology of breast and ovarian cancers: relationship between death from both malignancies and dietary prac...
Although breast and ovarian cancers are rare in Japan compared with other developed countries, the death rates for both are increasing. In Japan, dramatic lifestyle changes occurred after World War II. Over the past 50 years (1947-1997), the age-standardized death rates of breast and ovarian cancers increased about 2- and 4-fold, respectively, and the respective intake of milk, meat, and eggs increased 20-, 10-, and 7-fold. The increase in the annual death rates from breast and ovarian cancers might be due to the lifestyle changes (increased consumption of animal-derived food) that occurred after 1945. Among the food, milk and dairy products should receive particular attention since they contain considerable amounts of estrogens.
MED-1341
Skeletal health in adult patients with classic galactosemia.
SUMMARY: This study evaluated bone health in adults with galactosemia. Associations between bone mineral density (BMD) and nutritional and biochemical variables were explored. Calcium level predicted hip and spine BMD, and gonadotropin levels were inversely associated with spinal BMD in women. These results afford insights into management strategies for these patients. INTRODUCTION: Bone loss is a complication of galactosemia. Dietary restriction, primary ovarian insufficiency in women, and disease-related alterations of bone metabolism may contribute. This study examined relationships between clinical factors and BMD in patients with galactosemia. METHODS: This cross-sectional sample included 33 adults (16 women) with classic galactosemia, mean age 32.0 ± 11.8 years. BMD was measured by dual-energy X-ray absorptiometry, and was correlated with age, height, weight, fractures, nutritional factors, hormonal status, and bone biomarkers. RESULTS: There was a significant difference in hip BMD between women and men (0.799 vs. 0.896 g/cm(2), p = 0.014). The percentage of subjects with BMD-Z <-2.0 was also greater for women than men [33 vs. 18 % (spine), 27 vs. 6 % (hip)], and more women reported sustaining fractures. Bivariate analyses yielded correlations between BMI and BMD-Z [at the hip in women (r = 0.58, p < 0.05) and spine in men (r = 0.53, p < 0.05)]. In women, weight was also correlated with BMD-Z (r = 0.57, p < 0.05 at hip), and C-telopeptides (r = -0.59 at spine and -0.63 hip, p < 0.05) and osteocalcin (r = -0.71 at spine and -0.72 hip, p < 0.05) were inversely correlated with BMD-Z. In final regression models, higher gonadotropin levels were associated with lower spinal BMD in women (p = 0.017); serum calcium was a significant predictor of hip (p = 0.014) and spine (p = 0.013) BMD in both sexes. CONCLUSIONS: Bone density in adults with galactosemia is low, indicating the potential for increased fracture risk, the etiology of which appears to be multifactorial.
MED-1211
Temporal and Regional Trends in the Prevalence of Healthy Lifestyle Characteristics: United States, 1994–2007
Objectives. We examined temporal and regional trends in the prevalence of health lifestyles in the United States. Methods. We used 1994 to 2007 data from the Behavioral Risk Factor Surveillance System to assess 4 healthy lifestyle characteristics: having a healthy weight, not smoking, consuming fruits and vegetables, and engaging in physical activity. The concurrent presence of all 4 characteristics was defined as a healthy overall lifestyle. We used logistic regression to assess temporal and regional trends. Results. The percentages of individuals who did not smoke (4% increase) and had a healthy weight (10% decrease) showed the strongest temporal changes from 1994 to 2007. There was little change in fruit and vegetable consumption or physical activity. The prevalence of healthy lifestyles increased minimally over time and varied modestly across regions; in 2007, percentages were higher in the Northeast (6%) and West (6%) than in the South (4%) and Midwest (4%). Conclusions. Because of the large increases in overweight and the declines in smoking, there was little net change in the prevalence of healthy lifestyles. Despite regional differences, the prevalence of healthy lifestyles across the United States remains very low.
MED-2062
Oligo-antigenic diet in the treatment of chronic anal fissures. Evidence for a relationship between food hypersensitivity and anal fissures.
OBJECTIVES: Patients with chronic constipation due to food hypersensitivity (FH) had an elevated anal sphincter resting pressure. No studies have investigated a possible role of FH in anal fissures (AFs). We aimed to evaluate (1) the effectiveness of diet in curing AFs and to evaluate (2) the clinical effects of a double-blind placebo-controlled (DBPC) challenge, using cow's milk protein or wheat. METHODS: One hundred and sixty-one patients with AFs were randomized to receive a "true-elimination diet" or a "sham-elimination diet" for 8 weeks; both groups also received topical nifedipine and lidocaine. Sixty patients who were cured with the "true-elimination diet" underwent DBPC challenge in which cow's milk and wheat were used. RESULTS: At the end of the study, 69% of the "true-diet group" and 45% of the "sham-diet group" showed complete healing of AFs (P<0.0002). Thirteen of the 60 patients had AF recurrence during the 2-week cow's milk DBPC challenge and 7 patients had AF recurrence on wheat challenge. At the end of the challenge, anal sphincter resting pressure significantly increased in the patients who showed AF reappearance (P<0.0001), compared with the baseline values. The patients who reacted to the challenges had a significantly higher number of eosinophils in the lamina propria and intraepithelial lymphocytes than those who did not react to the challenges. CONCLUSIONS: An oligo-antigenic diet combined with medical treatment improved the rate of chronic AF healing. In more than 20% of the patients receiving medical and dietary treatment, AFs recurred on DBPC food challenge.
MED-4447
Lignan contents of Dutch plant foods: a database including lariciresinol, pinoresinol, secoisolariciresinol and matairesinol.
Enterolignans (enterodiol and enterolactone) can potentially reduce the risk of certain cancers and cardiovascular diseases. Enterolignans are formed by the intestinal microflora after the consumption of plant lignans. Until recently, only secoisolariciresinol and matairesinol were considered enterolignan precursors, but now several new precursors have been identified, of which lariciresinol and pinoresinol have a high degree of conversion. Quantitative data on the contents in foods of these new enterolignan precursors are not available. Thus, the aim of this study was to compile a lignan database including all four major enterolignan precursors. Liquid chromatography-tandem mass spectrometry was used to quantify lariciresinol, pinoresinol, secoisolariciresinol and matairesinol in eighty-three solid foods and twenty-six beverages commonly consumed in The Netherlands. The richest source of lignans was flaxseed (301,129 microg/100 g), which contained mainly secoisolariciresinol. Also, lignan concentrations in sesame seeds (29,331 microg/100 g, mainly pinoresinol and lariciresinol) were relatively high. For grain products, which are known to be important sources of lignan, lignan concentrations ranged from 7 to 764 microg/100 g. However, many vegetables and fruits had similar concentrations, because of the contribution of lariciresinol and pinoresinol. Brassica vegetables contained unexpectedly high levels of lignans (185-2321 microg/100 g), mainly pinoresinol and lariciresinol. Lignan levels in beverages varied from 0 (cola) to 91 microg/100 ml (red wine). Only four of the 109 foods did not contain a measurable amount of lignans, and in most cases the amount of lariciresinol and pinoresinol was larger than that of secoisolariciresinol and matairesinol. Thus, available databases largely underestimate the amount of enterolignan precursors in foods.
MED-2884
A 12-wk egg intervention increases serum zeaxanthin and macular pigment optical density in women.
Two carotenoids found in egg yolk, lutein and zeaxanthin, accumulate in the macular retina where they may reduce photostress. Increases in serum lutein and zeaxanthin were observed in previous egg interventions, but no study measured macular carotenoids. The objective of this project was to determine whether increased consumption of eggs would increase retinal lutein and zeaxanthin, or macular pigment. Twenty-four females, between 24 and 59 y, were assigned to a pill treatment (PILL) or 1 of 2 egg treatments for 12 wk. Individuals in the PILL treatment consumed 1 sugar-filled capsule/d. Individuals in the egg treatments consumed 6 eggs/wk, containing either 331 microg (EGG 1) or 964 microg (EGG 2) of lutein and zeaxanthin/yolk. Serum cholesterol, serum carotenoids, and macular pigment OD (MPOD) were measured at baseline and after 4, 8, and 12 wk of intervention. Serum cholesterol concentrations did not change in either egg treatment group, but total cholesterol (P = 0.04) and triglycerides (P = 0.02) increased in the PILL group. Serum zeaxanthin, but not serum lutein, increased in both the EGG 1 (P = 0.04) and EGG 2 (P = 0.01) groups. Likewise, MPOD increased in both the EGG 1 (P = 0.001) and EGG 2 (P = 0.049) groups. Although the aggregate concentration of carotenoid in 1 egg yolk may be modest relative to other sources, such as spinach, their bioavailability to the retina appears to be high. Increasing egg consumption to 6 eggs/wk may be an effective method to increase MPOD.
MED-4763
An obesity-associated gut microbiome with increased capacity for energy harvest.
The worldwide obesity epidemic is stimulating efforts to identify host and environmental factors that affect energy balance. Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is associated with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through metagenomic and biochemical analyses that these changes affect the metabolic potential of the mouse gut microbiota. Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait is transmissible: colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota'. These results identify the gut microbiota as an additional contributing factor to the pathophysiology of obesity.
MED-1219
Diverse Sources of C. difficile Infection Identified on Whole-Genome Sequencing
BACKGROUND It has been thought that Clostridium difficile infection is transmitted predominantly within health care settings. However, endemic spread has hampered identification of precise sources of infection and the assessment of the efficacy of interventions. METHODS From September 2007 through March 2011, we performed whole-genome sequencing on isolates obtained from all symptomatic patients with C. difficile infection identified in health care settings or in the community in Oxfordshire, United Kingdom. We compared single-nucleotide variants (SNVs) between the isolates, using C. difficile evolution rates estimated on the basis of the first and last samples obtained from each of 145 patients, with 0 to 2 SNVs expected between transmitted isolates obtained less than 124 days apart, on the basis of a 95% prediction interval. We then identified plausible epidemiologic links among genetically related cases from data on hospital admissions and community location. RESULTS Of 1250 C. difficile cases that were evaluated, 1223 (98%) were successfully sequenced. In a comparison of 957 samples obtained from April 2008 through March 2011 with those obtained from September 2007 onward, a total of 333 isolates (35%) had no more than 2 SNVs from at least 1 earlier case, and 428 isolates (45%) had more than 10 SNVs from all previous cases. Reductions in incidence over time were similar in the two groups, a finding that suggests an effect of interventions targeting the transition from exposure to disease. Of the 333 patients with no more than 2 SNVs (consistent with transmission), 126 patients (38%) had close hospital contact with another patient, and 120 patients (36%) had no hospital or community contact with another patient. Distinct subtypes of infection continued to be identified throughout the study, which suggests a considerable reservoir of C. difficile. CONCLUSIONS Over a 3-year period, 45% of C. difficile cases in Oxfordshire were genetically distinct from all previous cases. Genetically diverse sources, in addition to symptomatic patients, play a major part in C. difficile transmission. (Funded by the U.K. Clinical Research Collaboration Translational Infection Research Initiative and others.)
MED-1778
Dairy intake and semen quality among men attending a fertility clinic
Objective To examine the relationship between dairy food intake and semen parameters Design Longitudinal study Setting Men attending academic medical center fertility clinic in Boston, MA Patients 155 men Interventions None Main Outcome Measures total sperm count, sperm concentration, progressive motility, and morphology Results Low-fat dairy intake was positively related to sperm concentration and progressive motility. On average, men in the highest quartile of intake (1.22–3.54 servings/day) had 33% (95% confidence interval (CI) 1, 55) higher sperm concentration and 9.3 (95%CI 1.4, 17.2) percentage units higher sperm motility than men in the lowest quartile of intake (≤0.28 servings/day). These associations were primarily explained by intake of low-fat milk. The corresponding results for low-fat milk were 30% (95%CI 1,51) higher sperm concentration and 8.7 (95%CI 3.0, 14.4) percentage units higher sperm motility. Cheese intake was associated with lower sperm concentration among ever smokers. In this group, men in the highest tertile of intake (0.82–2.43 servings/day) had 53.2% (95%CI 9.7, 75.7) lower sperm concentration than men in the lowest tertile of cheese intake (<0.43 servings/day). Conclusions Our findings suggest that low-fat dairy intake, particularly low-fat milk, is related to higher sperm concentration and progressive motility, while cheese intake to lower sperm concentration among past or current smokers.
MED-4680
Diet throughout childhood and age at menarche in a contemporary cohort of British girls.
OBJECTIVE: To investigate associations between dietary intakes throughout childhood and age at menarche, a possible indicator of future risk of disease, in a contemporary cohort of British girls. DESIGN: Diet was assessed by FFQ at 3 and 7 years of age, and by a 3 d unweighed food diary at 10 years. Age at menarche was categorised as before or after 12 years 8 months, a point close to the median age in this cohort. SETTING: Bristol, South-West England. SUBJECTS: Girls (n 3298) participating in the Avon Longitudinal Study of Parents and Children. RESULTS: Higher energy intakes at 10 years were positively associated with the early occurrence of menarche, but this association was removed on adjusting for body size. Total and animal protein intakes at 3 and 7 years were positively associated with age at menarche ≤12 years 8 months (adjusted OR for a 1 sd increase in protein at 7 years: 1·14 (95 % CI 1·04, 1·26)). Higher PUFA intakes at 3 and 7 years were also positively associated with early occurrence of menarche. Meat intake at 3 and 7 years was strongly positively associated with reaching menarche by 12 years 8 months (OR for menarche in the highest v. lowest category of meat consumption at 7 years: 1·75 (95 % CI 1·25, 2·44)). CONCLUSIONS: These data suggest that higher intakes of protein and meat in early to mid-childhood may lead to earlier menarche. This may have implications for the lifetime risk of breast cancer and osteoporosis.
MED-1515
Postprandial lipaemia: effects of sitting, standing and walking in healthy normolipidaemic humans.
Long periods of sedentary behaviour may adversely affect health irrespective of overall physical activity levels. This study compared the effects of sitting, standing and walking on postprandial lipaemia in healthy normolipidaemic Japanese men. 15 participants, aged 26.8±2.0 years (mean±SD), completed 3, 2-day trials in a random order: 1) sitting (control), 2) standing, and 3) walking. On day 1 of the sitting trial, participants rested. On day 1 of the standing trial, participants stood for six, 45-min periods. On day 1 of the walking trial, participants walked briskly for 30 min at approximately 60% of maximum heart rate. On day 2 of each trial, participants rested and consumed test meals for breakfast and lunch. Venous blood samples were collected in the morning and afternoon on day 1, and in the fasted state (0 h) and at 2, 4 and 6 h postprandially on day 2. On day 2 area under the serum triacylglycerol concentration vs. time curve was 18% lower on the walking trial than the sitting and standing trials (1-factor ANOVA, P=0.015). Hence postprandial lipaemia was not reduced after standing but was reduced after low-volume walking compared with sitting in healthy normolipidaemic Japanese men. © Georg Thieme Verlag KG Stuttgart · New York.
MED-2599
Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through reactive oxygen species-mediated upre...
Curcumin exhibits anti-inflammatory and antitumor activities. Although its functional mechanism has not been elucidated so far, numerous studies have shown that curcumin induces apoptosis in cancer cells. In the present study, we show that subtoxic concentrations of curcumin sensitize human renal cancer cells to the tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis. This apoptosis induced by the combination of curcumin and TRAIL is not interrupted by Bcl-2 overexpression. We found that treatment with curcumin significantly induces death receptor 5 (DR5) expression both at its mRNA and protein levels, accompanying the generation of the reactive oxygen species (ROS). Not only the pretreatment with N-acetylcystine but also the ectopic expression of peroxiredoxin II, an antioxidative protein, dramatically inhibited the apoptosis induced by curcumin and TRAIL in combination, blocking the curcumin-mediated DR5 upregulation. Taken together, the present study demonstrates that curcumin enhances TRAIL-induced apoptosis by ROS-mediated DR5 upregulation.
