insects
MED-3276
A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension.
Methionine is an essential amino acid with many key roles in mammalian metabolism such as protein synthesis, methylation of DNA and polyamine synthesis. Restriction of methionine may be an important strategy in cancer growth control particularly in cancers that exhibit dependence on methionine for survival and proliferation. Methionine dependence in cancer may be due to one or a combination of deletions, polymorphisms or alterations in expression of genes in the methionine de novo and salvage pathways. Cancer cells with these defects are unable to regenerate methionine via these pathways. Defects in the metabolism of folate may also contribute to the methionine dependence phenotype in cancer. Selective killing of methionine dependent cancer cells in co-culture with normal cells has been demonstrated using culture media deficient in methionine. Several animal studies utilizing a methionine restricted diet have reported inhibition of cancer growth and extension of a healthy life-span. In humans, vegan diets, which can be low in methionine, may prove to be a useful nutritional strategy in cancer growth control. The development of methioninase which depletes circulating levels of methionine may be another useful strategy in limiting cancer growth. The application of nutritional methionine restriction and methioninase in combination with chemotherapeutic regimens is the current focus of clinical studies. Copyright © 2012 Elsevier Ltd. All rights reserved.
MED-3277
Expression of the biochemical defect of methionine dependence in fresh patient tumors in primary histoculture.
Methionine dependence is a metabolic defect that occurs in many human tumor cell lines but not normal in unestablished cell strains. Methionine-dependent tumor cell lines are unable to proliferate and arrest in the late S/G2 phase of the cell cycle when methionine is replaced by its immediate precursor homocysteine in the culture medium (MET-HCY+ medium). However, it is not known whether methionine dependence occurs in fresh patient tumors as it does in cell lines. In order to determine whether methionine dependence occurs in fresh patient tumors as well as whether methionine dependence occurs in fresh patient tumors as well as in cell lines we took advantage of the technique of sponge-gel-supported histoculture to grow tumors directly from surgery. We then measured nuclear DNA content by image analysis to determine the cell cycle position in MET-HCY+ compared to MET+HCY- medium in 21 human patient tumors. Human tumor cell lines found to be methionine dependent by cell count were used as positive controls and were found to have marked reduction of cells in G1 compared to total cells in the cell cycle in MET-HCY+ medium with respect to the G1: total cell ratio in MET+HCY- medium. Therefore late cell cycle arrest was used as a marker of methionine dependence for histocultured patient tumors. We found that 5 human tumors of 21, including tumors of the colon, breast, ovary, prostate, and a melanoma, were methionine dependent based on cell cycle analysis. These data on fresh human tumors indicate that methionine dependence may frequently occur in the cancer patient population. Implications for potential therapy based on methionine dependence are discussed.
MED-3271
Can dietary methionine restriction increase the effectiveness of chemotherapy in treatment of advanced cancer?
Most metastatic tumors, such as those originating in the prostate, lung, and gastrointestinal tract, respond poorly to conventional chemotherapy. Novel treatment strategies for advanced cancer are therefore desperately needed. Dietary restriction of the essential amino acid methionine offers promise as such a strategy, either alone or in combination with chemotherapy or other treatments. Numerous in vitro and animal studies demonstrate the effectiveness of dietary methionine restriction in inhibiting growth and eventually causing death of cancer cells. In contrast, normal host tissues are relatively resistant to methionine restriction. These preclinical observations led to a phase I clinical trial of dietary methionine restriction for adults with advanced cancer. Preliminary findings from this trial indicate that dietary methionine restriction is safe and feasible for the treatment of patients with advanced cancer. In addition, the trial has yielded some preliminary evidence of antitumor activity. One patient with hormone-independent prostate cancer experienced a 25% reduction in serum prostate-specific antigen (PSA) after 12 weeks on the diet, and a second patient with renal cell cancer experienced an objective radiographic response. The possibility that methionine restriction may act synergistically with other cancer treatments such as chemotherapy is being explored. Findings to date support further investigation of dietary methionine restriction as a novel treatment strategy for advanced cancer.
MED-3278
Sniffer dogs as part of a bimodal bionic research approach to develop a lung cancer screening
Lung cancer (LC) continues to represent a heavy burden for health care systems worldwide. Epidemiological studies predict that its role will increase in the near future. While patient prognosis is strongly associated with tumour stage and early detection of disease, no screening test exists so far. It has been suggested that electronic sensor devices, commonly referred to as ‘electronic noses’, may be applicable to identify cancer-specific volatile organic compounds in the breath of patients and therefore may represent promising screening technologies. However, three decades of research did not bring forward a clinically applicable device. Here, we propose a new research approach by involving specially trained sniffer dogs into research strategies by making use of their ability to identify LC in the breath sample of patients.
MED-3272
Colorectal cancer screening with odour material by canine scent detection
Objective Early detection and early treatment are of vital importance to the successful treatment of various cancers. The development of a novel screening method that is as economical and non-invasive as the faecal occult blood test (FOBT) for early detection of colorectal cancer (CRC) is needed. A study was undertaken using canine scent detection to determine whether odour material can become an effective tool in CRC screening. Design Exhaled breath and watery stool samples were obtained from patients with CRC and from healthy controls prior to colonoscopy. Each test group consisted of one sample from a patient with CRC and four control samples from volunteers without cancer. These five samples were randomly and separately placed into five boxes. A Labrador retriever specially trained in scent detection of cancer and a handler cooperated in the tests. The dog first smelled a standard breath sample from a patient with CRC, then smelled each sample station and sat down in front of the station in which a cancer scent was detected. Results 33 and 37 groups of breath and watery stool samples, respectively, were tested. Among patients with CRC and controls, the sensitivity of canine scent detection of breath samples compared with conventional diagnosis by colonoscopy was 0.91 and the specificity was 0.99. The sensitivity of canine scent detection of stool samples was 0.97 and the specificity was 0.99. The accuracy of canine scent detection was high even for early cancer. Canine scent detection was not confounded by current smoking, benign colorectal disease or inflammatory disease. Conclusions This study shows that a specific cancer scent does indeed exist and that cancer-specific chemical compounds may be circulating throughout the body. These odour materials may become effective tools in CRC screening. In the future, studies designed to identify cancer-specific volatile organic compounds will be important for the development of new methods for early detection of CRC.
MED-3274
Olfactory detection of human bladder cancer by dogs: proof of principle study
Objective To determine whether dogs can be trained to identify people with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. Design Experimental, “proof of principle” study in which six dogs were trained to discriminate between urine from patients with bladder cancer and urine from diseased and healthy controls and then evaluated in tests requiring the selection of one bladder cancer urine sample from six controls. Participants 36 male and female patients (age range 48-90 years) presenting with new or recurrent transitional cell carcinoma of the bladder (27 samples used for training; 9 used for formal testing); 108 male and female controls (diseased and healthy, age range 18-85 years—54 samples used in training; 54 used for testing). Main outcome measure Mean proportion of successes per dog achieved during evaluation, compared with an expected value of 1 in 7 (14%). Results Taken as a group, the dogs correctly selected urine from patients with bladder cancer on 22 out of 54 occasions. This gave a mean success rate of 41% (95% confidence intervals 23% to 58% under assumptions of normality, 26% to 52% using bootstrap methods), compared with 14% expected by chance alone. Multivariate analysis suggested that the dogs' capacity to recognise a characteristic bladder cancer odour was independent of other chemical aspects of the urine detectable by urinalysis. Conclusions Dogs can be trained to distinguish patients with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. This suggests that tumour related volatile compounds are present in urine, imparting a characteristic odour signature distinct from those associated with secondary effects of the tumour, such as bleeding, inflammation, and infection.
MED-3275
The Effect of Replacement of Methionine by Homocystine on Survival of Malignant and Normal Adult Mammalian Cells in Culture
In tissue cultures of normal adult and malignant mammalian cells, homocystine has been substituted for methionine in a medium rich in folic acid and cyanocobalamin. Normal adult cells thrive. Three highly malignant cell types from three different species, including man, die.
MED-3282
Generation of gaseous sulfur-containing compounds in tumour tissue and suppression of gas diffusion as an antitumour treatment.
BACKGROUND AND AIMS: The mechanisms of cancer cell growth and metastasis are still not entirely understood, especially from the viewpoint of chemical reactions in tumours. Glycolytic metabolism is markedly accelerated in cancer cells, causing the accumulation of glucose (a reducing sugar) and methionine (an amino acid), which can non-enzymatically react and form carcinogenic substances. There is speculation that this reaction produces gaseous sulfur-containing compounds in tumour tissue. The aims of this study were to clarify the products in tumour and to investigate their effect on tumour proliferation. METHODS: Products formed in the reaction between glucose and methionine or its metabolites were analysed in vitro using gas chromatography. Flatus samples from patients with colon cancer and exhaled air samples from patients with lung cancer were analysed using near-edge x-ray fine adsorption structure spectroscopy and compared with those from healthy individuals. The tumour proliferation rates of mice into which HT29 human colon cancer cells had been implanted were compared with those of mice in which the cancer cells were surrounded by sodium hyaluronate gel to prevent diffusion of gaseous material into the healthy cells. RESULTS: Gaseous sulfur-containing compounds such as methanethiol and hydrogen sulfide were produced when glucose was allowed to react with methionine or its metabolites homocysteine or cysteine. Near-edge x-ray fine adsorption structure spectroscopy showed that the concentrations of sulfur-containing compounds in the samples of flatus from patients with colon cancer and in the samples of exhaled air from patients with lung cancer were significantly higher than in those from healthy individuals. Animal experiments showed that preventing the diffusion of sulfur-containing compounds had a pronounced antitumour effect. CONCLUSIONS: Gaseous sulfur-containing compounds are the main products in tumours and preventing the diffusion of these compounds reduces the tumour proliferation rate, which suggests the possibility of a new approach to cancer treatment.
MED-1148
Association between organic dietary choice during pregnancy and hypospadias in offspring: a study of mothers of 306 boys operated on for hypospadias.
PURPOSE: The etiology of hypospadias is poorly understood. Exposure to pesticides has been considered a risk factor, although findings are inconsistent. Diet constitutes a significant exposure route for pesticides, and pesticide residues are more frequently reported in conventional than organic food products. We examined the association between organic dietary choice during pregnancy and presence of hypospadias in the offspring. MATERIALS AND METHODS: Mothers of 306 boys operated on for hypospadias were frequency matched for geography and child birth year to 306 mothers of healthy boys in a case-control study. Telephone interviews were conducted regarding demographic and lifestyle factors, including intake and organic choice of selected food items (milk, dairy products, egg, fruit, vegetables and meat). Logistic regression models were constructed for dietary variables, and odds ratios were calculated controlling for maternal age, body mass index and alcohol consumption. RESULTS: Overall organic choice of food items during pregnancy was not associated with hypospadias in the offspring. However, frequent current consumption of high fat dairy products (milk, butter) while rarely or never choosing the organic alternative to these products during pregnancy was associated with increased odds of hypospadias (adjusted OR 2.18, 95% CI 1.09-4.36). CONCLUSIONS: This large case-control study of boys operated on for hypospadias suggests an association between hypospadias in the offspring and the mother not choosing the organic alternative, and having a high current intake of nonorganic butter and cheese. This finding could be due to chemical contamination of high fat dairy products. However, general lifestyle and health behavior related to choosing organic alternatives may also explain the finding. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
MED-1149
Profiles of Organic Food Consumers in a Large Sample of French Adults: Results from the Nutrinet-Santé Cohort Study
Background Lifestyle, dietary patterns and nutritional status of organic food consumers have rarely been described, while interest for a sustainable diet is markedly increasing. Methods Consumer attitude and frequency of use of 18 organic products were assessed in 54,311 adult participants in the Nutrinet-Santé cohort. Cluster analysis was performed to identify behaviors associated with organic product consumption. Socio-demographic characteristics, food consumption and nutrient intake across clusters are provided. Cross-sectional association with overweight/obesity was estimated using polytomous logistic regression. Results Five clusters were identified: 3 clusters of non-consumers whose reasons differed, occasional (OCOP, 51%) and regular (RCOP, 14%) organic product consumers. RCOP were more highly educated and physically active than other clusters. They also exhibited dietary patterns that included more plant foods and less sweet and alcoholic beverages, processed meat or milk. Their nutrient intake profiles (fatty acids, most minerals and vitamins, fibers) were healthier and they more closely adhered to dietary guidelines. In multivariate models (after accounting for confounders, including level of adherence to nutritional guidelines), compared to those not interested in organic products, RCOP participants showed a markedly lower probability of overweight (excluding obesity) (25≤body mass index<30) and obesity (body mass index ≥30): −36% and −62% in men and −42% and −48% in women, respectively (P<0.0001). OCOP participants (%) generally showed intermediate figures. Conclusions Regular consumers of organic products, a sizeable group in our sample, exhibit specific socio-demographic characteristics, and an overall healthy profile which should be accounted for in further studies analyzing organic food intake and health markers.
