Titanium Dioxide & Inflammatory Bowel Disease
MED-3960
Dietary microparticles and their impact on tolerance and immune responsiveness of the gastrointestinal tract
Dietary microparticles are non-biological bacterial-sized particles of the gastrointestinal lumen that occur due to endogenous formation (calcium phosphate) or following oral exposure (exogenous microparticle). In the UK, about 40 mg (1012) of exogenous microparticles are ingested per person per day, through exposure to food additives, pharmaceutical/supplement excipients or toothpaste constituents. Once ingested, exogenous microparticles are unlikely to pass through the gastrointestinal tract without adsorbing to their surfaces some ions and molecules of the intestinal lumen. Both entropy and ionic attraction drive such interactions. Calcium ions are especially well adsorbed by dietary microparticles which then provide a positively charged surface for the attraction (adsorption) of other organic molecules such as lipopolysaccharides, peptidoglycans or protein antigen from the diet or commensal flora. The major (but not only) sites of microparticle entry into intestinal tissue are the M-cell rich lymphoid aggregates (termed Peyer’s patches in the small bowel). Indeed, it is well established that this is an efficient transport route for non-biological microparticles although it is unclear why. We hypothesise that this pathway exists for “endogenous microparticles” of calcium phosphate, with immunological and physiological benefit, and that “exogenous dietary microparticles”, such as titanium dioxide and the silicates, hijack this route. This overview focuses on what is known of these microparticles and outlines their potential role in immune tolerance of the gut (endogenous microparticles) or immune activation (exogenous microparticles) and inflammation of the gut.
MED-3961
Lack of efficacy of a reduced microparticle diet in a multi-centred trial of patients with active Crohn's disease.
BACKGROUND AND AIMS: Dietary microparticles, which are bacteria-sized and non-biological, found in the modern Western diet, have been implicated in both the aetiology and pathogenesis of Crohn's disease. Following on from the findings of a previous pilot study, we aimed to confirm whether a reduction in the amount of dietary microparticles facilitates induction of remission in patients with active Crohn's disease, in a single-blind, randomized, multi-centre, placebo controlled trial. METHODS: Eighty-three patients with active Crohn's disease were randomly allocated in a 2 x 2 factorial design to a diet low or normal in microparticles and/or calcium for 16 weeks. All patients received a reducing dose of prednisolone for 6 weeks. Outcome measures were Crohn's disease activity index, Van Hees index, quality of life and a series of objective measures of inflammation including erythrocyte sedimentation rate, C-reactive protein, intestinal permeability and faecal calprotectin. After 16 weeks patients returned to their normal diet and were followed up for a further 36 weeks. RESULTS: Dietary manipulation provided no added effect to corticosteroid treatment on any of the outcome measures during the dietary trial (16 weeks) or follow-up (to 1 year); e.g., for logistic regression of Crohn's disease activity index based rates of remission (P=0.1) and clinical response (P=0.8), in normal versus low microparticle groups. CONCLUSIONS: Our adequately powered and carefully controlled dietary trial found no evidence that reducing microparticle intake aids remission in active Crohn's disease.
MED-3962
Biocompatibility of micro- and nano-particles in the colon. Part II.
Pathological colonic tissues were investigated with an Environmental Scanning Electron Microscope technique to verify the presence of inorganic, non-biodegradable pollutants, i.e. micro- and nano-debris of exogenous origin, after debris in liver and kidney had been discovered. In all, 18 samples of colon tissues affected by cancer and Crohn's disease were evaluated and found in all the cases to contain micro- and nano-particles. Their chemistry, detected with an X-ray microprobe, indicated a heterogeneous nature, whereas the size of the particles was homogeneous. Three control samples of healthy, young, cadavers were analysed and showed the absence of debris within the normal, healthy colon mucosa. The study reveals the presence of particulate debris, generally considered as biocompatible, in pathological specimens of human colon. The findings suggest a possible link between the presence of such particles and the underlying pathology in the cases analysed.
MED-3963
Dietary sources of inorganic microparticles and their intake in healthy subjects and patients with Crohn's disease.
Dietary microparticles are non-biological, bacterial-sized particles. Endogenous sources are derived from intestinal Ca and phosphate secretion. Exogenous sources are mainly titanium dioxide (TiO2) and mixed silicates (Psil); they are resistant to degradation and accumulate in human Peyer's patch macrophages and there is some evidence that they exacerbate inflammation in Crohn's disease (CD). However, whether their intake differs between those with and without CD has not been studied. We aimed to identify dietary microparticle sources and intakes in subjects with and without CD. Patients with inactive CD and matched general practice-based controls (ninety-one per group) completed 7 d food diaries. Intake data for dietary fibre and sucrose were compared as positive controls. All foods, pharmaceuticals and toothpastes were examined for microparticle content, and intakes of Ca and exogenous microparticles were compared between the two groups. Dietary intakes were significantly different between cases and controls for dietary fibre (12 (SD 5) v. 14 (SD 5) g/d; P=0.001) and sucrose (52 (SD 27) v. 45 (SD 18) g/d; P=0.04) but not for Ca. Estimated median TiO2 and Psil intakes (2.5 and 35 mg/individual per d respectively, totalling 10(12)-10(13) microparticles/individual per d) were broadly similar to per capita estimates and while there was wide variation in intakes between individuals there was no significant difference between subjects with CD and controls. Hence, if exposure to microparticles is associated with the inflammation of CD, then the present study rules out excess intake as the problem. Nonetheless, microparticle-containing foods have now been identified which allows a low-microparticle diet to be further assessed in CD.
MED-3964
Diet and risk of inflammatory bowel disease.
BACKGROUND: A better understanding of the environmental factors leading to inflammatory bowel disease should help to prevent occurrence of the disease and its relapses. AIM: To review current knowledge on dietary risk factors for inflammatory bowel disease. METHODS: The PubMed, Medline and Cochrane Library were searched for studies on diet and risk of inflammatory bowel disease. RESULTS: Established non-diet risk factors include family predisposition, smoking, appendectomy, and antibiotics. Retrospective case-control studies are encumbered with methodological problems. Prospective studies on European cohorts, mainly including middle-aged adults, suggest that a diet high in protein from meat and fish is associated with a higher risk of inflammatory bowel disease. Intake of the n-6 polyunsaturated fatty acid linoleic acid may confer risk of ulcerative colitis, whereas n-3 polyunsaturated fatty acids may be protective. No effect was found of intake of dietary fibres, sugar, macronutrients, total energy, vitamin C, D, E, Carotene, or Retinol (vitamin A) on risk of ulcerative colitis. No prospective data was found on risk related to intake of fruits, vegetables or food microparticles (titanium dioxide and aluminium silicate). CONCLUSIONS: A diet high in protein, particular animal protein, may be associated with increased risk of inflammatory bowel disease and relapses. N-6 polyunsaturated fatty acids may predispose to ulcerative colitis whilst n-3 polyunsaturated fatty acid may protect. These results should be confirmed in other countries and in younger subjects before dietary counselling is recommended in high risk subjects. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
MED-3965
Efficacy and tolerability of a low microparticle diet in a double blind, randomized, pilot study in Crohn's disease.
BACKGROUND: Ultrafine and fine particles are potent adjuvants in antigen-mediated immune responses, and cause inflammation in susceptible individuals. Following recent findings that microparticles accumulate in the phagocytes of intestinal lymphoid aggregates, this study is the first investigation of whether their reduction in the diet improves the symptoms of Crohn's disease. METHODS: In a double blind study, 20 patients with active corticosteroid-treated ileal or ileo-colonic Crohn's disease randomly received either a low microparticle diet (trial group; n = 10) or a control diet (n = 10) for 4 months. Crohn's disease activity index (CDAI) and corticosteroid requirements were compared. RESULTS: One patient in each group was withdrawn. In the trial group there was a progressive decrease in CDAI from entry (392 +/- 25) to month 4 (145 +/- 47) (P = 0.002 vs control group) and seven patients were in remission (CDAI <150). In contrast, the control group had returned to baseline levels (302 +/- 28 on entry and 295 +/- 25 at month 4), with none in remission. Corticosteroid intake was reduced more in the trial group although this did not reach significance. CONCLUSIONS: A low microparticle diet may be effective in the management of ileal Crohn's disease and could explain the efficacy of elemental diets, which similarly are low in microparticles.
MED-3966
Fine and ultrafine particles of the diet: influence on the mucosal immune response and association with Crohn's disease.
Crohn's disease is a modern Western disease characterised by transmural inflammation of the gastrointestinal tract. It is of unknown aetiology, but evidence suggests that it results from a combination of genetic predisposition and environmental factors. Bacterial-sized microparticles (0.1-1.0 microm) are potent adjuvants in model antigen-mediated immune responses and are increasingly associated with disease. Microparticles of TiO2 and aluminosilicate accumulate in macrophages of human gut-associated lymphoid tissue where the earliest signs of lesions in Crohn's disease are observed. Dietary microparticles are of endogenous or exogenous origin. Endogenous microparticles dominate and are calcium phosphate (most probably hydroxyapatite), which precipitates in the lumen of the mid-distal gastrointestinal tract due to secretion of Ca and phosphate in the succus entericus. Exogenous dietary microparticles are contaminants (soil and/or dust) and food additives. TiO2, for example, is a food colourant, and aluminosilicates are anti-caking agents, although some aluminosilicates occur as natural contaminants. Food additives alone account for ingestion of approximately 10(12) particles/person per d. Possible mechanisms for the role of exogenous and endogenous dietary microparticles in promoting toleragenic or immune responses of gastrointestinal mucosal phagocytosis are discussed. In a double-blind randomised pilot study we have shown that a diet low in Ca and exogenous microparticles appears to alleviate the symptoms of ileal Crohn's disease, with a significant (P= 0.002) improvement in the Crohn's disease activity index. A multi-centre trial and further mechanistic studies at the cellular level are underway.
MED-3967
Dietary microparticles implicated in Crohn's disease can impair macrophage phagocytic activity and act as adjuvants in the presence of bacterial st...
OBJECTIVE AND DESIGN: Western diets regularly expose the gastrointestinal tract (GI) to large quantities ( > 10(12)/day) of man-made, submicron-sized, particles derived from food additives and excipients. These are taken up by M cells, accumulate in gut macrophages, and may influence the aetiology of inflammatory bowel diseases (IBD). MATERIALS: We investigated the effects of common dietary microparticles on the function of macrophages from healthy donors or active Crohn's disease (CD) patients. METHODS: Macrophages were incubated for 24 h with microparticles before being assayed for cytokine production and phagocytic activity. RESULTS: Microparticles alone were non-stimulatory but, in the presence of bacterial antigens such as LPS, they could act as adjuvants to induce potent cytokine responses. Uptake of high concentrations of microparticles also impaired macrophage phagocytic capacity - but not their ability - to take up 2microM fluorescent beads. CONCLUSIONS: While dietary microparticles alone have limited effects on basic macrophage functions, their ability to act as adjuvants could aggravate ongoing inflammatory responses towards bacterial antigens in the GI tract.
MED-3968
Origin and fate of dietary nanoparticles and microparticles in the gastrointestinal tract.
Humans have evolved with oral exposure to dietary microparticles and nanoparticles as a normal occurrence but the ever-growing exploitation of nanotechnology is likely to increase exposure further, both qualitatively and quantitatively. Moreover, unlike the situation with respirable particles, relatively little is known about gastrointestinal intake and handling of nanoparticles. With a long term interest in gut exposure and responses to dietary microparticles, our group is now applying its expertise to nanoparticles in the gastrointestinal tract. Here we aim to address (i) the current challenges associated with the characterisation of particle-host or particle-cell interactions, (ii) the origin and mechanisms of uptake of particles in the gastrointestinal tract, especially via the Peyer's patch and (iii) potential cellular effects of nanoparticles in the generation of reactive oxygen species and inflammasome activation, or microparticles in their adjuvant activity in pro-inflammatory signalling and immune responsiveness. Copyright 2010 Elsevier Ltd. All rights reserved.
MED-3969
Titanium Dioxide Nanoparticles in Food and Personal Care Products
Titanium dioxide is a common additive in many food, personal care, and other consumer products used by people, which after use can enter the sewage system, and subsequently enter the environment as treated effluent discharged to surface waters or biosolids applied to agricultural land, incinerated wastes, or landfill solids. This study quantifies the amount of titanium in common food products, derives estimates of human exposure to dietary (nano-) TiO2, and discusses the impact of the nanoscale fraction of TiO2 entering the environment. The foods with the highest content of TiO2 included candies, sweets and chewing gums. Among personal care products, toothpastes and select sunscreens contained 1% to >10% titanium by weight. While some other crèmes contained titanium, despite being colored white, most shampoos, deodorants, and shaving creams contained the lowest levels of titanium (<0.01 μg/mg). For several high-consumption pharmaceuticals, the titanium content ranged from below the instrument detection limit (0.0001 μg Ti/mg) to a high of 0.014 μg Ti/mg. Electron microscopy and stability testing of food-grade TiO2 (E171) suggests that approximately 36% of the particles are less than 100 nm in at least one dimension and that it readily disperses in water as fairly stable colloids. However, filtration of water solubilized consumer products and personal care products indicated that less than 5% of the titanium was able to pass through 0.45 or 0.7 μm pores. Two white paints contained 110 μg Ti/mg while three sealants (i.e., prime coat paint) contained less titanium (25 to 40 μg Ti/mg). This research showed that while many white-colored products contained titanium, it was not a prerequisite. Although several of these product classes contained low amounts of titanium, their widespread use and disposal down the drain and eventually to WWTPs deserves attention. A Monte Carlo human exposure analysis to TiO2 through foods identified children as having the highest exposures because TiO2 content of sweets is higher than other food products, and that a typical exposure for a US adult may be on the order of 1 mg Ti per kilogram body weight per day. Thus, because of the millions of tons of titanium based white pigment used annually, testing should focus on food-grade TiO2 (E171) rather than that adopted in many environmental health and safety tests (i.e., P25), which is used in much lower amounts in products less likely to enter the environment (e.g., catalyst supports, photocatalytic coatings).
MED-3970
Immune potentiation of ultrafine dietary particles in normal subjects and patients with inflammatory bowel disease.
Various specific and non-specific environmental factors have been associated with the induction and/or exacerbation of disease activity in patients with Crohn's disease and ulcerative colitis. One such factor is the potential role of ingested ultrafine particles. In fact, based on a Western diet, recent data suggest that more than 10(12)ultrafine particles are ingested per person every day. These microparticles have been considered inert although they adsorb endogenous constituents of the intestinal lumen and are taken up by human intestinal lymphoid aggregates. Based on these observations, we determined whether one such dietary microparticle, titanium dioxide (TiO(2)), alters intestinal cell responsiveness to lipopolysaccharide (LPS) using colonic biopsy specimens from 28 patients with ulcerative colitis, 21 with Crohn's disease, and 36 healthy controls. These samples, as well as peripheral blood mononuclear cells when available, were incubated alone (control), or with either (a) LPS (1-2,000 ng/ml), (b) TiO(2)(5 microg/ml) or (c) LPS (1 ng/ml) adsorbed to TiO(2)(5 microg/ml). In each case, the levels of interleukin 1 (IL-1) produced in these assays were quantitated by bioassay and by ELISA. Interestingly, there was dramatic stimulation of peripheral blood mononuclear cells using the TiO(2)-LPS conjugate, with values 30-60-fold above controls and only minor stimulation with LPS or TiO(2)alone. In intestinal organ cultures there was no increase in IL-1 secretion when challenged with TiO(2)alone or with up to 2,000 ng/ml LPS. However, the TiO(2)-LPS conjugate produced a two-to-three-fold, significant increase in the intestinal secretion of IL-1. Our data demonstrate that ultrafine dietary particles are not immunologically inert and may be important adjuncts in overcoming normal gut cell hyporesponsiveness to endogenous luminal molecules. This may be particularly relevant to patients with inflammatory bowel disease where there is abnormal intestinal permeability. Copyright 2000 Academic Press.
MED-4068
The cooked meat-derived mammary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine promotes invasive behaviour of breast cancer cells.
The cooked meat derived genotoxic carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induces cancer of the colon, prostate and mammary gland when fed to rats. Epidemiology studies link these tumours to a Western diet and exposure to heterocyclic amines such as PhIP. We have shown that PhIP is also potently estrogenic and have proposed that this hormonal activity contributes to its target site carcinogenicity. We now postulate that the estrogenic properties of PhIP influence metastatic potential. We have used an in vitro assay for cell invasion based upon digestion and migration through a reconstituted basement membrane model. Zymography and immunoblotting were used to confirm PhIP-mediated changes associated with induction of the invasive phenotype. Treatment of the mammary cancer cell lines MCF-7 and T47D with PhIP induces cells to digest and migrate through a reconstituted basement membrane. The response was dose dependent, observed at sub-nanomolar concentrations of PhIP and was inhibited by the antiestrogen ICI 182,780. The PhIP-induced invasive phenotype was associated with expression of cathepsin D, cyclooxygenase-2 and matrix metalloproteinase activity. These findings emphasise the range and potency of the biological activities associated with this cooked meat product and mechanistically support the tissue-specific carcinogenicity of the chemical. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
MED-4069
Meat, fat and risk of breast cancer: a case-control study from Uruguay.
To examine whether meat intake modifies breast-cancer risk, a case-control study was conducted in Uruguay. Dietary patterns were assessed in detail (for cases, before diagnosis or symptoms occurred) using a food frequency questionnaire involving 64 food items, which allowed total energy intake to be calculated. Nutrient residuals were calculated through regression analysis. After adjustment for potential confounders (which included family history of breast cancer, menopausal status, body-mass index, total energy and total alcohol intake), an increased risk associated with consumption of total meat intake, red meat intake, total fat and saturated fat intake was observed. The strongest effect was observed for red meat intake (OR 4.2, 95% CL 2.3-7.7) for consumption in the upper quartile, after controlling for protein and fat intake. This suggests an independent effect for meat. Since experimental studies have shown a strong effect of heterocyclic amines in rat mammary carcinogenesis, further studies should be performed in human epidemiology, perhaps using biomarkers of heterocyclic amine exposure.
MED-4070
Intake of fried meat and risk of cancer: a follow-up study in Finland.
It has been suggested that mutagens in fried meat may be involved in the cancer process. Therefore the relationships between intake of fried meat and subsequent risk of cancers at different sites were studied among 9,990 Finnish men and women, 15-99 years of age and initially free of cancer. The baseline study was carried out in 1966-1972, and cases of cancer were identified through data linkage with the Finnish Cancer Registry. During a 24-year follow-up, 853 cancer cases were diagnosed. The intake of fried meat was estimated from a dietary history interview covering the total diet of the participants during the previous year. There was a positive association between fried meat intake and the risk of female-hormone-related cancers, i.e., cancer of the breast, endometrium and ovary combined. The relative risk of these cancers combined between persons in the highest and lowest tertiles of daily intake of fried meat adjusted for age, personal characteristics and intake of other main food groups was 1.77 (95% confidence interval = 1.11-2.84). Pancreatic and nervous system cancers also presented non-significant suggestive associations. No associations were observed with respect to other single cancer sites studied or to all sites of cancer combined. Further epidemiological efforts are needed to ascertain the potential link between fried-food mutagens and cancer risk.
MED-4071
Detection of PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) in the milk of healthy women.
An increased risk of breast cancer has been observed in women who consume "very well-done" meats. Heterocyclic amines are mutagenic and carcinogenic pyrolysis products formed during high temperature cooking of meats. In the present study, human milk samples were analyzed for PhIP, one of the most abundant dietary heterocyclic amine. A protocol was developed with a mixed-mode cation exchange sorbent for the extraction of heterocyclic amines from milk. Milk samples were acquired from healthy Canadian women. With LC/MS analysis and the method of isotope dilution for quantification, levels of PhIP were determined in human milk samples. PhIP was detected in 9 of the 11 milk samples, at levels as high as 59 pg/mL (ppt). No PhIP was detected in the milk of the vegetarian donor. Detection of PhIP in milk indicates that ductal mammary epithelial cells are directly exposed to this carcinogen, suggesting that heterocyclic amines are possible human mammary carcinogens.
MED-4072
Dietary intake of meat and meat-derived heterocyclic aromatic amines and their correlation with DNA adducts in female breast tissue.
It was the aim of this study to examine the association of the consumption of meat in general, meat prepared by different cooking methods and the dietary intake of heterocyclic aromatic amines (HCA) with the level of DNA adducts in the breast tissue of women undergoing reduction mammoplasty. Dietary intake of meat and HCA were assessed via questionnaire in 44 women undergoing reduction mammoplasty. DNA adduct analysis in breast tissue was performed by (32)P-postlabelling analysis. Spearman rank correlation coefficients (r) were calculated to examine the association of meat consumption and dietary HCA intake with tissue DNA adduct levels. A median DNA adduct level of 18.45 (interquartile range 12.81-25.65) per 10(9) nucleotides in breast tissue was observed; median HCA intake was 40.43 ng/day (interquartile range 19.55-102.33 ng/day). Total HCA intake (r = 0.33, P = 0.03), consumption of fried meat (r = 0.39, P = 0.01), beef (r = 0.32, P = 0.03) and processed meat (r = 0.51, P = 0.0004) were statistically significantly correlated with the level of DNA adducts in breast tissue. The detected DNA adducts could not be confirmed to be specific HCA-derived DNA adducts by comparison with external standards, using the (32)P-postlabelling assay. We observed strong correlations of dietary HCA intake and consumption of fried and processed meat with DNA adduct levels in breast tissue of 44 women. Since the detected DNA adducts were not necessarily specific only for HCA, it is possible that HCA intake is a surrogate of other genotoxic substances, such as polycyclic aromatic hydrocarbons, in meat prepared at high temperatures.
MED-4073
The cooked food derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine is a potent oestrogen: a mechanistic basis for its tissue-speci...
The cooked meat carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induces tumours of the breast, colon and prostate in rats. Here we show that in addition to its well-established genotoxicity, which can be detected at concentrations >10(-6) M, PhIP is also oestrogenic. In COS-1 cells transiently transfected with an oestrogen-responsive reporter gene, PhIP (10(-10)-10(-6) M) mediated transcription through oestrogen receptor (ER) alpha, but not ER-beta, and inhibition by the pure ER antagonist ICI 182 780 demonstrated a requirement for a functional ER. In contrast, the structurally related food-derived carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) failed to induce reporter gene transcription. Additionally, we show that in a hormonally responsive breast cancer cell line (MCF-7 cells), PhIP induced transcriptional activation using endogenously expressed ER. Examination of the genotoxic potential of PhIP using a model mammalian cell mutation assay (hprt(-) locus) demonstrated that the genetic toxicology of PhIP was readily detectable, but separate, in terms of effective concentration, from its oestrogenic activity. To determine whether the oestrogenicity of PhIP could mediate oestrogen-dependent responses such as cell growth, we examined the growth of hormonally responsive cells (MCF-7 cells). We show that PhIP can stimulate cell proliferation and, again, this was dependent upon a functional ER. Using ligand blotting, we further show that PhIP can stimulate the expression of progesterone receptor (PR-A and PR-B) and c-MYC and activate the MAPK signal transduction pathway. These responses were similar to that produced by oestradiol, in terms of temporal aspects, potency and a requirement for a functional ER. Each of these dose-dependent mitogenic responses occurred at concentrations of PhIP ( approximately 10(-9)-10(-11)M) that are likely to be equivalent to systemic human exposure via consumption of cooked meat. Thus PhIP can induce cellular responses that encompass altered gene expression and mitogenesis. We suggest that the combination of genetic toxicology and oestrogen-like promotion of genomic and cellular events provide a mechanism for the tissue-specific tumorigenicity of this compound.
MED-5197
Cooked meat and risk of breast cancer--lifetime versus recent dietary intake.
BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HCAs) are carcinogens formed in or on the surface of well-done meat, cooked at high temperature. METHODS: We estimated breast cancer risk in relation to intake of cooked meat in a population-based, case-control study (1508 cases and 1556 controls) conducted in Long Island, NY from 1996 to 1997. Lifetime intakes of grilled or barbecued and smoked meats were derived from the interviewer-administered questionnaire data. Dietary intakes of PAH and HCA were derived from the self-administered modified Block food frequency questionnaire of intake 1 year before reference date. Unconditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Modest increased risk was observed among postmenopausal, but not premenopausal, women consuming the most grilled or barbecued and smoked meats over the life course (OR = 1.47; CI = 1.12-1.92 for highest vs. lowest tertile of intake). Postmenopausal women with low fruit and vegetable intake, but high lifetime intake of grilled or barbecued and smoked meats, had a higher OR of 1.74 (CI = 1.20-2.50). No associations were observed with the food frequency questionnaire-derived intake measures of PAHs and HCAs, with the possible exception of benzo(alpha)pyrene from meat among postmenopausal women whose tumors were positive for both estrogen receptors and progesterone receptors (OR = 1.47; CI = 0.99-2.19). CONCLUSIONS: These results support the accumulating evidence that consumption of meats cooked by methods that promote carcinogen formation may increase risk of postmenopausal breast cancer.
MED-4075
Formation of a mutagenic heterocyclic aromatic amine from creatinine in urine of meat eaters and vegetarians.
Liquid chromatography electrospray ionization mass spectrometry (MS) with a triple quadrupole MS was used to identify known and novel heterocyclic aromatic amines (HAAs) in human urine. The identities of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (8-MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) were confirmed by their product ion spectra. The constant neutral loss scan mode was employed to probe for other analytes in urine that display the transition [M+H]+-->[M+H-CH3*]+*, which is common to HAAs containing an N-methylimidazo moiety, and led to the detection of a previously unreported isomer of 8-MeIQx [Holland, R., et al. (2004) Chem. Res. Toxicol. 17, 1121-1136]. We now report the identification of another novel HAA, 2-amino-1-methylimidazo[4,5-b]quinoline (IQ[4,5-b]), an isomer of the powerful animal carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). The amounts of IQ[4,5-b] measured in the urine of human volunteers who consumed grilled beef ranged from 15 to 135% of the ingested dose, while the amounts of 8-MeIQx and PhIP excreted in urine were on average <2% of the ingested dose. Base treatment of urine at 70 degrees C increased the concentrations of 8-MeIQx and PhIP by as much as 6-fold, indicating the presence of phase II conjugates; however, the amount of IQ[4,5-b] increased by more than 100-fold. IQ[4,5-b] was also detected in the urine of vegetarians following base hydrolysis. The formation of IQ[4,5-b], but not IQ, 8-MeIQx, or PhIP, also occurred in urine incubated at 37 degrees C. Creatinine and 2-aminobenzaldehyde are likely precursors of IQ[4,5-b]. The detection of IQ[4,5-b] in the urine of both meat eaters and vegetarians suggests that this HAA may be present in nonmeat staples or that IQ[4,5-b] formation may occur endogenously within the urinary bladder or other biological fluids.