MED-4884
An investigation of the structural aspects of the tomato fruit by means of quantitative nuclear magnetic resonance imaging.
In this study, magnetic resonance imaging (MRI) was applied to study the structural aspects of the tomato fruit. The main study was performed on tomatoes (cv. Tradiro) using a 0.2-T electromagnet scanner. Spin-echo images were acquired to visualize the tomato macrostructure. The air bubble content in tissues was evaluated by exploiting susceptibility effects using multiple gradient echo images. The microstructure was further studied by measuring spin-spin (T(2)) and spin-lattice (T(1)) relaxation time distributions. Nuclear magnetic resonance relaxometry, macro vision imaging and chemical analysis were used as complementary and independent experimental methods in order to emphasize the MRI results. MRI images showed that the air bubble content varied between tissues. The presence of gas was attested by macro vision images. Quantitative imaging showed that T(2) and T(1) maps obtained by MRI reflected the structural differences between tomato tissues and made it possible to distinguish between them. The results indicated that cell size and chemical composition contribute to the relaxation mechanism.
MED-874
Vanillin enhances TRAIL-induced apoptosis in cancer cells through inhibition of NF-kappaB activation.
BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent which selectively kills cancer cells with little effect on normal cells. However, TRAIL resistance is widely found in cancer cells. We have previously reported antimetatstatic and antiangiogenic effects of vanillin, a flavoring agent from vanilla. Here we have evaluated the sensitizing effect of vanillin on a TRAIL-resistant human cervical cancer cell line, HeLa. MATERIALS AND METHODS: Cell viability after treatments was determined by the WST-1 cell counting kit. Apoptosis was demonstrated by detection of caspase-3 activation and cleavage of poly (ADP-ribose) polymerase using immunoblot analysis. Effect of treatments on TRAIL signaling pathway and nuclear factor kappaB (FN-kappaB) activation was studied using immunoblot analysis and luciferase reporter assay. RESULTS: Pretreatment of HeLa cells with vanillin enhanced TRAIL-induced cell death through the apoptosis pathway. Vanillin pretreatment inhibited TRAIL-induced phosphorylation of p65 and transcriptional activity of NF-kappaB. CONCLUSION: Vanillin sensitizes HeLa cells to TRAIL-induced apoptosis by inhibiting NF-kappaB activation.
MED-5278
Brachial artery ultrasound: a noninvasive tool in the assessment of triglyceride-rich lipoproteins.
In recent years, endothelial dysfunction has been identified as an early feature of atherosclerosis. Endothelial function can be measured noninvasively by using brachial artery ultrasound. A variety of factors associated with atherosclerosis also impair endothelial function. Some of these factors are lipoproteins such as various forms of low-density lipoproteins, postprandial chylomicron remnants, fasting triglyceride-rich particles, and free fatty acids. A high-fat diet also has an adverse effect on endothelial function. Several interventions can improve endothelial function and, at the same time, reduce cardiovascular events. Measuring endothelial function may eventually serve as a useful index to determine an individual's risk for coronary artery disease.
MED-5370
Long chain omega-3 fatty acids intake, fish consumption and mental disorders in the SUN cohort study.
BACKGROUND: Very long chain omega-3 fatty acids (w-3 PUFA) intake and fish consumption have been suggested as protective factors against neuropsychiatric disorders but there is scarcity of large cohort studies assessing this association. AIM OF THE STUDY: To assess the association between w-3-PUFA intake and fish consumption and mental disorders. METHODS: A prospective cohort study was performed in 7,903 participants. W-3 PUFA intake and fish consumption were ascertained through a validated semi-quantitative food frequency questionnaire. The outcomes after 2 years of follow-up were: (1) Incident mental disorder (depression, anxiety, or stress), (2) incident depression, and (3) incident anxiety. Logistic regression models and generalized additive models were fit to assess the relationship between w-3 PUFA intake or fish consumption and the incidence of these outcomes. Odds ratios (OR) and their 95% confidence intervals (CI) were calculated. RESULTS: 173 cases of depression, 335 cases of anxiety, and 4 cases of stress were observed during 2-year follow-up. ORs (95% CI) of mental disorder for successive quintiles of energy-adjusted w-3 PUFA intake were 1 (reference), 0.72 (0.52-0.99), 0.79 (0.58-1.08), 0.65 (0.47-0.90), and 1.04 (0.78-1.40). Subjects with a moderate consumption of fish (third and fourth quintiles of consumption: median of each quintile 83.3 and 112 g/day, respectively) had a relative risk reduction higher than 30%. CONCLUSIONS: A potential benefit of w-3 PUFA intake on total mental disorders is suggested, although no linear trend was apparent.
MED-3384
Trends of outpatient prescription drug utilization in US children, 2002-2010.
OBJECTIVE: To describe trends in outpatient prescription drug utilization in US children and the changes in major areas of pediatric therapeutic use for the years 2002 through 2010. METHODS: Large prescription databases (the IMS Vector One: National and Total Patient Tracker) were used to examine national drug utilization patterns for the US pediatric population (ages 0-17 years) from 2002 through 2010. RESULTS: In 2010, a total of 263.6 million prescriptions were dispensed to the US pediatric population, 7% lower than in 2002, while prescriptions dispensed to the adult population increased 22% during the same time. Analysis of pediatric drug utilization trends for the top 12 therapeutic areas in 2010 compared with 2002 showed decreases in systemic antibiotics (-14%), allergies (-61%), pain (-14%), depression (-5%), and cough/cold without expectorant (-42%) prescriptions, whereas asthma (14%), attention-deficit/hyperactivity disorder (46%), and contraceptive (93%) prescriptions increased. In 2010, amoxicillin was the most frequently dispensed prescription in infants (aged 0-23 months) and children (aged 2-11 years). Methylphenidate was the top prescription dispensed to adolescents (aged 12-17 years). Off-label use was identified, particularly for lansoprazole; ~358,000 prescriptions were dispensed in 2010 for infants <1 year old. CONCLUSIONS: Changes in the patterns of pediatric drug utilization were observed from 2002 to 2010. Changes include a decrease in antibiotic use and an increase in attention-deficit/hyperactivity disorder medication use during the examined time. This article provides an overview of pediatric outpatient drug utilization, which could set the stage for further in-depth analyses.
MED-5043
Hibiscus sabdariffa L. extracts inhibit the mutagenicity in microsuspension assay and the proliferation of HeLa cells.
Hibiscus sabdariffa L. is used as a refreshing beverage and as a traditional medicine. The objective of this study was to determine the in vitro effect of phenolic compounds present in aqueous, ethyl acetate, and chloroform extracts of H. sabdariffa against mutagenicity of 1-nitropyrene (1-NP), and also the antiproliferative effect of these extracts. Inhibition of cell proliferation and DNA fragmentation were tested on transformed human HeLa cells. The hot aqueous extract (HAE) contained 22.27 +/- 2.52 mg of protocatechuic acid (PCA) per gram of lyophilized dried extract, and was not statistically different from the cold aqueous or chloroform extracts; the ethyl acetate extract produced the least amount of PCA. The H. sabdariffa extracts inhibited mutagenicity of 1-NP in a dose-response manner. The inhibition rate on HeLa cells of HAE was also dose-dependent. The HAE did not induce DNA fragmentation. The results suggest that H. sabdariffa L. extracts have antimutagenic activity against 1-NP and decrease the proliferation of HeLa cells, probably due to phenolic acid composition.
MED-1671
Postprandial glucose, insulin, and free fatty acid responses to sucrose consumed with blackcurrants and lingonberries in healthy women.
BACKGROUND: Sucrose induces high postprandial glucose and insulin responses. In vitro studies suggest that berries may reduce the digestion and absorption of sucrose and thereby suppress postprandial glycemia, but the evidence in humans is limited. OBJECTIVE: We investigated the effects of sucrose ingested with blackcurrants (Ribes nigrum) and lingonberries (Vaccinium vitis-idaea) on postprandial glucose, insulin, and free fatty acid responses. DESIGN: Twenty healthy women participated in a randomized, controlled, crossover meal study. They consumed whole blackcurrants or lingonberries (150 g served as purées) or blackcurrant or lingonberry nectars (300 mL), each with 35 g added sucrose. Sucrose alone (35 g in 300 mL water) was used as a reference. Blood samples were collected at 0, 15, 30, 45, 60, 90, and 120 min. RESULTS: In comparison with sucrose alone, ingestion of sucrose with whole berries resulted in reduced glucose and insulin concentrations during the first 30 min and a slower decline during the second hour and a significantly improved glycemic profile. Berries prevented the sucrose-induced late postprandial hypoglycemic response and the compensatory free fatty acid rebound. Nearly similar effects were observed when sucrose was consumed with berry nectars. The improved responses were evident despite the higher content of available carbohydrate in the berry and nectar meals, because of the natural sugars present in berries. CONCLUSIONS: Blackcurrants and lingonberries, as either whole berries or nectars, optimize the postprandial metabolic responses to sucrose. The responses are consistent with delayed digestion of sucrose and consequent slower absorption of glucose.
MED-4430
Guillain-barré syndrome: modern theories of etiology.
Guillain-Barré syndrome (GBS) is a classic failure of the immune system with a life-threatening attack upon a critical self-component. The active phase of the disease is short, concordant with the latency of a primary adaptive immune response. Triggers for GBS include infection and (rarely) vaccination; cross-reactivity between infectious and neural epitopes has been well demonstrated, particularly for Campylobacter jejuni and motor axonal forms of GBS in which non-protein gangliosides are antigenic. Most people are probably exposed to a GBS trigger, but only rarely does the disease develop. We propose that GBS illustrates competing determinants of the immune system's decision about whether to mount a response, and that in unlucky affected individuals, co-presentation of cross-reactive antigens with danger signals activating pattern-recognition receptors overcomes normal self-recognition such that a primary response is initiated that attacks the nerve. Then, in most cases of GBS, the response rapidly turns off, and second attacks rarely occur. This suggests active restoration of tolerance, and specific privileged site attributes of nerve and declining danger signals as the trigger wanes may contribute to this restoration. Standard immunosuppression has not been effective in GBS. We suggest this is because immune tolerance is already being restored by the time such therapies are initiated. This in turn suggests that improvements in GBS outcomes are likely to come from better protection of the nerve cells under attack while normal resumption of tolerance is permitted to proceed rather than exploring more aggressive immunosuppressive approaches.
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-3467
Antioxidant diet supplementation enhances aerobic performance in amateur sportsmen.
The effects of antioxidant diet supplements on blood lactate concentration and on the aerobic and anaerobic thresholds and their adaptations to training were analysed. Fifteen amateur male athletes were randomly assigned to either a placebo group or an antioxidant-supplemented group (90 days supplementation with 500 mg x day(-1) of vitamin E and 30 mg x day(-1) of beta-carotene, and the last 15 days also with 1 g x day(-1) of vitamin C). Before and after the antioxidant supplements, the sportsmen performed a maximal exercise test on a cycle ergometer and maximal and submaximal physiological parameters were assessed together with blood lactate concentration. Maximal oxygen uptake (VO(2max)), maximal blood lactate concentration, and the maximal workload attained rose significantly in both groups after the 3 months of training. At the end of the study, maximal blood lactate concentration was lower in the group that took supplements than in the placebo group. The percentage of VO(2max) attained at the anaerobic threshold rose significantly in both groups after 3 months of training, although the final value in the supplemented group was higher than that in the placebo group. Antioxidant diet supplements induced lower increases in blood lactate concentration after a maximal exercise test and could improve the efficiency in which aerobic energy is obtained.
MED-3754
A survey of placebo use in a general hospital.
Two hundred thirty registered nurses and seventy physicians participated in a retrospective study scrutinizing placebo effects, prescribing patterns, and staff attitudes in a university-based general hospital setting. Despite copious experimental literature devoted to placebo effects over the past thirty years, the medical and surgical use of placebos seems to disregard experimental data. Although 80% of the staff had used placebos in the hospital, their knowledge of placebo effects was in many respects deficient. Within the hospital, 89% of placebo use was directed toward the amelioration of "pain"; the authors believe that emphasis should be placed on the education of staff to perceive emotional, social, and physiological concomitants of pain rather than resorting to a purely physicalistic approach. A need to acknowledge staff conflicts over the ethical use of placebos should be a significant part of this educational approach.
MED-2179
Cooking frequency may enhance survival in Taiwanese elderly.
OBJECTIVE: To investigate the association between cooking behaviour and long-term survival among elderly Taiwanese. DESIGN: Cohort study. The duration of follow-up was the interval between the date of interview and the date of death or 31 December 2008, when censored for survivors. Information used included demographics, socio-economic status, health behaviours, cooking frequencies, physical function, cognitive function, nutrition knowledge awareness, eating out habits and food and nutrient intakes. These data were linked to death records. Cox proportional-hazards models were used to evaluate cooking frequency on death from 1999 to 2008 with related covariate adjustments. SETTING: Elderly Nutrition and Health Survey in Taiwan, 1999-2000. SUBJECTS: Nationally representative free-living elderly people aged ≥65 years (n 1888). RESULTS: During a 10-year follow-up, 695 participants died. Those who cooked most frequently were younger, women, unmarried, less educated, non-drinkers of alcohol, non-smokers, without chewing difficulty, had spouse as dinner companion, normal cognition, who walked or shopped more than twice weekly, who ate less meat and more vegetables. Highly frequent cooking (>5 times/week, compared with never) predicted survival (hazard ratio (HR) = 0·47; 95 % CI, 0·36, 0·61); with adjustment for physical function, cognitive function, nutrition knowledge awareness and other covariates, HR was 0·59 (95 % CI, 0·41, 0·86). Women benefited more from cooking more frequently than did men, with decreased HR, 51 % v. 24 %, when most was compared with least. A 2-year delay in the assessment of survivorship led to similar findings. CONCLUSIONS: Cooking behaviour favourably predicts survivorship. Highly frequent cooking may favour women more than men.
MED-3197
Beef in an Optimal Lean Diet study: effects on lipids, lipoproteins, and apolipoproteins
Background: A Step I diet with lean beef compared with lean white meat both decrease LDL cholesterol. To our knowledge, no studies have evaluated a low–saturated fatty acid (SFA) (<7% calories) diet that contains lean beef. Objective: We studied the effect on LDL cholesterol of cholesterol-lowering diets with varying amounts of lean beef [ie, Dietary Approaches to Stop Hypertension (DASH): 28 g beef/d; Beef in an Optimal Lean Diet (BOLD): 113 g beef/d; and Beef in an Optimal Lean Diet plus additional protein (BOLD+): 153 g beef/d] compared with that of a healthy American diet (HAD). Design: Thirty-six hypercholesterolemic participants (with LDL-cholesterol concentrations >2.8 mmol/L) were randomly assigned to consume each of the 4 diets (HAD: 33% total fat, 12% SFA, 17% protein, and 20 g beef/d), DASH (27% total fat, 6% SFA, 18% protein, and 28 g beef/d), BOLD (28% total fat, 6% SFA, 19% protein, and 113 g beef/d), and BOLD+ (28% total fat, 6% SFA, 27% protein, and 153 g beef/d) for 5 wk. Results: There was a decrease in total cholesterol (TC) and LDL-cholesterol concentrations (P < 0.05) after consumption of the DASH (−0.49 ± 0.11 and −0.37 ± 0.09 mmol/L, respectively), BOLD (−0.48 ± 0.10 and −0.35 ± 0.9 mmol/L, respectively), and BOLD+ (−0.50 ± 0.10 and −0.345 ± 0.09 mmol/L, respectively) diets compared with after consumption of the HAD (−0.22 ± 0.10 and −0.14 ± 0.10 mmol/L, respectively). Apolipoprotein A-I, C-III, and C-III bound to apolipoprotein A1 particles decreased after BOLD and BOLD+ diets compared with after the HAD, and there was a greater decrease in apolipoprotein B after consumption of the BOLD+ diet than after consumption of the HAD (P < 0.05 for both). LDL cholesterol and TC decreased after consumption of the DASH, BOLD, and BOLD+ diets when the baseline C-reactive protein (CRP) concentration was <1 mg/L; LDL cholesterol and TC decreased when baseline CRP concentration was >1 mg/L with the BOLD and BOLD+ diets. Conclusions: Low-SFA, heart-healthy dietary patterns that contain lean beef elicit favorable effects on cardiovascular disease (CVD) lipid and lipoprotein risk factors that are comparable to those elicited by a DASH dietary pattern. These results, in conjunction with the beneficial effects on apolipoprotein CVD risk factors after consumption of the BOLD and BOLD+ diets, which were greater with the BOLD+ diet, provide support for including lean beef in a heart-healthy dietary pattern. This trial was registered at clinicaltrials.gov as NCT00937898.