MED-1150
Organically Grown Food Provides Health Benefits to Drosophila melanogaster
The “organic food” market is the fastest growing food sector, yet it is unclear whether organically raised food is nutritionally superior to conventionally grown food and whether consuming organic food bestows health benefits. In order to evaluate potential health benefits of organic foods, we used the well-characterized fruit fly Drosophila melanogaster as a model system. Fruit flies were raised on a diets consisting of extracts of either conventionally or organically raised produce (bananas, potatoes, raisins, soy beans). Flies were then subjected to a variety of tests designed to assess overall fly health. Flies raised on diets made from organically grown produce had greater fertility and longevity. On certain food sources, greater activity and greater stress resistance was additionally observed, suggesting that organic food bestows positive effects on fly health. Our data show that Drosophila can be used as a convenient model system to experimentally test potential health effects of dietary components. Using this system, we provide evidence that organically raised food may provide animals with tangible benefits to overall health.
MED-1151
Organic food consumption and the incidence of cancer in a large prospective study of women in the United Kingdom
Background: Organically produced foods are less likely than conventionally produced foods to contain pesticide residues. Methods: We examined the hypothesis that eating organic food may reduce the risk of soft tissue sarcoma, breast cancer, non-Hodgkin lymphoma and other common cancers in a large prospective study of 623 080 middle-aged UK women. Women reported their consumption of organic food and were followed for cancer incidence over the next 9.3 years. Cox regression models were used to estimate adjusted relative risks for cancer incidence by the reported frequency of consumption of organic foods. Results: At baseline, 30%, 63% and 7% of women reported never, sometimes, or usually/always eating organic food, respectively. Consumption of organic food was not associated with a reduction in the incidence of all cancer (n=53 769 cases in total) (RR for usually/always vs never=1.03, 95% confidence interval (CI): 0.99–1.07), soft tissue sarcoma (RR=1.37, 95% CI: 0.82–2.27), or breast cancer (RR=1.09, 95% CI: 1.02–1.15), but was associated for non-Hodgkin lymphoma (RR=0.79, 95% CI: 0.65–0.96). Conclusions: In this large prospective study there was little or no decrease in the incidence of cancer associated with consumption of organic food, except possibly for non-Hodgkin lymphoma.
MED-1152
Pesticide exposure and serum organochlorine residuals among testicular cancer patients and healthy controls.
The incidence of testicular cancer (TC) has been increasing worldwide during the last decades. The reasons of the increase remains unknown, but recent findings suggest that organochlorine pesticides (OPs) could influence the development of TC. A hospital-based case-control study of 50 cases and 48 controls was conducted to determine whether environmental exposure to OPs is associated with the risk of TC, and by measuring serum concentrations of OPs, including p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) isomer and hexachlorobenzene (HCB) in participants. A significant association was observed between TC and household insecticide use (odds ratio [OR] = 3.01, 95 % CI: 1.11-8.14; OR(adjusted) = 3.23, 95 % CI: 1.15-9.11). Crude and adjusted ORs for TC were also significantly associated with higher serum concentrations of total OPs (OR = 3.15, 95 % CI: 1.00-9.91; OR(adjusted) = 3.34, 95 % CI: 1.09-10.17) in cases compared with controls. These findings give additional support to the results of previous research that suggest that some environmental exposures to OPs may be implicated in the pathogenesis of TC.
MED-1153
ATTENTION DEFICIT/HYPERACTIVITY DISORDER AND URINARY METABOLITES OF ORGANOPHOSPHATE PESTICIDES IN U.S. CHILDREN 8–15 YEARS
Context Exposure to organophosphate (OP) pesticides is common, and although these compounds have known neurotoxic properties, few studies examined risks for children in the general population. Objective To examine the association between the concentrations of urinary dialkyl phosphate (DAP) metabolites of OPs and attention deficit/hyperactivity disorder (ADHD) in children age 8 to 15 years. Participants and Methods Cross-sectional data from the National Health and Nutrition Examination Survey (2000–2004) were available for 1,139 children representative of the general U.S. population. A structured interview with a parent was used to ascertain ADHD diagnostic status, based on slightly modified criteria of the Diagnostic and Statistical Manual of Mental Disorders-IV. Results One hundred nineteen children met the diagnostic criteria for ADHD. Children with higher concentrations of urinary DAPs, especially dimethyl alkylphosphates (DMAP), were more likely to be diagnosed with ADHD. A 10-fold increase in DMAP concentration was associated with an odds ratio (OR) of 1.55 (95% confidence intervals [CI], 1.14–2.10), after adjusting for sex, age, race/ethnicity, poverty-income ratio, fasting duration, and urinary creatinine concentration. For the most commonly detected DMAP metabolite, dimethylthiophosphate, children with levels higher than the median of detectable concentrations had double the odds of ADHD (adjusted OR, 1.93 [95% CI, 1.23–3.02]) compared with those with non-detectable levels. Conclusions These findings support the hypothesis that OP exposure, at levels common in U.S. children, may contribute to ADHD prevalence. Prospective studies are needed to establish whether this association is causal.
MED-1179
Organic foods: health and environmental advantages and disadvantages.
The US market for organic foods has grown from $3.5 billion in 1996 to $28.6 billion in 2010, according to the Organic Trade Association. Organic products are now sold in specialty stores and conventional supermarkets. Organic products contain numerous marketing claims and terms, only some of which are standardized and regulated. In terms of health advantages, organic diets have been convincingly demonstrated to expose consumers to fewer pesticides associated with human disease. Organic farming has been demonstrated to have less environmental impact than conventional approaches. However, current evidence does not support any meaningful nutritional benefits or deficits from eating organic compared with conventionally grown foods, and there are no well-powered human studies that directly demonstrate health benefits or disease protection as a result of consuming an organic diet. Studies also have not demonstrated any detrimental or disease-promoting effects from an organic diet. Although organic foods regularly command a significant price premium, well-designed farming studies demonstrate that costs can be competitive and yields comparable to those of conventional farming techniques. Pediatricians should incorporate this evidence when discussing the health and environmental impact of organic foods and organic farming while continuing to encourage all patients and their families to attain optimal nutrition and dietary variety consistent with the US Department of Agriculture's MyPlate recommendations. This clinical report reviews the health and environmental issues related to organic food production and consumption. It defines the term "organic," reviews organic food-labeling standards, describes organic and conventional farming practices, and explores the cost and environmental implications of organic production techniques. It examines the evidence available on nutritional quality and production contaminants in conventionally produced and organic foods. Finally, this report provides guidance for pediatricians to assist them in advising their patients regarding organic and conventionally produced food choices.
MED-1181
Higher antioxidant and lower cadmium concentrations and lower incidence of pesticide residues in organically grown crops: a systematic literature review and meta-analyses
Demand for organic foods is partially driven by consumers' perceptions that they are more nutritious. However, scientific opinion is divided on whether there are significant nutritional differences between organic and non-organic foods, and two recent reviews have concluded that there are no differences. In the present study, we carried out meta-analyses based on 343 peer-reviewed publications that indicate statistically significant and meaningful differences in composition between organic and non-organic crops/crop-based foods. Most importantly, the concentrations of a range of antioxidants such as polyphenolics were found to be substantially higher in organic crops/crop-based foods, with those of phenolic acids, flavanones, stilbenes, flavones, flavonols and anthocyanins being an estimated 19 (95 % CI 5, 33) %, 69 (95 % CI 13, 125) %, 28 (95 % CI 12, 44) %, 26 (95 % CI 3, 48) %, 50 (95 % CI 28, 72) % and 51 (95 % CI 17, 86) % higher, respectively. Many of these compounds have previously been linked to a reduced risk of chronic diseases, including CVD and neurodegenerative diseases and certain cancers, in dietary intervention and epidemiological studies. Additionally, the frequency of occurrence of pesticide residues was found to be four times higher in conventional crops, which also contained significantly higher concentrations of the toxic metal Cd. Significant differences were also detected for some other (e.g. minerals and vitamins) compounds. There is evidence that higher antioxidant concentrations and lower Cd concentrations are linked to specific agronomic practices (e.g. non-use of mineral N and P fertilisers, respectively) prescribed in organic farming systems. In conclusion, organic crops, on average, have higher concentrations of antioxidants, lower concentrations of Cd and a lower incidence of pesticide residues than the non-organic comparators across regions and production seasons.
MED-1156
A Prospective Study of Organochlorines in Adipose Tissue and Risk of Non-Hodgkin Lymphoma
Background: Exposure to organochlorines has been examined as a potential risk factor for non-Hodgkin lymphoma (NHL), with inconsistent results that may be related to limited statistical power or to imprecise exposure measurements. Objective: Our purpose was to examine associations between organochlorine concentrations in prediagnostic adipose tissue samples and the risk of NHL. Methods: We conducted a case–cohort study using a prospective Danish cohort of 57,053 persons enrolled between 1993 and 1997. Within the cohort we identified 256 persons diagnosed with NHL in the population-based nationwide Danish Cancer Registry and randomly selected 256 subcohort persons. We measured concentrations of 8 pesticides and 10 polychlorinated biphenyl (PCB) congeners in adipose tissue collected upon enrollment. Associations between the 18 organochlorines and NHL were analyzed in Cox regression models, adjusting for body mass index. Results: Incidence rate ratios and confidence intervals (CIs) for interquartile range increases in concentrations of dichlorodiphenyltrichlorethane (DDT), cis-nonachlor, and oxychlordane were 1.35 (95% CI: 1.10, 1.66), 1.13 (95% CI: 0.94, 1.36), and 1.11 (95% CI: 0.89, 1.38), respectively, with monotonic dose–response trends for DDT and cis-nonachlor based on categorical models. The relative risk estimates were higher for men than for women. In contrast, no clear association was found between NHL and PCBs. Conclusion: We found a higher risk of NHL in association with higher adipose tissue levels of DDT, cis-nonachlor, and oxychlordane, but no association with PCBs. This is the first study of organochlorines and NHL using prediagnostic adipose tissue samples in the exposure assessment and provides new environmental health evidence that these organochlorines contribute to NHL risk.
MED-2337
Management of childhood urticaria: current knowledge and practical recommendations.
Urticaria, defined by the presence of wheals and/or angio-edema, is a common condition in children, prompting parents to consult physicians. For its successful management, paediatric-specific features must be taken into account, regarding the identification of eliciting triggers and pharmacological therapy. This review systematically discusses the current best-available evidence on spontaneous acute and chronic urticaria as well as physical and other urticaria types in children. Potential underlying causes, namely infections, food and drug hypersensitivity, autoreactivity and autoimmune or other conditions, and eliciting stimuli are considered, with practical recommendations for specific diagnostic approaches. Second-generation antihistamines are the mainstay of pharmacological treatment aimed at relief of symptoms, which require dose adjustment for pae-diatric use. Other therapeutic interventions are also discussed. In addition, unmet needs are highlighted, aiming to promote research into the paediatric population, ultimately aiming at the effective management of childhood urticaria.
MED-2338
Anisakis simplex hypersensitivity is associated with chronic urticaria in endemic areas.
BACKGROUND: Chronic urticaria (CU) may affect up to 1% of the general population. Anisakis simplex hypersensitivity is frequent in areas where raw fish is consumed and A. simplex allergy represents a relevant cause of acute urticaria. We assessed the possible association between CU and A. simplex sensitization in an area where marinated fish is very frequently eaten. METHODS: A thorough history of CU was sought in 919 adults seen at the Allergy Center, Bari. CU patients and 187 controls underwent skin-prick testing with a commercial extract of A. simplex, and reactors were recommended a 6-month raw-fish-free diet regimen. Responders were followed after a further 3 months. RESULTS: Of 919 subjects, 213 (23%) met the criteria for CU and 106/213 (49.7%) were sensitized to A. simplex with a significant difference between patients aged >65 or <65 years (56 vs. 41%, respectively; p < 0.05). All patients hypersensitive to A. simplex were regular consumers of marinated fish. In a control population without CU, the prevalence of A. simplex sensitization was 16% (p < 0.001). The 6-month diet regimen led to the disappearance of urticaria in 82/106 cases (77%) versus 1/42 (2%) subjects who did not change their dietary habits (p < 0.001). All nonresponders were sensitized to house-dust mites. Of 75 responders who were followed-up after 3 months, CU relapsed in 88% of those who had reintroduced raw fish versus 14% of those who were still on the diet (p < 0.001). CONCLUSION: In areas where raw or marinated fish is frequently eaten, A. simplex hypersensitivity is a frequent cause of CU. Copyright © 2012 S. Karger AG, Basel.