MED-4853
Effects of a very low-fat, vegan diet in subjects with rheumatoid arthritis.
OBJECTIVE: To demonstrate the effects of a very low-fat, vegan diet on patients with rheumatoid arthritis (RA). DESIGN: Single-blind dietary intervention study. SUBJECTS AND STUDY INTERVENTIONS: This study evaluated the influence of a 4-week, very low-fat (approximately 10%), vegan diet on 24 free-living subjects with RA, average age, 56 +/- 11 years old. OUTCOME MEASUREMENTS: Prestudy and poststudy assessment of RA symptomatology was performed by a rheumatologist blind to the study design. Biochemical measures and 4-day diet data were also collected. Subjects met weekly for diet instruction, compliance monitoring, and progress assessments. RESULTS: There were significant (p < 0.001) decreases in fat (69%), protein (24%), and energy (22%), and a significant increase in carbohydrate (55%) intake. All measures of RA symptomatology decreased significantly (p < 0.05), except for duration of morning stiffness (p > 0.05). Weight also decreased significantly (p < 0.001). At 4 weeks, C-reactive protein decreased 16% (ns, p > 0.05), RA factor decreased 10% (ns, p > 0.05), while erythrocyte sedimentation rate was unchanged (p > 0.05). CONCLUSION: This study showed that patients with moderate-to-severe RA, who switch to a very low-fat, vegan diet can experience significant reductions in RA symptoms.
MED-4128
Validation of a method for the detection of virulent Yersinia enterocolitica and their distribution in slaughter pigs from conventional and alterna...
Various methods have been described in the literature for the detection of virulent Yersinia enterocolitica in pigs. The risk factors for pig herd contamination have yet to be determined. The objective of this study was to validate a sensitive method for the detection of Y. enterocolitica and to describe the distribution of the bacteria in pigs at slaughter from conventional and alternative ("organic") housing systems. First, samples were collected from tonsils, caecum with caecal contents, and the caecal lymph nodes of 60 slaughter pigs. These samples were used to compare the sensitivity of six different laboratory culture methods either in common use or described in the literature with that of a polymerase chain reaction with two primer pairs (multiplex PCR). Then, only PCR was used to examine tonsils, caecum and caecal lymph nodes from two groups of slaughter pigs: 210 from six conventional fattening farms and 200 from three with alternative housing. The results of the multiplex PCR were positive in 28 cases. All culture methods proved inferior to PCR in sensitivity. In the second part of the study, PCR detected 36 (18%) positive pigs from alternative housing and 60 (29%) from conventional housing (p<0.05). The highest rate of Y. enterocolitica contamination was found in tonsils (11% alternative, 22% conventional; p<0.05), followed by caecum (5%, 11%) and lymph nodes (2%, 7%). The housing system appears to be one important factor in the prevalence of this common pathogen in pig herds, as we found important differences between the two systems studied here. In the conventional system, the main risk factors appeared to be sourcing pigs from different pig suppliers, use of commercial feed and transportation to slaughter.
MED-4129
Contamination of carcasses with human pathogenic Yersinia enterocolitica 4/O:3 originates from pigs infected on farms.
Pigs are considered as a major reservoir of human pathogenic Yersinia enterocolitica and a source of human yersiniosis. However, the transmission route of Y. enterocolitica from farm to pork is still unclear. The transmission of pathogenic Y. enterocolitica from pigs to carcasses and pluck sets was investigated by collecting samples from 364 individual ear-tagged pigs on the farm and at the slaughterhouse. In addition, isolated strains were analyzed, using pulsed-field gel electrophoresis. Isolation of similar genotypes of pathogenic Y. enterocolitica 4/O:3 in animals on the farm and at the slaughterhouse and in carcasses shows that carcass contamination originates from the strains a pig carries during the fattening period. Direct contamination from the carrier pig to its subsequent pluck set is also the primary contamination route for pluck sets, but cross-contamination appears to have a larger impact on pluck set contamination than on carcasses. In this study, the within-farm prevalence of pathogenic Y. enterocolitica varied from 0% to 100%, indicating specific farm factors affect the prevalence of Y. enterocolitica in pigs. The association of farm factors with the high prevalence of pathogenic Y. enterocolitica on farms was studied for the first time, using correlation and two-level logistic regression analyses. Specific farm factors, i.e. drinking from a nipple, absence of coarse feed or bedding for slaughter pigs, and no access of pest animals to pig house, were associated with a high prevalence of pathogenic Y. enterocolitica 4/O:3.
MED-4130
Prevalence of Yersinia enterocolitica shedding and bioserotype distribution in Ontario finisher pig herds in 2001, 2002, and 2004.
We investigated characteristics of Yersinia enterocolitica infection in Ontario finisher pig herds. Our specific objectives were to estimate or test: prevalence of Y. enterocolitica shedding in finisher pigs, bioserotype distribution, agreement between the herd-level tests based on sampling pig and pooled fecal samples, whether bioserotypes cluster by farms, and whether Y. enterocolitica-positive herds cluster spatially. In total, 3747 fecal samples were collected from 100 farms over the years 2001, 2002, and 2004 (250 total herd visits). Fecal samples were tested by culture and positive isolates were biotyped and serotyped. Apparent pig-level prevalence of Y. enterocolitica was 1.8%, 3.2%, and 12.5% in 2001, 2002, and 2004, respectively. Estimated true pig-level prevalence of Y. enterocolitica was 5.1%, 9.1%, and 35.1% in 2001, 2002, and 2004, respectively. Herd-level prevalence was 16.3%, 17.9%, and 37.5% in 2001, 2002, and 2004, respectively. In all years, the most common bioserotype was 4, O:3, followed by bioserotype 2, O:5,27. Kappa between herd-level status based on pig and pooled samples ranged between 0.51 and 0.68 for biotype 1A and bioserotype 4, O:3, respectively. For 4, O:3, a significant bias in discordant pairs was detected, indicating that pig samples were more sensitive than pooled samples in declaring a herd as positive. Farms tended to be repeatedly positive with the same bioserotype, but positive study farms did not cluster spatially (suggesting lack of between herd transmission and lack of a common geographic risk factor). Copyright 2009 Elsevier B.V. All rights reserved.
MED-4131
Annual cost of illness and quality-adjusted life year losses in the United States due to 14 foodborne pathogens.
In this article we estimate the annual cost of illness and quality-adjusted life year (QALY) loss in the United States caused by 14 of the 31 major foodborne pathogens reported on by Scallan et al. (Emerg. Infect. Dis. 17:7-15, 2011), based on their incidence estimates of foodborne illness in the United States. These 14 pathogens account for 95 % of illnesses and hospitalizations and 98 % of deaths due to identifiable pathogens estimated by Scallan et al. We estimate that these 14 pathogens cause $14.0 billion (ranging from $4.4 billion to $33.0 billion) in cost of illness and a loss of 61,000 QALYs (ranging from 19,000 to 145,000 QALYs) per year. Roughly 90 % of this loss is caused by five pathogens: nontyphoidal Salmonella enterica ($3.3 billion; 17,000 QALYs), Campylobacter spp. ($1.7 billion; 13,300 QALYs), Listeria monocytogenes ($2.6 billion; 9,400 QALYs), Toxoplasma gondii ($3 billion; 11,000 QALYs), and norovirus ($2 billion; 5,000 QALYs). A companion article attributes losses estimated in this study to the consumption of specific categories of foods. To arrive at these estimates, for each pathogen we create disease outcome trees that characterize the symptoms, severities, durations, outcomes, and likelihoods of health states associated with that pathogen. We then estimate the cost of illness (medical costs, productivity loss, and valuation of premature mortality) for each pathogen. We also estimate QALY loss for each health state associated with a given pathogen, using the EuroQol 5D scale. Construction of disease outcome trees, outcome-specific cost of illness, and EuroQol 5D scoring are described in greater detail in a second companion article.
MED-4132
Ranking the disease burden of 14 pathogens in food sources in the United States using attribution data from outbreak investigations and expert elic...
Understanding the relative public health impact of major microbiological hazards across the food supply is critical for a risk-based national food safety system. This study was conducted to estimate the U.S. health burden of 14 major pathogens in 12 broad categories of food and to then rank the resulting 168 pathogen-food combinations. These pathogens examined were Campylobacter, Clostridium perfringens, Escherichia coli O157:H7, Listeria monocytogenes, norovirus, Salmonella enterica, Toxoplasma gondii, and all other FoodNet pathogens. The health burden associated with each pathogen was measured using new estimates of the cost of illness and loss of quality-adjusted life years (QALYs) from acute and chronic illness and mortality. A new method for attributing illness to foods was developed that relies on both outbreak data and expert elicitation. This method assumes that empirical data are generally preferable to expert judgment; thus, outbreak data were used for attribution except where evidence suggests that these data are considered not representative of food attribution. Based on evaluation of outbreak data, expert elicitation, and published scientific literature, outbreak-based attribution estimates for Campylobacter, Toxoplasma, Cryptosporidium, and Yersinia were determined not representative; therefore, expert-based attribution were included for these four pathogens. Sensitivity analyses were conducted to assess the effect of attribution data assumptions on rankings. Disease burden was concentrated among a relatively small number of pathogen-food combinations. The top 10 pairs were responsible for losses of over $8 billion and 36,000 QALYs, or more than 50 % of the total across all pairs. Across all 14 pathogens, poultry, pork, produce, and complex foods were responsible for nearly 60 % of the total cost of illness and loss of QALYs.
MED-4133
Too early to dismiss Yersinia enterocolitica infection in the aetiology of Graves' disease: evidence from a twin case-control study.
BACKGROUND: Yersinia enterocolitica (YE) infection has long been implicated in the pathogenesis of Graves' disease (GD). The association between YE and GD could, however, also be due to common genetic or environmental factors affecting the development of both YE infection and GD. This potential confounding can be minimized by investigation of twin pairs discordant for GD. AIM: To examine whether YE infection is associated with GD. DESIGN: We first conducted a classical case-control study of individuals with (61) and without (122) GD, and then a case-control study of twin pairs (36) discordant for GD. METHODS: Immunoglobulin (Ig)A and IgG antibodies to virulence-associated Yersinia outer membrane proteins (YOPs) were measured. MAIN OUTCOME MEASURES: The prevalence of YOP IgA and IgG antibodies. RESULTS: Subjects with GD had a higher prevalence of YOP IgA (49%vs. 34%, P = 0.054) and YPO IgG (51%vs. 35%, P = 0.043) than the external controls. The frequency of chronic YE infection, reflected by the presence of both IgA and IgG YOP antibodies, was also higher among cases than controls (49%vs. 33%, P = 0.042). Similar results were found in twin pairs discordant for GD. In the case-control analysis, individuals with GD had an increased odds ratio (OR) of YE infection: IgA 1.84 (95% CI 0.99-3.45) and IgG 1.90 (95% CI 1.02-3.55). In the co-twin analysis, the twin with GD also had an increased OR of YE infection: IgA 5.5 (95% CI 1.21-24.81) and IgG 5.0 (95% CI 1.10-22.81). CONCLUSION: The finding of an association between GD and YE in the case-control study and within twin pairs discordant for GD supports the notion that YE infection plays an aetiological role in the occurrence of GD, or vice versa. Future studies should examine the temporal relationship of this association in more depth.
MED-4134
Prevalence of Pathogenic Yersinia enterocolitica Strains in Pigs in the United States
Yersinia enterocolitica is considered an important food-borne pathogen impacting the pork production and processing industry in the United States. Since this bacterium is a commensal of swine, the primary goal of this study was to determine the prevalence of pathogenic Y. enterocolitica in pigs in the United Sates using feces as the sample source. A total of 2,793 fecal samples were tested for its presence in swine. Fecal samples were collected from late finisher pigs from 77 production sites in the 15 eastern and midwestern pork-producing states over a period of 27 weeks (6 September 2000 to 20 March 2001). The prevalence of ail-positive Y. enterocolitica was determined in samples using both a fluorogenic 5′ nuclease PCR assay and a culture method. The mean prevalence was 13.10% (366 of 2,793 fecal samples tested) when both PCR- and culture-positive results were combined. Forty-one of 77 premises (53.25%) contained at least one fecal sample positive for the ail sequence. The PCR assay indicated a contamination rate of 12.35% (345/2,793) compared to 4.08% (114/2,793) by the culture method. Of the 345 PCR-positive samples, 252 were culture negative, while of the 114 culture-positive samples, 21 were PCR negative. Among 77 premises, the PCR assay revealed a significantly (P < 0.05) higher percentage (46.75%, n = 36 sites) of samples positive for the pathogen (ail sequence) than the culture method (22.08%, n = 17 sites). Thus, higher sensitivity, with respect to number of samples and sites identified as positive for the PCR method compared with the culture method for detecting pathogenic Y. enterocolitica, was demonstrated in this study. The results support the hypothesis that swine are a reservoir for Y. enterocolitica strains potentially pathogenic for humans.
MED-4135
Behavior of Yersinia enterocolitica in Foods
Yersinia enterocolitica are ubiquitous, being isolated frequently from soil, water, animals, and a variety of foods. They comprise a biochemically heterogeneous group that can survive and grow at refrigeration temperatures. The ability to propagate at refrigeration temperatures is of considerable significance in food hygiene. Virulent strains of Yersinia invade mammalian cells such as HeLa cells in tissue culture. Two chromosomal genes, inv and ail, were identified for cell invasion of mammalian. The pathogen can cause diarrhoea, appendicitis and post-infection arthritis may occur in a small proportion of cases. The most common transmission route of pathogenic Y. enterocolitica is thought to be fecal-oral via contaminated food. Direct person-to-person contact is rare. Occasionally, pathogenic Y. enterocolitica has been detected in vegetables and environmental water; thus, vegetables and untreated water are also potential sources of human yersiniosis. However, the isolation rates of pathogenic Y. enterocolitica have been low, which may be due to the limited sensitivity of the detection methods. To identify other possible transmission vehicles, different food items should be studied more extensively. Many factors related to the epidemiology of Y. enterocolitica, such as sources, transmission routes, and predominating genotypes remain obscure because of the low sensitivity of detection methods.
MED-4136
Vital signs: incidence and trends of infection with pathogens transmitted commonly through food--foodborne diseases active surveillance network, 10...
BACKGROUND: In the United States, contaminated food causes approximately 1,000 reported disease outbreaks and an estimated 48 million illnesses, 128,000 METHODS: The Foodborne Diseases Active Surveillance Network (FoodNet) conducts surveillance among 15% of the U.S. population for laboratory-confirmed infections with nine pathogens transmitted commonly through food. Overall and pathogen-specific changes in incidence were estimated from 1996-1998 to 2010 and from 2006-2008 to 2010.hospitalizations, and 3,000 deaths annually. This report summarizes 2010 surveillance data and describes trends since 1996. RESULTS: A total of 19,089 infections, 4,247 hospitalizations, and 68 deaths were reported from FoodNet sites in 2010. Salmonella infection was the most common infection reported (17.6 illnesses per 100,000 persons) and was associated with the largest number of hospitalizations (2,290) and deaths (29); no significant change in incidence of Salmonella infection has occurred since the start of surveillance during 1996-1998. Shiga toxin-producing Escherichia coli (STEC) O157 infection caused 0.9 illnesses per 100,000. Compared with 1996-1998, overall incidence of infection with six key pathogens in 2010 was 23% lower, and pathogen-specific incidence was lower for Campylobacter, Listeria, STEC O157, Shigella, and Yersinia infection but higher for Vibrio infection. Compared with a more recent period, 2006--2008, incidence in 2010 was lower for STEC O157 and Shigella infection but higher for Vibrio infection. CONCLUSIONS: The incidence of STEC O157 infection has declined to reach the 2010 national health objective target of ≥1 case per 100,000. This success, as well as marked declines since 1996-1998 in overall incidence of six key foodborne infections, demonstrates the feasibility of preventing foodborne illnesses. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Salmonella infection should be targeted because it has not declined significantly in more than a decade, and other data indicate that it is one of the most common foodborne infections, resulting in an estimated $365 million in direct medical costs annually. The prevention measures that reduced STEC O157 infection need to be applied more broadly to reduce Salmonella and other infections. Effective measures from farm to table include preventing contamination of meat during slaughter and of all foods, including produce, during processing and preparation; cooking meat thoroughly; vigorously detecting and investigating outbreaks; and recalling contaminated food.
MED-4137
Prevalence of Yersinia enterocolitica in different phases of production on swine farms.
Swine have been identified as the primary reservoir of pathogenic Yersinia enterocolitica (YE), but little research has focused on the epidemiology of YE at the farm level. The objective of this study was to describe the prevalence of YE in different production phases on swine farms. In this cross-sectional study, individual pigs on eight swine operations were sampled for the presence of YE. On each farm, both feces and oral-pharyngeal swabs were collected from pigs in five different production phases: gestating, farrowing, suckling, nursery, and finishing. A pig was considered positive if either sample tested positive. Samples were cultured with cold enrichment followed by isolation on selective media plates. Presumptive isolates were confirmed as YE and assayed for the presence of ail with a multiplex PCR. Of the 2,349 pigs sampled, 120 (5.1%) tested positive, and of those, 51 were ail positive (42.5% of YE isolates). On all farms, there was a trend of increasing prevalence as pigs mature. Less than 1% of suckling piglets tested positive for YE. Only 1.4% (44.4% of which were ail positive) of nursery pigs tested positive, but 10.7% (48.1% of which were ail positive) of finishing pigs harbored YE. Interestingly, gestating sows had the second highest prevalence of YE at 9.1% (26.7% of which were ail positive), yet YE was never detected from the farrowing sows. These results represent the first on-farm description of YE in U.S. herds and provide the initial step for designing future studies of YE.
MED-4138
Yersinia enterocolitica: a brief review of the issues relating to the zoonotic pathogen, public health challenges, and the pork production chain.
Yersinia enterocolitica is a zoonotic agent that causes gastrointestinal disease in humans, as well as reactive arthritis and erythema nodosum. Enteropathogenic Yersinia are the etiological agents for yersiniosis, which can be acquired through the consumption of contaminated foods. As porcine animals are the main carriers of Y. enterocolitica, food safety measures to minimize human infection are of increasing interest to the scientific and medical community. In this review, we examine why it is imperative that information on the reservoirs, prevalence, virulence, and ability of this pathogen to survive in different environments is further investigated to provide rational measures to prevent or decrease associated disease risks.
MED-4139
Prevalence of Yersinia enterocolitica in market weight hogs in the United States.
Pigs are the major animal reservoir for Yersinia enterocolitica strains, which are potentially pathogenic for humans. The goals of this study were (i) to estimate the individual animal and on-farm prevalences of Y. enterocolitica in hogs based on tonsil samples collected during National Animal Health Monitoring System Swine 2002 study and (ii) to use these data with data previously published for fecal samples to determine on-farm risk factors for Y. enterocolitica. Tonsil swabs (1,218) and fecal samples (2,847) were collected on 124 farms located in the top 17 pork-producing states. Ten percent of tonsils (122 of 1,218 samples) were positive in irgasan-tiracillin-chlorate (ITC) enrichment broth by real-time PCR, but only 5.6% of samples (68 of 1,218) were positive after subculture on the more selective cefsulodin-irgasan-novobiocin (CIN) agar. For tonsils, the on-farm prevalence based on real-time PCR detection of the ail gene in ITC enrichment broth cultures was 32% (32 of 100 premises sampled); the prevalence based on subculture in CIN agar was 19.6% (20 of 102 premises). Results of bacteriological isolation and real-time PCR analysis of tonsils and feces were combined to estimate prevalence (individual animal and farm), which was subsequently correlated with 40 farm management practices. Four factors and their accompanying odds ratios (ORs) were identified in the final regression model: location in a central state (OR = 0.3), vaccination for Escherichia coli (OR = 3.0), percentage of deaths due to scours (OR = 3.5), and presence of meat or bone meal in grower-finisher diet (OR = 4.1).
MED-4140
Factors related to the prevalence of pathogenic Yersinia enterocolitica on pig farms.
A survey of 788 pigs from 120 farms was conducted to determine the within-farm prevalence of pathogenic Yersinia enterocolitica and a questionnaire of management conditions was mailed to the farms afterwards. A univariate statistical analysis with carriage and shedding as outcomes was conducted with random-effects logistic regression with farm as a clustering factor. Variables with a P value <0·15 were included into the respective multivariate random-effects logistic regression model. The use of municipal water was discovered to be a protective factor against carriage and faecal shedding of the pathogen. Organic production and buying feed from a certain feed manufacturer were also protective against total carriage. Tonsillar carriage, a different feed manufacturer, fasting pigs before transport to the slaughterhouse, higher-level farm health classification, and snout contacts between pigs were risk factors for faecal shedding. We concluded that differences in management can explain different prevalences of Y. enterocolitica between farms.
MED-4141
Piglets Are a Source of Pathogenic Yersinia enterocolitica on Fattening-Pig Farms
To study the origin and spread of Yersinia enterocolitica among pigs, fecal and blood samples were repeatedly taken on a fattening farm. A few piglets were found to be already infected on breeding farms. After the piglets were mixed, the infection spread through the whole unit. Eventually, all the pigs excreted the pathogen.
MED-4142
Human pathogens and tetracycline-resistant bacteria in bioaerosols of swine confinement buildings and in nasal flora of hog producers.
Swine confinement buildings in eastern Canada are enclosed and equipped with modern production systems to manage waste. Bioaerosols of these swine confinement buildings could be contaminated by human pathogens and antimicrobial resistant bacteria which could colonize exposed workers. We therefore wanted to analyze bioaerosols of swine confinement buildings and nasal flora of Canadian hog producers to evaluate possible colonization with human pathogens and tetracycline-resistant bacteria. Culturable and non-culturable human pathogens and tet genes were investigated in the bioaerosols of 18 barns. The nasal passages of 35 hog producers were sampled and total DNA was extracted from the calcium-alginate swabs to detect, by PCR, Campylobacter, C. perfringens, Enterococcus, E. coli, Y. enterocolitica, tetA/tetC, tetG and ribosomal protection protein genes. Airborne culturable C. perfringens, Enterococcus, E. coli, and Y. enterocolitica were present in the bioaerosols of 16, 17, 11 and 6 of the 18 facilities. Aerosolized total (culturable/non culturable) Campylobacter, C. perfringens, Enterococcus, E. coli and Y. enterocolitica were detected in 10, 6, 15, 18 and 2 barns, respectively. Tet genes were found in isolates of culturable human pathogens. TetA/tetC, tetG and ribosomal protection protein genes were detected in the bioaerosols of all 18 studied buildings. Campylobacter, C. perfringens, Enterococcus, E. coli, and Y. enterocolitica were found respectively in 4, 9, 17, 14 and one nasal flora of workers. One and 10 workers were positive for tetA/tetC and tetG genes, respectively. In swine confinement buildings, hog producers are exposed to aerosolized human pathogens and tetracycline-resistant bacteria that can contaminate the nasal flora. Copyright © 2010 Elsevier GmbH. All rights reserved.
MED-4143
Yersinia enterocolitica infection in diarrheal patients.
In this study, we hoped to provide valuable clinical information on yersiniosis for clinicians. Two thousand six hundred stool samples were collected from in- and outpatients with diarrhea, which were tested with both culture method and real-time polymerase chain reaction (RT-PCR). In total, 188 positive samples were detected by RT-PCR (178) and culture method (160), while the incidence was about 7.23%. The detection rate of RT-PCR was significantly higher than culture method and a higher incidence in autumn-winter was also noticeably identified than in spring-summer. Infection sources mostly focused on unboiled foods (101) and pets (45), while clinical manifestation mainly presented as gastroenteritis (156), pseudoappendicitis (32), and extraintestinal complications (46). The morbidity of extraintestinal complications in adults was significantly higher than in children and it was the same for high-risk patients between adults over the age of 60 years (4.7%) and children under the age of 3 years (1.4%), whereas the constituent ratio of children versus adults with yersiniosis in different systems was not significant. Of 160 isolates tested for antimicrobial susceptibility, the majority were susceptible to third-generation cephalosporins, aminoglycosides, fluoroquinolones, and trimethoprim-sulfamethoxazole, whereas only a small portion was susceptible to the first-generation cephalosporins and penicillins. During autumn-winter months, clinicians should pay more attention to clinical manifestation, early diagnosis, and treatment with susceptible antibiotics of yersiniosis and its complications, targeting high-risk patients.
MED-4167
Influence of water and food consumption on inadvertent antibiotics intake among general population.
Antibiotic entry into the water environment has been of growing concern. However, few investigations have been performed to examine the potential for indirect human exposure to environmental antibiotic residues. We evaluated the contribution of drinking water and major food consumption to inadvertent intake of antibiotic residues among general human population in Korea. We estimated daily human intake of six antibiotics, i.e., sulfamethazine (SMZ), sulfamethoxazole (SMX), sulfathiazole (STZ), trimethoprim (TMP), enrofloxacin (EFX), and roxithromycin (RTM), by measuring the concentrations of the antibiotics and their major metabolites in urine from general population in Korea (n=541). In addition, we measured antibiotics from source water of drinking water as well as in tap water samples, and surveyed water consumption rates among the study population. To assess the contribution of dietary factor, we also surveyed consumption pattern for several major foods which are suspected of antibiotics residue. SMZ, Sulfamethazine-N4-acetyl (SMZ-N4), TMP, EFX, ciprofloxacin (CFX), and RTM were detected up to 448, 6210, 11,900, 6970, 32,400, and 151pg/ml in the urine samples, respectively. Estimates of daily intake of major antibiotics did not appear to be related with consumption of drinking water although antibiotics were frequently detected in source waters (10-67ng/l). Consumption of several foods correlated significantly with urinary excretion of several antibiotics. Daily intake estimates of EFX and CFX were associated with consumption of beef, pork, and dairy products; those of SMZ and TMP associated with pork and dairy products; and that of TMP related with raw fish. Daily antibiotics intake estimates however did not exceed the acceptable daily intake levels. Copyright 2010 Elsevier Inc. All rights reserved.
MED-4168
Influence of a five-day vegetarian diet on urinary levels of antibiotics and phthalate metabolites: a pilot study with "Temple Stay" participants.