MED-2652
Xeno-estrogenic compounds in precipitation.
The exposure to some chemicals can lead to hormone disrupting effects. Presently, much attention is focused on so-called xeno-estrogens, synthetic compounds that interact with hormone receptors causing a number of reactions that eventually lead to effects related to reproduction and development. The current study was initiated to investigate the presence of a number of such compounds in precipitation as a follow-up on a previous study in which pesticide concentrations in air and precipitation were determined. Rainwater samples were collected at about 50 locations in The Netherlands in a four week period. The samples were analysed for bisphenol-A, alkylphenols and alkylphenol ethoxylates, phthalates, flame retardants and synthetic musk compounds. The results clearly indicated the presence of these compounds in precipitation. The concentrations ranged from the low ng l(-1) range for flame retardants to several thousands of ng l(-1) for the phthalates. Bisphenol-A was found in 30% of the samples in concentrations up to 130 ng l(-1), while alkylphenols and alkylphenol ethoxylates were found in virtually all locations in concentrations up to 920 ng l(-1) for the individual compounds. Phthalates were by far the most abundant xeno-estrogens in the precipitation samples and were found in every sample. Di-isodecyl phthalate was found in a surprisingly high concentration of almost 100 000 ng l(-1). Polybrominated flame retardants were found in the low ng l(-1) range and generally in less than 20% of the samples. Noticeable was the finding of hexabromocyclododecane, a replacement for the polybrominted diphenyl ethers at one location in a concentration of almost 2000 ng l(-1). Finally, as expected, synthetic musk compounds were detected in almost all samples. This is especially true for the polycyclic musks HHCB and AHTN. Nitro musks were found, but only on a few locations. Kriging techniques were used to calculate precipitation concentrations in between actual sampling locations to produce contour plots for a number of compounds. These plots clearly show located emission sources for a number of compounds such as bisphenol-A, nonylphenol ethoxylate, phthalates and AHTN. On the contrary, the results for HHCB and some phthalates indicated diffuse emission patterns, probably as the result of the use of consumer products containing these compounds.
MED-2519
Caloric restriction in humans: potential pitfalls and health concerns.
To date, the only intervention that has consistently been shown to slow the rate of aging, and to increase mean and maximum lifespan in short-lived species, is life-long calorie restriction. It is yet unclear whether long-term calorie restriction in longer lived species (i.e. primates and humans) will have a similar effect. In humans, several studies investigating short-term calorie restriction or "weight loss" programs suggest beneficial outcomes on parameters of cardiovascular disease. Studies on long-term calorie restriction are performed on a self-selected group of human subjects and show similar effects. However, few studies are currently investigating the quality of life and potential pitfalls of long-term calorie restriction in humans. It is likely that some of the physiological and psychological effects of caloric restriction that occur in animals may impact the human life very differently. For certain, calorie restriction has a plethora of health benefits in mammals, such as a reduction in age-related diseases such as cancer. However, despite the "magic" of CR, this intervention in humans may present itself with a number of health concerns, which may not be applicable to or impact the life of experimental animals, but may do so in humans. These potential pitfalls and "side effects" are not clearly addressed in the literature and will be a focus of this review.
MED-4055
Diallyl sulfide inhibits PhIP-induced DNA strand breaks in normal human breast epithelial cells.
Heterocyclic amines (HCAs) are formed when meat products such as beef, chicken, pork and fish are cooked at high temperatures. The most abundant HCA found in the human diet is 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP). PhIP causes mammary carcinomas in female rats and mice, and is associated with an increased risk of developing colon, breast, and prostate cancer in humans. PhIP is metabolized by cytochrome P-450s producing N-OH-PhIP. The N-OH-PhIP can be esterified by phase II enzymes forming an arylnitrenium ion that binds to DNA causing adducts. Furthermore, N-OH-PhIP may be reduced by cytochrome b5 reductase producing superoxide anions and hydroxyl radicals causing DNA strand breaks. Diallyl sulfide (DAS) has been shown to prevent cancer in several animal models, presumably by metabolic modulation. We hypothesize that PhIP produces reactive oxygen species causing DNA strand breaks and that DAS will inhibit the formation of PhIP induced DNA strand breaks. To test this hypothesis we treated normal breast epithelial (MCF-10A) cells with PhIP, DAS and a combination of PhIP and DAS. The detection of lipid peroxides was used as a surrogate for ROS. Lipid peroxides were detected using a PeroxiDetect kit (Sigma). PhIP increased the production of lipid peroxides and DAS decreased the PhIP-induced peroxidation by 47%. To determine if PhIP causes DNA strand breaks in MCF-10A cells, cells were treated for 3, 6, 9, and 24 h with PhIP (100 microM), DAS (100 microM) and a combination of PhIP (100 microM) and DAS (100 microM). DNA strand breaks were evaluated using the Comet assay. PhIP produced DNA strand breaks in a dose- and time-dependent fashion. We have shown that DAS inhibits PhIP-induced DNA strand breaks by inhibiting the production of reactive oxygen species. Therefore, we propose that DAS can prevent PhIP-induced breast cancer.
MED-4593
Detection and quantification of methicillin-resistant Staphylococcus aureus (MRSA) clones in retail meat products.
AIMS: The objective of the study was to determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) contamination of retail meat and to determine the level of contamination. METHODS AND RESULTS: Pork (pork chops and ground pork), ground beef and chicken (legs, wings and thighs) were purchased at retail outlets in four Canadian provinces and tested for the presence of methicillin-resistant Staph. aureus using qualitative and quantitative methods. MRSA was isolated from 9.6% of pork, 5.6% of beef and 1.2% of chicken samples (P = 0.0002). Low levels of MRSA were typically present, with 37% below the detection threshold for quantification and <100 CFU g(-1) present in most quantifiable samples. All isolates were classified as Canadian epidemic MRSA-2 (CMRSA-2) by pulsed field gel electrophoresis (PFGE), with two different PFGE subtypes, and were spa type 24/t242. CONCLUSIONS: MRSA contamination of retail meat is not uncommon. While CMRSA-2, a human epidemic clone, has been found in pigs in Canada, the lack of isolation of livestock-associated ST398 was surprising. SIGNIFICANCE AND IMPACT OF THE STUDY: The relevance of MRSA contamination of meat is unclear but investigation is required because of the potential for exposure from food handling. Sources of contamination require investigation because these results suggest that human or animal sources could be involved.
MED-861
Associations of whole-blood fatty acids and dietary intakes with prostate cancer in Jamaica.
OBJECTIVE: To investigate the association of whole-blood fatty acids and reported intakes of fats with risk of prostate cancer (PCa). DESIGN: Case-control study of 209 men 40-80 years old with newly diagnosed, histologically confirmed prostate cancer and 226 cancer-free men attending the same urology clinics. Whole-blood fatty acid composition (mol%) was measured by gas chromatography and diet assessed by food frequency questionnaire. RESULTS: High whole-blood oleic acid composition (tertile 3 vs. tertile 1: OR, 0.37; CI, 0.14-0.0.98) and moderate palmitic acid proportions (tertile 2: OR, 0.29; CI, 0.12-0.70) (tertile 3: OR, 0.53; CI, 0.19-1.54) were inversely related to risk of PCa, whereas men with high linolenic acid proportions were at increased likelihood of PCa (tertile 3 vs. tertile 1: OR, 2.06; 1.29-3.27). Blood myristic, stearic and palmitoleic acids were not associated with PCa. Higher intakes of dietary MUFA were inversely related to prostate cancer (tertile 3 vs. tertile 1: OR, 0.39; CI 0.16-0.92). The principal source of dietary MUFA was avocado intake. Dietary intakes of other fats were not associated with PCa. CONCLUSIONS: Whole-blood and dietary MUFA reduced the risk of prostate cancer. The association may be related to avocado intakes. High blood linolenic acid was directly related to prostate cancer. These associations warrant further investigation.
MED-5324
Effects of a high-fat meal on pulmonary function in healthy subjects.
Obesity has important health consequences, including elevating risk for heart disease, diabetes, and cancer. A high-fat diet is known to contribute to obesity. Little is known regarding the effect of a high-fat diet on pulmonary function, despite the dramatic increase in the prevalence of respiratory ailments (e.g., asthma). The purpose of our study was to determine whether a high-fat meal (HFM) would increase airway inflammation and decrease pulmonary function in healthy subjects. Pulmonary function tests (PFT) (forced expiratory volume in 1-s, forced vital capacity, forced expiratory flow at 25-75% of vital capacity) and exhaled nitric oxide (eNO; airway inflammation) were performed in 20 healthy (10 men, 10 women), inactive subjects (age 21.9 +/- 0.4 years) pre and 2 h post HFM (1 g fat/1 kg body weight; 74.2 +/- 4.1 g fat). Total cholesterol, triglycerides, and C-reactive protein (CRP; systemic inflammation) were determined via a venous blood sample pre and post HFM. Body composition was measured via dual energy X-ray absorptiometry. The HFM significantly increased total cholesterol by 4 +/- 1%, and triglycerides by 93 +/- 3%. ENO also increased (p < 0.05) due to the HFM by 19 +/- 1% (pre 17.2 +/- 1.6; post 20.6 +/- 1.7 ppb). ENO and triglycerides were significantly related at baseline and post-HFM (r = 0.82, 0.72 respectively). Despite the increased eNO, PFT or CRP did not change (p > 0.05) with the HFM. These results demonstrate that a HFM, which leads to significant increases in total cholesterol, and especially triglycerides, increases exhaled NO. This suggests that a high-fat diet may contribute to chronic inflammatory diseases of the airway and lung.
MED-4925
MULTIVITAMIN USE AND RISK OF CANCER AND CARDIOVASCULAR DISEASE IN THE WOMEN’S HEALTH INITIATIVE COHORTS
Context Millions of postmenopausal women use multivitamins, often believing that supplements prevent chronic diseases such as cancer and cardiovascular disease. Objective To examine associations between multivitamin use and risk of cancer, cardiovascular disease and mortality in postmenopausal women. Design, Setting and Participants 161,808 participants from the Women’s Health Initiative Clinical Trials (n=68,132 in three overlapping trials of hormone therapy, dietary modification and calcium-vitamin D) or Observational Study (n=93,676). Detailed data were collected on multivitamin use at baseline and follow-up time points. Study enrollment occurred between 1993–1998; women were followed for a median of 8.0 years in the clinical trials and 7.9 years in the observational study. Disease endpoints were collected through 2005. Outcome Measures Cancers of the breast (invasive), colon/rectum, endometrium, kidney, bladder, stomach, ovary and lung; cardiovascular disease (myocardial infarction, stroke, venous thrombosis); and total mortality. Results 41.5% of participants used multivitamins. After a median of 8.0 years of follow-up in the CT and 7.9 years in the OS, 9,619 cases of breast, colorectal, endometrium, kidney, bladder, stomach lung or ovary cancer; 8,751 CVD events and 9,865 deaths were reported. Multivariate-adjusted analyses revealed no association of multivitamins with risk of cancer (breast HR=0.98, 95%CI 0.91–1.05; colorectal HR = 0.99, 95% CI 0.88–1.11; endometrial HR = 1.05, 95%CI= 0.90–1.21; lung HR = 1.0, 95% CI=0.88–1.13; ovary HR = 1.07, 95%CI =0.88–1.29); CVD (MI HR= 0.96, 95%CI= 0.89–1.03; stroke HR = 0.99, 95%CI =0.91–1.07; VT HR = 1.05, 95%CI =0.85–1.29); or mortality (HR = 1.02, 95% CI=0.97–1.07). Conclusion After a median follow-up of 8.0 and 7.9 years in the CT and OS, respectively, the WHI cohorts provide convincing evidence that multivitamin use has little or no influence on the risk of common cancers, cardiovascular disease or total mortality in postmenopausal women. Clinical Trial Registration clinicaltrials.gov identifier: NCT00000611
MED-3060
The Neural Correlates of “Food Addiction”
Context Research has implicated an addictive process in the development and maintenance of obesity. Although parallels in neural functioning between obesity and substance dependence have been found, no studies have examined the neural correlates of addictive-like eating behavior. Objective To test the hypothesis that elevated “food addiction” scores are associated with similar patterns of neural activation as substance dependence. Design Between-Subjects fMRI study. Participants Forty-eight healthy adolescent females ranging from lean to obese recruited for a healthy weight maintenance trial. Main Outcome Measure The relation between elevated “food addiction” scores and blood oxygen level-dependent fMRI activation in response to receipt and anticipated receipt of palatable food (chocolate milkshake). Results Food addiction scores (N = 39) correlated with greater activation in the anterior cingulate cortex (ACC), medial orbitofrontal cortex (OFC), and amygdala in response to anticipated receipt of food (P <0.05, false-discovery rate (FDR) corrected for multiple comparisons in small volumes). Participants with higher (n=15) versus lower (n=11) food addiction scores showed greater activation in the dorsolateral prefrontal cortex (DLPFC) and the caudate in response to anticipated receipt of food, but less activation in the lateral OFC in response to receipt of food (pFDR <0.05). Conclusions Similar patterns of neural activation are implicated in addictive-like eating behavior and substance dependence; elevated activation in reward circuitry in response to food cues and reduced activation of inhibitory regions in response to food intake.
MED-2073
Antiproliferative effects of fresh and thermal processed green and red cultivars of curly kale (Brassica oleracea L. convar. acephala var. sabellica).
Brassica vegetables contain a diverse range of phytochemicals with biological properties such as antioxidant and anticancer activity. However, knowledge about how biological activities are affected by processing is lacking. A green cultivar and a red cultivar of curly kale were evaluated for water/methanol-soluble phytochemicals before and after processing involving blanching, freeze storage, and boil-in-bag heat treatment. In both kale cultivars, processing resulted in a significant decrease of total phenolics, antioxidant capacity, and content and distribution of flavonols, anthocyanins, hydroxycinnamic acids, glucosinolates, and vitamin C. Interestingly, the red curly kale cultivar had a higher capacity to withstand thermal loss of phytochemicals. The extracts of both green and red curly kale inhibited the cell proliferation of three human colon cancer cell lines (Caco-2, HT-29, and HCT 116). However, extracts from fresh plant material had a significantly stronger antiproliferative effect than extracts from processed plant material.
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-4919
Long-term health and quality-of-life consequences of mass screening for childhood celiac disease: a 10-year follow-up study.