MED-2339
Anisakis simplex allergy after eating chicken meat.
BACKGROUND: Allergic reactions to food can be produced by contaminants that induce sensitization. Among these, Anisakis simplex can cause seafood infestation, and allergic symptoms (urticaria-angioedema, anaphylaxis, and asthma) can follow the eating or handling of affected fish. Although seafood is the principal source of human infections by this parasite, we have found allergic symptoms in 8 patients previously diagnosed as having A simplex sensitization after they ate chicken meat. Chicken feed usually has a high proportion of fishmeal, which might possibly be contaminated by this nematode. OBJECTIVE: The aim of our study was to determine whether parasite proteins present in chicken meat could be responsible for the symptoms reported by these subjects. METHODS: We carried out in vivo tests (prick, bronchial challenge, and double-blind placebo-controlled challenge with meat chicken) in these 8 patients. We performed immunoblotting using the sera from the 8 patients and controls in order to detect A simplex sensitization. We also investigated the presence of A simplex proteins in sera from chickens fed with fishmeal and in other sera from chickens fed only with cereals. We excluded sensitization to other chicken nematodes by serologic methods. RESULTS: All 8 patients presented positive prick and challenges to A simplex. When we used serum from chickens fed with fishmeal as the antigen in blotting, patients 3, 4, 5, 6, 7, and 8 recognized a band of 16 kd, also obtained when using pools of fish-shellfish and A simplex larva. No detection was observed with sera from chickens fed with only cereals. CONCLUSION: We provide evidence, based on in vivo and in vitro tests, that subjects highly sensitized to A simplex can detect the presence of Anisakis species allergens in chicken meat.
MED-2340
Allergic cross-reactions between cat and pig serum albumin. Study at the protein and DNA levels.
After observing a patient allergic to cat dander and pork but devoid of other allergies, we prospectively screened patients known to be allergic to cat for a second sensitization to pork. After collecting the sera of 10 young patients found to contain specific IgE to cat dander and pork, we undertook this study to detect the possible cross-reactive allergen, define its molecular characteristics, and evaluate its clinical relevance. Through immunoblotting techniques, cat and porcine serum albumin were found to be jointly recognized molecules. These findings were further analyzed by specific anti-albumin IgE titrations and cross-inhibition experiments. Cat serum albumin cDNA was obtained from cat liver, and the corresponding amino acid sequence was deduced and compared to the known porcine and human serum albumin sequences. Inhibition experiments showed that the spectrum of IgE reactivity to cat serum albumin completely contained IgE reactivity to porcine serum albumin, suggesting that sensitization to cat was the primary event. In two cohorts of cat-allergic persons, the frequency of sensitization to cat serum albumin was found to lie between 14% and 23%. Sensitization to porcine albumin was found to lie between 3% and 10%. About 1/3 of these persons are likely to experience allergic symptoms in relation to pork consumption. Sensitization to cat serum albumin should be considered a useful marker of possible cross-sensitization not only to porcine serum albumin but also to other mammalian serum albumins.
MED-2341
Beef, pork, and milk allergy (cross reactivity with each other and pet allergies).
OBJECTIVE: The purposes of this study were to examine milk allergic patients to determine concomitant reactivity between milk, beef, pork and cat and dog dander and other common inhalant allergens. METHODS: 19 patients were selected according to their Immuno-CAP results, which had increased Ig-E levels against milk, pork or beef. Patients were also tested against Johnson grass, short ragweed, cat/dog dander and d. farina. RESULTS: Pearson's test revealed strong correlation between beef and pork, beef and milk, pork and milk Ig-E counts (consecutively r2 = 0.89, r2 = 0.81, r2 = 0.60 and p < 0.01. All cat allergic patients also appeared to be allergic to either beef/pork meat or milk. The correlation between pork and dog dander Ig-E counts was also significant (r2 = 0.38, p < 0.01). No correlation detected between milk-meat-pet and grass-weed-dust allergies. DISCUSSION AND CONCLUSION: Patients who are known to have pet allergies may need to be screened for meat and milk allergy. Milk allergic patients may also need to avoid cows and pork meat.
MED-2355
Delayed Anaphylaxis to Red Meat in Patients with IgE Specific for Galactose alpha-1,3-Galactose (alpha-gal)
Anaphylaxis is a severe allergic reaction that can be rapidly progressing and fatal. In instances where the triggering allergen is not known, establishing the etiology of anaphylaxis is pivotal to long-term risk management. Our recent work has identified a novel IgE antibody (Ab) response to a mammalian oligosaccharide epitope, galactose-alpha-1,3-galactose (alpha-gal), that has been associated with two distinct forms of anaphylaxis: (1) immediate onset anaphylaxis during first exposure to intravenous cetuximab, and (2) delayed onset anaphylaxis 3–6 h after ingestion of mammalian food products (e.g., beef and pork). The results of our studies strongly suggest that tick bites are a cause, if not the only significant cause, of IgE Ab responses to alpha-gal in the southern, eastern and central United States. Patients with IgE Ab to alpha-gal continue to emerge and, increasingly, these cases involve children. This IgE Ab response cross-reacts with cat and dog but does not appear to pose a risk for asthma; however, it may impair diagnostic testing in some situations.
MED-2356
The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose
Background In 2009, we reported a novel form of delayed anaphylaxis to red meat, which is related to serum IgE antibodies to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal). Most of these patients had tolerated meat for many years previously. The implication is that some exposure in adult life had stimulated the production of these IgE antibodies. Objectives To investigate possible causes of this IgE antibody response, focusing on evidence related to tick bites, which are common in the region where these reactions occur. Methods Serum assays were carried out using biotinylated proteins and extracts bound to a streptavidin ImmunoCAP. Results Prospective studies on IgE antibodies in three subjects following tick bites showed an increase in IgE to alpha-gal of twenty-fold or greater. Other evidence included i) a strong correlation between histories of tick bites and IgE to alpha-gal (χ2=26.8, p<0.001), ii) evidence that these IgE antibodies are common in areas where the tick Amblyomma americanum is common, and iii) a significant correlation between IgE antibodies to alpha-gal and IgE antibodies to proteins derived from A. americanum (rs=0.75, p<0.001). Conclusion The results presented here provide evidence that tick bites are a cause, or possibly the only cause, of IgE specific for alpha-gal in this area of the United States. Both the number of subjects becoming sensitized and the titer of IgE antibodies to alpha-gal are striking. Here we report the first example of a response to an ectoparasite giving rise to an important form of food allergy.
MED-2344
Fish and shellfish allergy in children: review of a persistent food allergy.
The increased consumption of fish and shellfish has resulted in more frequent reports of adverse reactions to seafood, emphasizing the need for more specific diagnosis and treatment of this condition and exploring reasons for the persistence of this allergy. This review discusses interesting and new findings in the area of fish and shellfish allergy. New allergens and important potential cross-reacting allergens have been identified within the fish family and between shellfish, arachnids, and insects. The diagnostic approach may require prick to-prick tests using crude extracts of both raw and cooked forms of seafood for screening seafood sensitization before a food challenge or where food challenge is not feasible. Allergen-specific immunotherapy can be important; mutated less allergenic seafood proteins have been developed for this purpose. The persistence of allergy because of seafood proteins' resistance after rigorous treatment like cooking and extreme pH is well documented. Additionally, IgE antibodies from individuals with persistent allergy may be directed against different epitopes than those in patients with transient allergy. For a topic as important as this one, new areas of technological developments will likely have a significant impact, to provide more accurate methods of diagnosing useful information to patients about the likely course of their seafood allergy over the course of their childhood and beyond. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.
MED-2345
Anisakiasis, an underestimated infection: effect on intestinal permeability of Anisakis simplex-sensitized patients.
Anisakis simplex is a parasite that, if present in uncooked and contaminated saltwater fish, can invade the human gut. Two different clinical situations are recognized: the first, known as a gastrointestinal disease, varying from an asymptomatic episode to vomiting and diarrhea, and the second, classified as an adverse reaction to food, characterized by a wide spectrum of allergic reactions like rhinitis, conjunctivitis, or even anaphylaxis causing hypotension and/or shock. The intestinal epithelium, the major defense system against external molecules, represents an open gate for toxins and allergens if its protective function is compromised. Previous data have demonstrated a strict relationship between an altered intestinal permeability (I.P.) and worsening of the clinical manifestations in patients with adverse reactions to the food. In this article we evaluated the sensitization to A. simplex among patients who referred clinical symptoms of allergy. All subjects underwent commonly used alimentary skin prick test for food allergens, to which Ani s1, an A. simplex allergen, was added. In addition, in A. simplex-sensitized subjects, I.P. was determined upon their enrolment to the study (time 0) and after 6 months of consuming a raw fish-free diet (time 6). Five hundred and forty subjects were screened, and 170 had a positive skin prick test, 87 (51.2%) of whom were positive to Ani s1. Increased I.P. was evidenced in A. simplex-sensitized subjects with worse clinical symptoms, which receded after 6 months' elimination of raw seafood. With our data we demonstrated that the alimentary habit to eat raw fish represents a high risk for the integrity of the intestinal mucosa, and we suggest that this pathological situation may constitute an ideal, under-estimated, open gate for molecules that predispose to other, more important pathologies.
MED-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-2347
Evidence-based evaluation and management of chronic urticaria in children.
Urticaria affects nearly 25% of the population at some time in their lives. In a subset of children, urticaria will develop into a chronic condition that can greatly affect quality of life. Although numerous causes and triggers are proposed for chronic urticaria (CU) in children, ranging from infections, allergens, and medications to physical factors and autoimmune disease, the exact etiology is not always identifiable. Accordingly, a large subset of cases are designated "chronic idiopathic urticaria." Because of the clinical complexities of CU, as well as the confusing literature on this topic, we have developed a conceptual framework based on the cumulative evidence to assist with the categorization, clinical evaluation, and treatment of CU in children. © 2011 Wiley Periodicals, Inc.
MED-2348
Galactose-α-1,3-galactose and Delayed Anaphylaxis, Angioedema, and Urticaria in Children
BACKGROUND AND OBJECTIVE: Despite a thorough history and comprehensive testing, many children who present with recurrent symptoms consistent with allergic reactions elude diagnosis. Recent research has identified a novel cause for “idiopathic” allergic reactions; immunoglobulin E (IgE) antibody specific for the carbohydrate galactose-α-1,3-galactose (α-Gal) has been associated with delayed urticaria and anaphylaxis that occurs 3 to 6 hours after eating beef, pork, or lamb. We sought to determine whether IgE antibody to α-Gal was present in sera of pediatric patients who reported idiopathic anaphylaxis or urticaria. METHODS: Patients aged 4 to 17 were enrolled in an institutional review board–approved protocol at the University of Virginia and private practice allergy offices in Lynchburg, VA. Sera was obtained and analyzed by ImmunoCAP for total IgE and specific IgE to α-Gal, beef, pork, cat epithelium and dander, Fel d 1, dog dander, and milk. RESULTS: Forty-five pediatric patients were identified who had both clinical histories supporting delayed anaphylaxis or urticaria to mammalian meat and IgE antibody specific for α-Gal. In addition, most of these cases had a history of tick bites within the past year, which itched and persisted. CONCLUSIONS: A novel form of anaphylaxis and urticaria that occurs 3 to 6 hours after eating mammalian meat is not uncommon among children in our area. Identification of these cases may not be straightforward and diagnosis is best confirmed by specific testing, which should certainly be considered for children living in the area where the Lone Star tick is common.
MED-2349
An update on childhood urticaria and angioedema.