Diet is purported to be means of exposure to many environmental contaminants. The purpose of this study is to understand the influence of dietary change on the levels of exposure to several environmental chemicals - in particular, antibiotics and phthalates. For this purpose, we examined the extent to which short-term changes in diet influenced the inadvertent exposure levels to these chemicals in an adult population. We recruited participants (n=25) of a five-day 'Temple Stay' program in Korea and collected urine samples before and after the program. We also conducted a questionnaire survey on participants' dietary patterns prior to their participation. During the program, participants followed the daily routines of Buddhist monks and maintained a vegetarian diet. Urinary levels of three antibiotics and their major metabolites, metabolites of four major phthalates, and malondialdehyde (MDA) as an oxidative stress biomarker were analyzed. The frequency and levels of detection for antibiotics and phthalates noticeably decreased during the program. Urinary MDA levels were significantly lower than before program participation (0.16 versus 0.27mg/g creatinine). Although the exposure to target compounds might be influenced by other behavioral patterns, these results suggest that even short-term changes in dietary behavior may significantly decrease inadvertent exposure to antibiotics and phthalates and hence may reduce oxidative stress levels. Copyright 2010 Elsevier Inc. All rights reserved.
MED-4333
High Fat Intake Leads to Acute Postprandial Exposure to Circulating Endotoxin in Type 2 Diabetic Subjects
OBJECTIVE To evaluate the changes in circulating endotoxin after a high–saturated fat meal to determine whether these effects depend on metabolic disease state. RESEARCH DESIGN AND METHODS Subjects (n = 54) were given a high-fat meal (75 g fat, 5 g carbohydrate, 6 g protein) after an overnight fast (nonobese control [NOC]: age 39.9 ± 11.8 years [mean ± SD], BMI 24.9 ± 3.2 kg/m2, n = 9; obese: age 43.8 ± 9.5 years, BMI 33.3 ± 2.5 kg/m2, n = 15; impaired glucose tolerance [IGT]: age 41.7 ± 11.3 years, BMI 32.0 ± 4.5 kg/m2, n = 12; type 2 diabetic: age 45.4 ± 10.1 years, BMI 30.3 ± 4.5 kg/m2, n = 18). Blood was collected before (0 h) and after the meal (1–4 h) for analysis. RESULTS Baseline endotoxin was significantly higher in the type 2 diabetic and IGT subjects than in NOC subjects, with baseline circulating endotoxin levels 60.6% higher in type 2 diabetic subjects than in NOC subjects (P < 0.05). Ingestion of a high-fat meal led to a significant rise in endotoxin levels in type 2 diabetic, IGT, and obese subjects over the 4-h time period (P < 0.05). These findings also showed that, at 4 h after a meal, type 2 diabetic subjects had higher circulating endotoxin levels (125.4%↑) than NOC subjects (P < 0.05). CONCLUSIONS These studies have highlighted that exposure to a high-fat meal elevates circulating endotoxin irrespective of metabolic state, as early as 1 h after a meal. However, this increase is substantial in IGT and type 2 diabetic subjects, suggesting that metabolic endotoxinemia is exacerbated after high fat intake. In conclusion, our data suggest that, in a compromised metabolic state such as type 2 diabetes, a continual snacking routine will cumulatively promote their condition more rapidly than in other individuals because of the greater exposure to endotoxin.
MED-4337
The capacity of foodstuffs to induce innate immune activation of human monocytes in vitro is dependent on food content of stimulants of Toll-like r...
The ingestion of fatty meals is associated with a transient, low-grade systemic inflammatory response in human subjects, involving the activation of circulating monocytes and the secretion of pro-inflammatory cytokines. However, it is not yet clear how different foodstuffs may promote inflammatory signalling. In a screen of forty filter-sterilised soluble extracts from common foodstuffs, seven were found to induce the secretion of TNF-α and IL-6 from human monocytes in vitro. To investigate what may differentiate inflammatory from non-inflammatory food extracts, stimulants of Toll-like receptor (TLR) 2 and TLR4 were quantified using human embryonic kidney-293 cells transfected with each TLR, and calibrated with defined bacterial lipopeptide (BLP) and lipopolysaccharide (LPS) standards. These assays revealed that while most foods contained undetectable levels of TLR2 or TLR4 stimulants, all TNF-α-inducing foods contained stimulants of either TLR2 (up to 1100 ng BLP-equivalent/g) or TLR4 (up to 2700 ng LPS-equivalent/g) in both the soluble and insoluble fractions. TLR stimulants were present mainly in meat products and processed foods, but were minimal or undetectable in fresh fruit and vegetables. The capacity of food extracts to induce TNF-α secretion in monocytes correlated with the content of both TLR2 (r 0·837) and TLR4 stimulants (r 0·748), and was completely abolished by specific inhibition of TLR2 and TLR4. LPS and BLP were found to be highly resistant to typical cooking times and temperatures, low pH and protease treatment. In conclusion, apparently unspoiled foodstuffs can contain large quantities of stimulants of TLR2 and TLR4, both of which may regulate their capacity to stimulate inflammatory signalling.
MED-4342
Animal protein intake and risk of inflammatory bowel disease: The E3N prospective study.
OBJECTIVES: Diet composition has long been suspected to contribute to inflammatory bowel disease (IBD), but has not been thoroughly assessed, and has been assessed only in retrospective studies that are prone to recall bias. The aim of the present study was to evaluate the role of dietary macronutrients in the etiology of IBD in a large prospective cohort. METHODS: The Etude Épidémiologique des femmes de la Mutuelle Générale de l'Education Nationale cohort consists of women living in France, aged 40-65 years, and free of major diseases at inclusion. A self-administered questionnaire was used to record dietary habits at baseline. Questionnaires on disease occurrence and lifestyle factors were completed every 24 months. IBDs were assessed in each questionnaire until June 2005, and subsequently validated using clinical and pathological criteria. We estimated the association between nutrients or foods and IBD using Cox proportional hazards models adjusted for energy intake. RESULTS: Among 67,581 participants (705,445 person-years, mean follow-up since completion of the baseline dietary questionnaire 10.4 years), we validated 77 incident IBD cases. High total protein intake, specifically animal protein, was associated with a significantly increased risk of IBD, (hazards ratio for the third vs. first tertile and 95% confidence interval being 3.31 and 1.41-7.77 (P trend=0.007), and 3.03 and 1.45-6.34 (P trend=0.005) for total and animal protein, respectively). Among sources of animal protein, high consumption of meat or fish but not of eggs or dairy products was associated with IBD risk. CONCLUSIONS: High protein intake is associated with an increased risk of incident IBD in French middle-aged women.
MED-4349
Anti-inflammatory effects of plant-based foods and of their constituents.
Inflammation is a pathological condition underlying a number of diseases including cardiovascular diseases, cancer, and chronic inflammatory diseases. In addition, healthy, obese subjects also express markers of inflammation in their blood. Diet provides a variety of nutrients as well as non-nutritive bioactive constituents which modulate immunomodulatory and inflammatory processes. Epidemiological data suggest that dietary patterns strongly affect inflammatory processes. Primarily the intake of fruit and vegetables as well as of whole wheat is inversely associated with the risk of inflammation. In addition to observational studies there are also data from human intervention studies suggesting an anti-inflammatory potential of these plant foods. At the level of bioactive compounds occurring in plant foods, primarily carotenoids and flavonoids seem to modulate inflammatory as well as immunological processes. In conclusion, there is convincing evidence that plant foods and non-nutritive constituents associated with these foods modulate immunological and inflammatory processes. By means of anti-inflammatory activities a plant-based diet may contribute to the lower risk of cardiovascular diseases and cancer. A high intake of vegetables, fruit, and whole wheat as recommended by all international nutrition authorities provides a wide spectrum of bioactive compounds at health-promoting concentrations.
MED-5326
Red meat and colon cancer: should we become vegetarians, or can we make meat safer?
The effect of meat consumption on cancer risk is a controversial issue. However, recent meta-analyses show that high consumers of cured meats and red meat are at increased risk of colorectal cancer. This increase is significant but modest (20-30%). Current WCRF-AICR recommendations are to eat no more than 500 g per week of red meat, and to avoid processed meat. Moreover, our studies show that beef meat and cured pork meat promote colon carcinogenesis in rats. The major promoter in meat is heme iron, via N-nitrosation or fat peroxidation. Dietary additives can suppress the toxic effects of heme iron. For instance, promotion of colon carcinogenesis in rats by cooked, nitrite-treated and oxidized high-heme cured meat was suppressed by dietary calcium and by α-tocopherol, and a study in volunteers supported these protective effects in humans. These additives, and others still under study, could provide an acceptable way to prevent colorectal cancer. Copyright © 2011 Elsevier B.V. All rights reserved.
MED-4488
Epidemilogical trends strongly suggest exposures as etiologic agents in the pathogenesis of sporadic Alzheimer's disease, diabetes mellitus, and no...
Nitrosamines mediate their mutagenic effects by causing DNA damage, oxidative stress, lipid peroxidation, and pro-inflammatory cytokine activation, which lead to increased cellular degeneration and death. However, the very same pathophysiological processes comprise the "unbuilding" blocks of aging and insulin-resistance diseases including, neurodegeneration, diabetes mellitus (DM), and non-alcoholic steatohepatitis (NASH). Previous studies demonstrated that experimental exposure to streptozotocin, a nitrosamine-related compound, causes NASH, and diabetes mellitus Types 1, 2 and 3 (Alzheimer (AD)-type neurodegeneration). Herein, we review evidence that the upwardly spiraling trends in mortality rates due to DM, AD, and Parkinson's disease typify exposure rather than genetic-based disease models, and parallel the progressive increases in human exposure to nitrates, nitrites, and nitrosamines via processed/preserved foods. We propose that such chronic exposures have critical roles in the pathogenesis of our insulin resistance disease pandemic. Potential solutions include: 1) eliminating the use of nitrites in food; 2) reducing nitrate levels in fertilizer and water used to irrigate crops; and 3) employing safe and effective measures to detoxify food and water prior to human consumption. Future research efforts should focus on refining our ability to detect and monitor human exposures to nitrosamines and assess early evidence of nitrosamine-mediated tissue injury and insulin resistance.
MED-4489
The nitrate story--no end in sight.
It has been demonstrated that nitrates are reduced to nitrites in humans, possibly through bacterial activity. Nitrites, together with ubiquitous amines, can lead to an in-vivo synthesis of carcinogenic nitrosamines. The average daily intake of nitrates depends upon the amount of vegetables consumed and on the nitrate concentration in drinking water. Agricultural practices play an important part in the concentration of nitrate in both water and vegetables. If nitrate is taken up by the plant and not metabolised to amino acids, proteins or nucleic acids, it is stored in cell vacuoles as a reserve. However, with an over-supply of nitrate relative to possible photosynthesis, this stored nitrate is still present at harvest and leads to high concentrations in plant tissue. The nitrate content in plants also depends upon other factors, such as plant variety (cultivar), kind and amount of fertiliser, time of harvest and environmental factors such as light intensity, temperature, etc. It is suggested that we should try to meet the recommendations of toxicologists who believe a dramatic reduction nitrate intake for humans is necessary. It has been demonstrated that modern biological-organic farming methods clearly lead both to lower leaching of nitrates and to lower nitrate content in vegetables. Since no synthetic fungicides are used in this farming method, problems with the reaction of metabolites of such products and nitrites e.g. to highly cancerogenic and multigenic nitroso-ethylenethiourea do not exist.
MED-4490
A survey of feeding N-nitrosodimethylamine (NDMA) to domestic animals over an 18 year period.
Sodium nitrite and formalin have been used as preservatives in the fish meal industry in Norway since 1953. In 1957, fur farms suffered losses of mink due to a new, malignant liver disease. Experimental feeding of herring meal to cows and sheep resulted in the death of some of the animals. Further studies showed that amines (TMAO) normally present in fish, can react with sodium nitrite used as preservative, or nitrogen oxides from the combustion of fuel oils used during processing, to produce the toxic agent, NDMA. Mink and fox may consume considerable amounts of fish meal in their diets. If the fish meal contains sufficient NDMA, the incidence of liver failure or tumours can be quite high. Long-term exposure to as little as 0.1 mg NDMA/kg b.w./day in the diet of mink, cows and sheep can produce fibro-occlusive changes in the hepatic vessels. These lesions can later cause capillary ectasies-like changes in cows, which are similar in appearance to hemangiomas seen in mink. The mink liver hemangiomas develop into hemangiosarcomas. We currently consider capillary ectasies-like changes in cows exposed to NDMA to represent pre-cancerous lesions.
MED-4491
Nutritional composition of dry-cured ham and its role in a healthy diet.
Dry-cured ham is a traditional product with a strong presence in markets in the Mediterranean area. It is very popular with European consumers and is of enormous economic importance for the meat industry in the Mediterranean area. Although the great palatability of ham largely outweighs other considerations, aspects relating to health and wellbeing are increasingly important factors in consumer decisions. The potential role of ham in a context of healthy nutrition has not been clearly elucidated, especially considering that origins and production methods of dry-cured hams can induce differences in composition. The object of this review was on the one hand to provide an analysis of the components of dry-cured ham and their role in a healthy diet, and on the other hand to suggest possible strategies for improving its nutritional composition. 2009 Elsevier Ltd. All rights reserved.
MED-4492
A meta-analysis of maternal cured meat consumption during pregnancy and the risk of childhood brain tumors.
OBJECTIVE: N-Nitroso compounds (NOCs) are recognized neural carcinogens in animal models and are suspected human carcinogens. A meta-analysis was performed examining the possible association of maternal intake of cured meat (an important source of dietary NOCs) during pregnancy and the risk of pediatric brain tumors. METHODS: Data from epidemiological studies were pooled using a general variance-based meta-analytic method employing confidence intervals described by Greenland in 1986. The outcome of interest was a summary relative risk (RR) reflecting the risk of childhood brain tumor (CBT) development associated with maternal intake of cured meats during pregnancy. Sensitivity analyses were performed when necessary to explain any observed statistical heterogeneity. RESULTS: Seven observational studies were found that met the protocol-specified inclusion criteria. Analysis for heterogeneity demonstrated a lack of statistical heterogeneity (p = 0.59), indicating that the data could be statistically combined. Pooling data from the 6 reports containing data on maternal cured meat intake of all types yielded an RR of 1.68 (1.30- 2.17), being a statistically significant result. Analyzing CBT risk by type of cured meat ingested showed that hot dog consumption increased CBT risk by 33% (1.08-1.66), with a similar increase shown by frequent ingestion of sausage, i.e. 44%. CONCLUSION: The data provide support for the suspected causal association between ingestion of NOCs from cured meats during pregnancy and subsequent CBT in offspring. Limitations in study design preclude definitive conclusions, but the relationship warrants exploration via additional observational and laboratory-based studies. Copyright 2004 S. Karger AG, Basel
MED-4604
The comet assay with 8 mouse organs: results with 39 currently used food additives.
We determined the genotoxicity of 39 chemicals currently in use as food additives. They fell into six categories-dyes, color fixatives and preservatives, preservatives, antioxidants, fungicides, and sweeteners. We tested groups of four male ddY mice once orally with each additive at up to 0.5xLD(50) or the limit dose (2000mg/kg) and performed the comet assay on the glandular stomach, colon, liver, kidney, urinary bladder, lung, brain, and bone marrow 3 and 24h after treatment. Of all the additives, dyes were the most genotoxic. Amaranth, Allura Red, New Coccine, Tartrazine, Erythrosine, Phloxine, and Rose Bengal induced dose-related DNA damage in the glandular stomach, colon, and/or urinary bladder. All seven dyes induced DNA damage in the gastrointestinal organs at a low dose (10 or 100mg/kg). Among them, Amaranth, Allura Red, New Coccine, and Tartrazine induced DNA damage in the colon at close to the acceptable daily intakes (ADIs). Two antioxidants (butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT)), three fungicides (biphenyl, sodium o-phenylphenol, and thiabendazole), and four sweeteners (sodium cyclamate, saccharin, sodium saccharin, and sucralose) also induced DNA damage in gastrointestinal organs. Based on these results, we believe that more extensive assessment of food additives in current use is warranted.
MED-4605
Genotoxicity and cell transformation studies with sorbates in Syrian hamster embryo fibroblasts.
Sorbic acid, sodium sorbate and potassium sorbate were tested for their genotoxic potential in the Syrian hamster embryo (SHE) fibroblast micronucleus assay and the SHE cell transformation test in vitro. Sorbic acid and potassium sorbate showed no activity in either test system. When freshly prepared sodium sorbate solutions were used, no genotoxic or cell-transforming activity was detected. However, sodium sorbate as stored solution, which previously had been heated and sonicated to facilitate solubilization, yielded a positive response in both test systems. It is concluded that oxidation products of sodium sorbate that possess genotoxic and cell-transforming properties are formed under conditions of heating, sonication and storage.
MED-4606
Does potassium sorbate induce genotoxic or mutagenic effects in lymphocytes?
The present study evaluates the genotoxic potential of potassium sorbate (PS) in cultured and isolated human lymphocytes. To assess the damage caused by PS in humans, we designed in vitro experiments by measuring chromosomal aberrations (CAs), sister-chromatid exchanges (SCEs), micronucleus (MN) and comet assays. Lymphocytes were treated with negative control (sterile distilled water), positive control (MMC for cultured lymphocytes, and H(2)O(2) for isolated lymphocytes) and four concentrations (125, 250, 500, and 1000 microg/ml) of PS. According to the results, PS treatment significantly increases the CAs (with or without gaps at 500 and 1000 microg/ml concentrations) and SCEs (at 250, 500, 1000 microg/ml for 24h and 125, 250, 500, 1000 microg/ml for 48h) compared with vehicle control. Following treatment of the isolated lymphocytes for 1h, significant PS-induced DNA strand breaks were observed, at all concentrations. However, PS failed to significantly affect the MN assay. On the contrary, PS does not cause cell cycle delay as noted by the non-significant decrease in the cytokinesis-block proliferation index (CBPI) and replicative index (RI). Only a slight decrease was observed in the mitotic index (MI) at the highest concentration for both treatment times. From the results, PS is clearly seen to be genotoxic to the human peripheral blood lymphocytes in vitro. Copyright (c) 2009 Elsevier Ltd. All rights reserved.
MED-4607
Effects of sorbic acid and its salts on chromosome aberrations, sister chromatid exchanges and gene mutations in cultured Chinese hamster cells.
The ability of sorbic acid and its potassium and sodium salts to induce chromosome aberrations, sister chromatid exchanges (SCE) and gene mutations in cultured Chinese hamster V79 cells was examined. Sodium sorbate caused significant induction of chromosome aberrations and SCE, and also induced 6-thioguanine-resistant mutations in a dose-dependent manner. The clastogenic potency of sodium sorbate was found to be less than one hundredth of that of the potent clastogen N-methyl-N'-nitro-N-nitrosoguanidine. The induction of SCE by sodium sorbate was twice the control level, whereas that by methyl methanesulphonate, a potent inducer of SCE, was 14 times the control level. The mutagenic potency of sodium sorbate was less than one-tenth that of ethyl methanesulphonate, a potent inducer of mutation, when compared at an equitoxic level. Sorbic acid and its potassium salt induced chromosome aberrations, but only at the highest doses tested. These compounds also induced 1.2 times the control level of SCE, but neither compound induced 6-thioguanine-resistant mutations. The cytogenetic activity of sodium sorbate was concluded not to be due to the effect of osmotic pressure or an impurity. These results indicate that sodium sorbate is a genotoxic agent, although its potency seems to be weak, and that sorbic acid and potassium sorbate are less genotoxic than the sodium salt.
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-4908
Aluminium and lead: molecular mechanisms of brain toxicity.
The fact that aluminium (Al) and lead (Pb) are both toxic metals to living organisms, including human beings, was discovered a long time ago. Even when Al and Pb can reach and accumulate in almost every organ in the human body, the central nervous system is a particular target of the deleterious effects of both metals. Select human population can be at risk of Al neurotoxicity, and Al is proposed to be involved in the etiology of neurodegenerative diseases. Pb is a widespread environmental hazard, and the neurotoxic effects of Pb are a major public health concern. In spite of the numerous efforts and the accumulating evidence in this area of research, the mechanisms of Al and Pb neurotoxicity are still not completely elucidated. This review will particularly address the involvement of oxidative stress, membrane biophysics alterations, deregulation of cell signaling, and the impairment of neurotransmission as key aspects involved Al and Pb neurotoxicity.
MED-4909
Aluminum bioavailability from basic sodium aluminum phosphate, an approved food additive emulsifying agent, incorporated in cheese
Oral aluminum (Al) bioavailability from drinking water has been previously estimated, but there is little information on Al bioavailability from foods. It was suggested that oral Al bioavailability from drinking water is much greater than from foods. The objective was to further test this hypothesis. Oral Al bioavailability was determined in the rat from basic [26Al]-sodium aluminum phosphate (basic SALP) in a process cheese. Consumption of ~ 1 gm cheese containing 1.5 or 3% basic SALP resulted in oral Al bioavailability (F) of ~ 0.1 and 0.3%, respectively, and time to maximum serum 26Al concentration (Tmax) of 8 to 9 h. These Al bioavailability results were intermediate to previously reported results from drinking water (F ~ 0.3%) and acidic-SALP incorporated into a biscuit (F ~ 0.1%), using the same methods. Considering the similar oral bioavailability of Al from food vs. water, and their contribution to the typical human’s daily Al intake (~ 95 and 1.5%, respectively), these results suggest food contributes much more Al to systemic circulation, and potential Al body burden, than does drinking water. These results do not support the hypothesis that drinking water provides a disproportionate contribution to total Al absorbed from the gastrointestinal tract.
MED-4936
Algal-oil capsules and cooked salmon: nutritionally equivalent sources of docosahexaenoic acid.
Food and nutrition professionals question whether supplement-sourced nutrients appear to be equivalent to those derived from natural food sources. We compared the nutritional availability of docosahexaenoic acid (DHA) from algal-oil capsules to that from assayed cooked salmon in 32 healthy men and women, ages 20 to 65 years, in a randomized, open-label, parallel-group study. In this 2-week study comparing 600 mg DHA/day from algal-oil capsules to that from assayed portions of cooked salmon, mean change from baseline in plasma phospholipids and erythrocyte DHA levels was analyzed and DHA levels were compared by Student's t tests. In post-hoc analyses to determine bioequivalence, least-squares mean ratios of percent change from baseline in plasma phospholipid and erythrocyte DHA levels were compared. DHA levels increased by approximately 80% in plasma phospholipids and by approximately 25% in erythrocytes in both groups. Changes in DHA levels in plasma phospholipids and erythrocytes were similar between groups. As measured by delivery of DHA to both plasma and erythrocytes, fish and algal-oil capsules were equivalent. Both regimens were generally well-tolerated. These results indicate that algal-oil DHA capsules and cooked salmon appear to be bioequivalent in providing DHA to plasma and red blood cells and, accordingly, that algal-oil DHA capsules represent a safe and convenient source of non-fish-derived DHA.
MED-4932
Aquaculture practices and potential human health risks: current knowledge and future priorities.
Annual global aquaculture production has more than tripled within the past 15 years, and by 2015, aquaculture is predicted to account for 39% of total global seafood production by weight. Given that lack of adequate nutrition is a leading contributor to the global burden of disease, increased food production through aquaculture is a seemingly welcome sign. However, as production surges, aquaculture facilities increasingly rely on the heavy input of formulated feeds, antibiotics, antifungals, and agrochemicals. This review summarizes our current knowledge concerning major chemical, biological and emerging agents that are employed in modern aquaculture facilities and their potential impacts on public health. Findings from this review indicate that current aquaculture practices can lead to elevated levels of antibiotic residues, antibiotic-resistant bacteria, persistent organic pollutants, metals, parasites, and viruses in aquacultured finfish and shellfish. Specific populations at risk of exposure to these contaminants include individuals working in aquaculture facilities, populations living around these facilities, and consumers of aquacultured food products. Additional research is necessary not only to fully understand the human health risks associated with aquacultured fish versus wild-caught fish but also to develop appropriate interventions that could reduce or prevent these risks. In order to adequately understand, address and prevent these impacts at local, national and global scales, researchers, policy makers, governments, and aquaculture industries must collaborate and cooperate in exchanging critical information and developing targeted policies that are practical, effective and enforceable.
MED-5062
Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled...
BACKGROUND: We undertook a randomised, double-blinded, placebo-controlled, crossover trial to test whether intake of artificial food colour and additives (AFCA) affected childhood behaviour. METHODS: 153 3-year-old and 144 8/9-year-old children were included in the study. The challenge drink contained sodium benzoate and one of two AFCA mixes (A or B) or a placebo mix. The main outcome measure was a global hyperactivity aggregate (GHA), based on aggregated z-scores of observed behaviours and ratings by teachers and parents, plus, for 8/9-year-old children, a computerised test of attention. This clinical trial is registered with Current Controlled Trials (registration number ISRCTN74481308). Analysis was per protocol. FINDINGS: 16 3-year-old children and 14 8/9-year-old children did not complete the study, for reasons unrelated to childhood behaviour. Mix A had a significantly adverse effect compared with placebo in GHA for all 3-year-old children (effect size 0.20 [95% CI 0.01-0.39], p=0.044) but not mix B versus placebo. This result persisted when analysis was restricted to 3-year-old children who consumed more than 85% of juice and had no missing data (0.32 [0.05-0.60], p=0.02). 8/9-year-old children showed a significantly adverse effect when given mix A (0.12 [0.02-0.23], p=0.023) or mix B (0.17 [0.07-0.28], p=0.001) when analysis was restricted to those children consuming at least 85% of drinks with no missing data. INTERPRETATION: Artificial colours or a sodium benzoate preservative (or both) in the diet result in increased hyperactivity in 3-year-old and 8/9-year-old children in the general population.
MED-5063
Food additives and hyperactivity
Evidence supports a trial period of eliminating colourings and preservatives from the diet
MED-4581
Fruit and vegetable consumption and cognitive decline in aging women.
We prospectively examined fruit and vegetable intake in relation to cognitive function and decline among aging women. Participants were followed from in 1976 with biennial questionnaires, and food frequency questionnaires were administered in 1984, 1986, and every 4 years thereafter. From 1995 to 2001, we administered, by telephone, six cognitive tests measuring general cognition, verbal memory, category fluency, and working memory. We repeated assessments two years later for 13,388 women (>90% follow-up). We averaged dietary intakes from 1984 through the first cognitive assessment, and used linear regression to obtain multivariable-adjusted mean differences in performance and decline in performance across intake levels. Fruits were not associated with cognition or cognitive decline. However, total vegetable intake was significantly associated with less decline. Specifically, on a global score combining all tests, women in the highest quintile of cruciferous vegetables declined slower (by 0.04 unit; 95% confidence interval, 0.003, 0.07; p trend = 0.1) compared with the lowest quintile. Women consuming the most green leafy vegetables also experienced slower decline than women consuming the least amount (by 0.05 unit; 95% confidence interval, 0.02, 0.09; p trend < 0.001). These mean differences were equivalent to those observed for women about 1 to 2 years apart in age.