OBJECTIVE: Mass screening for celiac disease is controversial. The objective of this study was to determine whether detection of childhood celiac disease by mass screening improves long-term health status and health-related quality of life. METHODS: We conducted a prospective 10-year follow-up study of 32 children who were aged 2 to 4 years, had celiac disease identified by mass screening, and had a gluten-free diet (19) or a normal gluten-containing diet (13). The follow-up included assessments of general health status, celiac disease-associated symptoms, celiac disease-associated serum antibodies, and health-related quality of life. RESULTS: Ten years after mass screening, 81% of the children were adhering to a gluten-free diet. The health status improved in 66% of the treated children: in 41% by early treatment and in 25% by prevention of the gluten-dependent symptoms that they developed after diagnosis. For 19% of the children, treatment after screening would not have improved their health status, because they had no symptoms at screening and have remained symptom-free while consuming gluten. The health-related quality of life of the children with symptoms improved significantly after 1 year of gluten-free diet. Ten years after screening, the health-related quality of life of the children with celiac disease was similar to that of the reference population. CONCLUSION: Identification by mass screening led 10 years later to health improvement in 66% of children without deterioration of generic health-related quality of life. There is a good compliance after mass screening. In a research setting, delaying treatment for children without symptoms seems to be an option after a positive screening test. Long-term follow-up studies are needed to assess possible long-term complications in untreated, nonsymptomatic celiac disease.
MED-2427
Elevated Levels of Cholesterol-Rich Lipid Rafts in Cancer Cells Are Correlated with Apoptosis Sensitivity Induced by Cholesterol-Depleting Agents
Lipid rafts/caveolae are membrane platforms for signaling molecules that regulate various cellular functions, including cell survival. To better understand the role of rafts in tumor progression and therapeutics, we investigated the effect of raft disruption on cell viability and compared raft levels in human cancer cell lines versus their normal counterparts. Here, we report that cholesterol depletion using methyl-β cyclodextrin caused anoikis-like apoptosis, which in A431 cells involved decreased raft levels, Bcl-xL down-regulation, caspase-3 activation, and Akt inactivation regardless of epidermal growth factor receptor activation. Cholesterol repletion replenished rafts on the cell surface and restored Akt activation and cell viability. Moreover, the breast cancer and the prostate cancer cell lines contained more lipid rafts and were more sensitive to cholesterol depletion-induced cell death than their normal counterparts. These results indicate that cancer cells contain increased levels of rafts and suggest a potential use of raft-modulating agents as anti-cancer drugs.
MED-691
Ginger in the prevention of nausea and vomiting: a review.
Nausea and vomiting are physiological processes experienced by every human being at some stage of their life. They are complex protective mechanisms and the symptoms are influenced by the emetogenic response and stimuli. However, when these symptoms recur frequently, they can significantly reduce the quality of life and can also be detrimental to health. The existing antiemetic agents are ineffective against certain stimuli, are expensive, and possess side effects. Herbal medicines have been shown to be effective antiemetics, and among the various plants studied, the rhizome of Zingiber officinale, commonly known as ginger, has been used as a broad-spectrum antiemetic in the various traditional systems of medicine for over 2000 years. Various preclinical and clinical studies have shown ginger to possess antiemetic effects against different emetogenic stimuli. However, conflicting reports especially in the prevention of chemotherapy-induced nausea and vomiting and motion sickness prevent us from drawing any firm conclusion. The current review for the first time summarizes the results. An attempt is also made to address the lacunae in these published studies and emphasize aspects that need further investigations for it to be of use in clinics in the future.
MED-2339
Anisakis simplex allergy after eating chicken meat.
BACKGROUND: Allergic reactions to food can be produced by contaminants that induce sensitization. Among these, Anisakis simplex can cause seafood infestation, and allergic symptoms (urticaria-angioedema, anaphylaxis, and asthma) can follow the eating or handling of affected fish. Although seafood is the principal source of human infections by this parasite, we have found allergic symptoms in 8 patients previously diagnosed as having A simplex sensitization after they ate chicken meat. Chicken feed usually has a high proportion of fishmeal, which might possibly be contaminated by this nematode. OBJECTIVE: The aim of our study was to determine whether parasite proteins present in chicken meat could be responsible for the symptoms reported by these subjects. METHODS: We carried out in vivo tests (prick, bronchial challenge, and double-blind placebo-controlled challenge with meat chicken) in these 8 patients. We performed immunoblotting using the sera from the 8 patients and controls in order to detect A simplex sensitization. We also investigated the presence of A simplex proteins in sera from chickens fed with fishmeal and in other sera from chickens fed only with cereals. We excluded sensitization to other chicken nematodes by serologic methods. RESULTS: All 8 patients presented positive prick and challenges to A simplex. When we used serum from chickens fed with fishmeal as the antigen in blotting, patients 3, 4, 5, 6, 7, and 8 recognized a band of 16 kd, also obtained when using pools of fish-shellfish and A simplex larva. No detection was observed with sera from chickens fed with only cereals. CONCLUSION: We provide evidence, based on in vivo and in vitro tests, that subjects highly sensitized to A simplex can detect the presence of Anisakis species allergens in chicken meat.
MED-2679
Commercial hickory-smoke flavouring is a human lymphoblast mutagen but does not induce lung adenomas in newborn mice.
Commercial aqueous wood-smoke flavouring induced significant increases in the 6-thioguanine resistance mutation frequency of TK6 human lymphoblasts at 0.1 microliter flavouring/ml of cell suspension. This corresponds to 6 micrograms/ml of dissolved 'solids' as determined by fully drying the aqueous flavouring in a vacuum desiccator. In AHH-1 human lymphoblasts, which contain a cytochrome P-450 monooxygenase system, mutations were induced at 0.3 microliter/ml, corresponding to 18 microliters/ml of dissolved 'solids'. The flavouring did not induce 8-azaguanine resistant mutations in Salmonella typhimurium at concentrations up to 1.5 microliter/ml. At higher concentrations the flavouring was toxic to bacteria. The flavouring did not induce lung adenomas or other tumours in newborn mice when injected ip with total doses of up to 26 microliters over a 3-wk period. Toxicity to the kidney, colon and rectum was observed in some mice at 15 wk of age.
MED-928
Incorporation of EPA and DHA into plasma phospholipids in response to different omega-3 fatty acid formulations - a comparative bioavailability study of fish oil vs. krill oil
Background Bioavailability of omega-3 fatty acids (FA) depends on their chemical form. Superior bioavailability has been suggested for phospholipid (PL) bound omega-3 FA in krill oil, but identical doses of different chemical forms have not been compared. Methods In a double-blinded crossover trial, we compared the uptake of three EPA+DHA formulations derived from fish oil (re-esterified triacylglycerides [rTAG], ethyl-esters [EE]) and krill oil (mainly PL). Changes of the FA compositions in plasma PL were used as a proxy for bioavailability. Twelve healthy young men (mean age 31 y) were randomized to 1680 mg EPA+DHA given either as rTAG, EE or krill oil. FA levels in plasma PL were analyzed pre-dose and 2, 4, 6, 8, 24, 48, and 72 h after capsule ingestion. Additionally, the proportion of free EPA and DHA in the applied supplements was analyzed. Results The highest incorporation of EPA+DHA into plasma PL was provoked by krill oil (mean AUC0-72 h: 80.03 ± 34.71%*h), followed by fish oil rTAG (mean AUC0-72 h: 59.78 ± 36.75%*h) and EE (mean AUC0-72 h: 47.53 ± 38.42%*h). Due to high standard deviation values, there were no significant differences for DHA and the sum of EPA+DHA levels between the three treatments. However, a trend (p = 0.057) was observed for the differences in EPA bioavailability. Statistical pair-wise group comparison's revealed a trend (p = 0.086) between rTAG and krill oil. FA analysis of the supplements showed that the krill oil sample contained 22% of the total EPA amount as free EPA and 21% of the total DHA amount as free DHA, while the two fish oil samples did not contain any free FA. Conclusion Further studies with a larger sample size carried out over a longer period are needed to substantiate our findings and to determine differences in EPA+DHA bioavailability between three common chemical forms of LC n-3 FA (rTAG, EE and krill oil). The unexpected high content of free EPA and DHA in krill oil, which might have a significant influence on the availability of EPA+DHA from krill oil, should be investigated in more depth and taken into consideration in future trials.
MED-4698
Role of mitochondrial oxidative stress to explain the different longevity between genders: protective effect of estrogens.
Females live longer than males. Work from our laboratory has shown that this may be due to the up-regulation of longevity-associated genes by estrogens. Estrogens bind to the estrogen receptors and subsequently activate the mitogen activated protein kinase and nuclear factor kappa B signalling pathways, resulting in an up-regulation of antioxidant enzymes. Estrogen administration, however, has serious undesirable effects and of course, cannot be administered to males because of its powerful feminizing effects. Thus, we tested the effect of genistein, a phytoestrogen of high nutritional importance whose structure is similar to estradiol, on the regulation of the expression of antioxidant, longevity-related genes and consequently on oxidant levels in mammary gland tumour cells in culture. Phytoestrogens mimic the protective effect of oestradiol using the same signalling pathway. The critical importance of up-regulating antioxidant genes, by hormonal and dietary manipulations, to increase longevity is discussed.
MED-4004
Coconut oil enhances tomato carotenoid tissue accumulation compared to safflower oil in the Mongolian gerbil ( Meriones unguiculatus ).
Evidence suggests that monounsaturated and polyunsaturated fats facilitate greater absorption of carotenoids than saturated fats. However, the comparison of consuming a polyunsaturated fat source versus a saturated fat source on tomato carotenoid bioaccumulation has not been examined. The goal of this study was to determine the influence of coconut oil and safflower oil on tomato carotenoid tissue accumulation in Mongolian gerbils ( Meriones unguiculatus ) fed a 20% fat diet. Coconut oil feeding increased carotenoid concentrations among many compartments including total carotenoids in the serum (p = 0.0003), adrenal glandular phytoene (p = 0.04), hepatic phytofluene (p = 0.0001), testicular all-trans-lycopene (p = 0.01), and cis-lycopene (p = 0.006) in the prostate-seminal vesicle complex compared to safflower oil. Safflower oil-fed gerbils had greater splenic lycopene concentrations (p = 0.006) compared to coconut oil-fed gerbils. Coconut oil feeding increased serum cholesterol (p = 0.0001) and decreased hepatic cholesterol (p = 0.0003) compared to safflower oil. In summary, coconut oil enhanced tissue uptake of tomato carotenoids to a greater degree than safflower oil. These results may have been due to the large proportion of medium-chain fatty acids in coconut oil, which might have caused a shift in cholesterol flux to favor extrahepatic carotenoid tissue deposition.
MED-1002
Polybrominated diphenyl ethers (PBDEs), hydroxylated PBDEs (OH-PBDEs), and measures of thyroid function in second trimester pregnant women in California
Prenatal exposure to polybrominated diphenyl ethers (PBDEs) may disrupt thyroid function and contribute to adverse neurodevelopmental outcomes. We conducted a pilot study to explore the relationship between serum concentrations of lower-brominated PBDEs (BDE-17 to -154), higher-brominated PBDEs (BDE-183 to -209), and hydroxylated PBDE metabolites (OH-PBDEs) with measures of thyroid function in pregnant women. Concentrations of PBDEs, OH-PBDEs, thyroid-stimulating hormone (TSH), total thyroxine (T4), and free T4 were measured in serum samples collected between 2008 and 2009 from 25 second trimester pregnant women in California. Median concentrations of lower-brominated PBDEs and OH-PBDEs were the highest reported to date in pregnant women. Median concentrations of BDE-47 and the sum of lower-brominated PBDEs (ΣPBDE5) were 43.1 ng/g lipid and 85.8 ng/g lipid; and 0.084 ng/mL for the sum of OH-PBDEs (ΣOH-PBDE4). We observed a positive association between the weighted sum of chemicals known to bind to transthyretin (ΣTTR binders) and TSH levels. We also found positive associations between TSH and ΣPBDE5, ΣOH-PBDE4, BDE-47, BDE-85, 5-OH-BDE47, and 4′-OH-BDE49; and an inverse association with BDE-207. Relationships with free and total T4 were weak and inconsistent. Our results indicate that PBDE exposures are elevated in pregnant women in California, and suggest a relationship with thyroid function. Further investigation is warranted to characterize the risks of PBDE exposures during pregnancy.
MED-4753
Exposure to exogenous estrogen through intake of commercial milk produced from pregnant cows.
BACKGROUND: Modern genetically improved dairy cows continue to lactate throughout almost the entire pregnancy. Therefore, recent commercial cow's milk contains large amounts of estrogens and progesterone. With regard to the exposure of prepubertal children to exogenous estrogens, the authors are particularly concerned about commercial milk produced from pregnant cows. The purpose of the present study was therefore to examine concentrations of serum and urine sex hormones after the intake of cow milk. METHODS: Subjects were seven men, six prepubertal children, and five women. The men and children drank 600 mL/m(2) of cow milk. Urine samples were collected 1 h before the milk intake and four times every hour after intake. In men the serum samples were obtained before and 15, 30, 45, 60, 90 and 120 min after milk intake. Women drank 500 mL of cow's milk every night for 21 days beginning on the first day of the second menstruation. In three successive menstrual cycles, the day of ovulation was examined using an ovulation checker. RESULTS: After the intake of cow milk, serum estrone (E1) and progesterone concentrations significantly increased, and serum luteinizing hormone, follicle-stimulating hormone and testosterone significantly decreased in men. Urine concentrations of E1, estradiol, estriol and pregnanediol significantly increased in all adults and children. In four out of five women, ovulation occurred during the milk intake, and the timing of ovulation was similar among the three menstrual cycles. CONCLUSIONS: The present data on men and children indicate that estrogens in milk were absorbed, and gonadotropin secretion was suppressed, followed by a decrease in testosterone secretion. Sexual maturation of prepubertal children could be affected by the ordinary intake of cow milk.
MED-4828
Association between statin-associated myopathy and skeletal muscle damage
Background Many patients taking statins often complain of muscle pain and weakness. The extent to which muscle pain reflects muscle injury is unknown. Methods We obtained biopsy samples from the vastus lateralis muscle of 83 patients. Of the 44 patients with clinically diagnosed statin-associated myopathy, 29 were currently taking a statin, and 15 had discontinued statin therapy before the biopsy (minimal duration of discontinuation 3 weeks). We also included 19 patients who were taking statins and had no myopathy, and 20 patients who had never taken statins and had no myopathy. We classified the muscles as injured if 2% or more of the muscle fibres in a biopsy sample showed damage. Using reverse transcriptase polymerase chain reaction, we evaluated the expression levels of candidate genes potentially related to myocyte injury. Results Muscle injury was observed in 25 (of 44) patients with myopathy and in 1 patient without myopathy. Only 1 patient with structural injury had a circulating level of creatine phosphokinase that was elevated more than 1950 U/L (10× the upper limit of normal). Expression of ryanodine receptor 3 was significantly upregulated in patients with biopsy evidence of structural damage (1.7, standard error of the mean 0.3). Interpretation Persistent myopathy in patients taking statins reflects structural muscle damage. A lack of elevated levels of circulating creatine phosphokinase does not rule out structural muscle injury. Upregulation of the expression of ryanodine receptor 3 is suggestive of an intracellular calcium leak.
MED-4211
Dietary soy and fats in relation to serum insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 levels in premenopausal Jap...