PURPOSE OF REVIEW: The present review serves to address urticaria - both acute and chronic - as well as the differential diagnosis of urticarial syndromes in the pediatric population. We also wish to update the reader on progress in the pathophysiology, diagnosis and treatment of urticaria. RECENT FINDINGS: Acute and chronic urticaria represent syndromes caused by a variety of triggers. Recent literature continues to describe subtypes of urticaria that may be differentially responsive to particular therapies. Recent associations highlight the need to fully evaluate patients for allergic and infectious triggers of urticaria. It is important to distinguish idiopathic urticaria from related conditions such as anaphylaxis, systemic conditions and autoimmune urticaria. Although antihistamines remain a cornerstone of therapy, particular urticaria subtypes may also respond to novel therapies such as omalizumab. Chronic urticaria has a significant impact on a patient's quality of life. SUMMARY: Urticaria is a common condition. Our understanding of distinct urticaria subtypes differentially responsive to targeted therapies continues to increase. Due to the myriad of triggers that may cause urticaria, careful individualized patient assessment is necessary to exclude potential etiologies prior to a diagnosis of idiopathic urticaria.
MED-2350
Analysis of food-allergic and anaphylactic events in the National Electronic Injury Surveillance System.
BACKGROUND: The National Electronic Injury Surveillance System (NEISS) captures a nationally representative probability sample from hospital emergency departments (EDs) in the United States. OBJECTIVE: Emergency department data from NEISS were analyzed to assess the magnitude and severity of adverse events attributable to food allergies. METHODS: Emergency department events describing food-related allergic symptomatology were identified from 34 participating EDs from August 1 to September 30, 2003. RESULTS: Extrapolation of NEISS event data predicts a total of 20,821 hospital ED visits, 2333 visits for anaphylaxis, and 520 hospitalizations caused by food allergy in the United States during the 2-month study period. The median age was 26 years; 24% of visits involved children < or =5 years old. Shellfish was the most frequently implicated food in persons > or =6 years old, whereas children < or =5 years old experienced more events from eggs, fruit, peanuts, and tree nuts. There were no reported deaths. Review of medical records found that only 19% of patients received epinephrine, and, using criteria established by a 2005 anaphylaxis symposium, 57% of likely anaphylactic events did not have an ED diagnosis of anaphylaxis. CONCLUSION: Analysis of NEISS data may be a useful tool for assessing the magnitude and severity of food-allergic events. A criteria-based review of medical records suggests underdiagnosis of anaphylactic events in EDs.
MED-2351
Specific stimulation of Graves' disease thyrocytes by the natural anti-Gal antibody from normal and autologous serum.
Anti-Gal is a natural Ab abundantly produced in humans. It interacts specifically with the carbohydrate epitope Gal alpha 1-3Gal beta 1-4GlcNAc-R (termed the alpha-galactosyl epitope). This epitope is expressed in large amounts on thyrocytes of nonprimate mammals, but not of humans. We have previously found that binding of anti-Gal to alpha-galactosyl epitopes on porcine thyrocytes results in stimulatory effects similar to those exerted by thyroid-stimulating hormone (thyrotropin). In the present study, we tested the hypothesis that anti-Gal may contribute to Graves' disease (GD) pathogenesis by stimulation of the thyrocytes of patients with this autoimmune disorder. Anti-Gal binding and stimulatory effects were assessed in primary thyrocyte cultures. Anti-Gal specifically bound to GD thyrocytes and induced an increase in cAMP synthesis, 125I uptake, and DNA synthesis in these cells. Furthermore, the stimulatory effects of autologous sera on GD thyrocytes were greatly reduced after specific depletion of anti-Gal from these sera. No binding and no stimulatory effects of anti-Gal were observed, however, with normal human thyrocytes and with thyrocytes from thyrotoxic patients who lack thyroid-stimulating Igs or thyrotropin binding inhibiting Igs. These in vitro stimulatory effects of anti-Gal on GD thyrocytes suggest that this natural Ab may contribute to the in vivo continuous stimulation of thyrocytes in GD patients. The possibility that anti-Gal may stimulate GD thyrocytes via interaction with aberrantly expressed alpha-galactosyl epitopes on the thyroid-stimulating hormone receptor is discussed.
MED-2352
Anaphylaxis to pork kidney is related to IgE antibodies specific for galactose-alpha-1,3-galactose.
BACKGROUND: Carbohydrate-specific IgE antibodies present on nonprimate mammalian proteins were incriminated recently in delayed meat anaphylaxis. The aim of this study was to explore whether anaphylaxis to mammalian kidney is also associated with galactose-α-1,3-galactose (αGal)-specific IgE. METHODS: Fourteen patients with anaphylaxis to pork or beef kidney underwent prick tests to meat and kidney. Some patients also underwent skin tests to Erbitux(®) (cetuximab). IgE antibodies to αGal, swine urine proteins, beef and pork meat, serum albumin proteins, cat, and rFel d 1 were measured by ImmunoCAP(®). The αGal levels were estimated in meats and kidney by ELISA inhibition assay. Cross-reactivity between αGal and pork kidney was studied with the ImmunoCAP(®) inhibition assay. RESULTS: Among the 14 patients, 12 presented with anaphylactic shock. Reactions occurred within 2 h from exposure in 67% of patients. Associated risk factors were observed in 10 cases, and alcohol was the main cofactor. Three patients underwent an oral challenge to pork kidney, and anaphylaxis occurred after ingestion of small quantities (1-2 g). Prick tests to kidney were positive in 54% of patients. All tested patients showed positive skin tests to Erbitux(®). All patients tested positive for IgE to αGal, with levels ranging from 0.4 to 294 kU/l. IgE binding to αGal was inhibited by raw pork kidney extract (mean, 77%; range, 55-87%), which showed a high amount of αGal determinants. CONCLUSIONS: Pork or beef kidney anaphylaxis is related to αGal IgE. Its peculiar severity could be due to an elevated content of αGal epitopes in kidney. © 2012 John Wiley & Sons A/S.
MED-2353
Anti-Gal: an abundant human natural antibody of multiple pathogeneses and clinical benefits
Summary Anti-Gal is the most abundant natural antibody in humans, constituting ∼ 1% of immunoglobulins. Anti-Gal is naturally produced also in apes and Old World monkeys. The ligand of anti-Gal is a carbohydrate antigen called the ‘α-gal epitope’ with the structure Galα1-3Galβ1-4GlcNAc-R. The α-gal epitope is present as a major carbohydrate antigen in non-primate mammals, prosimians and New World monkeys. Anti-Gal can contributes to several immunological pathogeneses. Anti-Gal IgE produced in some individuals causes allergies to meat and to the therapeutic monoclonal antibody cetuximab, all presenting α-gal epitopes. Aberrant expression of the α-gal epitope or of antigens mimicking it in humans may result in autoimmune processes, as in Graves' disease. α-Gal epitopes produced by Trypanosoma cruzi interact with anti-Gal and induce ‘autoimmune like’ inflammatory reactions in Chagas' disease. Anti-Gal IgM and IgG further mediate rejection of xenografts expressing α-gal epitopes. Because of its abundance, anti-Gal may be exploited for various clinical uses. It increases immunogenicity of microbial vaccines (e.g. influenza vaccine) presenting α-gal epitopes by targeting them for effective uptake by antigen-presenting cells. Tumour lesions are converted into vaccines against autologous tumour-associated antigens by intra-tumoral injection of α-gal glycolipids, which insert into tumour cell membranes. Anti-Gal binding to α-gal epitopes on tumour cells targets them for uptake by antigen-presenting cells. Accelerated wound healing is achieved by application of α-gal nanoparticles, which bind anti-Gal, activate complement, and recruit and activate macrophages that induce tissue regeneration. This therapy may be of further significance in regeneration of internally injured tissues such as ischaemic myocardium and injured nerves.
MED-2354
A unique natural human IgG antibody with anti-alpha-galactosyl specificity
A new natural anti-alpha-galactosyl IgG antibody (anti-Gal) was found to be present in high titer in the serum of every normal individual studied. The antibody was isolated by affinity chromatography on a melibiose-Sepharose column. The reactivity of the antibody was assessed by its interaction with alpha-galactosyl residues on rabbit erythrocytes (RabRBC). The specificity was determined by inhibition experiments with various carbohydrates. The anti-Gal interacts with alpha-galactosyl residues, possibly on glycolipids of human RBC (HuRBC), after removal of membrane proteins by treatment with pronase. In addition, the anti-Gal bind specifically to normal and pathologically senescent HuRBC, suggesting a physiological role for this natural antibody in the aging of RBC. The ubiquitous presence of anti-Gal in high titers throughout life implies a constant antigenic stimulation. In addition to the theoretical interest in the antibody, the study of the anti-Gal reactivity seems to bear immunodiagnostic significance. Decrease in the antibody titer was found to reflect humoral immunodeficiency disorders.
MED-2357
Evidence for a human-specific mechanism for diet and antibody-mediated inflammation in carcinoma progression
Patients with cancer have circulating heterophile antibodies that agglutinate animal red cells via recognition of the mammalian cell surface sialic acid N-glycolylneuraminic acid (Neu5Gc), which was long considered an oncofetal antigen in humans. However, humans are genetically deficient in Neu5Gc production and instead metabolically accumulate Neu5Gc from dietary sources, particularly red meats and milk products. Moreover, mice with a human-like defect showed no alternate pathway for Neu5Gc synthesis and even normal humans express anti-Neu5Gc antibodies. We show here that human tumors accumulate Neu5Gc that is covalently attached to multiple classes of glycans. The paradox of human tumor Neu5Gc accumulation in the face of circulating anti-Neu5Gc antibodies was hypothesized to be due to facilitation of tumor progression by the resulting low-grade chronic inflammation. Indeed, murine tumors expressing human-like levels of Neu5Gc show accelerated growth in syngeneic mice with a human-like Neu5Gc deficiency, coincident with the induction of anti-Neu5Gc antibodies and increased infiltration of inflammatory cells. Transfer of polyclonal monospecific syngeneic mouse anti-Neu5Gc serum also enhanced growth of transplanted syngeneic tumors bearing human-like levels of Neu5Gc, with tumors showing evidence for antibody deposition, enhanced angiogenesis and chronic inflammation. These effects were suppressed by a cyclooxygenase-2 inhibitor, a drug type known to reduce human carcinoma risk. Finally, affinity-purified human anti-Neu5Gc antibodies also accelerate growth of Neu5Gc-containing tumors in Neu5Gc-deficient mice. Taken together, the data suggest that the human propensity to develop diet-related carcinomas is contributed to by local chronic inflammation, resulting from interaction of metabolically-accumulated dietary Neu5Gc with circulating anti-Neu5Gc antibodies.
MED-3316
An outbreak of neurological autoimmunity with polyradiculoneuropathy in workers exposed to aerosolised porcine neural tissue: a descriptive study.
BACKGROUND: Between November, 2006, and May, 2008, a subacute neurological syndrome affected workers from two swine abattoirs in Minnesota and Indiana who had occupational exposure to aerosolised porcine brain. We aimed to describe the pathogenic and immunological characteristics of this illness. METHODS: All patients from two abattoirs who presented or were referred to the Mayo Clinic (Rochester, MN, USA) with neurological symptoms were included. We recorded details of exposure to aerosolised brain tissue and did comprehensive neurological, laboratory, neuroimaging, electrophysiological, pathological, and autoimmune serological assessments. Healthy controls were recruited from the community and from workers at the plant in Minnesota. FINDINGS: 24 patients were identified (21 from Minnesota, three from Indiana). The shortest duration from first exposure to symptom onset was 4 weeks. No infectious agent that could trigger disease was identified. All patients developed polyradiculoneuropathy, which was usually sensory predominant and painful. Two patients had initial CNS manifestations: transverse myelitis and meningoencephalitis. Nerve conduction studies localised abnormalities to the most proximal and distal nerve segments. Quantitative sensory and autonomic testing revealed involvement of large and small sensory fibres and sweat fibres. MRI showed prominent abnormalities of roots and ganglia. Nerve biopsies identified mild demyelination, axonal degeneration, and perivascular inflammation. Protein concentrations were high in the CSF of 18 (86%) of 21 patients. Sera from all patients and 29 (34%) of 85 unaffected workplace controls (but none of 178 community controls) had a distinctive neural-reactive IgG; 75% of patients' sera contained an IgG specific to myelin basic protein. Seropositivity correlated directly with exposure risk in patients and controls. 17 patients required immunomodulatory therapies, six improved spontaneously, and one was lost to follow-up after exposure stopped. INTERPRETATION: The neurological disorder described is autoimmune in origin and is related to occupational exposure to multiple aerosolised porcine brain tissue antigens. The pattern of nerve involvement suggests vulnerability of nerve roots and terminals where the blood-nerve barrier is most permeable. FUNDING: Mayo Clinic Foundation; Minnesota Department of Health; Centers for Disease Control and Prevention. Copyright 2010 Elsevier Ltd. All rights reserved.