MED-2546
Inositol hexaphosphate (IP6) inhibits key events of cancer metastasis: II. Effects on integrins and focal adhesions.
BACKGROUND: We have shown that inositol hexaphosphate (IP6), a natural compound and a potent anti-cancer agent, inhibited cancer cell adhesion to the extracellular matrix (ECM) proteins, thereby leading to inhibition of cell migration and invasion. Cell adhesion to ECM is mediated by specific cell surface integrins, which transduce intracellular signals through their interaction and activation of other proteins that are recruited to the focal adhesion. We hypothesize that IP6 decreases cell adhesion by suppressing the integrin receptors and their subsequent signaling pathway. MATERIALS AND METHODS: We analyzed integrin expressions of the highly invasive estrogen receptor-negative human breast cancer MDA-MB 231 cells exposed to IP6 by flow cytometry. The expression of focal adhesion proteins was investigated by immunocytochemistry and Western blotting. RESULTS: IP6 treatment caused a significant (P < 0.005) decrease in the expression of integrin heterodimers alpha 2 beta 1 (collagen receptor), alpha 5 beta 1 (fibronectin receptor) and alpha v beta 3 (vitronectin receptor); flow cytometry showed that it was the alpha 5 subunit that was down-regulated ( < 0.001). However, the expression of the alpha 2, alpha v, beta 1 and beta 3 subunits were not affected by IP6 treatment. When the expression of integrins on the cell surface was assessed, there was a dramatic 82% decrease in the expression of alpha 5 beta 1 on IP6-treated cells (P < 0.0001), indicating a decrease in cell surface expression of the heterodimers. No effect was seen when inositol hexasulfate (IS6), an analogue of IP6, was used as a control. Immunocytochemistry showed a lack of clustering of paxillin; tyrosine-phosphorylated proteins in IP6-treated cells were discontinuous and scattered around the cell periphery, whereas the patterns were more dense and localized in control cells. Consistent with these observations, focal adhesion kinase (FAK) autophosphorylation at tyrosine-397 residue was suppressed, albeit modestly, by IP6 treatment, suggesting a down-regulation in the integrin-mediated signaling pathway. CONCLUSION: The results of this study indicate that IP6-induced inhibition of cancer cell adhesion, migration and invasion may be mediated through the modulation of integrin dimerization, cell surface expression and integrin-associated signaling pathway.
MED-2975
Egg consumption and the risk of diabetes in adults, Jiangsu, China.
BACKGROUND: Although egg consumption has been associated with elevated plasma levels of cholesterol and triglyceride and with risk of cardiovascular disease in some populations, epidemiologic studies on egg consumption and the risk of diabetes are extremely sparse, particularly in the Chinese population. METHOD: Data from a household survey in the year 2002 among 2849 adults aged ≥20 y from a nationally representative sample in Jiangsu Province, China, were used. Dietary information was assessed by a validated food frequency questionnaire and 3 d weighed food records. Fasting blood specimens were collected. RESULTS: After the adjustment for age, total calorie intake, education, smoking, family history of diabetes, and sedentary activity, egg consumption was significantly and positively associated with diabetes risk, particularly in women. The odds ratios (OR) (95% CI) of diabetes associated with egg consumption <2/wk, 2-6/wk, and ≥1/d in the total sample were 1.00, 1.75, 2.28 (1.14-4.54), respectively (P for trend 0.029). Corresponding ORs (95% CI) in women were 1.00, 1.66, and 3.01 (1.12, 8.12), respectively (P for trend 0.022). Additional adjustment of body mass index attenuated the association, but it remained significant. There was a similar, however, not statistically significant association in men. In addition, plasma triglyceride and total cholesterol levels were significantly higher in women who consumed ≥2 eggs/wk than those who consumed eggs less often. CONCLUSION: Egg consumption was positively associated with the risk of diabetes among the Chinese, particularly in women. Copyright Â© 2011 Elsevier Inc. All rights reserved.
MED-2845
Iron intake and the risk of type 2 diabetes in women: a prospective cohort study.
OBJECTIVE: Epidemiological studies suggest that high body iron stores are associated with insulin resistance and type 2 diabetes. The aim of this study was to evaluate the association between dietary intake of iron and the risk of type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted a prospective cohort study within the Nurses' Health Study. We followed 85,031 healthy women aged 34-59 years from 1980 to 2000. Dietary data were collected every 4 years, and data on medical history and lifestyle factors were updated biennially. RESULTS: During the 20 years of follow-up, we documented 4,599 incident cases of type 2 diabetes. We found no association between total, dietary, supplemental, or nonheme iron and the risk of type 2 diabetes. However, heme iron intake (derived from animal products) was positively associated with risk; relative risks (RRs) across increasing quintiles of cumulative intake were 1.00, 1.08 (95% CI 0.97-1.19), 1.20 (1.09-1.33), 1.27 (1.14-1.41), and 1.28 (1.14-1.45) (P(trend) < 0.0001) after controlling for age, BMI, and other nondietary and dietary risk factors. In addition, when we modeled heme iron in seven categories, the multivariate RR comparing women who consumed > or =2.25 mg/day and those with intake <0.75 mg/day was 1.52 (1.22-1.88). The association between heme iron and the risk of diabetes was significant in both overweight and lean women. CONCLUSIONS: This large cohort study suggests that higher heme iron intake is associated with a significantly increased risk of type 2 diabetes.
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-1350
A Pill for the Ill? Patients’ Reports of Their Experience of the Medical Encounter in the Treatment of Depression
Background Starting in the 1960s, a broad-based patients’ rights movement began to question doctors’ paternalism and to demand disclosure of medical information, informed consent, and active participation by the individual in personal health care. According to scholars, these changes contributed to downplay the biomedical approach in favor of a more patient-oriented perspective. The Swedish non-profit organization Consumer Association for Medicines and Health (KILEN) has offered the possibility for consumers to report their perceptions and experiences from their use of medicines in order to strengthen consumer rights within the health care sector. Methodology In this paper, qualitative content analysis was used to analyze 181 KILEN consumer reports of adverse events from antidepressant medications in order to explore patients’ views of mental ill health symptoms and the doctor-patient interaction. Principal Findings Overall, the KILEN stories contained negative experiences of the patients’ medical encounters. Some reports indicated intense emotional outrage and strong feelings of abuse by the health care system. Many reports suggested that doctors and patients had very different accounts of the nature of the problems for which the patient was seeking help. Although patients sought help for problems like tiredness and sleeplessness (often with a personal crisis of some sort as a described cause), the treating doctor in most cases was exceptionally quick in both diagnosing depression and prescribing antidepressant treatment. When patients felt they were not being listened to, trust in the doctor was compromised. This was evident in the cases when the doctor tried to convince them to take part in medical treatment, sometimes by threatening to withdraw their sick-listing. Conclusions Overall, this study suggests that the dynamics happening in the medical encounter may still be highly affected by a medical dominance, instead of a patient-oriented perspective. This may contribute to a questionable medicalization and/or pharmaceuticalization of depression.
MED-2298
A guide to exercise prescription.
Exercise is a fundamental component of good health. The American College of Sports Medicine and "Exercise is Medicine" recommend treating exercise as a vital sign, and assessing and prescribing physical activity at every medical visit. Meeting the recommended goals of physical activity results in a significant reduction in all-cause mortality. Physicians can improve health by prescribing exercise. Copyright © 2013 Elsevier Inc. All rights reserved.
MED-5322
Characterization of bacteria, clostridia and Bacteroides in faeces of vegetarians using qPCR and PCR-DGGE fingerprinting.
BACKGROUND/AIMS: This study aimed to investigate the quantitative and qualitative changes of bacteria, Bacteroides, Bifidobacterium and Clostridium cluster IV in faecal microbiota associated with a vegetarian diet. METHODS: Bacterial abundances were measured in faecal samples of 15 vegetarians and 14 omnivores using quantitative PCR. Diversity was assessed with PCR-DGGE fingerprinting, principal component analysis (PCA) and Shannon diversity index. RESULTS: Vegetarians had a 12% higher abundance of bacterial DNA than omnivores, a tendency for less Clostridium cluster IV (31.86 +/- 17.00%; 36.64 +/- 14.22%) and higher abundance of Bacteroides (23.93 +/- 10.35%; 21.26 +/- 8.05%), which were not significant due to high interindividual variations. PCA suggested a grouping of bacteria and members of Clostridium cluster IV. Two bands appeared significantly more frequently in omnivores than in vegetarians (p < 0.005 and p < 0.022). One was identified as Faecalibacterium sp. and the other was 97.9% similar to the uncultured gut bacteriumDQ793301. CONCLUSIONS: A vegetarian diet affects the intestinal microbiota, especially by decreasing the amount and changing the diversity of Clostridium cluster IV. It remains to be determined how these shifts might affect the host metabolism and disease risks. Copyright 2009 S. Karger AG, Basel.
MED-4163
Protein dietary reference intakes may be inadequate for vegetarians if low amounts of animal protein are consumed.
OBJECTIVE: The health benefits of vegetarian diets are well-recognized; however, long-term adherence to these diets may be associated with nutrient inadequacies, particularly vitamins B12 and D, calcium, iron, zinc, and protein. The dietary reference intakes (DRIs) expert panels recommended adjustments to the iron, zinc, and calcium DRIs for vegetarians to account for decreased bioavailability, but no adjustments were considered necessary for the protein DRI under the assumption that vegetarians consume about 50% of protein from animal (dairy/egg) sources. This study examined dietary protein sources in a convenience sample of 21 young adult vegetarian women who completed food logs on 4 consecutive days (3 weekdays and 1 weekend day). METHODS: The daily contribution percentages of protein consumed from cereals, legumes, nuts/seeds, fruits/vegetables, and dairy/egg were computed, and the protein digestibility corrected amino acid score of the daily diets was calculated. RESULTS: The calculated total dietary protein digestibility score for participants was 82 ± 1%, which differed significantly (P < 0.001) from the DRI reference score, 88%, and the 4-d average protein digestibility corrected amino acid score for the sample was 80 ± 2%, which also differed significantly (P < 0.001) from the DRI reference value, 100%. The analyses indicated that animal protein accounted for only 21% of dietary protein. CONCLUSION: This research suggests that the protein DRI for vegetarians consuming less than the expected amounts of animal protein (45% to 50% of total protein) may need to be adjusted from 0.8 to about 1.0 g/kg to account for decreased protein bioavailability. Copyright © 2011 Elsevier Inc. All rights reserved.
MED-3205
Prospective study of the association between grapefruit intake and risk of breast cancer in the European Prospective Investigation into Cancer and ...
Grapefruit inhibits cytochrome P450 3A4 and may affect estrogen metabolism. In the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined the relationships of grapefruit intake with risk of breast cancer and with serum sex hormone levels. 114,504 women with information on dietary intake of grapefruit and on reproductive and lifestyle risk factors were followed for a median 9.5 years and 3,747 incident breast cancers were identified. Fifty-nine percent of women reported eating grapefruit, 4% ate > or = 60 g/day. Cox proportional hazard models were used to estimate the hazard ratio (HR) for breast cancer according to grapefruit intake, adjusting for study centre, reproductive factors, body mass index, energy intake, and alcohol intake. Grapefruit intake was not related to the risk of breast cancer: compared with women who ate no grapefruit, women with the highest intake of > or =60 g/day had a HR of 0.93 (95% CI 0.77-1.13), p for linear trend = 0.5. There was no relationship between grapefruit intake and breast cancer risk among premenopausal women, all postmenopausal women, or postmenopausal women categorized by hormone replacement therapy use (all p>0.05). There was no association between grapefruit intake and estradiol or estrone among postmenopausal women. In this study, we found no evidence of an association between grapefruit intake and risk of breast cancer.
MED-3490
Science in Liquid Dietary Supplement Promotion: The Misleading Case of Mangosteen Juice
Liquid dietary supplements represent a fast growing market segment, including botanically-based beverages containing mangosteen, acai, and noni. These products often resemble fruit juice in packaging and appearance, but may contain pharmacologically active ingredients. While little is known about the human health effects or safety of consuming such products, manufacturers make extensive use of low-quality published research to promote their products. This report analyzes the science-based marketing claims of two of the most widely consumed mangosteen liquid dietary supplements, and compares them to the findings of the research being cited. The reviewer found that analyzed marketing claims overstate the significance of findings, and fail to disclose severe methodological weaknesses of the research they cite. If this trend extends to other related products that are similarly widely consumed, it may pose a public health threat by misleading consumers into assuming that product safety and effectiveness are backed by rigorous scientific data.
MED-4288
Out-of-hand nut consumption is associated with improved nutrient intake and health risk markers in US children and adults: National Health and Nutr...
The purpose of this study was to determine the association of out-of-hand nut (OOHN) consumption with nutrient intake, diet quality, and the prevalence of risk factors for cardiovascular disease and metabolic syndrome. Data from 24-hour recalls from individuals aged 2+ years (n = 24,385) participating in the 1999-2004 National Health and Nutrition Examination Survey were used. The population was divided into children aged 2 to 11, 12 to 18, and adults 19+ years, and each group was dichotomized into OOHN consumers and nonconsumers. Out-of-hand nut consumers were defined as those individuals consuming ¼ oz of nuts or more per d. Means, standard errors, and covariate-adjusted analyses of variance were determined using appropriate sample weights. Diet quality was determined using the Healthy Eating Index-2005. Significance was set at P < .05. The percent of OOHN consumers increased with age: 2.1% ± 0.3%, 2.6% ± 0.3%, 6.5% ± 0.5%, and 9.6% ± 0.5% those aged 2 to 11, 12 to 18, 19 to 50, and 51+ years, respectively. The 2 latter groups were combined into a single group of consumers aged 19+ years for subsequent analyses. Consumers of OOHN from all age groups had higher intakes of energy, monounsaturated and polyunsaturated fatty acids, dietary fiber, copper, and magnesium and lower intakes of carbohydrates, cholesterol, and sodium than did nonconsumers. Diet quality was higher in OOHN consumers of all age groups. In children aged 2 to 11 years, consumers had a higher prevalence of overweight/obesity. In those aged 12 to 18 years, weight and percent overweight were lower in consumers. Adult consumers had higher high-density lipoprotein cholesterol, red blood cell folate, and serum folate levels and lower insulin, glycohemoglobin, and C-reactive protein levels than did nonconsumers. Adult consumers also had a 19% decreased risk of hypertension and a 21% decreased risk of low high-density lipoprotein cholesterol levels. Data suggested that OOHN consumption was associated with improved nutrient intake, diet quality, and, in adults, a lower prevalence of 2 risk factors for metabolic syndrome. Consumption of OOHN, as part of a healthy diet, should be encouraged by health professionals. Copyright © 2012 Elsevier Inc. All rights reserved.
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-1438
Serum concentration of an inflammatory glycotoxin, methylglyoxal, is associated with increased cognitive decline in elderly individuals
Background Advanced glycations end products increase oxidant stress, inflammation, and neurotoxicity. Serum levels are increased in diabetes and aging. We examined the relationship between serum methylglyoxal derivatives (sMG), and cognitive decline, in 267 non-demented elderly. Methods Tobit mixed regression models assessed the association of baseline sMG with cognitive decline in the Mini Mental State Exam (MMSE) over time, controlling for sociodemographic factors (age, sex, and years of education), cardiovascular risk factors (diabetes and presence of an APOE4 allele), and kidney function. sMG was assessed by ELISA. Results The fully adjusted model showed an annual decline of 0.26 MMSE points per unit increase in baseline sMG (p=0.03). Significance was unchanged as additional risk factors were added to the model. The interactions of sMG with diabetes, sex, age, kidney function, and APOE4 genotype were not significant. Conclusions Higher levels of baseline sMG were associated with a faster rate of cognitive decline, after adjusting for several sociodemographic and clinical characteristics. This relationship did not differ by sex, APOE4 genotype, or diabetes status suggesting its generality. Since subjects were cognitively normal at the beginning of the study, elevated sMG may be indicative of brain cell injury initiated before clinically evident cognitive compromise.
MED-3695
Probiotics for the prevention of pediatric antibiotic-associated diarrhea.
BACKGROUND: Antibiotics alter the microbial balance within the gastrointestinal tract. Probiotics may prevent antibiotic-associated diarrhea (AAD) via restoration of the gut microflora. Antibiotics are prescribed frequently in children and AAD is common in this population. OBJECTIVES: To assess the efficacy and adverse effects of probiotics (any specified strain or dose) for the prevention of antibiotic-associated diarrhea in children. To assess adverse events associated with the use of probiotics when co-administered with antibiotics in children. SEARCH STRATEGY: MEDLINE, EMBASE, CENTRAL, CINAHL , AMED, and the Web of Science (inception to August 2006) were searched along with specialized registers including the Cochrane IBD/FBD Review Group, CISCOM, Chalmers PedCAM Research Register and trial registries from inception to 2005. Letters were sent to authors of included trials, nutra/pharmaceutical companies, and experts in the field requesting additional information on ongoing or unpublished trials. Conference proceedings, dissertation abstracts, and reference lists from included and relevant articles were hand searched. SELECTION CRITERIA: Randomized, parallel, controlled (placebo, active, or no treatment) trials comparing co-administered probiotics with antibiotics for the prevention of diarrhea secondary to antibiotic use in children (0 to 18 years). DATA COLLECTION AND ANALYSIS: Methodological quality assessment and data extraction were conducted independently by two authors (BCJ, AS). Dichotomous data (incidence of diarrhea, adverse events) were combined using pooled relative risks, and continuous data (mean duration of diarrhea, mean daily stool frequency) as weighted mean differences, along with their corresponding 95% confidence intervals. Adverse events were summarized using risk difference. For overall pooled results on the incidence of diarrhea, a priori sensitivity analyses included per protocol versus intention to treat, random versus fixed effects, and methodological quality criterion. Subgroup analysis were conducted on probiotic strain, dose, definition of antibiotic-associated diarrhea, and antibiotic agent. MAIN RESULTS: Ten studies met the inclusion criteria. Trials included treatment with either Lactobacilli spp., Bifidobacterium spp., Streptococcus spp., or Saccharomyces boulardii alone or in combination. Six studies used a single strain probiotic agent and four combined two probiotic strains. The per protocol analysis for 9/10 trials reporting on the incidence of diarrhea show statistically significant results favouring probiotics over active/non active controls (RR 0.49; 95% CI 0.32 to 0.74). However, intention to treat analysis showed non-significant results overall (RR 0.90; 95% CI 0.50 to 1.63). Five of ten trials monitored for adverse events (n = 647); none reported a serious adverse event. AUTHORS' CONCLUSIONS: Probiotics show promise for the prevention of pediatric AAD. While per protocol analysis yields treatment effect estimates that are both statistically and clinically significant, as does analysis of high quality studies, the estimate from the intention to treat analysis was not statistically significant. Future studies should involve probiotic strains and doses with the most promising evidence (e.g., Lactobacillus GG, Lactobacillus sporogenes, Saccharomyces boulardii at 5 to 40 billion colony forming units/day). Research done to date does not permit determination of the effect of age (e.g., infant versus older children) or antibiotic duration (e.g., 5 days versus 10 days). Future trials would benefit from a validated primary outcome measure for antibiotic-associated diarrhea that is sensitive to change and reflects what treatment effect clinicians, parents, and children consider important. The current data are promising, but it is premature to routinely recommend probiotics for the prevention of pediatric AAD.
MED-2969
Orange juice or fructose intake does not induce oxidative and inflammatory response.
OBJECTIVE: We have previously shown that 300 kcal from glucose intake induces a significant increase in reactive oxygen species (ROS) generation and nuclear factor-kappaB (NF-kappaB) binding in the circulating mononuclear cells in healthy normal subjects. We hypothesized that the intake of 300 calories as orange juice or fructose, the other major carbohydrate in orange juice, would induce a significantly smaller response than that of glucose. RESEARCH DESIGN AND METHODS: Four groups (eight subjects each) of normal-weight subjects were given a 300-cal drink of glucose (75 g), fructose (75 g), or orange juice or water sweetened with saccharin (control group) to drink, and then blood samples were collected. RESULTS: There was a significant increase in ROS generation by mononuclear cells (by 130 +/- 18%, P < 0.001), polymorph nuclear cells (by 95 +/- 22%, P < 0.01), and in NF-kappaB binding in mononuclear cells by 82 +/- 16% (P < 0.01) over the baseline after 2 h of glucose intake. These changes were absent following fructose, orange juice, or water intake. There was significantly lower ROS generation and NF-kappaB binding following orange juice, fructose, and water compared with glucose (P < 0.001 for all). Furthermore, incubation of mononuclear cells in vitro with 50 mmol/l of the flavonoids hesperetin or naringenin reduced ROS generation by 52 +/- 7% and 77 +/- 8% (P < 0.01), respectively, while fructose or ascorbic acid did not cause any change. CONCLUSIONS: Caloric intake in the form of orange juice or fructose does not induce either oxidative or inflammatory stress, possibly due to its flavonoids content and might, therefore, represent a potentially safe energy source.
MED-4679
Pubertal Assessment Method and Baseline Characteristics in a Mixed Longitudinal Study of Girls
OBJECTIVES The objective of this study was to describe the assessment methods and maturation status for a multisite cohort of girls at baseline recruitment and at ages 7 and 8 years. METHODS The method for pubertal maturation staging was developed collaboratively across 3 sites. Girls at ages 6 to 8 years were recruited at 3 sites: East Harlem, New York; greater Cincinnati metropolitan area; and San Francisco Bay area, California. Baseline characteristics were obtained through interviews with caregivers and anthropometric measurements by trained examiners; breast stage 2 was defined as onset of pubertal maturation. The κ statistic was used to evaluate agreement between master trainers and examiners. Logistic regression models were used to identify factors that are associated with pubertal maturation and linear regression models to examine factors that are associated with height velocity. RESULTS The baseline cohort included 1239 girls. The proportion of girls who had attained breast stage 2 varied by age, race/ethnicity, BMI percentile, and site. At 7 years, 10.4% of white, 23.4% of black non-Hispanic, and 14.9% of Hispanic girls had attained breast stage ≥2; at 8 years, 18.3%, 42.9%, and 30.9%, respectively, had attained breast stage ≥2. The prime determinant of height velocity was pubertal status. CONCLUSIONS In this multisite study, there was substantial agreement regarding pubertal staging between examiners across sites. The proportion of girls who had breast development at ages 7 and 8 years, particularly among white girls, is greater than that reported from studies of girls who were born 10 to 30 years earlier.
MED-3424
Subclinical endothelial dysfunction and low-grade inflammation play roles in the development of erectile dysfunction in young men with low risk of ...
The purpose of this study is to investigate the possible underlying pathogenesis of erectile dysfunction(ED) in young men with low risk of coronary heart disease and no well-known aetiology. To conduct this study, 122 patients with ED under the age of 40 were enrolled, along with 33 age-matched normal control subjects. The patients with ED had significantly higher levels of systolic blood pressure (SBP), total cholesterol and triglyceride, high sensitivity C-reactive protein (hs-CRP), greater carotid intima-media thickness (CIMT) and Framingham risk score (FRS) than the control group, though all of these values were within the respective normal range. Further, the brachial artery flow- mediated vasodilation (FMD) values were significantly lower in ED patients and correlated positively with the severity of ED (r = 0.714, p < 0.001). When these significant factors were studied in the multivariate logistic regression model, FMD, SBP, hs-CRP and FRS remained the statistical significance. The receiver-operating characteristic (ROC) analysis demonstrated that FMD had a high ability to predict ED in young male with low FRS [area under the curve (AUC) 0.921, p < 0.001]. The cutoff value of FMD <10.25% had sensitivity of 82.8% and specificity of 100% for diagnosis of ED. FRS and hs- CRP were also proven to be predictors of ED (AUC 0.812, p < 0.001; AUC 0.645, p = 0.011, respectively). The results of this study validated that subclinical endothelial dysfunction and low-grade inflammation may be the underlying pathogenesis of ED with no well-known aetiology. Young patients complaining of ED should be screened for cardiovascular risk factors and possible subclinical atherosclerosis. Measurement of FMD, hs-CRP and FRS can improve our ability to predict and treat ED, as well as subclinical cardiovascular disease early for young male. © 2012 The Authors. International Journal of Andrology © 2012 European Academy of Andrology.
MED-4258
Plant and animal protein intake and its association with overweight and obesity among the Belgian population.
The objective of the present study was to assess animal and plant protein intakes in the Belgian population and to examine their relationship with overweight and obesity (OB). The subjects participated in the Belgian National Food Consumption Survey conducted in 2004. Food consumption was assessed by using two non-consecutive 24 h dietary recalls. About 3083 participants ( ≥ 15 years of age; 1546 males, 1537 females) provided completed dietary information. Animal protein intake (47 g/d) contributed more to total protein intakes of 72 g/d than plant protein intake, which accounted for 25 g/d. Meat and meat products were the main contributors to total animal protein intakes (53 %), whereas cereals and cereal products contributed most to plant protein intake (54 %). Males had higher animal and plant protein intakes than females (P < 0·001). Legume and soya protein intakes were low in the whole population (0·101 and 0·174 g/d, respectively). In males, animal protein intake was positively associated with BMI (β = 0·013; P = 0·001) and waist circumference (WC; β = 0·041; P = 0·002). Both in males and females, plant protein intake was inversely associated with BMI (males: β = - 0·036; P < 0·001; females: β = - 0·046; P = 0·001) and WC (male: β = - 0·137; P < 0·001; female: β = - 0·096; P = 0·024). In conclusion, plant protein intakes were lower than animal protein intakes among a representative sample of the Belgian population and decreased with age. Associations with anthropometric data indicated that plant proteins could offer a protective effect in the prevention of overweight and OB in the Belgian population.
MED-1768
Is milk responsible for male reproductive disorders?
The role of environmental compounds with estrogenic activity in the development of male reproductive disorders has been a source of great concern. Among the routes of human exposure to estrogens, we are particularly concerned about cows' milk, which contains considerable amounts of estrogens. The major sources of animal-derived estrogens in the human diet are milk and dairy products, which account for 60-70% of the estrogens consumed. Humans consume milk obtained from heifers in the latter half of pregnancy, when the estrogen levels in cows are markedly elevated. The milk that we now consume may be quite unlike that consumed 100 years ago. Modern genetically-improved dairy cows, such as the Holstein, are usually fed a combination of grass and concentrates (grain/protein mixes and various by-products), allowing them to lactate during the latter half of pregnancy, even at 220 days of gestation. We hypothesize that milk is responsible, at least in part, for some male reproductive disorders. Copyright 2001 Harcourt Publishers Ltd.
MED-2363
A pattern of anti-carbohydrate antibody responses present in patients with advanced atherosclerosis.