Circulating levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) have each been associated with premenopausal breast cancer risks. We analyzed data from a cross-sectional study of 261 premenopausal Japanese women aged 20-54 yr with adequate nutritional status to evaluate the relationships between concentrations of IGF-1 and IGFBP-3 in serum and dietary intakes of soy, fats and other nutrients. Diet was assessed by a semiquantitative food frequency questionnaire. There was no significant correlation between soy product as well as soy isoflavone intake and serum IGF-1 or IGFBP-3 levels after controlling for age, total energy, percent body fat, and education level. Total fat intake was significantly inversely correlated with serum IGFBP-3 level (r = -0.13, P = 0.04). The correlations of saturated and monounsaturated fats with serum IGFBP-3 were of borderline significance (r = -0.12, P = 0.06 and r = -0.11, P = 0.07, respectively).
MED-4566
Taking vitamin D with the largest meal improves absorption and results in higher serum levels of 25-hydroxyvitamin D.
Many patients treated for vitamin D deficiency fail to achieve an adequate serum level of 25-hydroxyvitamin D [25(OH)D] despite high doses of ergo- or cholecalciferol. The objective of this study was to determine whether administration of vitamin D supplement with the largest meal of the day would improve absorption and increase serum levels of 25(OH)D. This was a prospective cohort study in an ambulatory tertiary-care referral center. Patients seen at the Cleveland Clinic Foundation Bone Clinic for the treatment of vitamin D deficiency who were not responding to treatment make up the study group. Subjects were instructed to take their usual vitamin D supplement with the largest meal of the day. The main outcome measure was the serum 259(OH)D level after 2 to 3 months. Seventeen patients were analyzed. The mean age (+/-SD) and sex (F/M) ratio were 64.5 +/- 11.0 years and 13 females and 4 males, respectively. The dose of 25(OH)D ranged from 1000 to 50,000 IU daily. The mean baseline serum 25(OH)D level (+/-SD) was 30.5 +/- 4.7 ng/mL (range 21.6 to 38.8 ng/mL). The mean serum 25(OH)D level after diet modification (+/-SD) was 47.2 +/- 10.9 ng/mL (range 34.7 to 74.0 ng/mL, p < .01). Overall, the average serum 25(OH)D level increased by 56.7% +/- 36.7%. A subgroup analysis based on the weekly dose of vitamin D was performed, and a similar trend was observed.Thus it is concluded that taking vitamin D with the largest meal improves absorption and results in about a 50% increase in serum levels of 25(OH)D levels achieved. Similar increases were observed in a wide range of vitamin D doses taken for a variety of medical conditions. Copyright 2010 American Society for Bone and Mineral Research.
MED-3001
Towards a new system of health: the challenge of Western disease.
Over the last three decades, the concept of Western disease has become well established. Medicine has approached this group of diseases by searching for new cures but has achieved relatively little success. We argue that medicine should now accept the failure of this strategy and place a major emphasis on prevention. The key objective is to change the climate of opinion so that prevention is taken seriously by the general population. The chief activity should be a wide ranging public education campaign so as to persuade people to live a healthier lifestyle. Medicine will require restructuring in order to carry out this work. Medical education needs to be reformed so that medical students receive the necessary training. This must be done as part of an integrated approach in which government, industry and medical research all play a major role. Governments should use taxation and subsidies in areas such as food and tobacco so as to shift consumption patterns towards healthier products. Governments must also tighten laws on tobacco sales and advertising, support health education, and improve food labelling. Industry must be made far more responsive to the health needs of the population. This should be done both by public education, so as to alter demand, and by government action. Medical research should change its emphasis from studying the detailed mechanisms of disease ("complex research") to studying the role of lifestyle factors ("simple research").
MED-1262
Effect of fruit restriction on glycemic control in patients with type 2 diabetes – a randomized trial
Background Medical nutrition therapy is recognized as an important treatment option in type 2 diabetes. Most guidelines recommend eating a diet with a high intake of fiber-rich food including fruit. This is based on the many positive effects of fruit on human health. However some health professionals have concerns that fruit intake has a negative impact on glycemic control and therefore recommend restricting the fruit intake. We found no studies addressing this important clinical question. The objective was to investigate whether an advice to reduce the intake of fruit to patients with type 2 diabetes affects HbA1c, bodyweight, waist circumference and fruit intake. Methods This was an open randomized controlled trial with two parallel groups. The primary outcome was a change in HbA1c during 12 weeks of intervention. Participants were randomized to one of two interventions; medical nutrition therapy + advice to consume at least two pieces of fruit a day (high-fruit) or medical nutrition therapy + advice to consume no more than two pieces of fruit a day (low-fruit). All participants had two consultations with a registered dietitian. Fruit intake was self-reported using 3-day fruit records and dietary recalls. All assessments were made by the “intention to treat” principle. Results The study population consisted of 63 men and women with newly diagnosed type 2 diabetes. All patients completed the trial. The high-fruit group increased fruit intake with 125 grams (CI 95%; 78 to 172) and the low-fruit group reduced intake with 51 grams (CI 95%; -18 to −83). HbA1c decreased in both groups with no difference between the groups (diff.: 0.19%, CI 95%; -0.23 to 0.62). Both groups reduced body weight and waist circumference, however there was no difference between the groups. Conclusions A recommendation to reduce fruit intake as part of standard medical nutrition therapy in overweight patients with newly diagnosed type 2 diabetes resulted in eating less fruit. It had however no effect on HbA1c, weight loss or waist circumference. We recommend that the intake of fruit should not be restricted in patients with type 2 diabetes. Trial registration http://www.clinicaltrials.gov; Identifier: NCT01010594.
MED-4117
Immunological enhancement of breast cancer.
Breast cancer is a complex disease. Its aetiology is multifactorial, its period of development can span decades, and its clinical course is highly variable. Evaluation of the role of the immune response in either the development or control of breast cancer is also complex. Nevertheless, there is substantial information that in this disease, the immune response is not a host defence reaction and may even serve to facilitate cancer development. This evidence comes from a variety of sources including clinical-pathological investigations in women that show a correlation between the intensity of lymphocytic infiltration into the tumour mass with poor prognosis, studies in breast cancer patients that demonstrate a similar correlation between delayed hypersensitivity reactivity or in vitro assays of immune reactivity to tumour cell membranes or non-specific antigens and poor prognosis, and analyses of cancer incidence in chronically immunosuppressed, kidney transplant recipients who develop an unexpectedly low incidence of breast cancer. The overall conclusions from these human studies are corroborated by observations in mouse mammary tumour models that also demonstrate immune enhancement of breast cell proliferation in vitro and of breast cancer development in vivo. Potential mechanisms for these effects include production, by inflammatory cell infiltrates, of direct or indirect modulators of breast cell growth, e.g. cytokines, peptide or steroid hormones, enzymes involved in steroid metabolism, as well as of antibodies to growth factors or their receptors. These immune facilitatory mechanisms must be overcome if immune-based therapies are to be applied successfully in breast cancer.
MED-921
Old wine in new bottles: vitamin D in the treatment and prevention of tuberculosis.
Tuberculosis (TB) is a major cause of mortality, responsible for 1·68 million deaths worldwide in 2009. The global prevalence of latent Mycobacterium tuberculosis infection is estimated to be 32%, and this carries a 5-20% lifetime risk of reactivation disease. The emergence of drug-resistant organisms necessitates the development of new agents to enhance the response to antimicrobial therapy for active TB. Vitamin D was used to treat TB in the pre-antibiotic era, and its active metabolite, 1,25-dihydoxyvitamin D, has long been known to enhance the immune response to mycobacteria in vitro. Vitamin D deficiency is common in patients with active TB, and several clinical trials have evaluated the role of adjunctive vitamin D supplementation in its treatment. Results of these studies are conflicting, reflecting variation between studies in baseline vitamin D status of participants, dosing regimens and outcome measures. Vitamin D deficiency is also recognised to be highly prevalent among people with latent M. tuberculosis infection in both high- and low-burden settings, and there is a wealth of observational epidemiological evidence linking vitamin D deficiency with increased risk of reactivation disease. Randomised controlled trials of vitamin D supplementation for the prevention of active TB have yet to be performed, however. The conduct of such trials is a research priority, given the safety and low cost of vitamin D supplementation, and the potentially huge public health consequences of positive results.
MED-3648
Genetic evidence supporting the fecal-perineal-urethral hypothesis in cystitis caused by Escherichia coli.
PURPOSE: The fecal-perineal-urethral hypothesis to explain the cause of urinary tract infections (UTI) by enteric bacteria has been supported by longitudinal studies using methods of serotyping and detecting urovirulence factors such as P fimbriae. However, genetic techniques to more accurately characterize Escherichia coli strains have not been exploited. MATERIALS AND METHODS: A total of 2,700 E. coli colonies isolated from the urine and rectal swabs of 9 female subjects with acute uncomplicated cystitis and from the rectal swabs of 30 healthy women were serotyped and examined for genes encoding various urovirulence factors by colony hybridization test. The clonality of the urine and fecal isolates of E. coli from the cystitis subjects was further evaluated by pulsed-field gel electrophoresis (PFGE). RESULTS: E. coli strains causing cystitis dominated the rectal flora of 7 of 9 patients. In the remaining 2 patients, similar clones comprised at least 20% of the fecal flora. Carriage of E. coli strains with a variety of urovirulence factors was quite common among healthy women. PFGE demonstrated that most of the isolates sharing the same serotypic characteristics and virulence factors in the urine and rectal swab samples from each subject were identical. CONCLUSIONS: Based upon precise genetic techniques, our results clearly support the fecal-perineal-urethral hypothesis, indicating that E. coli strains residing in the rectal flora serve as a reservoir for urinary tract infections, e.g., cystitis.
MED-2345
Anisakiasis, an underestimated infection: effect on intestinal permeability of Anisakis simplex-sensitized patients.
Anisakis simplex is a parasite that, if present in uncooked and contaminated saltwater fish, can invade the human gut. Two different clinical situations are recognized: the first, known as a gastrointestinal disease, varying from an asymptomatic episode to vomiting and diarrhea, and the second, classified as an adverse reaction to food, characterized by a wide spectrum of allergic reactions like rhinitis, conjunctivitis, or even anaphylaxis causing hypotension and/or shock. The intestinal epithelium, the major defense system against external molecules, represents an open gate for toxins and allergens if its protective function is compromised. Previous data have demonstrated a strict relationship between an altered intestinal permeability (I.P.) and worsening of the clinical manifestations in patients with adverse reactions to the food. In this article we evaluated the sensitization to A. simplex among patients who referred clinical symptoms of allergy. All subjects underwent commonly used alimentary skin prick test for food allergens, to which Ani s1, an A. simplex allergen, was added. In addition, in A. simplex-sensitized subjects, I.P. was determined upon their enrolment to the study (time 0) and after 6 months of consuming a raw fish-free diet (time 6). Five hundred and forty subjects were screened, and 170 had a positive skin prick test, 87 (51.2%) of whom were positive to Ani s1. Increased I.P. was evidenced in A. simplex-sensitized subjects with worse clinical symptoms, which receded after 6 months' elimination of raw seafood. With our data we demonstrated that the alimentary habit to eat raw fish represents a high risk for the integrity of the intestinal mucosa, and we suggest that this pathological situation may constitute an ideal, under-estimated, open gate for molecules that predispose to other, more important pathologies.
MED-4959
Public health response to puffer fish (Tetrodotoxin) poisoning from mislabeled product.
Tetrodotoxin is a neurotoxin that occurs in select species of the family Tetraodontidae (puffer fish). It causes paralysis and potentially death if ingested in sufficient quantities. In 2007, two individuals developed symptoms consistent with tetrodotoxin poisoning after ingesting home-cooked puffer fish purchased in Chicago. Both the Chicago retailer and the California supplier denied having sold or imported puffer fish but claimed the product was monkfish. However, genetic analysis and visual inspection determined that the ingested fish and others from the implicated lot retrieved from the supplier belonged to the family Tetraodontidae. Tetrodotoxin was detected at high levels in both remnants of the ingested meal and fish retrieved from the implicated lot. The investigation led to a voluntary recall of monkfish distributed by the supplier in three states and placement of the supplier on the U.S. Food and Drug Administration's Import Alert for species misbranding. This case of tetrodotoxin poisoning highlights the need for continued stringent regulation of puffer fish importation by the U.S. Food and Drug Administration, education of the public regarding the dangers of puffer fish consumption, and raising awareness among medical providers of the diagnosis and management of foodborne toxin ingestions and the need for reporting to public health agencies.
MED-3177
Neurocysticercosis: the enigmatic disease.
Neurocysticercosis (NCC) is an infection of the central nervous system (CNS) caused by the metacestode larval form of the parasite Taenia sp. Many factors can contribute to the endemic nature of cysticercosis. The inflammatory process that occurs in the tissue surrounding the parasite and/or distal from it can result from several associated mechanisms and may be disproportionate with the number of cysts. This discrepancy may lead to difficulty with the proper diagnosis in people from low endemic regions or regions that lack laboratory resources. In the CNS, the cysticerci have two basic forms, isolated cysts (Cysticercus cellulosae=CC) and racemose cysts (Cysticercus racemosus=CR), and may be meningeal, parenchymal, or ventricular or have a mixed location. The clinical manifestations are based on two fundamental syndromes that may occur in isolation or be associated: epilepsy and intracranial hypertension. They may be asymptomatic, symptomatic or fatal; have an acute, sub-acute or chronic picture; or may be in remission or exacerbated. The cerebrospinal fluid (CSF) may be normal, even in patients with viable cysticerci, until the patients begin to exhibit the classical syndrome of NCC in the CSF, or show changes in one or more routine analysed parameters. Computed tomography (CT) and magnetic resonance imaging (MRI) have allowed non-invasive diagnoses, but can lead to false negatives. Treatment is a highly controversial issue and is characterised by individualised therapy sessions. Two drugs are commonly used, praziquantel (PZQ) and albendazole (ABZ). The choice of anti-inflammatory drugs includes steroids and dextrochlorpheniramine (DCP). Hydrocephalus is a common secondary effect of NCC. Surgical cases of hydrocephalus must be submitted to ventricle-peritoneal shunt (VPS) immediately before cysticidal treatment, and surgical extirpation of the cyst may lead to an absence of the surrounding inflammatory process. The progression of NCC may be simple or complicated, have remission with or without treatment and may exhibit symptoms that can disappear for long periods of time or persist until death. Unknown, neglected and controversial aspects of NCC, such as the impaired fourth ventricle syndrome, the presence of chronic brain oedema and psychic complaints, in addition to the lack of detectable glucose in the CSF and re-infection are discussed.
MED-5144
Arsenic in seaweed--forms, concentration and dietary exposure.
This study has measured the content of total and inorganic forms of arsenic in seaweed available on retail sale for consumption, to provide data for dietary exposure estimates and to support advice to consumers. A total of 31 samples covering five varieties of seaweed were collected from various retail outlets across London and the internet. All of the samples were purchased as dried product. For four of the five varieties, soaking was advised prior to consumption. The recommended method of preparation for each individual sample was followed, and total and inorganic arsenic were analysed both before and after preparation. The arsenic remaining in the water used for soaking was also measured. Arsenic was detected in all samples with total arsenic at concentrations ranging from 18 to 124 mg/kg. Inorganic arsenic, which can cause liver cancer, was only found in the nine samples of hijiki seaweed that were analysed, at concentrations in the range 67-96 mg/kg. Other types of seaweed were all found to contain less than 0.3mg/kg inorganic arsenic, which was the limit of detection for the method used. Since consumption of hijiki seaweed could significantly increase dietary exposure to inorganic arsenic, the UK Food Standards Agency (FSA) issued advice to consumers to avoid eating it.
MED-3155
Aerobic fitness is associated with lower proportions of senescent blood T-cells in man.