MED-2359
Anti-Gal titers in healthy adults and inflammatory bowel disease patients.
INTRODUCTION: ALPHA-GAL is a glycoconjugate present on cell membranes of mammals and bacteria but not humans who display anti-Gal antibodies (AB) in high titers provoked by the commensal gut flora. In the present study, we sought to determine the longitudinal course of alpha-Gal specific AB titers of all isotypes over 8 weeks among healthy adult subjects. Furthermore, we hypothesized that inflammatory bowel disease (IBD) patients display increased anti-Gal titers. MATERIALS AND METHODS: We drew serum from healthy probands (n=20) weekly for 8 weeks and obtained plasma samples of from patients suffering from Crohn's disease (n=20) and ulcerative colitis (n=20). We measured anti-Gal ABs of all isotypes and total immunoglobulin (Ig) content using an enzyme-linked immunosorbent assay technique. For statistical evaluation of the longitudinal titers, we calculated confidence intervals for the slopes of a random intercept model, comparing variances between and within the probands. For group comparisons, we performed paired student t-tests and Pearson correlations. RESULTS: Alpha-Gal specific IgG, IgM, IgD, and IgA titers remained unvaried within a narrow range upon longitudinal observation. Most probands did not display alpha-Gal specific IgE ABs. Crohn's disease patients showed highly increased alpha-Gal-specific IgA titers compared with control subjects (P<.01). CONCLUSION: Apart from IgE, alpha-Gal-specific ABs of all isotypes remained constant over longer time periods in healthy subjects. Thus, significant titer changes actually represent increased antigen exposure and a specific anti-alpha-Gal response. Crohn's disease patients display increased anti-Gal IgA titers compared with healthy controls, which reflects a chronically impaired mucosal gut barrier in this patient cohort. Copyright © 2011 Elsevier Inc. All rights reserved.
MED-2360
STARI, or Masters disease: Lone Star tick-vectored Lyme-like illness.
Lyme-like illness (also known as southern tick-associated rash illness [STARI] or Masters disease) is vectored by the Lone Star tick (Amblyomma americanum). Lyme-like illness lesions, which are similar to the erythema migrans rash of Lyme disease, tend to have lymphocytic dermal infiltrates. With the exception of Borrelia lonestari, the possible causative agent or agents of Lyme-like illness have not been cultured. More research is needed to fully understand this newly recognized zoonosis. Clinicians are encouraged to increase their knowledge and awareness of this Lyme disease mimic.
MED-2361
Southern Tick-Associated Rash Illness (STARI) in the North: STARI following a tick bite in Long Island, New York.
The most common clinical manifestation of Lyme disease is the characteristic rash, erythema migrans (EM). In the 1980s EM-like eruptions were reported in Missouri and other southeastern states. The EM-like eruptions, which were of unknown etiology, often followed the bite of the Lone Star tick (Amblyomma americanum) and the rash is called STARI (southern tick-associated rash illness). Although the Lone Star tick is found in the Lyme disease-endemic areas of New England and Mid-Atlantic regions of the United States, STARI has been reported only once from the Northeast and Mid-Atlantic regions. We report a child from Connecticut who visited Long Island, New York, and developed a rash that was thought to be EM. Because the patient failed to respond to antibiotics used to treat Lyme disease, an investigation ensued, and the diagnosis of STARI was established.
MED-2362
Distribution of Gal alpha 1----3Gal beta 1----4GlcNAc residues on secreted mammalian glycoproteins (thyroglobulin, fibrinogen, and immunoglobulin G...
The study of the expression of Gal alpha 1----3Gal beta 1----4GlcNAc residues on mammalian glycoconjugates is of particular interest since as many as 1% of circulating IgG antibodies in man (the natural anti-Gal antibody) interact specifically with this carbohydrate residue. In recent studies, we have found that Gal alpha 1----3Gal beta 1----4GlcNAc residues are abundant on red cells and nucleated cells of nonprimate mammals, prosimians, and New World monkeys, but their expression is diminished in Old World monkeys, apes, and humans. In the present work, we have analyzed the expression of these residues on secreted mammalian glycoproteins. For this purpose, we have developed a radioimmunoassay (RIA) which enables the quantification of Gal alpha 1----3Gal beta 1----4GlcNAc residues on the secreted glycoproteins. Purified biotinylated anti-Gal was used as the antibody in the RIA, and bovine thyroglobulin enriched for Gal alpha 1----3Gal beta 1----4GlcNAc residues served as a solid-phase antigen. In this study, it is reported for the first time that the evolutionary pattern of Gal alpha 1----3Gal beta 1----4GlcNAc residue distribution in in vivo secreted glycoproteins is similar to that observed in membranes of cell lines and of red cells. Thyroglobulin, fibrinogen, or IgG molecules from nonprimate mammals and from New World monkeys express varying amounts of Gal alpha 1----3Gal beta 1----4GlcNAc residues ranging between 0.01 and 11 residues per molecule, whereas no such residues are present on any of these glycoproteins of human or Old World monkey origin.(ABSTRACT TRUNCATED AT 250 WORDS)
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-2364
Natural human anti-Gal alpha(1,3)Gal antibodies react with human mucin peptides.
We have recently demonstrated that both antibodies to Gal alpha(1,3)Gal, and the Gal alpha(1,3)Gal binding lectin (IB4), bind a synthetic peptide (DAHWESWL), there being a similar recognition of carbohydrate and peptide structures. We now report that the anti-Gal alpha(1,3)Gal antibodies and IB4 lectin also react with peptides encoded by mucin genes (MUC 1, 3, 4)-sequences known to be rich in serine, threonine and proline. This activity was demonstrated (1) by the ability of mucin derived peptides to block the reaction of anti-Gal alpha(1,3)Gal antibodies and IB4 lectin with a Gal alpha(1,3)Gal+ pig endothelial cell line; the reactions were specific and did not occur with a random peptide containing the same sequences or with other mucin peptides; (2) by the fact that anti-mucin1 antibodies could react with the Gal alpha(1,3)Gal expressed after transfection of COS cells (Gal alpha(1,3)Gal-,Muc1-) with cDNA encoding the pig alpha, 3galactosyltransferase; and (3) that the IB4 lectin and anti-Gal alpha(1,3)Gal antibodies could react with mucin 1 found on the surface of human breast cancer cells. Thus natural occurring anti-Gal alpha(1,3)Gal antibodies found in all human serum can react with self (Muc1) peptides expressed in large amounts on the surface of tumour cells but not on normal cells. The findings are of interest and serve to explain the previously reported findings that human cells can, at times, express Gal alpha(1,3)Gal; such expression is an artefact, the reaction is due to the phenomenon described herein, i.e. that anti-Gal alpha(1,3)Gal antibodies react with mucin peptides.
MED-2365
An association between tick bite reactions and red meat allergy in humans.
Twenty-five patients living in a tick-endemic region of Sydney, New South Wales developed red meat allergy after experiencing large local reactions to tick bites. This represents a potentially novel cross-reaction between an arthropod and a food protein. (MJA 2009; 190: 510-511).
MED-2366
A possible role for the alpha 1-->3 galactosyl epitope and the natural anti-gal antibody in oncogenesis.
Glycoconjugates and their antibodies are vital components of host-tumor interaction. This review concentrates on the oncological implications of research concerning the alpha gal triad; the alpha 1-->3 galactosyl epitope (alpha Gal), the enzyme responsible for its construction, alpha 1,3 galactosyl transferase (alpha 1-3GT), and its associated antibody: anti-gal. Alpha gal epitopes, previously assumed to be absent from human tissue, have been demonstrated on several human cancer cell lines, senescent red blood cells, and Graves' disease thyrocytes. Alpha-gal presence on neoplastic lines is correlated with increased metastatic formation in animal models. The mechanisms of human response to these neoantigens are complex, as natural anti-gal antibodies exist in high titers in normal sera, thus predicting immunological recognition of cells expressing alpha gal epitopes. Hypotheses vary regarding the pathogenic contributions of metastasis-associated phenomena such as de novo expression of alpha gal and its unmasking by desialylation. The means by which alpha gal is sporadically expressed in human tissue remain unknown, as the galactosyl transferase which produces this epitope in constitutively expressive animals has undergone significant mutation at the genomic level in humans. Pathological re-expression is presumed to require permissive changes at a cellular level. Detailing these alterations is a prerequisite to the comprehension of the metastatic phenotype. In this context, the possibility of therapeutic strategies affecting alpha gal expression are also discussed.
MED-2367
Naturally developing memory T cell xenoreactivity to swine antigens in human peripheral blood lymphocytes.
Naturally developing xenospecific Abs are well-documented barriers to xenograft transplantation in humans, but whether analogous xenoreactive T cell immunity develops is not known. We used an enzyme-linked immunospot assay to determine the frequency and cytokine profiles of xenoreactive PBLs from a panel of human volunteers. Because naive T cells produce only IL-2 in short term culture, IFN-gamma production by this approach is a measure of a memory immune response. Stimulation of human PBLs or purified T lymphocytes with stimulator cells from inbred swine revealed a high frequency of IFN-gamma producers with 5-fold fewer IL-2 producers. In contrast, lymphocytes obtained from neonatal umbilical cord blood contained swine-specific IL-2 producers but few IFN-gamma producers, which is what one would expect to find with a naive phenotype. Moreover, PBLs from adults with a history of abstention from pork consumption responded to swine cells with a significantly lower frequency of IFN-gamma producers than PBLs from adults with unrestricted diets did, suggesting that pork consumption may result in priming of swine-specific T cell immunity. Our findings provide the first evidence for naturally occurring xenospecific T cell immunity in humans. The detected strength of this memory response suggests that it will present a formidable barrier to transplantation of swine organs.
MED-2368
Proteomics, metabolomics, and immunomics on microparticles derived from human atherosclerotic plaques.
BACKGROUND: Microparticles (MPs) with procoagulant activity are present in human atherosclerosis, but no detailed information is available on their composition. METHODS AND RESULTS: To obtain insights into the role of MPs in atherogenesis, MP proteins were identified by tandem mass spectrometry, metabolite profiles were determined by high-resolution nuclear magnetic resonance spectroscopy, and antibody reactivity was assessed against combinatorial antigen libraries. Plaque MPs expressed surface antigens consistent with their leukocyte origin, including major histocompatibility complex classes I and II, and induced a dose-dependent stimulatory effect on T-cell proliferation. Notably, taurine, the most abundant free organic acid in human neutrophils, which scavenges myeloperoxidase-catalyzed free radicals, was highly enriched in plaque MPs. Moreover, fluorescent labeling of proteins on the MP surface suggested immunoglobulins to be trapped inside, which was confirmed by flow cytometry analysis on permeabilized and nonpermeabilized plaque MPs. Colabeling for CD14 and IgG established that more than 90% of the IgG containing MPs were CD14(+), indicating a macrophage origin. Screening against an antigen library revealed that the immunologic profiles of antibodies in MPs were similar to those found in plaques but differed profoundly from antibodies in plasma and unexpectedly, showed strong reactions with oligosaccharide antigens, in particular blood group antigen A. CONCLUSIONS: This study provides the first evidence that immunoglobulins are present within MPs derived from plaque macrophages, that the portfolio of plaque antibodies is different from circulating antibodies in plasma, and that anticarbohydrate antibodies are retained in human atherosclerotic lesions.
MED-2369
Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-α-1,3-galactose
Background Carbohydrate moieties are frequently encountered in food and can elicit IgE responses, the clinical significance of which has been unclear. Recent work, however, has shown that IgE antibodies to galactose-α-1,3-galactose (α-gal), a carbohydrate commonly expressed on nonprimate mammalian proteins, are capable of eliciting serious, even fatal, reactions. Objective We sought to determine whether IgE antibodies to α-gal are present in sera from patients who report anaphylaxis or urticaria after eating beef, pork, or lamb. Methods Detailed histories were taken from patients presenting to the University of Virginia Allergy Clinic. Skin prick tests (SPTs), intradermal skin tests, and serum IgE antibody analysis were performed for common indoor, outdoor, and food allergens. Results Twenty-four patients with IgE antibodies to α-gal were identified. These patients described a similar history of anaphylaxis or urticaria 3 to 6 hours after the ingestion of meat and reported fewer or no episodes when following an avoidance diet. SPTs to mammalian meat produced wheals of usually less than 4 mm, whereas intradermal or fresh-food SPTs provided larger and more consistent wheal responses. CAP-RAST testing revealed specific IgE antibodies to beef, pork, lamb, cow’s milk, cat, and dog but not turkey, chicken, or fish. Absorption experiments indicated that this pattern of sensitivity was explained by an IgE antibody specific for α-gal. Conclusion We report a novel and severe food allergy related to IgE antibodies to the carbohydrate epitope α-gal. These patients experience delayed symptoms of anaphylaxis, angioedema, or urticaria associated with eating beef, pork, or lamb.