We have previously shown that an antibody pool present in normal human serum binds cytokine receptors in vitro and may therefore interfere with assays that capture cytokines using their receptors. Here we show that this antibody pool is the same as the natural antibody termed anti-gal, that binds to the alpha-galactosyl carbohydrate epitope (alpha-gal) and which is the predominant obstacle to xenotransplantation. We report that there are high levels of IgD anti alpha-gal in most volunteers, in addition to the IgG2, IgA and IgM immunoglobulin isotypes against alpha-gal previously described. To determine if anti-gal may interfere with assays that depend on capture of cytokine with its receptor, we measured levels of several anti-carbohydrate antibodies in a cohort of patients with advanced atherosclerosis that had previously been used to measure levels of active TGF-beta using such an assay. For many isotype / carbohydrate combinations, there is a large and significant difference between the levels of anti-carbohydrate antibodies in patients with atherosclerosis and controls, after adjustment for age, sex and blood group. These results are similar to the previous data obtained for active TGF-beta, and therefore we cannot discount the possibility that anti-gal contributed to the previous data. Following further adjustment for several risk factors associated with cardiovascular disease, several anti-carbohydrate antibodies were still significantly different between patients and controls. Therefore, anti-carbohydrate antibodies may represent a new class of risk factors that may be associated with presence of advanced atherosclerosis, although larger studies will be required to confirm this hypothesis.
MED-4978
Biomonitoring of urinary metabolites of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) following human consumption of cooked chicken.
Human risk assessment of exposure to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) through the diet may be improved by conducting biomonitoring studies comparing metabolism in humans and rodents. Eleven volunteers ingested a meal of cooked chicken containing 4 -OH-PhIP and PhIP in amounts of 0.6 and 0.8microg/kg, respectively and urine was collected for the next 16h. The large number of PhIP metabolites was by treatment of the urine samples with hydrazine hydrate and hydrolytic enzymes reduced to three substances, 4'-OH-PhIP, PhIP and 5-OH-PhIP of which the first is a biomarker for detoxification and the last a biomarker for activation. The eleven volunteers eliminated large amounts of 4'-OH-PhIP in the urine. The majority of which could be accounted for by the presence of 4'-OH-PhIP in the fried chicken, showing that PhIP only to a small extent (11%) was metabolised to 4'-OH-PhIP. A larger fraction of the PhIP exposure, 38%, was recovered as PhIP and the largest fraction (51%) was recovered as 5-OH-PhIP suggesting that PhIP in humans to a large extent is metabolised to reactive substances. In rats, less than 1% of the dose of PhIP was eliminated as 5-OH-PhIP, suggesting that human cancer risk from exposure to PhIP is considerable higher than risk estimations based on extrapolation from rodent bioassays.
MED-4946
Sub-clinical neurobehavioral abnormalities associated with low level of mercury exposure through fish consumption.
In order to assess early neurotoxic effects associated with relatively low levels of mercury absorbed through fish eating, two groups of 22 adult male subjects, habitual consumers of tuna fish, and 22 controls were examined using a cross-sectional field study. The assessment included neurobehavioral tests of vigilance and psychomotor function, hand tremor measurements and serum prolactin assessment. Mercury in urine (U-Hg) and serum prolactin (sPRL) were measured in all exposed subjects and controls, whereas measurements of the organic component of mercury in blood (O-Hg) were available for only 10 exposed and six controls. U-Hg was significant higher among exposed subjects (median 6.5 microg/g of creatinine, range 1.8-21.5) than controls (median 1.5 microg/g of creatinine, range 0.5-5.3). The median values of O-Hg were 41.5 microg/l among the tuna fish eaters and 2.6 microg/l in the control group. Both U-Hg and O-Hg were significantly correlated with the quantity of fish consumed per week. Significant differences in sPRL were found between exposed (12.6 ng/ml) and controls (9.1 ng/ml). Individual sPRL were significantly correlated with both U-Hg and O-Hg levels. The neurobehavioral performance of subjects who consumed tuna fish regularly was significantly worse on color word reaction time, digit symbol reaction time and finger tapping speed (FT). After considering the education level and other covariates, the multiple stepwise regression analysis indicated that O-Hg concentration was most significantly associated with individual performance on these tests, accounting for about 65% of the variance in test scores.
MED-4239
A low-fat diet and/or strenuous exercise alters the IGF axis in vivo and reduces prostate tumor cell growth in vitro.
BACKGROUND: Prostate cancer is the most common solid-tumor cancer in US males but is rare in Asian males. When Asian men adopt the US lifestyle, clinical prostate cancer increases greatly. Epidemiological data from men in the US indicate that regular activity may reduce the risk for prostate cancer. METHODS: Serum was obtained from three groups of similar-aged men, Control, Diet and Exercise, and Exercise alone were used to stimulate LNCaP cells in culture. Growth and apoptosis of tumor cells were measured. Serum samples were also used to measure insulin, IGF-1, IGFBP-1. RESULTS: The Diet and Exercise and the Exercise alone groups had lower serum insulin and IGF-1 but higher IGFBP-1 compared to Controls. LNCaP cell growth was reduced in both groups compared to Control and there was a major increase in apoptosis of tumor cells. CONCLUSIONS: A low-fat diet and/or intensive exercise results in change in serum hormones and growth factors in vivo that can reduce growth and induce apoptosis of LNCaP prostate tumor cells in vitro. Copyright 2003 Wiley-Liss, Inc.
MED-846
Antifungal mechanisms supporting boric acid therapy of Candida vaginitis.
BACKGROUND: Boric acid is a commonly cited treatment for recurrent and resistant yeast vaginitis, but data about the extent and mechanism of its antifungal activity are lacking. OBJECTIVES: The aim of this study was to use in vitro methods to understand the spectrum and mechanism of boric acid as a potential treatment for vaginal infection. METHODS: Yeast and bacterial isolates were tested by agar dilution to determine the intrinsic antimicrobial activity of boric acid. Established microbial physiology methods illuminated the mechanism of the action of boric acid against Candida albicans. RESULTS: C. albicans strains (including fluconazole-resistant strains) were inhibited at concentrations attainable intravaginally; as were bacteria. Broth dilution MICs were between 1563 and 6250 mg/L and boric acid proved fungistatic (also reflected by a decrease in CO(2) generation); prolonged culture at 50,000 mg/L was fungicidal. Several organic acids in yeast nitrogen broth yielded a lower pH than equimolar boric acid and sodium borate but were less inhibitory. Cold or anaerobic incubation protected yeast at high boric acid concentrations. Cells maintained integrity for 6 h in boric acid at 37 degrees C, but after 24 h modest intrusion of propidium iodide occurred; loss of plate count viability preceded uptake of vital stain. Growth at sub-MIC concentrations of boric acid decreased cellular ergosterol. The drug efflux pump CDR1 did not protect Candida as CDR1 expression was abrogated by boric acid. Boric acid interfered with the development of biofilm and hyphal transformation. CONCLUSIONS: Boric acid is fungistatic to fungicidal depending on concentration and temperature. Inhibition of oxidative metabolism appears to be a key antifungal mechanism, but inhibition of virulence probably contributes to therapeutic efficacy in vivo.
MED-1244
Examination of the effectiveness of peppermint aromatherapy on nausea in women post C-section.
PURPOSE: This study examined the effect of peppermint spirits on postoperative nausea in women following a scheduled C-section. DESIGN: A pretest-posttest research design with three groups was used. The peppermint group inhaled peppermint spirits, the placebo aromatherapy control group inhaled an inert placebo, green-colored sterile water, and the standard antiemetic therapy control group received standard antiemetics, usually intravenous ondansetron or promethazine suppositories. METHODS: Women were randomly assigned to a group on admission to the hospital. If they became nauseated, nurses on the mother-baby unit assessed their nausea (baseline), administered the assigned intervention, and then reassessed participants' nausea 2 and 5 minutes after the initial intervention. Participants rated their nausea using a 6-point nausea scale. FINDINGS: Thirty-five participants became nauseated post-operatively. Participants in all three intervention groups had similar levels of nausea at baseline. The nausea levels of participants in the peppermint spirits group were significantly lower than those of participants in the other two groups 2 and 5 minutes after the initial intervention. CONCLUSIONS: Peppermint spirits may be a useful adjunct in the treatment of postoperative nausea. This study should be replicated with more participants, using a variety of aromatherapies to treat nausea in participants with different preoperative diagnoses.
MED-915
Heavy metals in wild rice from northern Wisconsin.
Wild rice grain samples from various parts of the world have been found to have elevated concentrations of heavy metals, raising concern for potential effects on human health. It was hypothesized that wild rice from north-central Wisconsin could potentially have elevated concentrations of some heavy metals because of possible exposure to these elements from the atmosphere or from water and sediments. In addition, no studies of heavy metals in wild rice from Wisconsin had been performed, and a baseline study was needed for future comparisons. Wild rice plants were collected from four areas in Bayfield, Forest, Langlade, Oneida, Sawyer and Wood Counties in September, 1997 and 1998 and divided into four plant parts for elemental analyses: roots, stems, leaves and seeds. A total of 194 samples from 51 plants were analyzed across the localities, with an average of 49 samples per part depending on the element. Samples were cleaned of soil, wet digested, and analyzed by ICP for Ag, As, Cd, Cr, Cu, Hg, Mg, Pb, Se and Zn. Roots contained the highest concentrations of Ag, As, Cd, Cr, Hg, Pb, and Se. Copper was highest in both roots and seeds, while Zn was highest just in seeds. Magnesium was highest in leaves. Seed baseline ranges for the 10 elements were established using the 95% confidence intervals of the medians. Wild rice plants from northern Wisconsin had normal levels of the nutritional elements Cu, Mg and Zn in the seeds. Silver, Cd, Hg, Cr, and Se were very low in concentration or within normal limits for food plants. Arsenic and Pb, however, were elevated and could pose a problem for human health. The pathway for As, Hg and Pb to the plants could be atmospheric.
MED-3867
High alpha-linolenic acid flaxseed (Linum usitatissimum): some nutritional properties in humans.
Although high alpha-linolenic acid flaxseed (Linum usitatissimum) is one of the richest dietary sources of alpha-linolenic acid and is also a good source of soluble fibre mucilage, it is relatively unstudied in human nutrition. Healthy female volunteers consumed 50 g ground, raw flaxseed/d for 4 weeks which provided 12-13% of energy intake (24-25 g/100 g total fat). Flaxseed raised alpha-linolenic acid and long-chain n-3 fatty acids in both plasma and erythrocyte lipids, as well as raising urinary thiocyanate excretion 2.2-fold. Flaxseed also lowered serum total cholesterol by 9% and low-density-lipoprotein-cholesterol by 18%. Changes in plasma alpha-linolenic acid were equivalent when 12 g alpha-linolenic acid/d was provided as raw flaxseed flour (50 g/d) or flaxseed oil (20 g/d) suggesting high bioavailability of alpha-linolenic acid from ground flaxseed. Test meals containing 50 g carbohydrate from flaxseed or 25 g flaxseed mucilage each significantly decreased postprandial blood glucose responses by 27%. Malondialdehyde levels in muffins containing 15 g flaxseed oil or flour/kg were similar to those in wheat-flour muffins. Cyanogenic glycosides (linamarin, linustatin, neolinustatin) were highest in extracted flaxseed mucilage but were not detected in baked muffins containing 150 g flaxseed/kg. We conclude that up to 50 g high-alpha-linolenic acid flaxseed/d is palatable, safe and may be nutritionally beneficial in humans by raising n-3 fatty acids in plasma and erythrocytes and by decreasing postprandial glucose responses.
MED-4898
Animal foods, protein, calcium and prostate cancer risk: the European Prospective Investigation into Cancer and Nutrition
We examined consumption of animal foods, protein and calcium in relation to risk of prostate cancer among 142 251 men in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by recruitment centre and adjusted for height, weight, education, marital status and energy intake. After an average of 8.7 years of follow-up, there were 2727 incident cases of prostate cancer, of which 1131 were known to be localised and 541 advanced-stage disease. A high intake of dairy protein was associated with an increased risk, with a hazard ratio for the top versus the bottom fifth of intake of 1.22 (95% confidence interval (CI): 1.07–1.41, Ptrend=0.02). After calibration to allow for measurement error, we estimated that a 35-g day−1 increase in consumption of dairy protein was associated with an increase in the risk of prostate cancer of 32% (95% CI: 1–72%, Ptrend=0.04). Calcium from dairy products was also positively associated with risk, but not calcium from other foods. The results support the hypothesis that a high intake of protein or calcium from dairy products may increase the risk for prostate cancer.
MED-1672
Sugar, Uric Acid, and the Etiology of Diabetes and Obesity
The intake of added sugars, such as from table sugar (sucrose) and high-fructose corn syrup has increased dramatically in the last hundred years and correlates closely with the rise in obesity, metabolic syndrome, and diabetes. Fructose is a major component of added sugars and is distinct from other sugars in its ability to cause intracellular ATP depletion, nucleotide turnover, and the generation of uric acid. In this article, we revisit the hypothesis that it is this unique aspect of fructose metabolism that accounts for why fructose intake increases the risk for metabolic syndrome. Recent studies show that fructose-induced uric acid generation causes mitochondrial oxidative stress that stimulates fat accumulation independent of excessive caloric intake. These studies challenge the long-standing dogma that “a calorie is just a calorie” and suggest that the metabolic effects of food may matter as much as its energy content. The discovery that fructose-mediated generation of uric acid may have a causal role in diabetes and obesity provides new insights into pathogenesis and therapies for this important disease.
MED-1006
Treatment of abdominal pain in irritable bowel syndrome.
Functional abdominal pain in the context of irritable bowel syndrome (IBS) is a challenging problem for primary care physicians, gastroenterologists and pain specialists. We review the evidence for the current and future non-pharmacological and pharmacological treatment options targeting the central nervous system and the gastrointestinal tract. Cognitive interventions such as cognitive behavioral therapy and hypnotherapy have demonstrated excellent results in IBS patients, but the limited availability and labor-intensive nature limit their routine use in daily practice. In patients who are refractory to first-line therapy, tricyclic antidepressants (TCA) and selective serotonin reuptake inhibitors are both effective to obtain symptomatic relief, but only TCAs have been shown to improve abdominal pain in meta-analyses. A diet low in fermentable carbohydrates and polyols (FODMAP) seems effective in subgroups of patients to reduce abdominal pain, bloating, and to improve the stool pattern. The evidence for fiber is limited and only isphagula may be somewhat beneficial. The efficacy of probiotics is difficult to interpret since several strains in different quantities have been used across studies. Antispasmodics, including peppermint oil, are still considered the first-line treatment for abdominal pain in IBS. Second-line therapies for diarrhea-predominant IBS include the non-absorbable antibiotic rifaximin and the 5HT3 antagonists alosetron and ramosetron, although the use of the former is restricted because of the rare risk of ischemic colitis. In laxative-resistant, constipation-predominant IBS, the chloride-secretion stimulating drugs lubiprostone and linaclotide, a guanylate cyclase C agonist that also has direct analgesic effects, reduce abdominal pain and improve the stool pattern.
MED-2007
Prevention of diabetes and reduction in major cardiovascular events in studies of subjects with prediabetes: meta-analysis of randomised controlled...
BACKGROUND: Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are pre-diabetic states, treatment of which may prevent or delay the onset of overt diabetes and thus potentially reduce major cardiovascular (CV) events. We therefore sought to determine whether interventions (including diet, exercise and pharmacological therapy), altered all-cause and cardiovascular related mortality in such subjects. METHODS: We performed a meta-analysis of prospective, randomised controlled trials (RCTs) that were identified in the medical literature and databases. Trials were eligible for inclusion if they reported all-cause mortality rates (at a minimum), recruited approximately 100 patients and had a minimum follow-up of one year. Interventions were divided into pharmacological and non-pharmacological. RESULTS: Ten RCTs that enrolled 23,152 patients met the above entry criteria. Trials ran for an average of 3.75 years. Diabetes was delayed or prevented by these interventions vs control (risk ratio 0.83, 95%CI 0.80-0.86). Non-drug approaches (n = 3495) were superior to drug-based approaches (n = 20,872) in diabetes prevention (0.52, 0.46-0.58 vs 0.70, 0.58-0.85, P < 0.05). There was no difference in risk of all-cause mortality in the intervention versus control group (0.96, 0.84-1.10) and no difference in CV death (1.04, 0.61-1.78). There was a non-significant trend towards reduction in fatal and non-fatal myocardial infarction (0.59, 0.23-1.50). Fatal and non-fatal stroke was borderline reduced (0.76, 0.58-0.99) with intervention versus control. CONCLUSIONS: Despite interventions being mostly successful in retarding progression to overt diabetes, this did not result in reductions in all-cause or cardiovascular mortality, or myocardial infarction, with the possible exception of stroke.
MED-3373
The Influence of Social Involvement, Neighborhood Aesthetics, and Community Garden Participation on Fruit and Vegetable Consumption
Objectives. We considered the relationship between an urban adult population's fruit and vegetable consumption and several selected social and psychological processes, beneficial aesthetic experiences, and garden participation. Methods. We conducted a population-based survey representing 436 residents across 58 block groups in Denver, Colorado, from 2006 to 2007. We used multilevel statistical models to evaluate the survey data. Results. Neighborhood aesthetics, social involvement, and community garden participation were significantly associated with fruit and vegetable intake. Community gardeners consumed fruits and vegetables 5.7 times per day, compared with home gardeners (4.6 times per day) and nongardeners (3.9 times per day). Moreover, 56% of community gardeners met national recommendations to consume fruits and vegetables at least 5 times per day, compared with 37% of home gardeners and 25% of nongardeners. Conclusions. Our study results shed light on neighborhood processes that affect food-related behaviors and provides insights about the potential of community gardens to affect these behaviors. The qualities intrinsic to community gardens make them a unique intervention that can narrow the divide between people and the places where food is grown and increase local opportunities to eat better.
MED-2813
Curcumin: getting back to the roots.
The use of turmeric, derived from the root of the plant Curcuma longa, for treatment of different inflammatory diseases has been described in Ayurveda and in traditional Chinese medicine for thousands of years. The active component of turmeric responsible for this activity, curcumin, was identified almost two centuries ago. Modern science has revealed that curcumin mediates its effects by modulation of several important molecular targets, including transcription factors (e.g., NF-kappaB, AP-1, Egr-1, beta-catenin, and PPAR-gamma), enzymes (e.g., COX2, 5-LOX, iNOS, and hemeoxygenase-1), cell cycle proteins (e.g., cyclin D1 and p21), cytokines (e.g., TNF, IL-1, IL-6, and chemokines), receptors (e.g., EGFR and HER2), and cell surface adhesion molecules. Because it can modulate the expression of these targets, curcumin is now being used to treat cancer, arthritis, diabetes, Crohn's disease, cardiovascular diseases, osteoporosis, Alzheimer's disease, psoriasis, and other pathologies. Interestingly, 6-gingerol, a natural analog of curcumin derived from the root of ginger (Zingiber officinalis), exhibits a biologic activity profile similar to that of curcumin. The efficacy, pharmacologic safety, and cost effectiveness of curcuminoids prompt us to "get back to our roots."
MED-1137
Diet and risk of kidney stones in the Oxford cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC).
The lifetime prevalence of kidney stones is around 10 % and incidence rates are increasing. Diet may be an important determinant of kidney stone development. Our objective was to investigate the association between diet and kidney stone risk in a population with a wide range of diets. This association was examined among 51,336 participants in the Oxford arm of the European Prospective Investigation into Cancer and Nutrition using data from Hospital Episode Statistics in England and Scottish Morbidity Records. In the cohort, 303 participants attended hospital with a new kidney stone episode. Cox proportional hazards regression was performed to calculate hazard ratios (HR) and their 95 % confidence intervals (95 % CI). Compared to those with high intake of meat (>100 g/day), the HR estimates for moderate meat-eaters (50-99 g/day), low meat-eaters (<50 g/day), fish-eaters and vegetarians were 0.80 (95 % CI 0.57-1.11), 0.52 (95 % CI 0.35-0.8), 0.73 (95 % CI 0.48-1.11) and 0.69 (95 % CI 0.48-0.98), respectively. High intakes of fresh fruit, fibre from wholegrain cereals and magnesium were also associated with a lower risk of kidney stone formation. A high intake of zinc was associated with a higher risk. In conclusion, vegetarians have a lower risk of developing kidney stones compared with those who eat a high meat diet. This information may be important to advise the public about prevention of kidney stone formation.
MED-4618
In vitro evaluation of genotoxicity of avocado (Persea americana) fruit and leaf extracts in human peripheral lymphocytes.
Persea americana is much sought after both for the nutritional value of its fruit and the medicinal values of its various plant parts. A chromosomal aberration assay was undertaken to evaluate the potential genotoxicity of crude extracts from avocado fruits and leaves. Chromosomal aberrations were observed in cultured human peripheral lymphocytes exposed to separately increasing concentrations of 50% methanolic extracts of Persea americana fruit and leaves. The groups exposed to leaf and fruit extracts, respectively, showed a concentration-dependent increase in chromosomal aberrations as compared to that in a control group. The mean percentage total aberrant metaphases at 100 mg/kg, 200 mg/kg, and 300 mg/kg concentrations of leaf extract were found respectively to be 58 ± 7.05, 72 ± 6.41, and 78 ± 5.98, which were significantly higher (p < 0.0001 each) than that in the control group (6 ± 3.39). The mean percentage total aberrant metaphases at 100 mg/kg, 200 mg/kg, and 300 mg/kg concentrations of fruit extract were found to be 18 ± 5.49, 40 ± 10.00, and 52 ± 10.20, respectively, which were significantly higher (p = 0.033, p < 0.0001, and p < 0.0001, respectively) than that for control (6 ± 3.39). Acrocentric associations and premature centromeric separation were the two most common abnormalities observed in both the exposed groups. The group exposed to leaf extracts also showed a significant number of a variety of other structural aberrations, including breaks, fragments, dicentrics, terminal deletion, minutes, and Robertsonian translocations. The group exposed to leaf extract showed higher frequency of all types of aberrations at equal concentrations as compared to the group exposed to fruit extract.
MED-3318
Cigarette Smoking and Pancreatic Cancer: A Pooled Analysis From the Pancreatic Cancer Cohort Consortium
Smoking is an established risk factor for pancreatic cancer; however, detailed examination of the association of smoking intensity, smoking duration, and cumulative smoking dose with pancreatic cancer is limited. The authors analyzed pooled data from the international Pancreatic Cancer Cohort Consortium nested case-control study (1,481 cases, 1,539 controls). Odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression. Smoking intensity effects were examined with an excess odds ratio model that was linear in pack-years and exponential in cigarettes smoked per day and its square. When compared with never smokers, current smokers had a significantly elevated risk (odds ratio (OR) = 1.77, 95% confidence interval (CI): 1.38, 2.26). Risk increased significantly with greater intensity (≥30 cigarettes/day: OR = 1.75, 95% CI: 1.27, 2.42), duration (≥50 years: OR = 2.13, 95% CI: 1.25, 3.62), and cumulative smoking dose (≥40 pack-years: OR = 1.78, 95% CI: 1.35, 2.34). Risk more than 15 years after smoking cessation was similar to that for never smokers. Estimates of excess odds ratio per pack-year declined with increasing intensity, suggesting greater risk for total exposure delivered at lower intensity for longer duration than for higher intensity for shorter duration. This finding and the decline in risk after smoking cessation suggest that smoking has a late-stage effect on pancreatic carcinogenesis.
MED-3538
The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restricti...
OBJECTIVES: To inform the debate over whether human sleep can be chronically reduced without consequences, we conducted a dose-response chronic sleep restriction experiment in which waking neurobehavioral and sleep physiological functions were monitored and compared to those for total sleep deprivation. DESIGN: The chronic sleep restriction experiment involved randomization to one of three sleep doses (4 h, 6 h, or 8 h time in bed per night), which were maintained for 14 consecutive days. The total sleep deprivation experiment involved 3 nights without sleep (0 h time in bed). Each study also involved 3 baseline (pre-deprivation) days and 3 recovery days. SETTING: Both experiments were conducted under standardized laboratory conditions with continuous behavioral, physiological and medical monitoring. PARTICIPANTS: A total of n = 48 healthy adults (ages 21-38) participated in the experiments. INTERVENTIONS: Noctumal sleep periods were restricted to 8 h, 6 h or 4 h per day for 14 days, or to 0 h for 3 days. All other sleep was prohibited. RESULTS: Chronic restriction of sleep periods to 4 h or 6 h per night over 14 consecutive days resulted in significant cumulative, dose-dependent deficits in cognitive performance on all tasks. Subjective sleepiness ratings showed an acute response to sleep restriction but only small further increases on subsequent days, and did not significantly differentiate the 6 h and 4 h conditions. Polysomnographic variables and delta power in the non-REM sleep EEG-a putative marker of sleep homeostasis--displayed an acute response to sleep restriction with negligible further changes across the 14 restricted nights. Comparison of chronic sleep restriction to total sleep deprivation showed that the latter resulted in disproportionately large waking neurobehavioral and sleep delta power responses relative to how much sleep was lost. A statistical model revealed that, regardless of the mode of sleep deprivation, lapses in behavioral alertness were near-linearly related to the cumulative duration of wakefulness in excess of 15.84 h (s.e. 0.73 h). CONCLUSIONS: Since chronic restriction of sleep to 6 h or less per night produced cognitive performance deficits equivalent to up to 2 nights of total sleep deprivation, it appears that even relatively moderate sleep restriction can seriously impair waking neurobehavioral functions in healthy adults. Sleepiness ratings suggest that subjects were largely unaware of these increasing cognitive deficits, which may explain why the impact of chronic sleep restriction on waking cognitive functions is often assumed to be benign. Physiological sleep responses to chronic restriction did not mirror waking neurobehavioral responses, but cumulative wakefulness in excess of a 15.84 h predicted performance lapses across all four experimental conditions. This suggests that sleep debt is perhaps best understood as resulting in additional wakefulness that has a neurobiological "cost" which accumulates over time.
MED-5045
Suppressive Effects of Selected Food Phytochemicals on CD74 Expression in NCI-N87 Gastric Carcinoma Cells
Helicobacter pylori (H. pylori) is one of the most widespread human pathogens, and plays major roles in chronic gastritis and gastric cancer. CD74 of gastric epithelial cells has recently been identified as an adhesion molecule to urease in H. pylori. In this study, we found that CD74 is highly expressed in a constitutive manner in NCI-N87 human gastric carcinoma cells at both the protein and mRNA levels as compared with Hs738St./Int fetal gastric cells. Subsequently, a novel cell-based ELISA able to rapidly screen the suppressive agents of CD74 expression was established. NCI-N87 cells were treated separately with 25 different food phytochemicals (4–100 µM) for 48 h and subjected to our novel assay. From those results, a citrus coumarin, bergamottin, was indicated to be the most promising compound with an LC50/IC50 value greater than 7.1, followed by luteolin (>5.4), nobiletin (>5.3), and quercetin (>5.1). Our findings suggest that these CD74 suppressants are unique candidates for preventing H. pylori adhesion and subsequent infection with reasonable action mechanisms.