Senescent T-cells accumulate with age, lowering the naïve T-cell repertoire and increasing host infection risk. As this response is likely to be influenced by certain lifestyle factors, we examined the association between aerobic fitness (VO(2max)) and the age-related accumulation of senescent T-cells. Blood lymphocytes from 102 healthy males (18-61 yr) were analyzed for KLRG1, CD57, CD28, CD45RA, CD45RO surface expression on CD4+ and CD8+ T-cells by 4-color flow cytometry. Advancing age (yr) was positively associated with the proportion (%) of senescent (KLRG1+/CD57+; KLRG1+/CD28-) CD4+ (B=1.00; 1.02) and CD8+ (B=0.429; 1.02) T-cells and inversely associated with naïve (KLRG1-/CD28+) CD4+ (B=-1.000) and CD8+ (B=-0.993) T-cells. VO(2max) was inversely associated with senescent CD4+ (B=-0.97) and CD8+ (B=-0.240). Strikingly, age was no longer associated with the proportions of senescent or naïve T-cells after adjusting for VO(2max), while the association between VO(2max) and these T-cell subsets withstood adjustment for age, BMI and percentage body fat. Ranking participants by age-adjusted VO(2max) revealed that the highest tertile had 17% more naïve CD8+ T-cells and 57% and 37% less senescent CD4+ and CD8+ T-cells, respectively, compared to the lowest tertile. VO(2max) was not associated with latent cytomegalovirus (CMV), Epstein-Barr virus (EBV) or herpes simplex virus-1 (HSV-1) infection, indicating that the moderating associations of VO(2max) were not confounded by persistent viral infections. This is the first study to show that aerobic fitness is associated with a lower age-related accumulation of senescent T-cells, highlighting the beneficial effects of maintaining a physically active lifestyle on the aging immune system. Copyright © 2011 Elsevier Inc. All rights reserved.
MED-5036
Meta-analysis of long-term mobile phone use and the association with brain tumours.
We evaluated long-term use of mobile phones and the risk for brain tumours in case-control studies published so far on this issue. We identified ten studies on glioma and meta-analysis yielded OR = 0.9, 95% CI = 0.8-1.1. Latency period of > or =10-years gave OR = 1.2, 95% CI = 0.8-1.9 based on six studies, for ipsilateral use (same side as tumour) OR = 2.0, 95% CI = 1.2-3.4 (four studies), but contralateral use did not increase the risk significantly, OR = 1.1, 95% CI = 0.6-2.0. Meta-analysis of nine studies on acoustic neuroma gave OR = 0.9, 95% CI = 0.7-1.1 increasing to OR = 1.3, 95% CI = 0.6-2.8 using > or =10-years latency period (four studies). Ipsilateral use gave OR = 2.4, 95% CI = 1.1-5.3 and contra-lateral OR = 1.2, 95% CI = 0.7-2.2 in the > or =10-years latency period group (three studies). Seven studies gave results for meningioma yielding overall OR = 0.8, 95% CI = 0.7-0.99. Using > or =10-years latency period OR = 1.3, 95% CI = 0.9-1.8 was calculated (four studies) increasing to OR = 1.7, 95% CI = 0.99-3.1 for ipsilateral use and OR = 1.0, 95% CI = 0.3-3.1 for contralateral use (two studies). We conclude that this meta-analysis gave a consistent pattern of an association between mobile phone use and ipsilateral glioma and acoustic neuroma using > or =10-years latency period.
MED-1666
Nutrition of the intervertebral disc.
STUDY DESIGN: A review of the literature on disc nutrition. OBJECTIVES: To summarize the information on disc nutrition in relation to disc degeneration. SUMMARY OF THE BACKGROUND DATA: The disc is avascular, and the disc cells depend on diffusion from blood vessels at the disc's margins to supply the nutrients essential for cellular activity and viability and to remove metabolic wastes such as lactic acid. The nutrient supply can fail due to changes in blood supply, sclerosis of the subchondral bone or endplate calcification, all of which can block transport from blood supply to the disc or due to changes in cellular demand. METHODS: A review of the studies on disc blood supply, solute transport, studies of solute transport in animal and human disc in vitro, and of theoretical modeling studies that have examined factors affecting disc nutrition. RESULTS: Small nutrients such as oxygen and glucose are supplied to the disc's cells virtually entirely by diffusion; convective transport, arising from load-induced fluid movement in and out of the disc, has virtually no direct influence on transport of these nutrients. Consequently, there are steep concentration gradients of oxygen, glucose, and lactic acid across the disc; oxygen and glucose concentrations are lowest in the center of the nucleus where lactic acid concentrations are greatest. The actual levels of concentration depend on the balance between diffusive transport and cellular demand and can fall to critical levels if the endplate calcifies or nutritional demand increases. CONCLUSIONS: Loss of nutrient supply can lead to cell death, loss of matrix production, and increase in matrix degradation and hence to disc degeneration.
MED-1040
Assessment of normal bowel habits in the general adult population: the Popcol study.
OBJECTIVE: Defining normal stool habit is important when evaluating diarrhoea or constipation, but common confounders such as irritable bowel syndrome (IBS) or the intake of medications with gastrointestinal side effects have not been considered in earlier population based studies defining what is normal. We hypothesized that the exclusion of subjects with common confounders would help to better understand what are "normal bowel habits". We aimed to prospectively study bowel habits in a carefully studied random sample of the general population. MATERIAL AND METHODS: Two hundred and sixty-eight randomly selected subjects between 18 and 70 years completed symptom diaries for one week and were clinically evaluated by a gastroenterologist. They also had a colonoscopy and laboratory investigations to exclude organic disease. RESULTS: One hundred and twenty-four subjects had no organic gastrointestinal abnormality, IBS, or relevant medication; 98% of them had between three stools per day and three per week. Seventy-seven percent of all stools were normal, 12% hard, and 10% loose in consistency. Urgency was reported by 36%; straining by 47% and incomplete defecation by 46%. After the exclusion of subjects with organic abnormalities, women had significantly more symptoms than men in terms of abdominal pain, bloating, constipation, urgency, and feeling of incomplete evacuation but these gender differences disappeared after excluding subjects with IBS. CONCLUSIONS: This study confirms that normal stool frequency is between three per week and three per day. We could not demonstrate any gender or age differences in terms of stool frequency, defecatory symptoms or abdominal bloating. Some degree of urgency, straining, and incomplete evacuation should be considered normal.
MED-5349
Rye Bread Consumption in Early Life and Reduced Risk of Advanced Prostate Cancer
Objective To determine whether consumption of whole-grain; rye bread, oatmeal, and whole-wheat bread, during different periods of life, is associated with risk of prostate cancer (PCa). Methods In 2002 to 2006, 2,268 men, aged 67-96 years, reported their dietary habits in the AGES-Reykjavik cohort study. Dietary habits were assessed for early-, mid- , and current life using a validated food frequency questionnaire (FFQ). Through linkage to cancer- and mortality registers, we retrieved information on PCa diagnosis and mortality through 2009. We used regression models to estimate odds ratios (ORs) and hazard ratios (HRs) for PCa according to whole grain consumption, adjusted for possible confounding factors including fish-, fish liver oil-, meat-, and milk intake. Results Of the 2,268 men, 347 had or were diagnosed with PCa during follow-up, 63 with advanced disease (stage 3+ or died of PCa). Daily rye bread consumption in adolescence (vs. less than daily) was associated with a decreased risk of PCa diagnosis (OR = 0.76, 95% Confidence interval (CI): 0.59-0.98), and of advanced PCa (OR = 0.47, 95% CI: 0.27-0.84). High intake of oatmeal in adolescence (≥5 vs. ≤4 times/ week) was not significantly associated with risk of PCa diagnosis (OR = 0.99, 95% CI: 0.77-1.27) nor advanced PCa (OR = 0.67, 95% CI: 0.37-1.20). Mid-, and late life consumption of rye bread, oatmeal, or whole-wheat bread was not associated with PCa risk. Conclusion Our results suggest that rye bread consumption in adolescence may be associated with reduced risk of PCa, particularly advanced disease.
MED-3722
Dietary patterns and the risk of esophageal cancer.
BACKGROUND: The role of dietary habits on esophageal cancer risk has been rarely considered in terms of dietary patterns. PATIENTS AND METHODS: We analyzed data from an Italian case-control study, including 304 cases with squamous cell carcinoma of the esophagus and 743 hospital controls. Dietary habits were evaluated using a food frequency questionnaire. A posteriori dietary patterns were identified through principal component factor analysis performed on 28 selected nutrients. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained from multiple logistic regression models applied on quartiles of factor scores, adjusting for potential confounding variables. RESULTS: We identified five major dietary patterns, named 'animal products and related components', 'vitamins and fiber', 'starch-rich', 'other polyunsaturated fatty acids and vitamin D', and 'other fats'. The 'animal products and related components' pattern was positively related to esophageal cancer (OR = 1.64, 95% CI:1.06-2.55, for the highest versus the lowest quartile of factor scores category). The 'vitamins and fiber' (OR = 0.50, 95% CI: 0.32-0.78) and the 'other polyunsaturated fatty acids and vitamin D' (OR = 0.48, 95% CI: 0.31-0.74) were inversely related to esophageal cancer. No significant association was observed for the other patterns. CONCLUSION: Our findings suggest that a diet rich in foods from animal origin and poor in foods containing vitamins and fiber increase esophageal cancer risk.
MED-1868
Hibiscus sabdariffa extract inhibits obesity and fat accumulation, and improves liver steatosis in humans.
Obesity is associated with a great diversity of diseases including non-alcoholic fatty liver disease. Our previous report suggested that Hibiscus sabdariffa extracts (HSE) had a metabolic-regulating and liver-protecting potential. In this study, we performed a clinical trial to further confirm the effect of HSE. Subjects with a BMI ≧ 27 and aged 18-65, were randomly divided into control (n = 17) and HSE-treated (n = 19) groups, respectively, for 12 weeks. Our data showed that consumption of HSE reduced body weight, BMI, body fat and the waist-to-hip ratio. Serum free fatty acid (FFA) was lowered by HSE. Anatomic changes revealed that HSE improved the illness of liver steatosis. Ingestion of HSE was well tolerated and there was no adverse effect during the trial. No alteration was found for serum α-amylase and lipase. The clinical effect should mainly be attributed to the polyphenols of HSE, since composition analysis showed that branched chain-amino acids, which is associated with obesity, is not obviously high. In conclusion, consumption of HSE reduced obesity, abdominal fat, serum FFA and improved liver steatosis. HSE could act as an adjuvant for preventing obesity and non-alcoholic fatty liver.
MED-4027
Dietary behavior and knowledge of dental erosion among Chinese adults
Objectives To study the dietary behavior and knowledge about dental erosion and self-reported symptoms that can be related to dental erosion among Chinese adults in Hong Kong. Methods Chinese adults aged 25-45 years were randomly selected from a list of registered telephone numbers generated by computer. A telephone survey was administered to obtain information on demographic characteristics, dietary habits, dental visits, and knowledge of and presence of self-reported symptoms that can be related to dental erosion. Results A total of 520 participants were interviewed (response rate, 75%; sampling error, ± 4.4%) and their mean age was 37. Most respondents (79%) had ever had caries, and about two thirds (64%) attended dental check-ups at least once a year. Respondents had a mean of 5.4 meals per day and 36% had at least 6 meals per day. Fruit (89%) and lemon tea/water (41%) were the most commonly consumed acidic food and beverage. When asked if they ever noticed changes in their teeth, most respondents (92%) said they had experienced change that can be related to erosion. However, many (71%) had never heard about dental erosion and 53% mixed up dental erosion with dental caries. Conclusion Hong Kong Chinese adults have frequent intake of food and many have experienced symptoms that can be related to dental erosion. Their level of awareness of and knowledge about dental erosion is generally low, despite most of them have regular dental check-ups. Dental health education is essential to help the public understand dental erosion and its damaging effects.
MED-4406
Longitudinal trends in gasoline price and physical activity: The CARDIA study
Objective To investigate longitudinal associations between community-level gasoline price and physical activity (PA). Method In the Coronary Artery Risk Development in Young Adults study, 5,115 black and white participants aged 18–30 at baseline 1985–86 were recruited from four U.S. cities (Birmingham, Chicago, Minneapolis and Oakland) and followed over time. We used data from 3 follow-up exams: 1992–93, 1995–96, and 2000–01, when the participants were located across 48 states. From questionnaire data, a total PA score was summarized in exercise units (EU) based on intensity and frequency of 13 PA categories. Using Geographic Information Systems, participants’ residential locations were linked to county-level inflation-adjusted gasoline price data collected by the Council for Community & Economic Research. We used a random-effect longitudinal regression model to examine associations between time-varying gasoline price and time-varying PA, controlling for age, race, gender, baseline study center, and time-varying education, marital status, household income, county cost of living, county bus fare, census block-group poverty, and urbanicity. Results Holding all control variables constant, a 25-cent increase in inflation-adjusted gasoline price was significantly associated with an increase of 9.9 EU in total PA (95%CI: 0.8–19.1). Conclusion Rising prices of gasoline may be associated with an unintended increase in leisure PA.
MED-4095
Mortality from Western cancers rose dramatically among African-Americans during the 20th century: are dietary animal products to blame?
Statistics compiled by the National Cancer Institute indicate that, between 1935 and 1974, age-adjusted mortality from most 'Western' cancers (those of the breast, colon, prostate, pancreas, ovary, and kidney) rose dramatically in African-Americans. This phenomenon is paralleled by marked increases in the incidence of these cancers in Asia and Southern Europe during the latter 20th century, in conjunction with increased intakes of dietary animal products. A credible case can be made that diets rich in animal products work in various complementary ways to up-regulate serum levels of insulin, free IGF-I, and free sex hormones: hormones that appear to have important promotional activity for Western cancers. It seems likely that dietary animal product intake by black Americans increased substantially during the 20th century, and that this fact is primarily responsible for their concurrent marked increase in mortality from Western cancers. A whole-food vegan diet rich in fruits and vegetables, especially if coupled with regular exercise and smoking avoidance, could be expected to have a remarkably positive impact on African-American cancer risk, reversing the increases in cancer risk incurred during the 20th century. Copyright 2001 Harcourt Publishers Ltd.
MED-2699
The Free Radical Theory of Aging Revisited: The Cell Signaling Disruption Theory of Aging
Significance: The free radical theory of aging has provided a theoretical framework for an enormous amount of work leading to significant advances in our understanding of aging. Up to the turn of the century, the theory received abundant support from observations coming from fields as far apart as comparative physiology or molecular biology. Recent Advances: Work from many laboratories supports the theory, for instance showing that overexpression of antioxidant enzymes results in increases in life-span. But other labs have shown that in some cases, there is an increased oxidative stress and increased longevity. The discovery that free radicals can not only cause molecular damage to cells, but also serve as signals; led to the proposal that they act as modulators of physiological processes. For instance, reactive oxygen species (ROS) stimulate physiological adaptations to physical exercise. Critical Issues: A critical blow to the free radical theory of aging came from epidemiological studies showing that antioxidant supplementation did not lower the incidence of many age-associated diseases but, in some cases, increased the risk of death. Moreover, recent molecular evidence has shown that increasing generation of ROS, in some cases, increases longevity. Future Directions: Gerontologists interested in free radical biology are at a crossroads and clearly new insights are required to clarify the role of ROS in the process of aging. The hurdles are, no doubt, very high, but the intellectual and practical promise of these studies is of such magnitude that we feel that all efforts will be generously rewarding. Antioxid. Redox Signal. 19, 779–787.
MED-1277
Is exposure to cyanobacteria an environmental risk factor for amyotrophic lateral sclerosis and other neurodegenerative diseases?