MED-3270
Protein methionine content and MDA-lysine adducts are inversely related to maximum life span in the heart of mammals.
Aging affects all organisms and its basic mechanisms are expected to be conserved across species. Oxidation of proteins has been proposed to be one of the basic mechanisms linking oxygen radicals with the basic aging process. If oxidative damage to proteins is involved in aging, long-lived animals (which age slowly) should show lower levels of markers of this kind of damage than short-lived ones. However, this possibility has not been investigated yet. In this study, steady-state levels of markers of different kinds of protein damage--oxidation (glutamic and aminoadipic semialdehydes), mixed glyco- and lipoxidation (carboxymethyl- and carboxyethyllysine), lipoxidation (malondialdehydelysine) and amino acid composition--were measured in the heart of eight mammalian species ranging in maximum life span (MLSP) from 3.5 to 46 years. Oxidation markers were directly correlated with MLSP across species. Mixed glyco- and lipoxidation markers did not correlate with MLSP. However, the lipoxidation marker malondialdehydelysine was inversely correlated with MLSP (r2=0.85; P<0.001). The amino acid compositional analysis revealed that methionine is the only amino acid strongly correlated MLSP and that such correlation is negative (r2=0.93; P<0.001). This trait may contribute to lower steady-state levels of oxidized methionine residues in cellular proteins. These results reinforce the notion that high longevity in homeothermic vertebrates is achieved in part by constitutively decreasing the sensitivity of both tissue proteins and lipids to oxidative damage. This is obtained by modifying the constituent structural components of proteins and lipids, selecting those less sensitive to oxidative modifications.
MED-3273
The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy.
Recent studies confirm that dietary methionine restriction increases both mean and maximal lifespan in rats and mice, achieving "aging retardant" effects very similar to those of caloric restriction, including a suppression of mitochondrial superoxide generation. Although voluntary caloric restriction is never likely to gain much popularity as a pro-longevity strategy for humans, it may be more feasible to achieve moderate methionine restriction, in light of the fact that vegan diets tend to be relatively low in this amino acid. Plant proteins - especially those derived from legumes or nuts - tend to be lower in methionine than animal proteins. Furthermore, the total protein content of vegan diets, as a function of calorie content, tends to be lower than that of omnivore diets, and plant protein has somewhat lower bioavailability than animal protein. Whole-food vegan diets that moderate bean and soy intake, while including ample amounts of fruit and wine or beer, can be quite low in methionine, while supplying abundant nutrition for health (assuming concurrent B12 supplementation). Furthermore, low-fat vegan diets, coupled with exercise training, can be expected to promote longevity by decreasing systemic levels of insulin and free IGF-I; the latter effect would be amplified by methionine restriction - though it is not clear whether IGF-I down-regulation is the sole basis for the impact of low-methionine diets on longevity in rodents.
MED-3279
Chitin synthesis and degradation as targets for pesticide action.
Various pesticides are being used to destabilize, perturb, or inhibit crucial biochemical and physiological targets related to metabolism, growth, development, nervous communication, or behavior in pestiferous organisms. Chitin is an eukaryotic extracellular aminosugar biopolymer, massively produced by most fungal systems and by invertebrates, notably arthropods. Being an integral supportive component in fungal cell wall, insect cuticle, and nematode egg shell, chitin has been considered as a selective target for pesticide action. Throughout the elaborate processes of chitin formation and deposition, only the polymerization events associated with the cell membrane compartment are so far available for chemical interference. Currently, the actinomycetes-derived nucleoside peptide fungicides such as the polyoxins and the insecticidal benzoylaryl ureas have reached commercial pesticide status. The polyoxins and other structurally-related antibiotics like nikkomycins are strong competitive inhibitors of the polymerizing enzyme chitin synthase. The exact biochemical lesion inflicted by the benzoylaryl ureas is still elusive, but a post-polymerization event, such as translocation of chitin chains across the cell membrane, is suggested. Hydrolytic degradation of the chitin polymer is essential for hyphal growth, branching, and septum formation in fungal systems as well as for the normal molting of arthropods. Recently, insect chitinase activity was strongly and specifically suppressed by allosamidin, an actimomycetes-derived metabolite. In part, the defense mechanism in plants against invasion of pathogens is associated with induced chitinases. Chitin, chitosan, and their oligomers are able to act as elicitors which induce enhanced levels of chitinases in various plants. Lectins which bind to N-acetyl-D-glucosamine strongly interfere with fungal and insect chitin synthases. Plant lectins with similar properties may be involved in plant-pathogen interaction inter alia by suppressing fungal invasion.
MED-3280
Methionine dependency and cancer treatment.
Conventional chemotherapies have showed their limits, notably for patients with advanced cancer. New therapeutic strategies must be identified, and the metabolic abnormalities of cancer cells offer such opportunities. Many human cancer cell lines and primary tumors have absolute requirements for methionine, an essential amino acid. In contrast, normal cells are relatively resistant to exogenous methionine restriction. The biochemical mechanism for methionine dependency has been studied extensively, but the fundamental mechanism remains unclear. A number of investigators have attempted to exploit the methionine dependence of tumors for therapeutic effects in vivo. To reduce in vivo methionine in plasma and tumours, dietary and pharmacological treatments have been used. Methionine-free diet or methionine-deprived total parenteral nutrition causes regression of a variety of animal tumours. Alternatively, methionine depletion was achieved by the use of methioninase. This enzyme specifically degrades methionine and inhibits tumour growth in preclinical models. Because of potential toxicity and quality of life problems, prolonged methionine restriction with diet or with methioninase is not suitable for clinical use. Methionine restriction may find greater application in association with various chemotherapeutic agents. Several preclinical studies have demonstrated synergy between methionine restriction and various cytotoxic chemotherapy drugs. The experimental results accumulated during the last three decades suggest that methionine restriction can become an additional cancer therapeutic strategy, notably in association with chemotherapy.
MED-3281
Targeting methionine auxotrophy in cancer: discovery & exploration.
INTRODUCTION: Amino acid auxotrophy or the metabolic defect which renders cancer incapable of surviving under amino acid depleted conditions is being exploited and explored as a therapeutic against cancer. Early clinical data on asparagine- and arginine-depleting drugs have demonstrated low toxicity and efficacy in melanoma, hepatocellular carcinoma and acute lymphoblastic leukemia. Methionine auxotrophy is a novel niche currently under exploration for targeting certain cancers. AREAS COVERED: In this review we explore the discovery of methionine auxotrophy followed by in vitro, in vivo and patient data on targeting cancer with methionine depletion. We end with a small discussion on bioengineering, pegylation and red blood cell encapsulation as mechanisms for decreasing immunogenicity of methionine-depleting drugs. We hope to provide a platform for future pharmacology, toxicology and cytotoxicity studies with methionine depletion therapy and drugs. EXPERT OPINION: Although methionine auxotrophy seems as a viable target, extensive research addressing normal versus cancer cell toxicity needs to be conducted. Further research also needs to be conducted into the molecular mechanism associated with methionine depletion therapy. Finally, novel methods need to be developed to decrease the immunogenicity of methionine-depleting drugs, a current issue with protein therapeutics.
MED-3283
Lowered methionine ingestion as responsible for the decrease in rodent mitochondrial oxidative stress in protein and dietary restriction possible i...
Available information indicates that long-lived mammals have low rates of reactive oxygen species (ROS) generation and oxidative damage at their mitochondria. On the other hand, many studies have consistently shown that dietary restriction (DR) in rodents also decreases mitochondrial ROS (mtROS) production and oxidative damage to mitochondrial DNA and proteins. It has been observed that protein restriction also decreases mtROS generation and oxidative stress in rat liver, whereas neither carbohydrate nor lipid restriction change these parameters. This is interesting because protein restriction also increases maximum longevity in rodents (although to a lower extent than DR) and is a much more practicable intervention for humans than DR, whereas neither carbohydrate nor lipid restriction seem to change rodent longevity. Moreover, it has been found that isocaloric methionine restriction also decreases mtROS generation and oxidative stress in rodent tissues, and this manipulation also increases maximum longevity in rats and mice. In addition, excessive dietary methionine also increases mtROS generation in rat liver. These studies suggest that the reduced intake of dietary methionine can be responsible for the decrease in mitochondrial ROS generation and the ensuing oxidative damage that occurs during DR, as well as for part of the increase in maximum longevity induced by this dietary manipulation. In addition, the mean intake of proteins (and thus methionine) of Western human populations is much higher than needed. Therefore, decreasing such levels to the recommended ones has a great potential to lower tissue oxidative stress and to increase healthy life span in humans while avoiding the possible undesirable effects of DR diets.
MED-4198
Insect food for astronauts: gas exchange in silkworms fed on mulberry and lettuce and the nutritional value of these insects for human consumption ...
In this study, silkworm moth (Bombyx mori L.) larvae were regarded as an animal protein source for astronauts in the bioregenerative life support system during long-term deep space exploration in the future. They were fed with mulberry and stem lettuce leaves during the first three instars and the last two instars, respectively. In addition, this kind of environmental approach, which utilised inedible biomass of plants to produce animal protein of high quality, can likewise be applied terrestrially to provide food for people living in extreme environments and/or impoverished agro-ecosystems, such as in polar regions, isolated military bases, ships, submarines, etc. Respiration characteristics of the larvae during development under two main physiological conditions, namely eating and not-eating of leaves, were studied. Nutrient compositions of silkworm powder (SP), ground and freeze-dried silkworms on the 3rd day of the 5th instar larvae, including protein, fat, vitamins, minerals and fatty acids, were measured using international standard methods. Silkworms' respiration rates, measured when larvae were eating mulberry leaves, were higher than those of similar larvae that hadn't eaten such leaves. There was a significant difference between silkworms fed on mulberry leaves and those fed on stem lettuce in the 4th and 5th instars (P<0.01). Amounts of CO2 exhaled by the silkworms under the two physiological regimes differed from each other (P<0.01). There was also a significant difference between the amount of O2 inhaled when the insects were under the two physiological statuses (P<0.01). Moreover, silkworms' respiration quotient under the eating regime was larger than when under the not-eating regime. The SP was found to be rich in protein and amino acids in total; 12 essential vitamins, nine minerals and twelve fatty acids were detected. Moreover, 359 kcal could be generated per 100 gram of SP (dry weight).
MED-4203
Evolution of dietary antioxidants.
Oxygen is vital for most organisms but, paradoxically, damages key biological sites. Oxygenic threat is met by antioxidants that evolved in parallel with our oxygenic atmosphere. Plants employ antioxidants to defend their structures against reactive oxygen species (ROS; oxidants) produced during photosynthesis. The human body is exposed to these same oxidants, and we have also evolved an effective antioxidant system. However, this is not infallible. ROS breach defences, oxidative damage ensues, accumulates with age, and causes a variety of pathological changes. Plant-based, antioxidant-rich foods traditionally formed the major part of the human diet, and plant-based dietary antioxidants are hypothesized to have an important role in maintaining human health. This hypothesis is logical in evolutionary terms, especially when we consider the relatively hypoxic environment in which humans may have evolved. In this paper, the human diet is discussed briefly in terms of its evolutionary development, different strategies of antioxidant defence are outlined, and evolution of dietary antioxidants is discussed from the perspectives of plant need and our current dietary requirements. Finally, possibilities in regard to dietary antioxidants, evolution, and human health are presented, and an evolutionary cost-benefit analysis is presented in relation to why we lost the ability to make ascorbic acid (vitamin C) although we retained an absolute requirement for it.
MED-4299
Evolution of the human diet: linking our ancestral diet to modern functional foods as a means of chronic disease prevention.