MED-5252
Caffeine does not increase the risk of atrial fibrillation: a systematic review and meta-analysis of observational studies.
BACKGROUND: Atrial fibrillation (AF) is the most prevalent sustained arrhythmia, and risk factors are well established. Caffeine exposure has been associated with increased risk of AF, but heterogeneous data exist in the literature. OBJECTIVE: To evaluate the association between chronic exposure to caffeine and AF. DESIGN: Systematic review and meta-analysis of observational studies. DATA SOURCES: PubMed, CENTRAL, ISI Web of Knowledge and LILACS to December 2012. Reviews and references of retrieved articles were comprehensively searched. STUDY SELECTION: Two reviewers independently searched for studies and retrieved their characteristics and data estimates. DATA SYNTHESIS: Random-effects meta-analysis was performed, and pooled estimates were expressed as OR and 95% CI. Heterogeneity was assessed with the I(2) test. Subgroup analyses were conducted according to caffeine dose and source (coffee). RESULTS: Seven observational studies evaluating 115 993 individuals were included: six cohorts and one case-control study. Caffeine exposure was not associated with an increased risk of AF (OR 0.92, 95% CI 0.82 to 1.04, I(2)=72%). Pooled results from high-quality studies showed a 13% odds reduction in AF risk with lower heterogeneity (OR 0.87; 95% CI 0.80 to 0.94; I(2)=39%). Low-dose caffeine exposure showed OR 0.85 (95% CI 0.78 to 92, I(2)=0%) without significant differences in other dosage strata. Caffeine exposure based solely on coffee consumption also did not influence AF risk. CONCLUSIONS: Caffeine exposure is not associated with increased AF risk. Low-dose caffeine may have a protective effect.
MED-953
Effects of acute consumption of a fruit and vegetable purée-based drink on vasodilation and oxidative status.
Epidemiological studies indicate that diets rich in fruits and vegetables (F&V) are protective against CVD. Puréed F&V products retain many beneficial components, including flavonoids, carotenoids, vitamin C and dietary fibres. The present study aimed to establish the physiological effects of acute ingestion of a F&V purée-based drink (FVPD) on vasodilation, antioxidant status, phytochemical bioavailability and other CVD risk factors. A total of twenty-four subjects, aged 30-70 years, completed the randomised, single-blind, controlled, crossover test meal study. Subjects consumed 400 ml of the FVPD, or a fruit-flavoured sugar-matched control, after following a low-flavonoid diet for 5 d. Blood and urine samples were collected throughout the study day, and vascular reactivity was assessed at 90 min intervals using laser Doppler iontophoresis. The FVPD significantly increased plasma vitamin C (P= 0·002) and total nitrate/nitrite (P= 0·001) concentrations. There was a near significant time by treatment effect on ex vivo LDL oxidation (P= 0·068), with a longer lag phase after consuming the FVPD. During the 6 h after juice consumption, the antioxidant capacity of plasma increased significantly (P= 0·003) and there was a simultaneous increase in plasma and urinary phenolic metabolites (P< 0·05). There were significantly lower glucose and insulin peaks after ingestion of the FVPD compared with control (P= 0·019 and 0·003) and a trend towards increased endothelium-dependent vasodilation following FVPD consumption (P= 0·061). Overall, FVPD consumption significantly increased plasma vitamin C and total nitrate/nitrite concentrations, with a trend towards increased endothelium-dependent vasodilation. Puréed F&V products are useful vehicles for increasing micronutrient status, plasma antioxidant capacity and in vivo NO generation, which may contribute to CVD risk reduction.
MED-2804
Epidemiology of OA
Osteoarthritis (OA) is the most common form of arthritis in the US, and a leading cause of disability. It is typically defined in epidemiologic studies on the basis of radiographic findings and consideration of symptoms. Its incidence and prevalence are rising, likely related to the aging of the population and increasing obesity. Risk factors for OA include a number of person-level factors, such as age, sex, obesity, and genetics, as well as joint-specific factors that are likely reflective of abnormal loading of the joints. A number of methodologic challenges exist in studying OA that can hamper our ability to identify pertinent relationships.
MED-1703
The Projected Impact of Risk Factor Reduction on Alzheimer's Disease Prevalence
There are currently approximately 33.9 million individuals with Alzheimer's disease (AD) worldwide, and prevalence is expected to triple over the next 40 years. The goal of this review was to summarize the evidence regarding seven potentially modifiable AD risk factors: diabetes, mid-life hypertension, mid-life obesity, smoking, depression, low educational attainment and physical inactivity. In addition, we projected the impact of risk factor reduction on AD prevalence by calculating population attributable risks (PARs, the percent of cases attributable to a given factor) and the number of AD cases that could potentially be prevented by 10% and 25% risk factor reductions worldwide and in the US. Together, these factors contributed to up to half of AD cases globally (17.2 million) and in the US (2.9 million). A 10%–25% reduction in all seven risk factors could potentially prevent as many as 1.1–3.0 million cases worldwide and 184,000–492,000 cases in the US.
MED-850
Folate intake, MTHFR polymorphisms, and risk of esophageal, gastric, and pancreatic cancer: a meta-analysis.
BACKGROUND & AIMS: Increasing evidence suggests that a low folate intake and impaired folate metabolism may be implicated in the development of gastrointestinal cancers. We conducted a systematic review with meta-analysis of epidemiologic studies evaluating the association of folate intake or genetic polymorphisms in 5,10-methylenetetrahydrofolate reductase (MTHFR), a central enzyme in folate metabolism, with risk of esophageal, gastric, or pancreatic cancer. METHODS: A literature search was performed using MEDLINE for studies published through March 2006. Study-specific relative risks were weighted by the inverse of their variance to obtain random-effects summary estimates. RESULTS: The summary relative risks for the highest versus the lowest category of dietary folate intake were 0.66 (95% confidence interval [CI], 0.53-0.83) for esophageal squamous cell carcinoma (4 case-control), 0.50 (95% CI, 0.39-0.65) for esophageal adenocarcinoma (3 case-control), and 0.49 (95% CI, 0.35-0.67) for pancreatic cancer (1 case-control, 4 cohort); there was no heterogeneity among studies. Results on dietary folate intake and risk of gastric cancer (9 case-control, 2 cohort) were inconsistent. In most studies, the MTHFR 677TT (variant) genotype, which is associated with reduced enzyme activity, was associated with an increased risk of esophageal squamous cell carcinoma, gastric cardia adenocarcinoma, noncardia gastric cancer, gastric cancer (all subsites), and pancreatic cancer; all but one of 22 odds ratios were >1, of which 13 estimates were statistically significant. Studies of the MTHFR A1298C polymorphism were limited and inconsistent. CONCLUSIONS: These findings support the hypothesis that folate may play a role in carcinogenesis of the esophagus, stomach, and pancreas.
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-3718
American Cancer Society Guidelines on Nutrition and Physical Activity for cancer prevention: reducing the risk of cancer with healthy food choices ...
The American Cancer Society (ACS) publishes Nutrition and Physical Activity Guidelines to serve as a foundation for its communication, policy, and community strategies and ultimately, to affect dietary and physical activity patterns among Americans. These Guidelines, published every 5 years, are developed by a national panel of experts in cancer research, prevention, epidemiology, public health, and policy, and as such, they represent the most current scientific evidence related to dietary and activity patterns and cancer risk. The ACS Guidelines include recommendations for individual choices regarding diet and physical activity patterns, but those choices occur within a community context that either facilitates or interferes with healthy behaviors. Community efforts are essential to create a social environment that promotes healthy food choices and physical activity. Therefore, this committee presents one key recommendation for community action to accompany the four recommendations for individual choices to reduce cancer risk. This recommendation for community action recognizes that a supportive social environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors. The ACS Guidelines are consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes, as well as for general health promotion, as defined by the Department of Health and Human Services' 2005 Dietary Guidelines for Americans.
MED-2305
Healthy living is the best revenge: findings from the European Prospective Investigation Into Cancer and Nutrition-Potsdam study.
BACKGROUND: Our objective was to describe the reduction in relative risk of developing major chronic diseases such as cardiovascular disease, diabetes, and cancer associated with 4 healthy lifestyle factors among German adults. METHODS: We used data from 23,153 German participants aged 35 to 65 years from the European Prospective Investigation Into Cancer and Nutrition-Potsdam study. End points included confirmed incident type 2 diabetes mellitus, myocardial infarction, stroke, and cancer. The 4 factors were never smoking, having a body mass index lower than 30 (calculated as weight in kilograms divided by height in meters squared), performing 3.5 h/wk or more of physical activity, and adhering to healthy dietary principles (high intake of fruits, vegetables, and whole-grain bread and low meat consumption). The 4 factors (healthy, 1 point; unhealthy, 0 points) were summed to form an index that ranged from 0 to 4. RESULTS: During a mean follow-up of 7.8 years, 2006 participants developed new-onset diabetes (3.7%), myocardial infarction (0.9%), stroke (0.8%), or cancer (3.8%). Fewer than 4% of participants had zero healthy factors, most had 1 to 3 healthy factors, and approximately 9% had 4 factors. After adjusting for age, sex, educational status, and occupational status, the hazard ratio for developing a chronic disease decreased progressively as the number of healthy factors increased. Participants with all 4 factors at baseline had a 78% (95% confidence interval [CI], 72% to 83%) lower risk of developing a chronic disease (diabetes, 93% [95% CI, 88% to 95%]; myocardial infarction, 81% [95% CI, 47% to 93%]; stroke, 50% [95% CI, -18% to 79%]; and cancer, 36% [95% CI, 5% to 57%]) than participants without a healthy factor. CONCLUSION: Adhering to 4 simple healthy lifestyle factors can have a strong impact on the prevention of chronic diseases.
MED-2459
Effect of dietary patterns on measures of lipid peroxidation: results from a randomized clinical trial.
BACKGROUND: Free radical-mediated oxidative damage to lipids is thought to be an important process in the pathogenesis of atherosclerosis. Although previous studies have demonstrated a beneficial impact of antioxidant vitamin supplements on lipid peroxidation, the effect of dietary patterns on lipid peroxidation is unknown. METHODS AND RESULTS: During the 3-week run-in period of a randomized trial, 123 healthy individuals were fed a control diet, low in fruits, vegetables, and dairy products, with 37% of calories from fat. Participants were then randomized to consume for 8 weeks: (1) the control diet, (2) a diet rich in fruits and vegetables but otherwise similar to the control diet, and (3) a combination diet rich in fruits, vegetables, and low-fat dairy products and reduced in fat. Serum oxygen radical-absorbing capacity, malondialdehyde (an in vitro measure of lipid peroxidation), and breath ethane (an in vivo measure of lipid peroxidation) were measured at the end of run-in and intervention periods. Between run-in and intervention, mean (95% CI) change in oxygen radical-absorbing capacity (U/mL) was -35 (-93, 13) in the control diet, 26 (-15, 67) in the fruits and vegetables diet (P=0.06 compared with control), and 19 (-22, 54) in the combination diet (P=0.10 compared with control). Median (interquartile range) change in ethane was 0.84 (0.10, 1.59) in the control diet, 0.02 (-0.61, 0.83) in the fruits and vegetables diet (P=0.04 compared with control), and -1.00 (-1.97, 0.25) in the combination diet (P=0.005 compared with control). Change in malondialdehyde did not differ between diets. CONCLUSIONS: This study demonstrates that modification of diet can favorably affect serum antioxidant capacity and protect against lipid peroxidation.
MED-1140
Organic food: buying more safety or just peace of mind? A critical review of the literature.
Consumer concern over the quality and safety of conventional food has intensified in recent years, and primarily drives the increasing demand for organically grown food, which is perceived as healthier and safer. Relevant scientific evidence, however, is scarce, while anecdotal reports abound. Although there is an urgent need for information related to health benefits and/or hazards of food products of both origins, generalized conclusions remain tentative in the absence of adequate comparative data. Organic fruits and vegetables can be expected to contain fewer agrochemical residues than conventionally grown alternatives; yet, the significance of this difference is questionable, inasmuch as actual levels of contamination in both types of food are generally well below acceptable limits. Also, some leafy, root, and tuber organic vegetables appear to have lower nitrate content compared with conventional ones, but whether or not dietary nitrate indeed constitutes a threat to human health is a matter of debate. On the other hand, no differences can be identified for environmental contaminants (e.g. cadmium and other heavy metals), which are likely to be present in food from both origins. With respect to other food hazards, such as endogenous plant toxins, biological pesticides and pathogenic microorganisms, available evidence is extremely limited preventing generalized statements. Also, results for mycotoxin contamination in cereal crops are variable and inconclusive; hence, no clear picture emerges. It is difficult, therefore, to weigh the risks, but what should be made clear is that 'organic' does not automatically equal 'safe.' Additional studies in this area of research are warranted. At our present state of knowledge, other factors rather than safety aspects seem to speak in favor of organic food.
MED-1180
Antioxidant levels and inhibition of cancer cell proliferation in vitro by extracts from organically and conventionally cultivated strawberries.
The effects of extracts from five cultivars of strawberries on the proliferation of colon cancer cells HT29 and breast cancer cells MCF-7 were investigated, and possible correlations with the levels of several antioxidants were analyzed. In addition, the effects of organic cultivation compared to conventional cultivation on the content of antioxidants in the strawberries and strawberry extracts on the cancer cell proliferation were investigated. The ratio of ascorbate to dehydroascorbate was significantly higher in the organically cultivated strawberries. The strawberry extracts decreased the proliferation of both HT29 cells and MCF-7 cells in a dose-dependent way. The inhibitory effect for the highest concentration of the extracts was in the range of 41-63% (average 53%) inhibition compared to controls for the HT29 cells and 26-56% (average 43%) for MCF-7 cells. The extracts from organically grown strawberries had a higher antiproliferative activity for both cell types at the highest concentration than the conventionally grown, and this might indicate a higher content of secondary metabolites with anticarcinogenic properties in the organically grown strawberries. For HT29 cells, there was a negative correlation at the highest extract concentration between the content of ascorbate or vitamin C and cancer cell proliferation, whereas for MCF-7 cells, a high ratio of ascorbate to dehydroascorbate correlated with a higher inhibition of cell proliferation at the second highest concentration. The significance of the effect of ascorbate on cancer cell proliferation might lie in a synergistic action with other compounds.
MED-2790
A clinical review of different formulations of Vasa (Adhatoda vasica) on Tamaka Shwasa (asthma)
Vasa (Adhatoda vasica Linn.) is a well known and easily available drug in almost all the seasons. Easy availability of any drug gains popularity among physicians as well as pharmaceuticals and this is the reason why almost every Kalpana of Vasa is found described in the Ayurvedika text. The different dosage forms of Vasa like Kvatha, Avaleha, Sneha, and Sandhana have been used for the treatment of Shwasa Roga. A number of research studies have been performed on different formulations of Vasa and its effect on Shwasa Roga. Therefore, a review study has been carried out on the Vasa extract, Vasa Avaleha (prepared from Svarasa and Kvatha), Vasa Ghrita, Vasarishta, and Vasakasava on Shwasa Roga, to know which formulation is better. It was found in the review that Vasa Ghana, Vasa Ghrita (1), and Vasa Avaleha have shown good results on Tamaka Shwasa.
MED-5151
The emerging role of flavonoid-rich cocoa and chocolate in cardiovascular health and disease.
Cocoa and chocolate have recently been found to be rich plant-derived sources of antioxidant flavonoids with beneficial cardiovascular properties. These favorable physiological effects include: antioxidant activity, vasodilation and blood pressure reduction, inhibition of platelet activity, and decreased inflammation. Increasing evidence from experimental and clinical studies using cocoa-derived products and chocolate suggest an important role for these high-flavanol-containing foods in heart and vascular protection.
MED-2593
Frequency of nut consumption and mortality risk in the PREDIMED nutrition intervention trial
Background Prospective studies in non-Mediterranean populations have consistently related increasing nut consumption to lower coronary heart disease mortality. A small protective effect on all-cause and cancer mortality has also been suggested. To examine the association between frequency of nut consumption and mortality in individuals at high cardiovascular risk from Spain, a Mediterranean country with a relatively high average nut intake per person. Methods We evaluated 7,216 men and women aged 55 to 80 years randomized to 1 of 3 interventions (Mediterranean diets supplemented with nuts or olive oil and control diet) in the PREDIMED (‘PREvención con DIeta MEDiterránea’) study. Nut consumption was assessed at baseline and mortality was ascertained by medical records and linkage to the National Death Index. Multivariable-adjusted Cox regression and multivariable analyses with generalized estimating equation models were used to assess the association between yearly repeated measurements of nut consumption and mortality. Results During a median follow-up of 4.8 years, 323 total deaths, 81 cardiovascular deaths and 130 cancer deaths occurred. Nut consumption was associated with a significantly reduced risk of all-cause mortality (P for trend <0.05, all). Compared to non-consumers, subjects consuming nuts >3 servings/week (32% of the cohort) had a 39% lower mortality risk (hazard ratio (HR) 0.61; 95% CI 0.45 to 0.83). A similar protective effect against cardiovascular and cancer mortality was observed. Participants allocated to the Mediterranean diet with nuts group who consumed nuts >3 servings/week at baseline had the lowest total mortality risk (HR 0.37; 95% CI 0.22 to 0.66). Conclusions Increased frequency of nut consumption was associated with a significantly reduced risk of mortality in a Mediterranean population at high cardiovascular risk. Please see related commentary: http://www.biomedcentral.com/1741-7015/11/165. Trial registration Clinicaltrials.gov. International Standard Randomized Controlled Trial Number (ISRCTN): 35739639. Registration date: 5 October 2005.
MED-4427
Left subclavian arterioesophageal fistula induced by chicken bone with upper gastrointestinal hemorrhage and unexpected death: report of a case.
Left subclavian arterioesophageal fistula resulting from chicken bone ingestion is a rare occurrence. The authors report the death of a 42-year-old Thai female with mental retardation who presented to the hospital with severe hematemesis and arrested Death occurred about 24 hours after laparotomy due to hypovolemic shock Postmortem examination revealed a chicken bone embedded in middle part of esophagus with fistula between the esophagus and the left subclavian artery.
MED-3834
Dietary lignan intakes in relation to survival among women with breast cancer: the Western New York Exposures and Breast Cancer (WEB) Study
Dietary lignan intakes have been associated with reduced breast cancer risks; however, no previous studies have investigated whether lignan intake might be associated with breast cancer survival. We examined the association of dietary lignan intakes with survival in 1122 women with primary, incident, histologically confirmed breast cancer identified between 1996 and 2001, and with vital status determined through December 31, 2006. Diet in the 12–24 months before diagnosis was assessed with an extensive food frequency questionnaire, and potential confounders assessed from an extensive epidemiologic interview and abstracted clinical data. Lignan intake was calculated using published food composition data. Hazard ratios (HR), and 95% confidence intervals (CIs) for dietary lignan intakes with all cause, and breast cancer mortality were estimated using Cox proportional hazards adjusting for age, education, race, total energy intake, tumor stage, and body mass index. Of the 1122 women with complete dietary data, 160 had died by the end of follow-up. Among postmenopausal women only, those in the highest versus lowest quartile of lignan intakes had a statistically significant reduction in the risk of all cause mortality (HR 0.49, 95% CI 0.26–0.91) and a significantly reduced risk of breast cancer mortality (HR 0.29, 95% CI 0.11–0.76). Higher intakes of dried beans (HR 0.61, 95% CI 0.36–1.03), but not fruits, vegetables, or grains, were also weakly associated with overall mortality. In summary, our results suggest that higher lignan intakes may be associated with improved survival among postmenopausal women with breast cancer.
MED-4732
Polychlorinated Biphenyl-77 Induces Adipocyte Differentiation and Proinflammatory Adipokines and Promotes Obesity and Atherosclerosis
Background Obesity, an inflammatory condition linked to cardiovascular disease, is associated with expansion of adipose tissue. Highly prevalent coplanar polychlorinated biphenyls (PCBs) such as 3,3′,4,4′-tetrachlorobiphenyl (PCB-77) accumulate in adipose tissue because of their lipophilicity and increase with obesity. However, the effects of PCBs on adipocytes, obesity, and obesity-associated cardiovascular disease are unknown. Objectives In this study we examined in vitro and in vivo effects of PCB-77 on adipocyte differentiation, proinflammatory adipokines, adipocyte morphology, body weight, serum lipids, and atherosclerosis. Methods PCB-77 or 2,2′,4,4,5,5′-hexachlorobiphenyl (PCB-153) was incubated with 3T3-L1 adipocytes either during differentiation or in mature adipocytes. Concentration-dependent effects of PCB-77 were contrasted with those of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). For in vivo studies, we treated C57BL/6 wild-type (WT) or aryl hydrocarbon receptor (AhR)−/− mice with vehicle or PCB-77 (49 mg/kg, by intraperitoneal injection) and examined body weight gain. In separate studies, we injected ApoE−/− mice with vehicle or PCB-77 over a 6-week period and examined body weight, adipocyte size, serum lipids, and atherosclerosis. Results Low concentrations of PCB-77 or TCDD increased adipocyte differentiation, glycerol–3-phosphate dehydrogenase activity, and expression of peroxisome proliferator–activated receptor γ, whereas higher concentrations inhibited adipocyte differentiation. Effects of PCB-77 were abolished by the AhR antagonist α-naphthoflavone. PCB-77 promoted the expression and release of various proinflammatory cytokines from 3T3-L1 adipocytes. Administration of PCB-77 increased body weight gain in WT but not AhR−/− mice. ApoE−/− mice injected with PCB-77 exhibited greater body weight, adipocyte hypertrophy, serum dyslipidemia, and augmented atherosclerosis. Conclusions Our findings suggest that PCB-77 may contribute to the development of obesity and obesity-associated atherosclerosis.
MED-1577
Treatment-related progressive multifocal leukoencephalopathy: current understanding and future steps
Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disorder of the brain caused by a ubiquitous polyomavirus, JC virus. PML is almost always associated with some underlying immunosuppression and acquired immune deficiency syndrome has been the most common predisposing disorder. Recently, different pharmacological agents have been demonstrated to increase the risk of PML. Therapies that predispose people to PML can be classified into three categories: therapies that uniquely increase the risk for the disorder, such as the monoclonal antibodies natalizumab and efalizumab; therapies that appear to increase the risk in individuals already at risk of PML due to pre-existing conditions, such as rituximab and mycophenolate mofetil; and therapies with a mechanism of action that might suggest a potential for increased PML risk and/or with which rare cases of PML have been observed. Unlike the latter two classes, therapeutic agents uniquely increasing the risk of PML are associated with a much greater prevalence of the disorder and a latent interval from the time of drug initiation to the development of PML. PML development with pharmacological agents has provided new insight into the pathogenesis of this devastating disorder. This review focuses on the risks of PML with multiple pharmacological agents, the proposed pathogenesis with these agents, and potential risk mitigation strategies.
MED-969
Spatial and temporal dynamics of the endothelium.
The endothelium is a highly metabolically active organ that is involved in many physiological processes, including the control of vasomotor tone, barrier function, leukocyte adhesion and trafficking, inflammation, and hemostasis. Endothelial cell phenotypes are differentially regulated in space and time. Endothelial cell heterogeneity has important implications for developing strategies in basic research, diagnostics and therapeutics. The goals of this review are to: (i) consider mechanisms of endothelial cell heterogeneity; (ii) discuss the bench-to-bedside gap in endothelial biomedicine; (iii) revisit definitions for endothelial cell activation and dysfunction; and (iv) propose new goals in diagnosis and therapy. Finally, these themes will be applied to an understanding of vascular bed-specific hemostasis.
MED-2346
Anisakis simplex: from Obscure Infectious Worm to Inducer of Immune Hypersensitivity
Summary: Infection of humans with the nematode worm parasite Anisakis simplex was first described in the 1960s in association with the consumption of raw or undercooked fish. During the 1990s it was realized that even the ingestion of dead worms in food fish can cause severe hypersensitivity reactions, that these may be more prevalent than infection itself, and that this outcome could be associated with food preparations previously considered safe. Not only may allergic symptoms arise from infection by the parasites (“gastroallergic anisakiasis”), but true anaphylactic reactions can also occur following exposure to allergens from dead worms by food-borne, airborne, or skin contact routes. This review discusses A. simplex pathogenesis in humans, covering immune hypersensitivity reactions both in the context of a living infection and in terms of exposure to its allergens by other routes. Over the last 20 years, several studies have concentrated on A. simplex antigen characterization and innate as well as adaptive immune response to this parasite. Molecular characterization of Anisakis allergens and isolation of their encoding cDNAs is now an active field of research that should provide improved diagnostic tools in addition to tools with which to enhance our understanding of pathogenesis and controversial aspects of A. simplex allergy. We also discuss the potential relevance of parasite products such as allergens, proteinases, and proteinase inhibitors and the activation of basophils, eosinophils, and mast cells in the induction of A. simplex-related immune hypersensitivity states induced by exposure to the parasite, dead or alive.
MED-3763
A single sip of a strong alcoholic beverage causes exposure to carcinogenic concentrations of acetaldehyde in the oral cavity.
The aim of this study was to explore oral exposure to carcinogenic (group 1) acetaldehyde after single sips of strong alcoholic beverages containing no or high concentrations of acetaldehyde. Eight volunteers tasted 5 ml of ethanol diluted to 40 vol.% with no acetaldehyde and 40 vol.% calvados containing 2400 μM acetaldehyde. Salivary acetaldehyde and ethanol concentrations were measured by gas chromatography. The protocol was repeated after ingestion of ethanol (0.5 g/kg body weight). Salivary acetaldehyde concentration was significantly higher after sipping calvados than after sipping ethanol at 30s both with (215 vs. 128 μmol/l, p<0.05) and without (258 vs. 89 μmol/l, p<0.05) alcohol ingestion. From 2 min onwards there were no significant differences in the decreasing salivary acetaldehyde concentration, which remained above the level of carcinogenicity still at 10 min. The systemic alcohol distribution from blood to saliva had no additional effect on salivary acetaldehyde after sipping of the alcoholic beverages. Carcinogenic concentrations of acetaldehyde are produced from ethanol in the oral cavity instantly after a small sip of strong alcoholic beverage, and the exposure continues for at least 10 min. Acetaldehyde present in the beverage has a short-term effect on total acetaldehyde exposure. Copyright © 2011 Elsevier Ltd. All rights reserved.