There is a broad scientific consensus that amyotrophic lateral sclerosis (ALS) is caused by gene-environment interactions. Mutations in genes underlying familial ALS (fALS) have been discovered in only 5-10% of the total population of ALS patients. Relatively little attention has been paid to environmental and lifestyle factors that may trigger the cascade of motor neuron death leading to the syndrome of ALS, although exposure to chemicals including lead and pesticides, and to agricultural environments, smoking, certain sports, and trauma have all been identified with an increased risk of ALS. There is a need for research to quantify the relative roles of each of the identified risk factors for ALS. Recent evidence has strengthened the theory that chronic environmental exposure to the neurotoxic amino acid β-N-methylamino-L-alanine (BMAA) produced by cyanobacteria may be an environmental risk factor for ALS. Here we describe methods that may be used to assess exposure to cyanobacteria, and hence potentially to BMAA, namely an epidemiologic questionnaire and direct and indirect methods for estimating the cyanobacterial load in ecosystems. Rigorous epidemiologic studies could determine the risks associated with exposure to cyanobacteria, and if combined with genetic analysis of ALS cases and controls could reveal etiologically important gene-environment interactions in genetically vulnerable individuals.
MED-1127
Rheumatoid arthritis is caused by Proteus: the molecular mimicry theory and Karl Popper.
Rheumatoid arthritis is a crippling and disabling joint disease affecting over 20 million people. It occurs predominantly in women and smokers, and affects the HLA-DR1/4 individuals who carry the "shared epitope" of amino acids EQRRAA. The cause of this disease was investigated by the methods of the philosopher of science Karl Popper who suggested that scientific research should be based on bold conjectures and critical refutations. The "Popper sequences" generate new facts which then change or alter the original problem. The new facts must then be explained by any new theory. Using the "molecular mimicry" model, it was found that Proteus bacteria possess an amino acid sequence ESRRAL in haemolysin which resembles the, shared epitope, and another sequence in urease which resembles type XI collagen. Antibodies to Proteus bacteria have been found in 14 different countries. It would appear that rheumatoid arthritis is caused by an upper urinary tract infection by Proteus bacteria. Anti-Proteus therapy should be assessed in the management of this disease separately or in conjunction with existing modalities of therapy.
MED-1928
Telomeres, lifestyle, cancer, and aging
Purpose of review There has been growing evidence that lifestyle factors may affect the health and lifespan of an individual by affecting telomere length. The purpose of this review was to highlight the importance of telomeres in human health and aging and to summarize possible lifestyle factors that may affect health and longevity by altering the rate of telomere shortening. Recent findings Recent studies indicate that telomere length, which can be affected by various lifestyle factors, can affect the pace of aging and onset of age-associated diseases. Summary Telomere length shortens with age. Progressive shortening of telomeres leads to senescence, apoptosis, or oncogenic transformation of somatic cells, affecting the health and lifespan of an individual. Shorter telomeres have been associated with increased incidence of diseases and poor survival. The rate of telomere shortening can be either increased or decreased by specific lifestyle factors. Better choice of diet and activities has great potential to reduce the rate of telomere shortening or at least prevent excessive telomere attrition, leading to delayed onset of age-associated diseases and increased lifespan. This review highlights the role of telomeres in aging and describes the lifestyle factors which may affect telomeres, human health, and aging.
MED-2250
Urinary cadmium in the 1999-2008 U.S. National Health and Nutrition Examination Survey (NHANES).
Chronic low-level cadmium (Cd) exposure is linked to kidney and cardiovascular disease, fractures, and cancer. Diet and smoking are primary sources of exposure in the general population. We analyzed urinary Cd in NHANES 1999-2008 to determine whether levels declined significantly over the decade for U.S. children, teens, and adults (nonsmokers and smokers) and, if so, factors influencing the decline(s). For each subpopulation, we modeled log urinary Cd using variable-threshold censored multiple regression. Models included individual-level covariates (age, gender, BMI, income, race/ethnicity/country of origin, education, survey period), smoking, housing (home age, water source, filter use), and diet (supplement use; 24-h calorie, fat, protein, micronutrient, and Cd-containing food intakes), creatinine, and survey year variables. Geometric mean urinary Cd (ng/mL) declined 20-25% in these subpopulations, and the regressions showed statistically significant declines in later years for teens and adults. While certain covariates were significantly associated with Cd by subpopulation (creatinine; age; BMI; race/ethnicity/origin; education; smokers in the home; serum cotinine; 24-h fat, Mg, Fe intakes; use of dietary supplements), they did not help explain the declines. Instead, unidentified time-related factors appeared responsible. Despite the declines, millions of Americans remain potentially at risk of adverse outcomes associated with low-level Cd exposure.
MED-1098
Intake of dioxins and related compounds from food in the U.S. population.
The first U.S. nationwide food sampling with measurement of dioxins, dibenzofurans, and coplanar, mono-ortho and di-ortho polychlorinated biphenyls (PCBs) is reported in this study. Twelve separate analyses were conducted on 110 food samples divided into pooled lots by category. The samples were purchased in 1995 in supermarkets in Atlanta, GA, Binghamton, NY, Chicago, IL, Louisville, KY, and San Diego, CA. Human milk also was collected to estimate nursing infants' consumption. The food category with highest World Health Organization (WHO) dioxin toxic equivalent (TEQ) concentration was farm-grown freshwater fish fillet with 1.7 pg/g, or parts per trillion (ppt), wet, or whole, weight. The category with the lowest TEQ level was a simulated vegandiet, with 0.09 ppt. TEQ concentrations in ocean fish, beef, chicken, pork, sandwich meat, eggs, cheese, and ice cream, as well as human milk, were in the range O.33 to 0.51 ppt, wet weight. In whole dairy milk TEQ was 0.16 ppt, and in butter 1.1 ppt. Mean daily intake of TEQ for U.S. breast-fed infants during the first year of life was estimated at 42 pg/kg body weight. For children aged 1-11 yr the estimated daily TEQ intake was 6.2 pg/kg body weight. For males and females aged 12-19 yr, the estimated TEQ intake was 3.5 and 2.7 pg/kg body weight, respectively. For adult men and women aged 20-79 yr, estimated mean daily TEQ intakes were 2.4 and 2.2 pg/kg body weight, respectively. Estimated mean daily intake of TEQ declined with age to a low of 1.9 pg/kg body weight at age 80 yr and older. For all ages except 80 yr and over, estimates were higher for males than females. For adults, dioxins, dibenzofurans, and PCBs contributed 42%, 30%, and 28% of dietary TEQ intake, respectively. DDE was also analyzed in the pooled food samples.
MED-4697
Is there more to aging than mitochondrial DNA and reactive oxygen species?
Summary With the aging of the population, we are seeing a global increase in age-related disorders, especially in developed countries. Chronic diseases disproportionately affect the older segment of the population, contributing to disability, a diminished quality of life, and an increase in healthcare costs. Increased life expectancy reflects the success of contemporary medicine, which must now respond to the challenges created by this achievement, including the growing burden of chronic illnesses, injuries, and disabilities. A well-developed theoretical framework is required to understand the molecular basis of aging. This, in turn, is a prerequisite for developing the clinical interventions that will constitute an efficient response to the challenge of age-related health issues. This review critically analyzes the experimental evidence that supports and refutes the Free Radical/Mitochondrial Theory of Aging, which has dominated the field of aging research for almost half a century.
MED-1668
Review of postcontrast MRI studies on diffusion of human lumbar discs.
Diffusion is the only source of nutrition to the intervertebral discs, and alteration of diffusion is considered to be the final common pathway for disc degeneration. Yet diffusion remains poorly understood due to the paucity of reliable methods to study diffusion noninvasively in humans in vivo. In recent years, postcontrast MRI has emerged as a powerful and reliable tool for analyzing diffusion in lumbar discs. Since it is noninvasive and safe, it can be used to document the process of diffusion temporally over a period of 24 hours. Well-designed studies have shown that diffusion is a very slow process, and that the endplate is the main structure that controls the process of diffusion. Contrast MRI studies have also made it possible to identify endplate breaks in vivo. In the future this technique may be applied to study the influence of smoking, mechanical loading of the discs, abnormal posture, and atherosclerosis of the lumbar arteries on diffusion. These conditions have all been implicated in disc degeneration through a final common pathway of altered diffusion and decreased nutrition. This review article focuses on the current knowledge, methodology, various factors that influence the diffusion properties of the discs, and future applications of this promising technique. (c) 2007 Wiley-Liss, Inc.
MED-3398
Total cholesterol and high density lipoprotein cholesterol as important predictors of erectile dysfunction.
Although erectile dysfunction is frequently seen in patients with manifestations of arteriosclerotic disease, the independent contribution of serum cholesterol in predicting erectile dysfunction is unclear. The aim of this study was to examine the relation between serum cholesterol and erectile dysfunction. Medical histories, physical examinations, and blood tests were obtained at Cooper Clinic, Dallas, Texas, from 3,250 men aged 26-83 years (mean, 51 years) without erectile dysfunction at their first visit, who had one more clinic visit, all between 1987 and 1991. These men were followed 6-48 months after the first clinic visit (mean, 22 months). Erectile dysfunction was reported in 71 men (2.2%) during follow-up. Every mmol/liter of increase in total cholesterol was associated with 1.32 times the risk of erectile dysfunction (95% confidence interval 1.04-1.68), while every mmol/liter of increase in high density lipoprotein cholesterol was associated with 0.38 times the risk (95% confidence interval 0.18-0.80). Men with a high density lipoprotein cholesterol measurement over 1.55 mmol/liter (60 mg/dl) had 0.30 times the risk (95% confidence interval 0.09-1.03) as did men with less than 0.78 mmol/liter (30 mg/dl). Men with total cholesterol over 6.21 mmol/liter (240 mg/dl) had 1.83 times the risk (95% confidence interval 1.00-3.37) as did men with less than 4.65 mmol/liter (180 mg/dl). Those differences remained essentially unchanged after adjustment for other potential confounders. The authors conclude that a high level of total cholesterol and a low level of high density lipoprotein cholesterol are important risk factors for erectile dysfunction.
MED-1171
Chemical exposure early in life and the neurodevelopment of children--an overview of current epidemiological evidence.
A number of chemicals have been shown to demonstrate neurotoxic effects either in human or laboratory animal studies. This article aims at evaluating the impact of exposure to several chemicals including: organophosphate, organochlorine pesticides, polychlorinated biphenyls (PCBs), mercury and lead on the neurodevelopment of children by reviewing the most recent published literature, and answer the question whether any progress has been made in the epidemiology of the neurodevelopment of children induced by exposure to those chemicals. The result of the presented studies show that exposure to the above-mentioned chemicals may impair the neurodevelopment of children. Neonates exposed to organophosphate pesticides demonstrated a higher proportion of abnormal reflexes, and young children had more attention problems. Exposure to organochlorine pesticides in children was associated with alertness, quality of alert responsiveness, cost of attention and other potential attention associated measures. The majority of studies indicate the negative impact of lead exposure at the level <10 µg/dl or even <5 µg/dl on the neurodevelopment of children. The results of studies on exposure to PCBs, mercury, and their effect on neurodevelopment are inconsistent. Some suggest that prenatal exposure to PCBs and mercury is related to performance impairments, attention and concentration problems, while other do not present any statistically significant association. The studies were mostly well designed, using prospective cohorts with the exposure assessment based on the biomarker of exposure. Concerning the covariates and confounders affecting the endpoints in most of the presented studies, confounders were included in data analysis. In order to recognize the early cognitive, motor and language outcomes of chemical exposures, well standardized tools were used for evaluating the neurodevelopmental effects and offer an early and fairly comprehensive measure of child development. Because the neurotoxicants may cross the placenta and the fetal brain, exposure consideration regarding the reduction of exposure to those chemicals should be implemented.
MED-1448
The costs of obesity in the workplace.
OBJECTIVE: To quantify per capita and aggregate medical expenditures and the value of lost productivity, including absenteeism and presenteeism, because of overweight, and grade I, II, and III obesity among U.S. employees. METHODS: Cross-sectional analysis of the 2006 Medical Expenditure Panel Survey and the 2008 National Health and Wellness Survey. RESULTS: Among men, estimates range from -$322 for overweight to $6087 for grade III obese men. For women, estimates range from $797 for overweight to $6694 for grade III. In aggregate, the annual cost attributable to obesity among full-time employees is $73.1 billion. Individuals with a body mass index >35 represent 37% of the obese population but are responsible for 61% of excess costs. CONCLUSIONS: Successful efforts to reduce the prevalence of obesity, especially among those with a body mass index >35, could result in significant savings to employers.
MED-2157
Hepatocellular carcinoma and other liver lesions.
Patients with cirrhosis are at greatest risk for development of hepatocellular carcinoma (HCC) and should undergo semiannual surveillance using ultrasound, with or without alpha fetoprotein. Patients with positive surveillance testing should undergo contrast-enhanced MRI or 4-phase CT for diagnostic evaluation. There are therapeutic options for most patients with any tumor stage; however, treatment decisions must be individualized after accounting for degree of liver dysfunction and patient performance status. A multidisciplinary approach to care is recommended for optimal communication and treatment delivery. The aim of this review is to provide an up-to-date summary of the diagnosis and management of HCC. Copyright © 2014 Elsevier Inc. All rights reserved.
MED-2617
Teratological evaluation of FD&C Red no. 2 -a collaborative government-industry study. II. FDA's study.
Because of recent studies indicating possible embryolethality and teratogenicity of FD&C Red No. 2, and ad hoc committee was convened by the Food and Drug Administration to consider these questions. The committee suggested a collaborative study by three laboratories [Food and Drug Administration (FDA), Industrial Bio-Test Laboratories (IBT), and National Center for Toxicological Research (NCTR)] in which Red No. 2 was given at 200 mg/kg body weight, by gavage during days 0-19, 6-15, or 7-9 of gestation. FD&C Red No. 2 was also given at the same dose level via water bottle. Appropriate controls were utilized. FDA used Osborne-Mendel strain rats, IBT used Charles River, and NCTR used both strains. No significant increases in skeletal or visceral abnormalities were seen. No significant increase in resorptions was seen in the Osborne-Mendel strain, but the Charles River strain at IBT showed a significant increase in litters with two or more resorptions after dams had been given 200 mg/kg at 0-19 days of gestation. The NCTR study on the Charles River strain also showed an increase in the same parameter for the same dose level and in addition showed a significant increase in the percentage of resorptions per litter. It was concluded that because of the inherent variation and the absence of an increase in abnormalities or other indications of embryotoxicity, there is reason to doubt that this effect is either biologically significant or reproducible.
MED-3100
Flavones and flavonols at dietary levels inhibit a transformation of aryl hydrocarbon receptor induced by dioxin.
Dioxins invade the body mainly through the diet, and produce toxicity through the transformation of aryl hydrocarbon receptor (AhR). An inhibitor of the transformation should therefore protect against the toxicity and ideally be part of the diet. We examined flavonoids ubiquitously expressed in plant foods as one of the best candidates, and found that the subclasses flavones and flavonols suppressed antagonistically the transformation of AhR induced by 1 nM of 2,3,7,8-tetrachlorodibenzo-p-dioxin, without exhibiting agonistic effects that transform AhR. The antagonistic IC(50) values ranged from 0.14 to 10 microM, close to the physiological levels in human.