The evolution of the human diet over the past 10,000 years from a Paleolithic diet to our current modern pattern of intake has resulted in profound changes in feeding behavior. Shifts have occurred from diets high in fruits, vegetables, lean meats, and seafood to processed foods high in sodium and hydrogenated fats and low in fiber. These dietary changes have adversely affected dietary parameters known to be related to health, resulting in an increase in obesity and chronic disease, including cardiovascular disease (CVD), diabetes, and cancer. Some intervention trials using Paleolithic dietary patterns have shown promising results with favorable changes in CVD and diabetes risk factors. However, such benefits may be offset by disadvantages of the Paleolithic diet, which is low in vitamin D and calcium and high in fish potentially containing environmental toxins. More advantageous would be promotion of foods and food ingredients from our ancestral era that have been shown to possess health benefits in the form of functional foods. Many studies have investigated the health benefits of various functional food ingredients, including omega-3 fatty acids, polyphenols, fiber, and plant sterols. These bioactive compounds may help to prevent and reduce incidence of chronic diseases, which in turn could lead to health cost savings ranging from $2 to $3 billion per year as estimated by case studies using omega-3 and plant sterols as examples. Thus, public health benefits should result from promotion of the positive components of Paleolithic diets as functional foods.
MED-4205
Chemical safety of meat and meat products.
Since the Second World War the consumer behaviour in developed countries changed drastically. Primarily there existed the demand for sufficient food after a period of starvation, afterwards the desire for higher quality was arising, whereas today most people ask for safe and healthy food with high quality. Therefore a united approach comprising consistent standards, sound science and robust controls is required to ensure consumers' health and to maintain consumers' confidence and satisfaction. Chemical analysis along the whole food chain downstream (tracking) from primary production to the consumer and upstream (tracing) from the consumer to primary production is an important prerequisite to ensure food safety and quality. In this frame the focus of the following paper is the "chemical safety of meat and meat products" taking into account inorganic as well as organic residues and contaminants, the use of nitrite in meat products, the incidence of veterinary drugs, as well as a Failure Mode and Effect Analysis (FMEA) system assessing (prioritizing) vulnerable food chain steps to decrease or eliminate vulnerability.
MED-4206
Vegetarian diets and public health: biomarker and redox connections.
Vegetarian diets are rich in antioxidant phytochemicals. However, they may not act as antioxidants in vivo, and yet still have important signaling and regulatory functions. Some may act as pro-oxidants, modulating cellular redox tone and oxidizing redox sensitive sites. In this review, evidence for health benefits of vegetarian diets is presented from different perspectives: epidemiological, biomarker, evolutionary, and public health, as well as antioxidant. From the perspective of molecular connections between diet and health, evidence of a role for plasma ascorbic acid as a biomarker for future disease risk is presented. Basic concepts of redox-based cell signaling are presented, and effects of antioxidant phytochemicals on signaling, especially via redox tone, sulfur switches and the Antioxidant Response Element (ARE), are explored. Sufficient scientific evidence exists for public health policy to promote a plant-rich diet for health promotion. This does not need to wait for science to provide all the answers as to why and how. However, action and interplay of dietary antioxidants in the nonequilibrium systems that control redox balance, cell signaling, and cell function provide rich ground for research to advance understanding of orthomolecular nutrition and provide science-based evidence to advance public health in our aging population.
MED-4357
Effect of extracted housefly pupae peptide mixture on chilled pork preservation.
The peptide mixture from housefly pupae has broad spectrum antimicrobial activity but has not previously been reported as a food preservative. In this study, the preservation effects of a housefly pupae peptide mixture, nisin, and sodium dehydroacetate (DHA-S) on the number of mesophilic aerobic bacteria (MAB), total volatile basic nitrogen (TVB-N), and pH value of chilled pork were compared. All results showed that a good preservation effect was observed among 3 treatments with the peptide mixture of housefly pupae, nisin, and DHA-S and that there was no significant difference among them. These results indicate that housefly peptide mixture has a great potential as a food preservative. The results of scanning electron microscope and transmission electron microscopy suggest that the primary mechanism of housefly pupae peptide mixture may be bacterial cytoplasmic membrane lysis and pores induced in the membranes. Practical Applications: Peptide mixture extracted from housefly pupae using low-cost and simple method has broad spectrum antimicrobial activity. According to the effect on chilled pork preservation, extracted housefly peptide mixture has a great potential as a food preservative.
MED-4403
Identification of cheese mite species inoculated on Mimolette and Milbenkase cheese through cryogenic scanning electron microscopy.
Samples of Mimolette (France) and Milbenkase (Germany) cheeses traditionally ripened by mites were analyzed to determine the mite species present on each sample. Scientific literature was reviewed to understand which mite species most commonly infest cheese. Morphological features possessed by mites were then studied to understand what unique characteristics are required to ensure accurate identification. After identification and compilation of a detailed key of stored food mites (subclass Acari, order Astigmata) and their delineating features, the mites were viewed through a cryogenic scanning electron microscope. It was determined that Mimolette cheese is inoculated with Acarus siro L. The features studied to identify this mite species included idiosomal length and shape, setae length and arrangement, leg size, placement of anus and genitals, and solenidia shape. The Milbenkase cheese is inoculated with Tyrolichus casei Oudemans, which was evident after viewing the same features used to identify A. siro and the supracoxal seta shape. With this knowledge, further research can be conducted on the 2 cheese varieties to understand what chemical, physical, and microbial changes occur within the cheeses because of mites. It is important to identify the mite species present on each cheese variety to improve our understanding of their role in creating the distinctive characteristics that set these cheeses apart from others. Copyright (c) 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
MED-4913
Probabilistic modelling of exposure doses and implications for health risk characterization: glycoalkaloids from potatoes.
Potatoes are a source of glycoalkaloids (GAs) represented primarily by alpha-solanine and alpha-chaconine (about 95%). Content of GAs in tubers is usually 10-100 mg/kg and maximum levels do not exceed 200 mg/kg. GAs can be hazardous for human health. Poisoning involve gastrointestinal ailments and neurological symptoms. A single intake of >1-3 mg/kg b.w. is considered a critical effect dose (CED). Probabilistic modelling of acute and chronic (usual) exposure to GAs was performed in the Czech Republic, Sweden and The Netherlands. National databases on individual consumption of foods, data on concentration of GAs in tubers (439 Czech and Swedish results) and processing factors were used for modelling. Results concluded that potatoes currently available at the European market may lead to acute intakes >1 mg GAs/kg b.w./day for upper tail of the intake distribution (0.01% of population) in all three countries. 50 mg GAs/kg raw unpeeled tubers ensures that at least 99.99% of the population does not exceed the CED. Estimated chronic (usual) intake in participating countries was 0.25, 0.29 and 0.56 mg/kg b.w./day (97.5% upper confidence limit). It remains unclear if the incidence of GAs poisoning is underreported or if assumptions are the worst case for extremely sensitive persons.
MED-4914
Potato glycoalkaloids: true safety or false sense of security?
As one of the major agricultural crops, the cultivated potato is consumed each day by millions of people from diverse cultural backgrounds. A product of global importance, the potato tuber contains toxic glycoalkaloids (GAs) that cause sporadic outbreaks of poisoning in humans, as well as many livestock deaths. This article will discuss some aspects of the potato GAs, including their toxic effects and risk factors, methods of detection of GAs and biotechnological aspects of potato breeding. An attempt has been made to answer a question of vital importance - are potato GAs dangerous to humans and animals and, if so, to what extent?
MED-4915
A human dietary risk assessment associated with glycoalkaloid responses of potato to Colorado potato beetle defoliation.
A quantitative human dietary risk assessment was conducted using the glycoalkaloid concentrations measured from tubers of plants defoliated by Colorado potato beetles and undefoliated (control). There was a significantly greater production of glycoalkaloids for defoliated plants compared to control plants for both skin and inner tissue of tubers. The dietary risk posed to different human subgroups associated with the consumption of potatoes was estimated for the 50th, 95th, and 99.9th percentile US national consumption values. Exposures were compared to a toxic threshold of 1.0mg/kg body weight. Defoliation by Colorado potato beetles increased dietary risk by approximately 48%. Glycoalkaloid concentrations within the inner tissue of tubers, including undefoliated controls, exceeded the toxic threshold for all human subgroups at less than the 99.9th percentile of exposure, but not the 95th percentile.
MED-5029
Control of head lice with a coconut-derived emulsion shampoo.
OBJECTIVE: To evaluate a novel coconut-derived emulsion (CDE) shampoo against head lice infestation in children. DESIGN: A school trial in which pupils were treated on days 0 and 7 and checked on days 8 and 15 and a family trial where product was applied by parents three times in 2 weeks or used as a cosmetic shampoo and checked on days 14 and days 70. SETTING: UK schools in Bristol and Western-super-Mare and families in Northern Somerset. MAIN OUTCOME MEASURE: Numbers of children free from infestation after treatment. RESULTS: In the school trial, percentage cures at day 8 were 14% (permethrin, n=7) and 61% (CDE, n=37). In the family trial where all family members were treated, cure rate was 96% (n=28), and if the shampoo was subsequently used as a cosmetic shampoo, only 1 of 12 children became re-infested after 10 weeks. CONCLUSION: CDE shampoo is a novel effective method of controlling head lice and used after treatment as a cosmetic shampoo can aid in the reduction of re-infestation.
MED-3237
Diet-induced metabolic acidosis.
The modern Western-type diet is deficient in fruits and vegetables and contains excessive animal products, generating the accumulation of non-metabolizable anions and a lifespan state of overlooked metabolic acidosis, whose magnitude increases progressively with aging due to the physiological decline in kidney function. In response to this state of diet-derived metabolic acidosis, the kidney implements compensating mechanisms aimed to restore the acid-base balance, such as the removal of the non-metabolizable anions, the conservation of citrate, and the enhancement of kidney ammoniagenesis and urinary excretion of ammonium ions. These adaptive processes lower the urine pH and induce an extensive change in urine composition, including hypocitraturia, hypercalciuria, and nitrogen and phosphate wasting. Low urine pH predisposes to uric acid stone formation. Hypocitraturia and hypercalciuria are risk factors for calcium stone disease. Even a very mild degree of metabolic acidosis induces skeletal muscle resistance to the insulin action and dietary acid load may be an important variable in predicting the metabolic abnormalities and the cardiovascular risk of the general population, the overweight and obese persons, and other patient populations including diabetes and chronic kidney failure. High dietary acid load is more likely to result in diabetes and systemic hypertension and may increase the cardiovascular risk. Results of recent observational studies confirm an association between insulin resistance and metabolic acidosis markers, including low serum bicarbonate, high serum anion gap, hypocitraturia, and low urine pH. Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
MED-3892
Application of Bayesian Techniques to Model the Burden of Human Salmonellosis Attributable to U.S. Food Commodities at the Point of Processing: Adaptation of a Danish Model
Mathematical models that estimate the proportion of foodborne illnesses attributable to food commodities at specific points in the food chain may be useful to risk managers and policy makers to formulate public health goals, prioritize interventions, and document the effectiveness of mitigations aimed at reducing illness. Using human surveillance data on laboratory-confirmed Salmonella infections from the Centers for Disease Control and Prevention and Salmonella testing data from U.S. Department of Agriculture Food Safety and Inspection Service's regulatory programs, we developed a point-of-processing foodborne illness attribution model by adapting the Hald Salmonella Bayesian source attribution model. Key model outputs include estimates of the relative proportions of domestically acquired sporadic human Salmonella infections resulting from contamination of raw meat, poultry, and egg products processed in the United States from 1998 through 2003. The current model estimates the relative contribution of chicken (48%), ground beef (28%), turkey (17%), egg products (6%), intact beef (1%), and pork (<1%) across 109 Salmonella serotypes found in food commodities at point of processing. While interpretation of the attribution estimates is constrained by data inputs, the adapted model shows promise and may serve as a basis for a common approach to attribution of human salmonellosis and food safety decision-making in more than one country.
MED-1498
A modest proposal for a longitudinal study of dementia prevention (with apologies to Jonathan Swift, 1729).
Many studies have documented the role of risk and protective factors for late life dementing illnesses, particularly Alzheimer's disease. A "Systematic Review" from the US Agency for Healthcare Research and Quality and the National Institute on Aging concluded that because the overall quality of evidence was low, recommendations for public health could not be made. In order to gain evidence for the efficacy of lifestyle interventions, we propose a "Modest Proposal" to study 10,000 subjects over 40 years randomly assigned to groups of low or high saturated fat in the diet, head injury, and high or low levels of mental activity, physical activity, or inactivity as well as smoking or non-smoking. This proposed study cannot be accomplished. The "Modest Proposal" illustrates that the absence of definitive evidence should not restrict physicians from making reasonable recommendations based on the evidence that is available.