MED-1101
Exposure of human fetal penile cells to different PCB mixtures: transcriptome analysis points to diverse modes of interference on external genitali...
The effects exerted by three mixtures of Polychlorinated Biphenyls (PCBs) were evaluated on human fetal corpora cavernosa cells, as a model for male external genitalia development. The three mixtures feature congeners grouped according to potentially shared modes of action: one dioxin-like (DL) (Mix2) and two non dioxin-like (NDL) mixtures featuring congeners defined as estrogenic (Mix1) and highly persistent-cytochrome P-450 inducers (Mix3). Congeners concentrations used were derived from human internal exposure data. Toxicogenomic analysis revealed that all mixtures modulated critical genes involved in genitourinary development, however displaying three different expression profiles. The DL Mix2 modulated actin-related, cell-cell and epithelial-mesenchymal communication morphogenetic processes; Mix1 modulated smooth muscle function genes, whereas Mix3 mainly modulated genes involved in cell metabolism (e.g., steroid and lipid synthesis) and growth. Our data indicate that fetal exposure to environmentally relevant PCB levels modulates several patterns of genitourinary programming; moreover, NDL congener groups may have specific modes of action. Copyright © 2011 Elsevier Inc. All rights reserved.
MED-3540
Monoaminergic neurotransmission: the history of the discovery of antidepressants from 1950s until today.
The 1950s saw the clinical introduction of the first two specifically antidepressant drugs: iproniazid, a monoamine-oxidase inhibitor that had been used in the treatment of tuberculosis, and imipramine, the first drug in the tricyclic antidepressant family. Iproniazid and imipramine made two fundamental contributions to the development of psychiatry: one of a social-health nature, consisting in an authentic change in the psychiatric care of depressive patients; and the other of a purely pharmacological nature, since these agents have constituted an indispensable research tool for neurobiology and psychopharmacology, permitting, among other things, the postulation of the first aetiopathogenic hypotheses of depressive disorders. The clinical introduction of fluoxetine, a selective serotonin reuptake inhibitor, in the late 1980s, once again revolutionized therapy for depression, opening the way for new families of antidepressants. The present work reviews, from a historical perspective, the entire process that led to the discovery of these drugs, as well as their contribution to the development of the neuroscientific disciplines. However, all of these antidepressants, like the rest of those currently available for clinical practice, share the same action mechanism, which involves the modulation of monoaminergic neurotransmission at a synaptic level, so that the future of antidepressant therapy would seem to revolve around the search for extraneuronal non-aminergic mechanisms or mechanisms that modulate the intraneuronal biochemical pathways.
MED-2442
Double-blind, controlled, crossover study of cyclosporin in adults with severe refractory atopic dermatitis.
A few patients remain severely affected by atopic dermatitis into adult life despite treatment with systemic steroids, azathioprine, and photochemotherapy. 33 patients took part in a double-blind, placebo-controlled, crossover study to assess the efficacy and safety of cyclosporin (5 mg/kg per day) in adults with severe refractory atopic dermatitis. Treatments were given for eight weeks each with one group (n = 16) receiving placebo followed by cyclosporin and another (n = 17) receiving cyclosporin and then placebo. Disease activity, extent of disease, sleep and itch, topical steroid use, and adverse events were assessed every two weeks. Both extent and activity of dermatitis were significantly improved (p less than 0.001) as were subjective measures of disease. 20 patients receiving cyclosporin reported adverse events compared with 8 taking placebo, although no patient required withdrawal from the study. Cyclosporin therapy led to an increase in the mean serum urea, creatinine, and bilirubin concentrations, although only the rise in bilirubin was significant (p = 0.001). Our results confirm that cyclosporin is a safe and effective short-term treatment for severe, refractory atopic dermatitis.
MED-4093
Serum uric acid level as an independent risk factor for all-cause, cardiovascular, and ischemic stroke mortality: a Chinese cohort study.
OBJECTIVE: The association between hyperuricemia and cardiovascular events has been documented in high-risk groups, but is still undetermined in general populations, especially Chinese. This study assessed the temporal association between serum uric acid level, hyperuricemia, and cardiovascular mortality. METHODS: A prospective cohort study of 41,879 men and 48,514 women ages > or = 35 years was conducted using data from the MJ Health Screening Centers in Taiwan. Mortality from all causes, total cardiovascular disease (CVD), ischemic stroke, congestive heart failure, hypertensive disease, and coronary heart disease were compared according to increasing serum uric acid levels. RESULTS: A total of 1,151 (21.2%) events of 5,427 total deaths were ascribed to CVD (mean followup 8.2 years). Hazard ratios (HRs) for hyperuricemia (serum uric acid level >7 mg/dl) were estimated with Cox regression model after adjusting for age, sex, body mass index, cholesterol, triglycerides, diabetes, hypertension, heavy cigarette smoking, and frequent alcohol consumption. In all patients, HRs were 1.16 (P < 0.001) for all-cause mortality, 1.39 (P < 0.001) for total CVD, and 1.35 (P = 0.02) for ischemic stroke. In subgroup analysis, the HRs for cardiovascular risk remained significant in patients with hypertension (1.44, P < 0.001) and in patients with diabetes (1.64, P < 0.001). In addition, in a low metabolic risk subgroup, the HRs for all-cause mortality and total cardiovascular morbidity were 1.24 (P = 0.02) and 1.48 (P = 0.16), respectively. CONCLUSION: Hyperuricemia was an independent risk factor of mortality from all causes, total CVD, and ischemic stroke in the Taiwanese general population, in high-risk groups, and potentially in low-risk groups.
MED-897
Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages.
The effects of different polyphenol-containing beverages on Fe absorption from a bread meal were estimated in adult human subjects from the erythrocyte incorporation of radio-Fe. The test beverages contained different polyphenol structures and were rich in either phenolic acids (chlorogenic acid in coffee), monomeric flavonoids (herb teas, camomile (Matricaria recutita L.), vervain (Verbena officinalis L.), lime flower (Tilia cordata Mill.), pennyroyal (Mentha pulegium L.) and peppermint (Mentha piperita L.), or complex polyphenol polymerization products (black tea and cocoa). All beverages were potent inhibitors of Fe absorption and reduced absorption in a dose-dependent fashion depending on the content of total polyphenols. Compared with a water control meal, beverages containing 20-50 mg total polyphenols/serving reduced Fe absorption from the bread meal by 50-70%, whereas beverages containing 100-400 mg total polyphenols/serving reduced Fe absorption by 60-90%. Inhibition by black tea was 79-94%, peppermint tea 84%, pennyroyal 73%, cocoa 71%, vervain 59%, lime flower 52% and camomile 47%. At an identical concentration of total polyphenols, black tea was more inhibitory than cocoa, and more inhibitory than herb teas camomile, vervain, lime flower and pennyroyal, but was of equal inhibition to peppermint tea. Adding milk to coffee and tea had little or no influence on their inhibitory nature. Our findings demonstrate that herb teas, as well as black tea, coffee and coca can be potent inhibitors of Fe absorption. This property should be considered when giving dietary advice in relation to Fe nutrition.
MED-3556
Prevalence of HPV infection among females in the United States.
CONTEXT: Human papillomavirus (HPV) infection is estimated to be the most common sexually transmitted infection. Baseline population prevalence data for HPV infection in the United States before widespread availability of a prophylactic HPV vaccine would be useful. OBJECTIVE: To determine the prevalence of HPV among females in the United States. DESIGN, SETTING, AND PARTICIPANTS: The National Health and Nutrition Examination Survey (NHANES) uses a representative sample of the US noninstitutionalized civilian population. Females aged 14 to 59 years who were interviewed at home for NHANES 2003-2004 were examined in a mobile examination center and provided a self-collected vaginal swab specimen. Swabs were analyzed for HPV DNA by L1 consensus polymerase chain reaction followed by type-specific hybridization. Demographic and sexual behavior information was obtained from all participants. MAIN OUTCOME MEASURES: HPV prevalence by polymerase chain reaction. RESULTS: The overall HPV prevalence was 26.8% (95% confidence interval [CI], 23.3%-30.9%) among US females aged 14 to 59 years (n = 1921). HPV prevalence was 24.5% (95% CI, 19.6%-30.5%) among females aged 14 to 19 years, 44.8% (95% CI, 36.3%-55.3%) among women aged 20 to 24 years, 27.4% (95% CI, 21.9%-34.2%) among women aged 25 to 29 years, 27.5% (95% CI, 20.8%-36.4%) among women aged 30 to 39 years, 25.2% (95% CI, 19.7%-32.2%) among women aged 40 to 49 years, and 19.6% (95% CI, 14.3%-26.8%) among women aged 50 to 59 years. There was a statistically significant trend for increasing HPV prevalence with each year of age from 14 to 24 years (P<.001), followed by a gradual decline in prevalence through 59 years (P = .06). HPV vaccine types 6 and 11 (low-risk types) and 16 and 18 (high-risk types) were detected in 3.4% of female participants; HPV-6 was detected in 1.3% (95% CI, 0.8%-2.3%), HPV-11 in 0.1% (95% CI, 0.03%-0.3%), HPV-16 in 1.5% (95% CI, 0.9%-2.6%), and HPV-18 in 0.8% (95% CI, 0.4%-1.5%) of female participants. Independent risk factors for HPV detection were age, marital status, and increasing numbers of lifetime and recent sex partners. CONCLUSIONS: HPV is common among females in the United States. Our data indicate that the burden of prevalent HPV infection among females was greater than previous estimates and was highest among those aged 20 to 24 years. However, the prevalence of HPV vaccine types was relatively low.
MED-1248
Patients' attitudes to rectal drug administration.
One hundred adult patients attending for day case surgery were surveyed by anonymous questionnaire in order to determine their attitudes to rectal drug administration. Fifty four patients did not want an analgesic drug (diclofenac sodium) administered rectally whilst under anaesthesia, all preferring to take it orally if available. Ninety eight patients thought that drugs administered per rectum should always be discussed with them beforehand and a few had very strong feelings about this route of administration. We suggest that prescribers of rectal diclofenac should always discuss it with patients pre-operatively. Whilst many are happy to have suppositories, some young patients are sensitive about this and prefer to take such medication by mouth.
MED-4193
Crocus sativus L. (saffron) in the treatment of premenstrual syndrome: a double-blind, randomised and placebo-controlled trial.
OBJECTIVE: The aim of this double-blind and placebo-controlled trial was to investigate whether saffron (stigma of Crocus sativus L.) could relieve symptoms of premenstrual syndrome (PMS). DESIGN: Double-blind, randomised and placebo-controlled trial. SETTING: Departments of Gynaecology/Obstetrics and Psychiatry, Tehran and Zanjan University of Medical Sciences. POPULATION: Women aged 20-45 years with regular menstrual cycles and experience of PMS symptoms for at least 6 months were eligible for the study. METHOD: Women were randomly assigned to receive capsule saffron 30 mg/day (15 mg twice a day; morning and evening) (group A) or capsule placebo (twice a day) for a two menstrual cycles (cycles 3 and 4). MAIN OUTCOME MEASURES: The primary outcome measure was the Daily Symptom Report, and secondary outcome measure was the Hamilton Depression Rating Scale. RESULTS: In this trial, saffron was found to be effective in relieving symptoms of PMS. A significant difference was observed in efficacy of saffron in cycles 3 and 4 in the Total Premenstrual Daily Symptoms and Hamilton Depression Rating Scale. CONCLUSION: The results of this study indicate the efficacy of C. sativus L. in the treatment of PMS. However, a tolerable adverse effects profile of saffron may well confirm the application of saffron as an alternative treatment for PMS. These results deserved further investigations.
MED-1787
Evidence for decreasing quality of semen during past 50 years.
OBJECTIVE: To investigate whether semen quality has changed during the past 50 years. DESIGN: Review of publications on semen quality in men without a history of infertility selected by means of Cumulated Index Medicus and Current List (1930-1965) and MEDLINE Silver Platter database (1966-August 1991). SUBJECTS: 14,947 men included in a total of 61 papers published between 1938 and 1991. MAIN OUTCOME MEASURES: Mean sperm density and mean seminal volume. RESULTS: Linear regression of data weighted by number of men in each study showed a significant decrease in mean sperm count from 113 x 10(6)/ml in 1940 to 66 x 10(6)/ml in 1990 (p < 0.0001) and in seminal volume from 3.40 ml to 2.75 ml (p = 0.027), indicating an even more pronounced decrease in sperm production than expressed by the decline in sperm density. CONCLUSIONS: There has been a genuine decline in semen quality over the past 50 years. As male fertility is to some extent correlated with sperm count the results may reflect an overall reduction in male fertility. The biological significance of these changes is emphasised by a concomitant increase in the incidence of genitourinary abnormalities such as testicular cancer and possibly also cryptorchidism and hypospadias, suggesting a growing impact of factors with serious effects on male gonadal function.
MED-2013
Celiac disease, wheat allergy, and gluten sensitivity: when gluten free is not a fad.
As the gluten-free diet (GFD) gains in popularity with the general public, health practitioners are beginning to question its real health benefits. For those patients with celiac disease (CD), the GFD is considered medical nutrition therapy, as well as the only proven treatment that results in improvements in symptomatology and small bowel histology. Those with wheat allergy also benefit from the GFD, although these patients often do not need to restrict rye, barley, and oats from their diet. Gluten sensitivity is a controversial subject, where patients who have neither CD nor wheat allergy have varying degrees of symptomatic improvement on the GFD. Conditions in this category include dermatitis herpetiformis (DH), irritable bowel syndrome (IBS), and neurologic diseases such as gluten-sensitive ataxia and autism. It is important for patients and healthcare practitioners to understand the differences between these conditions, even though they may all respond to a GFD. Patients with CD can experience comorbid nutrition deficiencies and are at higher risk for the development of cancers and other autoimmune conditions. Those with wheat allergy and gluten sensitivity are thought not to be at higher risk for these complications. Defining the symptoms and biochemical markers for gluten-sensitive conditions is an important area for future investigations, and high-quality, large-scale randomized trials are needed to prove the true benefits of the GFD in this evolving field.
MED-1837
Dietary manganese intake and type of lipid do not affect clinical or neuropsychological measures in healthy young women.
Because manganese (Mn) is potentially toxic, and because dietary fat type may affect Mn absorption, the objectives of the current study were to determine whether diets containing very low or very high amounts of Mn and enriched in either saturated or unsaturated fats affected measures of neuropsychological and basic metabolic function. Healthy young women were fed for 8 wk each, in a crossover design, diets that provided 0.8 or 20 mg of Mn/d. One half of the subjects received 15% of energy as cocoa butter, and one half received 15% of energy as corn oil. A meal containing (54)Mn was fed after 4 wk, and subjects underwent whole-body counting for the next 21 d. Blood draws and neuropsychological tests were administered at regular intervals during the dietary periods. When subjects consumed the diets low in Mn, compared with the high Mn diets, they absorbed a significantly higher percentage of (54)Mn, but had a significantly longer biological half-life of the absorbed (54)Mn. Manganese intake did not affect any neurological measures and only minimally affected psychologic variables. These data show that efficient mechanisms operate to maintain Mn homeostasis over the range of intakes that may be encountered in a mixed Western diet. Thus, dietary intakes of Mn from 0.8 to 20 mg for 8 wk likely do not result in Mn deficiency or toxicity signs in healthy adults.
MED-2299
Health practices and mortality in Japan: combined effects of smoking, drinking, walking and body mass index in the Miyagi Cohort Study.
BACKGROUND: Evidence is limited regarding the association between the combinations of multiple health practices and mortality. METHODS: In 1990, 28,333 men and women in Miyagi Prefecture in rural northern Japan (40-64 year of age) completed a self-administered questionnaire. A lifestyle score was calculated by adding the number of high-risk practices (smoking, consuming > or = 22.8 g alcohol/d, walking < 1 hr/d, body mass index < 18.5 or > or = 30.0). Cox regression was used to estimate relative risk (RR) of mortality according to the lifestyle score, with adjustment for age, education, marital status, past history of diseases, and dietary variables. During 11 years of follow-up, 1,200 subjects had died. RESULTS: We observed linear increase in risk of death associated with increasing number of high-risk practices: compared with men who had no high-risk practices, multivariate RRs for men who had 1 to 4 practices were 1.20, 1.66, 1.94, and 3.96, respectively (P for trend<0.001), and corresponding RRs for women were 1.31, 2.14, 3.98, 5.56, respectively (P for trend<0.001). A unit increase in the number of high-risk practices corresponded to being 2.8 and 4.8 years older for men and women, respectively. CONCLUSIONS: In this prospective cohort study of middle-aged men and women in rural Japan, a larger number of high-risk practices was associated with linear increase in risk of all-cause mortality.
MED-4498
Trial of garlic as an adjunct therapy for multidrug resistant Pseudomonas aeruginosa pneumonia in a critically ill infant.
We present a case of a critically ill infant with severe multidrug-resistant Pseudomonas aeruginosa pneumonia and bacteremia who was treated with garlic and antibiotics after in vitro demonstration of a change in the resistance pattern via the disc diffusion method on garlic-treated Mueller Hinton agar. To our knowledge, this is the first report of therapeutic garlic use in a critically ill infant in the literature.
MED-2188
Stability of carotenoids, total phenolics and in vitro antioxidant capacity in the thermal processing of orange-fleshed sweet potato (Ipomoea batat...
Intervention strategies regarding the biofortification of orange-fleshed sweet potato, which is a rich source of carotenoids for combating vitamin A deficiency, are being developed in Brazil. This study was conducted to evaluate the concentrations of individual carotenoids, total phenolic compounds and antioxidant capacity in the roots of four biofortified sweet potato cultivars that were raw or processed by four common heat treatments. HPLC, Folin-Ciocalteu, DPPH and ABTS assays were used. All cultivars showed high levels of carotenoids in raw roots, predominantly all-trans-β-carotene (79.1-128.5 mg.100 g(-1) DW), suggesting a high estimated vitamin A activity. The CNPH 1194 cultivar reported carotenoids values highest than those of other cultivars (p < 0.05). The total phenolic compounds varied among cultivars and heat treatments (0.96-2.05 mg.g(-1) DW). In most cases, the heat treatments resulted in a significant decrease in the carotenoids and phenolic compounds contents as well as antioxidant capacity. Processing of flour presented the greatest losses of major carotenoids and phenolics. The phenolic compounds showed more stability than carotenoids after processing. There were significant correlations between the carotenoids and phenolic compounds and the antioxidant capacity.
MED-2816
Plant-derived health: the effects of turmeric and curcuminoids.
Plants contain numerous polyphenols, which have been shown to reduce inflammation and hereby to increase resistance to disease. Examples of such polyphenols are isothiocyanates in cabbage and broccoli, epigallocatechin in green tee, capsaicin in chili peppers, chalones, rutin and naringenin in apples, resveratrol in red wine and fresh peanuts and curcumin/curcuminoids in turmeric. Most diseases are maintained by a sustained discreet but obvious increased systemic inflammation. Many studies suggest that the effect of treatment can be improved by a combination of restriction in intake of proinflammatory molecules such as advanced glycation end products (AGE), advanced lipoperoxidation end products (ALE), and rich supply of antiinflammatory molecules such as plant polyphenols. To the polyphenols with a bulk of experimental documentation belong the curcuminoid family and especially its main ingredient, curcumin. This review summarizes the present knowledge about these turmericderived ingredients, which have proven to be strong antioxidants and inhibitors of cyclooxigenase-2 (COX-2), lipoxygenase (LOX) and nuclear factor kappa B (NF-kappaB) but also AGE. A plethora of clinical effects are reported in various experimental diseases, but clinical studies in humans are few. It is suggested that supply of polyphenols and particularly curcuminoids might be value as complement to pharmaceutical treatment, but also prebiotic treatment, in conditions proven to be rather therapy-resistant such as Crohn's, long-stayed patients in intensive care units, but also in conditions such as cancer, liver cirrhosis, chronic renal disease, chronic obstructive lung disease, diabetes and Alzheimer's disease.
MED-5075
Effect of meal composition and cooking duration on the fate of sulforaphane following consumption of broccoli by healthy human subjects.
The isothiocyanate, sulforaphane, has been implicated in the cancer-protective effects of brassica vegetables. When broccoli is consumed, sulforaphane is released from hydrolysis of glucoraphanin by plant myrosinase and/or colonic microbiota. The influence of meal composition and broccoli-cooking duration on isothiocyanate uptake was investigated in a designed experiment. Volunteers (n 12) were each offered a meal, with or without beef, together with 150 g lightly cooked broccoli (microwaved 2.0 min) or fully cooked broccoli (microwaved 5.5 min), or a broccoli seed extract. They received 3 g mustard containing pre-formed allyl isothiocyanate (AITC) with each meal. Urinary output of allyl (AMA) and sulforaphane (SFMA) mercapturic acids, the biomarkers of production of AITC and sulforaphane respectively, were measured for 24 h after meal consumption. The estimated yield of sulforaphane in vivo was about 3-fold higher after consumption of lightly cooked broccoli than fully cooked broccoli. Absorption of AITC from mustard was about 1.3-fold higher following consumption of the meat-containing meal compared with the non meat-containing alternative. The meal matrix did not significantly influence the hydrolysis of glucoraphanin and its excretion as SFMA from broccoli. Isothiocyanates may interact with the meal matrix to a greater extent if they are ingested pre-formed rather than after their production from hydrolysis of glucosinolates in vivo. The main influence on the production of isothiocyanates in vivo is the way in which brassica vegetables are cooked, rather than the effect of the meal matrix.
MED-2819
Biological actions of curcumin on articular chondrocytes.
OBJECTIVES: Curcumin (diferuloylmethane) is the principal biochemical component of the spice turmeric and has been shown to possess potent anti-catabolic, anti-inflammatory and antioxidant, properties. This article aims to provide a summary of the actions of curcumin on articular chondrocytes from the available literature with the use of a text-mining tool. We highlight both the potential benefits and drawbacks of using this chemopreventive agent for treating osteoarthritis (OA). We also explore the recent literature on the molecular mechanisms of curcumin mediated alterations in gene expression mediated via activator protein 1 (AP-1)/nuclear factor-kappa B (NF-kappaB) signalling in chondrocytes, osteoblasts and synovial fibroblasts. METHODS: A computer-aided search of the PubMed/Medline database aided by a text-mining tool to interrogate the ResNet Mammalian database 6.0. RESULTS: Recent work has shown that curcumin protects human chondrocytes from the catabolic actions of interleukin-1 beta (IL-1beta) including matrix metalloproteinase (MMP)-3 up-regulation, inhibition of collagen type II and down-regulation of beta1-integrin expression. Curcumin blocks IL-1beta-induced proteoglycan degradation, AP-1/NF-kappaB signalling, chondrocyte apoptosis and activation of caspase-3. CONCLUSIONS: The available data from published in vitro and in vivo studies suggest that curcumin may be a beneficial complementary treatment for OA in humans and companion animals. Nevertheless, before initiating extensive clinical trials, more basic research is required to improve its solubility, absorption and bioavailability and gain additional information about its safety and efficacy in different species. Once these obstacles have been overcome, curcumin and structurally related biochemicals may become safer and more suitable nutraceutical alternatives to the non-steroidal anti-inflammatory drugs that are currently used for the treatment of OA. Copyright 2009 Osteoarthritis Research Society International. All rights reserved.
MED-3098
Camel urine inhibits the cytochrome P450 1a1 gene expression through an AhR-dependent mechanism in Hepa 1c1c7 cell line.
AIM OF THE STUDY: Drinking camel urine has been used traditionally to treat numerous cases of cancer yet, the exact mechanism was not investigated. Therefore, we examined the ability of three different camel urines (virgin, lactating, and pregnant source) to modulate a well-known cancer-activating enzyme, the cytochrome P450 1a1 (Cyp1a1) in murine hepatoma Hepa 1c1c7 cell line. MATERIALS AND METHODS: The effect of different camel urines, compared to bovine urines, on Cyp1a1 mRNA was determined using real-time polymerase chain reaction. Cyp1a1 protein and catalytic activity levels were determined using Western blot analysis and 7-ethoxyresorufin as a substrate, respectively. The role of aryl hydrocarbon receptor (AhR)-dependent mechanism was determined using electrophoretic mobility shift assay (EMSA) and the AhR-dependent luciferase reporter gene. RESULTS: All types of camel, but not bovine, urines differentially inhibited the induction of Cyp1a1 gene expression by TCDD, the most potent Cyp1a1 inducer and known carcinogenic chemical. Importantly, virgin camel urine showed the highest degree of inhibition at the activity level, followed by lactating and pregnant camel urines. Furthermore, we have shown that virgin camel urine significantly inhibited the TCDD-mediated induction of Cyp1a1 at the mRNA and protein expression levels. Mechanistically, the ability of virgin camel urine to inhibit Cyp1a1 was strongly correlated with its ability to inhibit AhR-dependent luciferase activity and DNA binding as determined by EMSA, suggesting that AhR-dependent mechanism is involved. CONCLUSIONS: The present work provides the first evidence that camel urine but not that of bovine inhibits the TCDD-mediated toxic effect by inhibiting the expression of Cyp1a1, at both transcriptional and post-transcriptional levels through an AhR-dependent mechanism. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
MED-3150
Do circulating leucocytes and lymphocyte subtypes increase in response to brief exercise in children with and without asthma?
Background Exercise can alter health in children in both beneficial (eg reduced long‐term risk of atherosclerosis) and adverse (eg exercise‐induced asthma) ways. The mechanisms linking exercise and health are not known, but may rest, partly, on the ability of exercise to increase circulating immune cells. Little is known about the effect of brief exercise, more reflective of naturally occurring patterns of physical activity in children, on immune cell responses. Objectives To determine whether (1) a 6‐min bout of exercise can increase circulating inflammatory cells in healthy children and (2) the effect of brief exercise is greater in children with a history of asthma. Methods Children with mild–moderate persistent asthma and age‐matched controls (n = 14 in each group, mean age 13.6 years) performed a 6‐min bout of cycle‐ergometer exercise. Spirometry was performed at baseline and after exercise. Blood was drawn before and after exercise, leucocytes were quantified and key lymphocyte cell surface markers were assessed by flow cytometry. Results Exercise decreased spirometry only in children with asthma, but increased (p<0.001) most types of leucocytes (eg lymphocytes (controls, mean (SD) 1210 (208) cells/μl; children with asthma, 1119 (147) cells/μl) and eosinophils (controls, 104 (22) cells/μl; children with asthma, 88 (20) cells/μl)) to the same degree in both groups. Similarly, exercise increased T helper cells (controls, 248 (60) cells/μl; children with asthma, 232 (53) cells/μl) and most other lymphocyte subtypes tested. By contrast, although basophils (16 (5) cells/μl) and CD4+ CD45RO+ RA+ lymphocytes (19 (4) cells/μl) increased in controls, no increase in these cell types was found in children with asthma. Conclusions Exercise increased many circulating inflammatory cells in both children with asthma and controls. Circulating inflammatory cells did increase in children with asthma, but not to a greater degree than in controls. In fact, basophils and T helper lymphocyte memory transition cells did not increase in children with asthma, whereas they did increase in controls. Even brief exercise in children and adolescents robustly mobilises circulating immune cells.