MED-1978
High-density livestock operations, crop field application of manure, and risk of community-associated methicillin-resistant Staphylococcus aureus infection, Pennsylvania, USA
Context Nearly 80% of antibiotics in the United States are sold for use in livestock feeds. The manure produced by these livestock contains antibiotic-resistant bacteria, resistance genes, and antibiotics, and is subsequently applied to crop fields where it may put community members at risk for antibiotic-resistant infections. Objective To assess the association between individual exposure to swine and dairy/veal industrial agriculture and risk of methicillin-resistant Staphylococcus aureus (MRSA) infection. Design, Setting, and Participants A population-based, nested case-control study of Geisinger primary care patients in Pennsylvania from 2005–2010. Incident MRSA cases were identified using electronic health records, classified as community-associated or healthcare-associated, and frequency-matched to randomly selected controls and patients with skin and soft tissue infection. Nutrient management plans were used to create two exposure variables: seasonal crop field manure application and number of livestock at the operation. In a sub-study we collected 200 isolates from patients stratified by location of diagnosis and proximity to livestock operations. Main outcome measures Community-associated MRSA, healthcare associated-MRSA, and skin and soft tissue infection status (with no history of MRSA) compared to controls. Results From 446,480 patients, 1539 community-associated MRSA, 1335 healthcare-associated MRSA, 2895 skin and soft tissue infection cases, and 2914 controls were included. After adjustment for MRSA risk factors, the highest quartile of swine crop field exposure was significantly associated with community-associated MRSA, healthcare-associated MRSA, and skin and soft tissue infection case status (adjusted odds ratio, 1.38 [95% CI, 1.13–1.69], 1.30 [95% CI, 1.05–1.61], and 1.37 [95% CI, 1.18–1.60], respectively); and there was a trend of increasing odds across quartiles for each outcome (all P for trend ≤0.01). There were similar but weaker associations of swine operations with community-associated MRSA and skin and soft tissue infection. Molecular testing of 200 isolates identified 31 unique spa types, none of which corresponded to CC398, but some have been previously found in swine. Conclusion Proximity to swine manure application to crop fields and livestock operations each was associated with MRSA and skin and soft tissue infection. These findings contribute to the growing concern about the potential public health impacts of high-density livestock production.
MED-895
Asthma induced by sulphur dioxide, benzoate and tartrazine contained in orange drinks.
Of 272 patients with asthma, thirty (11%) gave a history of exacerbations occurring after ingestion, solutions of orange orange drinks. Fourteen of these were given provocation tests by drinking, on separate occasions of sulphur dioxide, sodium benzoate and tartrazine, which are present in all orange drinks. Eight reacted to sulphur dioxide with a fall in FEV1, four to sodium benzoate and one to tartrazine, and four did not react to any of these agents. Three of the benzoate patients were also sensitive to sulphur dioxide. The sulphur dioxide sensitive patients were predominantly young, with extrinsic asthma. The benzoate sensitive patients were predominantly middle-aged and the proportion with intrinsic asthma was higher. Prior inhalation of sodium cromoglycate by four patients inhibited the reaction to these substances. Sulphur dioxide has not previously been reported to cause exacerbations of asthma when ingested as a food preservative. It is used as a preservative in a wide range of acidic beverages and foods, and should be considered as possibly causal in patients suffering from apparently cryptogenic asthma, and asthma seemingly due to food allergy.
MED-1932
Exposure to violence during childhood is associated with telomere erosion from 5 to 10 years of age: a longitudinal study
There is increasing interest in discovering mechanisms that mediate the effects of childhood stress on late-life disease morbidity and mortality. Previous studies have suggested one potential mechanism linking stress to cellular aging, disease and mortality in humans: telomere erosion. We examined telomere erosion in relation to children’s exposure to violence, a salient early-life stressor, which has known long-term consequences for well-being and is a major public-health and social-welfare problem. In the first prospective-longitudinal study with repeated telomere measurements in children while they experienced stress, we tested the hypothesis that childhood violence exposure would accelerate telomere erosion from age 5 to age 10 years. Violence was assessed as exposure to maternal domestic violence, frequent bullying victimization and physical maltreatment by an adult. Participants were 236 children (49% females; 42% with one or more violence exposures) recruited from the Environmental-Risk Longitudinal Twin Study, a nationally representative 1994–1995 birth cohort. Each child’s mean relative telomere length was measured simultaneously in baseline and follow-up DNA samples, using the quantitative PCR method for T/S ratio (the ratio of telomere repeat copy numbers to single-copy gene numbers). Compared with their counterparts, the children who experienced two or more kinds of violence exposure showed significantly more telomere erosion between age-5 baseline and age-10 follow-up measurements, even after adjusting for sex, socioeconomic status and body mass index (B = −0.052, s.e. = 0.021, P = 0.015). This finding provides support for a mechanism linking cumulative childhood stress to telomere maintenance, observed already at a young age, with potential impact for life-long health.
MED-4704
Lipoid pneumonia presenting as non resolving community acquired pneumonia: a case report
Introduction Lipoid pneumonia is a rare form of pneumonia caused by inhalation or aspiration of fat containing substances like, petroleum jelly, mineral oils, few laxatives etc. It usually presents as insidious onset chronic respiratory illness simulating interstitial lung diseases. Rarely, it may present as an acute respiratory illness, specially, when exposure to fatty substance is acute and/or massive. Radiologically, it may mimic carcinoma, acute or chronic pneumonia, ARDS, or a localized granuloma. Diagnosis of LP requires demonstration of lipid laden macrophages in sputum, bronchoalveolar lavage fluid or fine needle aspiration cytology/biopsy from lung lesion. Treatment of this illness is poorly defined and constitutes supportive therapy and corticosteroids. Case presentation A 20-year old Indian farmer was referred to us with a diagnosis of non resolving community acquired pneumonia. Respiratory examination revealed signs of consolidation. Chest radiograph revealed findings suggestive of bilateral consolidation. Sputum and blood culture were sterile. He was treated with prolonged course of various antibiotics without any significant response. For evaluation of non resolving pneumonia fibreoptic bronchoscopy was done. Bronchoalveolar lavage fluid and biopsy from lung lesion showed lipid laden macrophages. Hence diagnosis of lipoid pneumonia was made. Patient was treated with course of corticosteroids with good response. Literature on this rare entity is discussed. Conclusion Lipoid pneumonia is a rare form of pneumonia which rarely present acutely resembling community acquired pneumonia and requires high degree of suspicion for diagnosis. Its treatment is difficult and poorly defined. However, prolonged corticosteroids may be effective.
MED-1455
Lipotoxicity: Effects of Dietary Saturated and Transfatty Acids
The ingestion of excessive amounts of saturated fatty acids (SFAs) and transfatty acids (TFAs) is considered to be a risk factor for cardiovascular diseases, insulin resistance, dyslipidemia, and obesity. The focus of this paper was to elucidate the influence of dietary SFA and TFA intake on the promotion of lipotoxicity to the liver and cardiovascular, endothelial, and gut microbiota systems, as well as on insulin resistance and endoplasmic reticulum stress. The saturated and transfatty acids favor a proinflammatory state leading to insulin resistance. These fatty acids can be involved in several inflammatory pathways, contributing to disease progression in chronic inflammation, autoimmunity, allergy, cancer, atherosclerosis, hypertension, and heart hypertrophy as well as other metabolic and degenerative diseases. As a consequence, lipotoxicity may occur in several target organs by direct effects, represented by inflammation pathways, and through indirect effects, including an important alteration in the gut microbiota associated with endotoxemia. Interactions between these pathways may perpetuate a feedback process that exacerbates an inflammatory state. The importance of lifestyle modification, including an improved diet, is recommended as a strategy for treatment of these diseases.
MED-4627
Diet and inflammation.
The emerging role of chronic inflammation in the major degenerative diseases of modern society has stimulated research into the influence of nutrition and dietary patterns on inflammatory indices. Most human studies have correlated analyses of habitual dietary intake as determined by a food frequency questionnaire or 24-hour recall with systemic markers of inflammation like high-sensitivity C-reactive protein (HS-CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). An occasional study also includes nutrition analysis of blood components. There have been several controlled interventions which evaluated the effect of a change in dietary pattern or of single foods on inflammatory markers in defined populations. Most studies reveal a modest effect of dietary composition on some inflammatory markers in free-living adults, although different markers do not vary in unison. Significant dietary influences have been established for glycemic index (GI) and load (GL), fiber, fatty acid composition, magnesium, carotenoids, and flavonoids. A traditional Mediterranean dietary pattern, which typically has a high ratio of monounsaturated (MUFA) to saturated (SFA) fats and ω-3 to ω-6 polyunsaturated fatty acid (PUFAs) and supplies an abundance of fruits, vegetables, legumes, and grains, has shown anti-inflammatory effects when compared with typical North American and Northern European dietary patterns in most observational and interventional studies and may become the diet of choice for diminishing chronic inflammation in clinical practice.
MED-2300
Exercise and longevity.
Aging is a natural and complex physiological process influenced by many factors, some of which are modifiable. As the number of older individuals continues to increase, it is important to develop interventions that can be easily implemented and contribute to "successful aging". In addition to a healthy diet and psychosocial well-being, the benefits of regular exercise on mortality, and the prevention and control of chronic disease affecting both life expectancy and quality of life are well established. We summarize the benefits of regular exercise on longevity, present the current knowledge regarding potential mechanisms, and outline the main recommendations. Exercise can partially reverse the effects of the aging process on physiological functions and preserve functional reserve in the elderly. Numerous studies have shown that maintaining a minimum quantity and quality of exercise decreases the risk of death, prevents the development of certain cancers, lowers the risk of osteoporosis and increases longevity. Training programs should include exercises aimed at improving cardiorespiratory fitness and muscle function, as well as flexibility and balance. Though the benefits of physical activity appear to be directly linked to the notion of training volume and intensity, further research is required in the elderly, in order to develop more precise recommendations, bearing in mind that the main aim is to foster long-term adherence to physical activity in this growing population. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
MED-4652
Ductal carcinoma in situ: terminology, classification, and natural history.
Ductal carcinoma in situ (DCIS) refers to breast epithelial cells that have become "cancerous" but still reside in their normal place in the ducts and lobules. In this setting, cancerous means that there is an abnormal increase in the growth of the epithelial cells, which accumulate within and greatly expand the ducts and lobules. DCIS is a nonlethal type of cancer because it stays in its normal place. However, DCIS is very important because it is the immediate precursor of invasive breast cancers, which are potentially lethal. This article provides a general overview of DCIS, including historical perspective, methods of classification, current perspective, and future goals.
MED-2195
The influence of deep frying using various vegetable oils on acrylamide formation in sweet potato (Ipomoea batatas L. Lam) chips.
The objective of this study was to evaluate the precursors of acrylamide formation in sweet potato (SP) (Ipomoea batatas L. Lam) chips and to determine the effect of different types of vegetable oils (VOs), that is, palm olein, coconut oil, canola oil, and soya bean oil, on acrylamide formation. The reducing sugars and amino acids in the SP slices were analyzed, and the acrylamide concentrations of SP chips were measured. SP chips that were fried in a lower degree of unsaturation oils contained a lower acrylamide concentration (1443 μg/kg), whereas those fried with higher degree of unsaturated oils contained a higher acrylamide concentration (2019 μg/kg). SP roots were found to contain acrylamide precursors, that is, 4.17 mg/g glucose and 5.05 mg/g fructose, and 1.63 mg/g free asparagine. The type of VO and condition used for frying, significantly influenced acrylamide formation. This study clearly indicates that the contribution of lipids in the formation of acrylamide should not be neglected. © 2013 Institute of Food Technologists®
MED-2805
Pathobiology of obesity and osteoarthritis: integrating biomechanics and inflammation
Obesity is a significant risk factor for developing osteoarthritis in weight-bearing and non-weight-bearing joints. Although the pathogenesis of obesity-associated osteoarthritis is not completely understood, recent studies indicate that pro-inflammatory metabolic factors contribute to an increase in osteoarthritis risk. Adipose tissue, and in particular infrapatellar fat, is a local source of pro-inflammatory mediators that are increased with obesity and have been shown to increase cartilage degradation in cell and tissue culture models. One adipokine in particular, leptin, may be a critical mediator of obesity-associated osteoarthritis via synergistic actions with other inflammatory cytokines. Biomechanical factors may also increase the risk of osteoarthritis by activating cellular inflammation and promoting oxidative stress. However, some types of biomechanical stimulation, such as physiologic cyclic loading, inhibit inflammation and protect against cartilage degradation. A high percentage of obese individuals with knee osteoarthritis are sedentary, suggesting that a lack of physical activity may increase the susceptibility to inflammation. A more comprehensive approach to understanding how obesity alters daily biomechanical exposures within joint tissues may provide new insight into the protective and damaging effects of biomechanical factors on inflammation in osteoarthritis.
MED-4505
Dietary nitrate reduces maximal oxygen consumption while maintaining work performance in maximal exercise.
The anion nitrate-abundant in our diet-has recently emerged as a major pool of nitric oxide (NO) synthase-independent NO production. Nitrate is reduced stepwise in vivo to nitrite and then NO and possibly other bioactive nitrogen oxides. This reductive pathway is enhanced during low oxygen tension and acidosis. A recent study shows a reduction in oxygen consumption during submaximal exercise attributable to dietary nitrate. We went on to study the effects of dietary nitrate on various physiological and biochemical parameters during maximal exercise. Nine healthy, nonsmoking volunteers (age 30+/-2.3 years, VO(2max) 3.72+/-0.33 L/min) participated in this study, which had a randomized, double-blind crossover design. Subjects received dietary supplementation with sodium nitrate (0.1 mmol/kg/day) or placebo (NaCl) for 2 days before the test. This dose corresponds to the amount found in 100-300 g of a nitrate-rich vegetable such as spinach or beetroot. The maximal exercise tests consisted of an incremental exercise to exhaustion with combined arm and leg cranking on two separate ergometers. Dietary nitrate reduced VO(2max) from 3.72+/-0.33 to 3.62+/-0.31 L/min, P<0.05. Despite the reduction in VO(2max) the time to exhaustion trended to an increase after nitrate supplementation (524+/-31 vs 563+/-30 s, P=0.13). There was a correlation between the change in time to exhaustion and the change in VO(2max) (R(2)=0.47, P=0.04). A moderate dietary dose of nitrate significantly reduces VO(2max) during maximal exercise using a large active muscle mass. This reduction occurred with a trend toward increased time to exhaustion implying that two separate mechanisms are involved: one that reduces VO(2max) and another that improves the energetic function of the working muscles. Copyright 2009 Elsevier Inc. All rights reserved.
MED-2011
Exploratory study of the relationship between hypertension and diet diversity among Saba Islanders.
The relationship between diet diversity and hypertension was examined in a cross-sectional exploratory study of 82 randomly selected adult residents of Saba Island, Netherlands Antilles, in the eastern Caribbean Basin. Blood pressure measurements, taken over 4 years, and the appropriate use of antihypertensive medications, were used to identify chronic hypertensives. A 24-hour dietary recall, semi-quantitative food frequency interviews, and ethnographic confirmation techniques were used to calculate diet diversity, a measure of the overall dietary pattern. Results suggest hypertension is associated with lack of an overall balance of food groups in the daily diet beyond any imbalance of a particular dietary cation such as sodium, potassium, or calcium. Bivariate analyses found a significant association between a poorly diversified diet and hypertension (odds ratio [OR] = 4.25, 95 percent confidence intervals [CI] = 1.47,12.30). Dietary intake of sodium, potassium, and calcium was also examined and found not to be associated with the presence of hypertension in bivariate analyses. Including these cations individually in logistic regression models, which also included diet diversity, did not diminish the diet diversity-hypertension association. Multiple logistic regression models in which other potential confounding variables were individually entered as a control variable (body fat, skin color, age, sex, perceived stress, alcohol intake, aerobic activity, and socioeconomic status) did not alter this result. Analysis of the presence or absence of individual food groups indicate a lack of legumes in the daily diet is also associated with the diagnosis of hypertension (OR = 4.71, 95 percent CI = [1.71,13.01]).