MED-3890
Detection of a Common and Persistent tet(L)-Carrying Plasmid in Chicken-Waste-Impacted Farm Soil
The connection between farm-generated animal waste and the dissemination of antibiotic resistance in soil microbial communities, via mobile genetic elements, remains obscure. In this study, electromagnetic induction (EMI) surveying of a broiler chicken farm assisted soil sampling from a chicken-waste-impacted site and a marginally affected site. Consistent with the EMI survey, a disparity existed between the two sites with regard to soil pH, tetracycline resistance (Tcr) levels among culturable soil bacteria, and the incidence and prevalence of several tet and erm genes in the soils. No significant difference was observed in these aspects between the marginally affected site and several sites in a relatively pristine regional forest. When the farm was in operation, tet(L), tet(M), tet(O), erm(A), erm(B), and erm(C) genes were detected in the waste-affected soil. Two years after all waste was removed from the farm, tet(L), tet(M), tet(O), and erm(C) genes were still detected. The abundances of tet(L), tet(O), and erm(B) were measured using quantitative PCR, and the copy numbers of each were normalized to eubacterial 16S rRNA gene copy numbers. tet(L) was the most prevalent gene, whereas tet(O) was the most persistent, although all declined over the 2-year period. A mobilizable plasmid carrying tet(L) was identified in seven of 14 Tcr soil isolates. The plasmid's hosts were identified as species of Bhargavaea, Sporosarcina, and Bacillus. The plasmid's mobilization (mob) gene was quantified to estimate its prevalence in the soil, and the ratio of tet(L) to mob was shown to have changed from 34:1 to 1:1 over the 2-year sampling period.
MED-2943
Long-term low-calorie low-protein vegan diet and endurance exercise are associated with low cardiometabolic risk.
BACKGROUND: Western diets, which typically contain large amounts of energy-dense processed foods, together with a sedentary lifestyle are associated with increased cardiometabolic risk. We evaluated the long-term effects of consuming a low-calorie low-protein vegan diet or performing regular endurance exercise on cardiometabolic risk factors. METHODS: In this cross-sectional study, cardiometabolic risk factors were evaluated in 21 sedentary subjects, who had been on a low-calorie low-protein raw vegan diet for 4.4 +/- 2.8 years, (mean age, 53.1 +/- 11 yrs), 21 body mass index (BMI)-matched endurance runners consuming Western diets, and 21 age- and gender-matched sedentary subjects, consuming Western diets. RESULTS: BMI was lower in the low-calorie low-protein vegan diet (21.3 +/- 3.1 kg/m(2)) and endurance runner (21.1 +/- 1.6 kg/m(2)) groups than in the sedentary Western diet group (26.5 +/- 2.7 kg/m(2)) (p < 0.005). Plasma concentrations of lipids, lipoproteins, glucose, insulin, C-reactive protein, blood pressure (BP), and carotid artery intima-media thickness were lower in the low-calorie low-protein vegan diet and runner groups than in the Western diet group (all p < 0.05). Both systolic and diastolic BP were lower in the low-calorie low-protein vegan diet group (104 +/- 15 and 62 +/- 11 mm Hg) than in BMI-matched endurance runners (122 +/- 13 and 72 +/- 9 mmHg) and Western diet group (132 +/- 14 and 79 +/- 8 mm Hg) (p < 0.001); BP values were directly associated with sodium intake and inversely associated with potassium and fiber intake. CONCLUSIONS: Long-term consumption of a low-calorie low-protein vegan diet or regular endurance exercise training is associated with low cardiometabolic risk. Moreover, our data suggest that specific components of a low-calorie low-protein vegan diet provide additional beneficial effects on blood pressure.
MED-2711
Accidental bullous phototoxic reactions to bergamot aromatherapy oil.
Oil of bergamot is an extract from the rind of bergamot orange (Citrus aurantium ssp bergamia) that has a pleasant, refreshing scent; until a few years ago it had been widely used as an ingredient in cosmetics but was restricted or banned in most countries because of certain adverse effects. More recently, oil of bergamot preparations have been gaining renewed popularity in aromatherapy. Oil of bergamot possesses photosensitive and melanogenic properties because of the presence of furocoumarins, primarily bergapten (5-methoxypsoralen [5-MOP]). However, 5-MOP is also potentially phototoxic and photomutagenic. Despite its increasing application, there are only a few recent reports of phototoxic reactions to bergamot aromatherapy oil. We describe two patients with localized and disseminated bullous phototoxic skin reactions developing within 48 to 72 hours after exposure to bergamot aromatherapy oil and subsequent ultraviolet exposure. One patient (case 2) had no history of direct contact with aromatherapy oil but developed bullous skin lesions after exposure to aerosolized (evaporated) aromatherapy oil in a sauna and subsequent UVA radiation in a tanning salon. This report highlights the potential health hazard related to the increasing use of psoralen-containing aromatherapy oils.
MED-4961
Haff disease after eating salmon.
While fish consumption is considered a component of a heart-healthy diet, many illnesses have been associated with eating contaminated fish. The authors describe two cases of muscle weakness and rhabdomyolysis that occurred after eating salmon. Cases of rhabdomyolysis and muscle weakness after consumption of fresh water fish have rarely been reported in the United States but have been frequently reported from the Baltic region. This illness is known as Haff disease. While the etiology is unknown, it is felt to be a toxin. Palytoxin, found in marine fish, has been associated with rhabdomyolysis, and may serve as a model for further study of the suspected toxin responsible for rhabdomyolysis after consumption of fresh water fish. If a case of Haff disease is suspected, contact the Centers for Disease Control and Prevention and collect any uneaten fish, which may be sent for laboratory analysis.
MED-5276
8:45-90:00. The Influence of a High Fat Meal Compared to an Olestra Meal on Coronary Artery Endothelial Dysfunction by Rubidium (Rb)-82 Positron Em...
Background: Cellular changes lead to coronary artery endothelial dysfunction (ED) and precede plaque formation. Clinical events, such as unstable angina and acute coronary syndromes, are common consequences of ED. Coronary artery ED, as characterized by Rb-82 PE, is a perfusion abnormality at rest, which improves following stress. In risk factor modification studies, particularly in cholesterol-lowering trials, coronary artery ED has been demonstrated to be reversible. Other studies have correlated low fat diet modification with improvement in coronary artery disease.Purpose: This study evaluates changes in myocardial perfusion following meals with low versus high TG content, and its influence on post prandial serum TG.Methods: With a randomized, double blind placebo controlled, cross over design, we investigated 19 patients (10 with ED and 9 with normal perfusion) with Rb-82 PET for myocardial blood flow at rest and with adenosine stress. PET images and serum triglycerides were obtained before and after an olestra (OA) meal (2.7g TG, 44g olestra) and a high-fat meal (46.7g TG). Meals were matched for carbohydrate, protein, and cholesterol content.Results: Myocardial perfusion (uCi/cc) increased 11 - 12% following the OA meal compared to the high-fat meal in patients with ED. For all patients combined, serum TG increased significantly (p < 0.01) in the non-OA group with the median change from baseline to 170.0 mg/dl, compared to 21.5 mg/dl in the OA group during the 6 hours following the meal.Conclusions: A single olestra meal significantly diminishes post prandial serum TG levels and improves myocardial perfusion in patients with endothelial disease.
MED-3417
Correlation between penile duplex findings and stress electrocardiography in men with erectile dysfunction.
The aim of this work is to assess the association between vasculogenic erectile dysfunction (ED) and coronary artery disease in men above the age of 40 y. The study included 40 patients above 40 y of age with vasculogenic ED of more than 3 months duration. A dynamic duplex study after intracavernosal injection of a bimix solution (60 mg papaverine + 2 mg phentolamine mesylate) was carried out using a color ultrasound machine. The patients underwent a stress ECG test, carried out on a motor-driven treadmill according to the 'Bruce Protocol'. A total of 12 patients were diagnosed with positive ischemic heart disease (IHD). Their mean peak systolic velocity (PSV) was PSV = 19.58 cm/s. In all, patients were diagnosed with negative IHD; their mean PSV was 36.21 cm/s. A statistically significant difference was observed between patients with positive IHD and patients with negative IHD regarding PSV (P = 0.003). The sensitivity of a PSV of less than 35 cm/s in predicting IHD was 50% with a specificity of 100%. Positive predictive value for abnormal stress ECG to predict a PSV of less than 35 cm/s was 100%. In conclusion, the PSV of cavernosal arteries is a reliable measure for predicting IHD in patients with vasculogenic ED. Patients with a PSV of less than 35 cm/s should be referred for cardiologic assessment as they carry a real risk of having silent IHD.
MED-2243
Turmeric and curcumin as topical agents in cancer therapy.
An ethanol extract of turmeric ("Curcuma longa") as well as an ointment of curcumin (its active ingredient) were found to produce remarkable symptomatic relief in patients with external cancerous lesions. Reduction in smell were noted in 90% of the cases and reduction in itching in almost all cases. Dry lesions were observed in 70% of the cases, and a small number of patients (10%) had a reduction in lesion size and pain. In many patients the effect continued for several months. An adverse reaction was noticed in only one of the 62 patients evaluated.
MED-1103
Dietary Acrylamide Intake and the Risk of Lymphatic Malignancies: The Netherlands Cohort Study on Diet and Cancer
Background Acrylamide, a probable human carcinogen, is present in many everyday foods. Since the finding of its presence in foods in 2002, epidemiological studies have found some suggestive associations between dietary acrylamide exposure and the risk of various cancers. The aim of this prospective study is to investigate for the first time the association between dietary acrylamide intake and the risk of several histological subtypes of lymphatic malignancies. Methods The Netherlands Cohort Study on diet and cancer includes 120,852 men and women followed-up since September 1986. The number of person years at risk was estimated by using a random sample of participants from the total cohort that was chosen at baseline (n  = 5,000). Acrylamide intake was estimated from a food frequency questionnaire combined with acrylamide data for Dutch foods. Hazard ratios (HRs) were calculated for acrylamide intake as a continuous variable as well as in categories (quintiles and tertiles), for men and women separately and for never-smokers, using multivariable-adjusted Cox proportional hazards models. Results After 16.3 years of follow-up, 1,233 microscopically confirmed cases of lymphatic malignancies were available for multivariable-adjusted analysis. For multiple myeloma and follicular lymphoma, HRs for men were 1.14 (95% CI: 1.01, 1.27) and 1.28 (95% CI: 1.03, 1.61) per 10 µg acrylamide/day increment, respectively. For never-smoking men, the HR for multiple myeloma was 1.98 (95% CI: 1.38, 2.85). No associations were observed for women. Conclusion We found indications that acrylamide may increase the risk of multiple myeloma and follicular lymphoma in men. This is the first epidemiological study to investigate the association between dietary acrylamide intake and the risk of lymphatic malignancies, and more research into these observed associations is warranted.
MED-5030
Association of Sleep Duration with Mortality from Cardiovascular Disease and Other Causes for Japanese Men and Women: the JACC Study
Study Objectives: To examine sex-specific associations between sleep duration and mortality from cardiovascular disease and other causes. Design: Cohort study. Setting: Community-based study. Participants: A total of 98,634 subjects (41,489 men and 57,145 women) aged 40 to 79 years from 1988 to 1990 and were followed until 2003. Interventions: N/A. Measurements and Results: During a median follow-up of 14.3 years, there were 1964 deaths (men and women: 1038 and 926) from stroke, 881 (508 and 373) from coronary heart disease, 4287 (2297 and 1990) from cardiovascular disease, 5465 (3432 and 2033) from cancer, and 14,540 (8548 and 5992) from all causes. Compared with a sleep duration of 7 hours, sleep duration of 4 hours or less was associated with increased mortality from coronary heart disease for women and noncardiovascular disease/noncancer and all causes in both sexes. The respective multivariable hazard ratios were 2.32 (1.19–4.50) for coronary heart disease in women, 1.49 (1.02–2.18) and 1.47 (1.01–2.15) for noncardiovascular disease/noncancer, and 1.29 (1.02–1.64) and 1.28 (1.03–1.60) for all causes in men and women, respectively. Long sleep duration of 10 hours or longer was associated with 1.5- to 2-fold increased mortality from total and ischemic stroke, total cardiovascular disease, noncardiovascular disease/noncancer, and all causes for men and women, compared with 7 hours of sleep in both sexes. There was no association between sleep duration and cancer mortality in either sex. Conclusions: Both short and long sleep duration were associated with increased mortality from cardiovascular disease, noncardiovascular disease/noncancer, and all causes for both sexes, yielding a U-shaped relationship with total mortality with a nadir at 7 hours of sleep. Citation: Ikehara S; Iso H; Date C; Kikuchi S; Watanabe Y; Wada Y; Inaba Y; Tamakoshi A. Association of sleep duration with mortality from cardiovascular disease and other causes for Japanese men and women: the JACC study. SLEEP 2009;32(3):259–301.
MED-1585
Effects of twin gestation on maternal morbidity.
As the incidence of twin gestation increases, it is important to consider the maternal risks associated with carrying multiples. Compared with singleton gestation, there are increased risks to the mother during the antepartum, intrapartum, and postpartum periods. Certain pregnancy complications are more likely to occur during a twin gestation, including preeclampsia and other hypertensive disorders, antepartum hospitalization for preterm labor or abnormal bleeding, nutritional deficiencies, cesarean delivery, and postpartum hemorrhage. Women carrying twins may benefit from early education regarding these issues, close maternal monitoring as well as physical therapy sessions, and nutrition counseling during their pregnancies. Copyright © 2012 Elsevier Inc. All rights reserved.
MED-3659
Results of patch testing with lavender oil in Japan.
We report the annual results of patch testing with lavender oil for a 9-year period from 1990 to 1998 in Japan. Using Finn Chambers and Scanpor tape, we performed 2-day closed patch testing with lavender oil 20% pet. on the upper back of each patient suspected of having cosmetic contact dermatitis. We compared the frequency of positive patch tests to lavender oil each year with those to other fragrances. We diagnosed contact allergy when patch test reactions were + or <+ at 1 day after removal. The positivity rate of lavender oil was 3.7% (0-13.9%) during the 9-year period from 1990 to 1998. The positivity rate of lavender oil increased suddenly in 1997. Recently, in Japan, there has been a trend for aromatherapy using lavender oil. With this trend, placing dried lavender flowers in pillows, drawers, cabinets, or rooms has become a new fashion. We asked patients who showed a positive reaction to lavender oil about their use of dried lavender flowers. We confirmed the use of dried lavender flowers in 5 cases out of 11 positive cases in 1997 and 8 out of 15 positive cases in 1998. We concluded that the increase in patch test positivity rates to lavender oil in 1997 and 1998 was due to the above fashion, rather than due to fragrances in cosmetic products.
MED-5355
Intake of whole-grain products and risk of prostate cancer among men in the Danish Diet, Cancer and Health cohort study.
OBJECTIVE: High intake of whole-grain products may protect against prostate cancer, but overall evidence is limited and inconclusive. The aim of the present study was to investigate the relationship between the intake of whole-grain products and risk of prostate cancer in a large prospective cohort. METHODS: A total of 26,691 men aged 50-64 years participated in the Diet, Cancer and Health cohort study and provided information about diet and potential prostate cancer risk factors. During a median follow-up of 12.4 years, we identified 1,081 prostate cancer cases. Associations between whole-grain product intake and prostate cancer incidence were analyzed using Cox's regression model. RESULTS: Overall, there was no association between total intake of whole-grain products and prostate cancer risk (adjusted incidence rate ratio per 50 g day(-1): 1.00 (95% confidence interval: 0.96, 1.05)) as well as between intake of the specific whole-grain products: whole-grain rye bread, whole-grain bread, and oatmeal, and risk of prostate cancer. No risk estimates did differ according to either stage or grade of disease. CONCLUSIONS: Results from this prospective study suggest that higher intakes of total or specific whole-grain products are not associated with risk of prostate cancer in a population of Danish middle-aged men.
MED-5173
Acute rhabdomyolysis caused by Spirulina (Arthrospira platensis).
Rhabdomyolysis is a potentially life-threatening disorder that occurs as a primary disease or as a complication of a broad spectrum of other diseases. We report the first case of acute rhabdomyolysis after ingestion of Spirulina (Arthrospira platensis), a plantonic blue-green alga, as a dietary supplement.
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-4183
Flame retardants in the serum of pet dogs and in their food.
A previous study from our laboratory showed that pet cats had much higher serum levels of flame retardants compared to humans, despite sharing the same household environment. Dogs, on the other hand, are expected to have lower serum levels of flame retardants because they are metabolically better equipped to degrade these compounds. Thus, we hypothesized that dogs might be more similar to humans in their response to these environmental stressors and be better indicators of human exposures to these contaminants. Serum samples and their food were collected from 18 dogs and analyzed for PBDEs and other emerging flame retardants. The concentrations of PBDEs in dog serum and dog food averaged 1.8 ± 0.4 ng/g wet weight (ww) and 1.1 ± 0.2 ng/g ww, respectively. While the dog serum samples were dominated by the tetra to hepta BDE congeners, BDE-209 was the most abundant congener in the dog food. This difference in congener pattern was analyzed in terms of half-lives. Assuming food as the main exposure source, the average half-life in dog serum was 450 ± 170 days for the less brominated congeners and 2.3 ± 0.5 days for BDE-209. Dust was also considered as an additional exposure source, giving unreasonable residence times. In addition to PBDEs, other flame retardants, including Dechlorane Plus, decabromodiphenylethane, and hexabromocyclododecane, were identified in these samples.
MED-4483
N-Nitroso compounds and cancer incidence: the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk Study.
BACKGROUND: Humans are exposed to preformed N-nitroso compounds (NOCs) and endogenous NOCs. Several NOCs are potential human carcinogens, including N-nitrosodimethylamine (NDMA), but evidence from population studies is inconsistent. OBJECTIVE: We examined the relation between dietary NOCs (NDMA), the endogenous NOC index, and dietary nitrite and cancer incidence in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk, United Kingdom, study. DESIGN: This was a prospective study of 23,363 men and women, aged 40-79 y, who were recruited in 1993-1997 and followed up to 2008. The baseline diet was assessed with food-frequency questionnaires. RESULTS: There were 3268 incident cancers after a mean follow-up of 11.4 y. Dietary NDMA intake was significantly associated with increased cancer risk in men and women [hazard ratio (HR): 1.14; 95% CI: 1.03, 1.27; P for trend = 0.03] and in men (HR: 1.24; 95% CI: 1.07, 1.44; P for trend = 0.005) when the highest quartile was compared with the lowest quartile in age- and sex-adjusted analyses but not in multivariate analyses (HR: 1.10; 95% CI: 0.97, 1.24; HR for men: 1.18; 95% CI: 1.00, 1.40; P for trend ≥ 0.05). When continuously analyzed, NDMA was associated with increased risk of gastrointestinal cancers (HR: 1.13; 95% CI: 1.00, 1.28), specifically of rectal cancer (HR: 1.46; 95% CI: 1.16, 1.84) per 1-SD increase after adjustment for age, sex, body mass index, cigarette smoking status, alcohol intake, energy intake, physical activity, education, and menopausal status (in women). The endogenous NOC index and dietary nitrite were not significantly associated with cancer risk. There was a significant interaction between plasma vitamin C concentrations and dietary NDMA intake on cancer incidence (P for interaction < 0.00001). CONCLUSIONS: Dietary NOC (NDMA) was associated with a higher gastrointestinal cancer incidence, specifically of rectal cancer. Plasma vitamin C may modify the relation between NDMA exposure and cancer risk.
MED-1710
Energy and Fructose From Beverages Sweetened With Sugar or High-Fructose Corn Syrup Pose a Health Risk for Some People
Sugar intake in the United States has increased by >40 fold since the American Revolution. The health concerns that have been raised about the amounts of sugar that are in the current diet, primarily as beverages, are the subject of this review. Just less than 50% of the added sugars (sugar and high-fructose corn syrup) are found in soft drinks and fruit drinks. The intake of soft drinks has increased 5-fold between 1950 and 2000. Most meta-analyses have shown that the risk of obesity, diabetes, cardiovascular disease, and metabolic syndrome are related to consumption of beverages sweetened with sugar or high-fructose corn syrup. Calorically sweetened beverage intake has also been related to the risk of nonalcoholic fatty liver disease, and, in men, gout. Calorically sweetened beverages contribute to obesity through their caloric load, and the intake of beverages does not produce a corresponding reduction in the intake of other food, suggesting that beverage calories are “add-on” calories. The increase in plasma triglyceride concentrations by sugar-sweetened beverages can be attributed to fructose rather than glucose in sugar. Several randomized trials of sugar-containing soft drinks versus low-calorie or calorie-free beverages show that either sugar, 50% of which is fructose, or fructose alone increases triglycerides, body weight, visceral adipose tissue, muscle fat, and liver fat. Fructose is metabolized primarily in the liver. When it is taken up by the liver, ATP decreases rapidly as the phosphate is transferred to fructose in a form that makes it easy to convert to lipid precursors. Fructose intake enhances lipogenesis and the production of uric acid. By worsening blood lipids, contributing to obesity, diabetes, fatty liver, and gout, fructose in the amounts currently consumed is hazardous to the health of some people.
MED-2738
Trends in U.S. consumers' safe handling and consumption of food and their risk perceptions, 1988 through 2010.
Although survey results measuring the safety of consumers' food handling and risky food consumption practices have been published for over 20 years, evaluation of trends is impossible because the designs of published studies are not comparable. The Food Safety Surveys used comparable methods to interview U.S. adults by telephone in 1988, 1993, 2001, 2006, and 2010 about food handling (i.e., cross-contamination prevention) and risky consumption practices (eating raw or undercooked foods from animals) and perceived risk from foodborne illness. Sample sizes ranged from 1,620 to 4,547. Responses were analyzed descriptively, and four indices measuring meat, chicken, and egg cross-contamination, fish cross-contamination, risky consumption, and risk perceptions were analyzed using generalized linear models. The extent of media coverage of food safety issues was also examined. We found a substantial improvement in food handling and consumption practices and an increase in perceived risk from foodborne illness between 1993 and 1998. All indices were stable or declined between 1998 and 2006. Between 2006 and 2010, the two safe food handling practice indices increased significantly, but risk perceptions did not change, and safe consumption declined. Women had safer food handling and consumption practices than men. The oldest and youngest respondents and those with the highest education had the least safe food handling behaviors. Changes in safety of practices over the survey years are consistent with the change in the number of media stories about food safety in the periods between surveys. This finding suggests that increased media attention to food safety issues may raise awareness of food safety hazards and increase vigilance in food handling by consumers.
MED-2005
Microvascular complications. Retinopathy and nephropathy.
Diabetic retinopathy and diabetic nephropathy extract an enormous toll on patients with diabetes and an enormous burden on the health care system. With aggressive control of glycemia and blood pressure, coupled with aggressive use of laser photocoagulation and treatment of microalbuminuria, these problems can largely be eliminated. In the future, specific interventions may emerge that will allow interdiction of the pathophysiologic processes that lead to initiation and progression of these microvascular complications. The challenge for the primary care physician and diabetologist is to attain excellent glycemic control and aggressive control of blood pressure, while assuring that every patient has appropriate dilated fundus examinations at least annually, preferably by an ophthalmologist or retinal specialist, and regular screening for microalbuminuria. With such medical management, appropriate intervention can occur to reduce the risk of blindness and renal failure and to lessen the burden from diabetic retinopathy and nephropathy.
MED-1204
Cholesterol crystals cause mechanical damage to biological membranes: a proposed mechanism of plaque rupture and erosion leading to arterial thromb...
BACKGROUND: Plaque rupture and/or erosion is the leading cause of cardiovascular events; however, the process is not well understood. Although certain morphologic characteristics have been associated with ruptured plaques, these observations are of static histological images and not of the dynamics of plaque rupture. To elucidate the process of plaque rupture, we investigated the transformation of cholesterol from liquid to solid crystal to determine whether growing crystals are capable of injuring the plaque cap. HYPOTHESIS: We hypothesized that during cholesterol crystallization the spatial configuration rapidly changes, causing forceful expansion of sharp-edged crystals that can damage the plaque cap. METHODS: Two experiments were performed in vitro: first, cholesterol powder was melted in graduated cylinders and allowed to crystallize at room temperature. Volume changes from liquid to solid state were measured and timed. Second, thin biological membranes (20-40 microm) were put in the path of growing crystals to determine damage during crystallization. RESULTS: As cholesterol crystallized, the peak volume increased rapidly by up to 45% over 3 min and sharp-tipped crystals cut through and tore membranes. The amount of cholesterol and peak level of crystal growth correlated directly (r = 0.98; p < 0.01), as did the amount of cholesterol and rate of crystal growth (r = 0.99; p < 0.01). CONCLUSIONS: These observations suggest that crystallization of supersaturated cholesterol in atherosclerotic plaques can induce cap rupture and/or erosion. This novel insight may help in the development of therapeutic strategies that can alter cholesterol crystallization and prevent acute cardiovascular events.
MED-3379
The urban rise and fall of air lead (Pb) and the latent surge and retreat of societal violence.
We evaluate air Pb emissions and latent aggravated assault behavior at the scale of the city. We accomplish this by regressing annual Federal Bureau of Investigation aggravated assault rate records against the rise and fall of annual vehicle Pb emissions in Chicago (Illinois), Indianapolis (Indiana), Minneapolis (Minnesota), San Diego (California), Atlanta (Georgia), and New Orleans (Louisiana). Other things held equal, a 1% increase in tonnages of air Pb released 22 years prior raises the present period aggravated assault rate by 0.46% (95% CI, 0.28 to 0.64). Overall our model explains 90% of the variation in aggravated assault across the cities examined. In the case of New Orleans, 85% of temporal variation in the aggravated assault rate is explained by the annual rise and fall of air Pb (total=10,179 metric tons) released on the population of New Orleans 22 years earlier. For every metric ton of Pb released 22 years prior, a latent increase of 1.59 (95% CI, 1.36 to 1.83, p<0.001) aggravated assaults per 100,000 were reported. Vehicles consuming fuel containing Pb additives contributed much larger quantities of Pb dust than generally recognized. Our findings along with others predict that prevention of children's lead exposure from lead dust now will realize numerous societal benefits two decades into the future, including lower rates of aggravated assault. Copyright © 2012 Elsevier Ltd. All rights reserved.