MED-4255
Resolving the Coronary Artery Disease Epidemic Through Plant-Based Nutrition.
The world's advanced countries have easy access to plentiful high-fat food; ironically, it is this rich diet that produces atherosclerosis. In the world's poorer nations, many people subsist on a primarily plant-based diet, which is far healthier, especially in terms of heart disease. To treat coronary heart disease, a century of scientific investigation has produced a device-driven, risk factor-oriented strategy. Nevertheless, many patients treated with this approach experience progressive disability and death. This strategy is a rear-guard defensive one. In contrast, compelling data from nutritional studies, population surveys, and interventional studies support the effectiveness of a plant-based diet and aggressive lipid lowering to arrest, prevent, and selectively reverse heart disease. In essence, this is an offensive strategy. The single biggest step toward adopting this strategy would be to have United States dietary guidelines support a plant-based diet. An expert committee purged of industrial and political influence is required to assure that science is the basis for dietary recommendations. (c)2001 CHF, Inc.
MED-1788
Micronutrients intake is associated with improved sperm DNA quality in older men.
OBJECTIVE: To investigate whether lifestyle factors such as increased dietary intake of micronutrients reduce the risks of sperm DNA damage, and whether older men benefit more than younger men. DESIGN: Cross-sectional study design with equalized assignments into age groups. SETTING: National laboratory and university. PATIENT(S): Nonclinical group of 22-80-year-old nonsmoking men (n = 80) who reported no fertility problems. MAIN OUTCOME MEASURE(S): Sperm DNA damage measured by alkaline and neutral DNA electrophoresis (i.e., sperm Comet assay). RESULT(S): Sociodemographics, occupational exposures, medical and reproductive histories, and lifestyle habits were determined by questionnaire. The average daily dietary and supplement intake of micronutrients (vitamin C, vitamin E, b-carotene, zinc, and folate) was determined using the 100-item Modified Block Food Frequency Questionnaire (FFQ). Men with the highest intake of vitamin C had approximately 16% less sperm DNA damage (alkaline sperm Comet) than men with the lowest intake, with similar findings for vitamin E, folate, and zinc (but not β-carotene). Older men (>44 years) with the highest vitamin C intake had approximately 20% less sperm DNA damage compared with older men with the lowest intake, with similar findings for vitamin E and zinc. The older men with the highest intake of these micronutrients showed levels of sperm damage that were similar to those of the younger men. However, younger men (<44 years) did not benefit from higher intakes of the micronutrients surveyed. CONCLUSION(S): Men with higher dietary and supplement intake of certain micronutrients may produce sperm with less DNA damage, especially among older men. This raises the broader question of how lifestyle factors, including higher intakes of antioxidants and micronutrients, might protect somatic as well as germ cells against age-associated genomic damage. Copyright © 2012. Published by Elsevier Inc.
MED-1985
Attained height of lacto-ovo vegetarian children and adolescents.
The relationship between diet and attained height was studied in children and adolescents in Southern California. Diet pattern was determined from an extensive food frequency questionnaire in 1765 Caucasian children of 7-18 years, attending state schools (452 m and 443 f) and Seventh-day Adventist schools (427 m and 443 f). The major difference in diet pattern between state and Adventist school children was in meat consumption. The Adventist children were split evenly between three categories of frequency in meat consumption (less than 1/week, 1/week-less than 1/d, and greater than or equal to 1/d), while 92 percent of state school children consumed meat daily. Vegetarians (those consuming meat less than 1/week) differed significantly in the consumption of other major food groups, such as fruit and vegetables. All school and diet subgroups were at or above the 50th percentile of the National Center for Health Statistics. Age-adjusted regression analysis showed that on average Adventist vegetarian children were taller than their meat-consuming classmates (2.5 and 2.0 cm for boys and girls, respectively). These results did not change materially when adjusting for other food groups. Nor did adjustment for parental height and socioeconomic factors in a sub-sample of 518 children. The results indicate that vegetarian children and adolescents on a balanced diet grow at least as tall as children who consume meat.
MED-4745
Dietary protein intake throughout childhood is associated with the timing of puberty.
Early puberty onset is associated with hormone-related cancers, but whether diet in childhood influences pubertal timing is controversial. We examined the association of protein intake in early and mid-childhood with the ages at take-off of the pubertal growth spurt (ATO), peak height velocity (APHV), and menarche in girls and voice break in boys using data from the longitudinal Dortmund Nutritional and Anthropometric Longitudinally Designed Study. Among participants who provided 3-d weighed dietary records at 12 mo, 18-24 mo, 3-4 y, and 5-6 y, 112 had sufficient anthropometric measurements between 6 and 13 y to allow estimation of ATO. Life-course plots were used to identify critical periods of total, animal, and vegetable protein intake (percentage of total energy intake) for pubertal timing. At these ages, the association between tertiles of protein intake (T1-T3) and the outcomes was investigated using multiple linear regression analysis. A higher total and animal protein intake at 5-6 y was related to an earlier ATO. In the highest tertile of animal protein intake at 5-6 y, ATO occurred 0.6 y earlier than in the lowest [(mean, 95% CI) T1: 9.6, 9.4-9.9 vs. T2: 9.4, 9.1-9.7 vs. T3: 9.0, 8.7-9.3 y; P-trend = 0.003, adjusted for sex, total energy, breast-feeding, birth year, and paternal university degree]. Similar findings were seen for APHV (P-trend = 0.001) and the timing of menarche/voice break (P-trend = 0.02). Conversely, a higher vegetable protein intake at 3-4 and 5-6 y was related to later ATO, APHV, and menarche/voice break (P-trend = 0.02-0.04). These results suggest that animal and vegetable protein intake in mid-childhood might be differentially related to pubertal timing.
MED-5053
Artificial sweetener consumption and urinary tract tumors in Cordoba, Argentina.
OBJECTIVE: To determine the role of the habitual use of the most common artificial sweeteners (AS) in the development of urinary tract tumors (UTT) in Argentina. METHODS: Case-control study of 197 patients with histologically confirmed UTT of transitional varieties, and 397 controls with acute, non-neoplastic, and non-urinary tract diseases, admitted to the same hospitals in Córdoba (Argentina) between 1999 and 2006. All subjects were interviewed about their use of AS and their exposure to other known or suspected risk factors for UTT. RESULTS: Fifty-one UTT patients (26%) and 87 controls (22%) used AS. The risk of UTT was significantly increased in long-term (> or =10 years) AS users compared with none-AS users. The OR (95% CI) for long-term consumers was 2.18 (1.22-3.89) and for short-term users was 1.10 (0.61-2.00) after adjustment for age, gender, BMI, social status. and years of tobacco use. CONCLUSION: Regular use of AS for 10 years or more was positively associated with UTT.
MED-3320
Industrial hygiene assessment of reticuloendotheliosis viruses exposure in the poultry industry.
OBJECTIVES: Reticuloendotheliosis viruses (REV) are a group of retroviruses like avian leukosis/sarcoma viruses (ALSV) that naturally infect and cause cancers in chickens. We recently found that ALSV antibody levels were associated with job tasks in the poultry industry. The objectives of this study are to examine whether a similar association can be found with REV antibody levels and to examine the correlation between REV and ALSV antibody levels. METHODS: Relative risk was estimated comparing REV antibody levels of 45 poultry workers with those of 44 controls. The expected mean antibody level was predicted for the association with employment by a generalized linear model. Correlation coefficient was measured between ALSV and REV antibody levels. RESULTS: REV antibody levels were significantly higher in poultry workers than in control subjects and were associated with gender and employment conditions, especially employment duration. The relative risk was significantly higher for some job categories. A significant correlation was observed between REV and ALSV antibody levels, which was strong among poultry workers, but weak among the control subjects. CONCLUSION: Antibody levels can be validly used to identify certain job tasks associated with high risk of exposure to REV in the workplace, and the practical implication is recommendations for protection at these job tasks. Importantly, in situations where there is exposure to multiple pathogens in the workplace, the analysis of antibody levels of one pathogen may sufficiently represent exposure to the other correlated pathogens. This suggested exposure assessment may hold true for pathogens with a similar route of transmission.
MED-5145
Comparative fracture risk in vegetarians and nonvegetarians in EPIC-Oxford.
OBJECTIVE: To compare fracture rates in four diet groups (meat eaters, fish eaters, vegetarians and vegans) in the Oxford cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Oxford). DESIGN: Prospective cohort study of self-reported fracture risk at follow-up. SETTING: The United Kingdom. SUBJECTS: A total of 7947 men and 26,749 women aged 20-89 years, including 19,249 meat eaters, 4901 fish eaters, 9420 vegetarians and 1126 vegans, recruited by postal methods and through general practice surgeries. METHODS: Cox regression. RESULTS: Over an average of 5.2 years of follow-up, 343 men and 1555 women reported one or more fractures. Compared with meat eaters, fracture incidence rate ratios in men and women combined adjusted for sex, age and non-dietary factors were 1.01 (95% CI 0.88-1.17) for fish eaters, 1.00 (0.89-1.13) for vegetarians and 1.30 (1.02-1.66) for vegans. After further adjustment for dietary energy and calcium intake the incidence rate ratio among vegans compared with meat eaters was 1.15 (0.89-1.49). Among subjects consuming at least 525 mg/day calcium the corresponding incidence rate ratios were 1.05 (0.90-1.21) for fish eaters, 1.02 (0.90-1.15) for vegetarians and 1.00 (0.69-1.44) for vegans. CONCLUSIONS: In this population, fracture risk was similar for meat eaters, fish eaters and vegetarians. The higher fracture risk in the vegans appeared to be a consequence of their considerably lower mean calcium intake. An adequate calcium intake is essential for bone health, irrespective of dietary preferences. SPONSORSHIP: The EPIC-Oxford study is supported by The Medical Research Council and Cancer Research UK.
MED-1326
Prevalence of diabetes among men and women in China.
BACKGROUND: Because of the rapid change in lifestyle in China, there is concern that diabetes may become epidemic. We conducted a national study from June 2007 through May 2008 to estimate the prevalence of diabetes among Chinese adults. METHODS: A nationally representative sample of 46,239 adults, 20 years of age or older, from 14 provinces and municipalities participated in the study. After an overnight fast, participants underwent an oral glucose-tolerance test, and fasting and 2-hour glucose levels were measured to identify undiagnosed diabetes and prediabetes (i.e., impaired fasting glucose or impaired glucose tolerance). Previously diagnosed diabetes was determined on the basis of self-report. RESULTS: The age-standardized prevalences of total diabetes (which included both previously diagnosed diabetes and previously undiagnosed diabetes) and prediabetes were 9.7% (10.6% among men and 8.8% among women) and 15.5% (16.1% among men and 14.9% among women), respectively, accounting for 92.4 million adults with diabetes (50.2 million men and 42.2 million women) and 148.2 million adults with prediabetes (76.1 million men and 72.1 million women). The prevalence of diabetes increased with increasing age (3.2%, 11.5%, and 20.4% among persons who were 20 to 39, 40 to 59, and > or = 60 years of age, respectively) and with increasing weight (4.5%, 7.6%, 12.8%, and 18.5% among persons with a body-mass index [the weight in kilograms divided by the square of the height in meters] of < 18.5, 18.5 to 24.9, 25.0 to 29.9, and > or = 30.0, respectively). The prevalence of diabetes was higher among urban residents than among rural residents (11.4% vs. 8.2%). The prevalence of isolated impaired glucose tolerance was higher than that of isolated impaired fasting glucose (11.0% vs. 3.2% among men and 10.9% vs. 2.2% among women). CONCLUSIONS: These results indicate that diabetes has become a major public health problem in China and that strategies aimed at the prevention and treatment of diabetes are needed. 2010 Massachusetts Medical Society
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-1669
The effect of two energy-restricted diets, a low-fructose diet versus a moderate natural fructose diet, on weight loss and metabolic syndrome param...
One of the proposed causes of obesity and metabolic syndrome is the excessive intake of products containing added sugars, in particular, fructose. Although the ability of excessive intake of fructose to induce metabolic syndrome is mounting, to date, no study has addressed whether a diet specifically lowering fructose but not total carbohydrates can reduce features of metabolic syndrome. A total of 131 patients were randomized to compare the short-term effects of 2 energy-restricted diets-a low-fructose diet vs a moderate natural fructose diet-on weight loss and metabolic syndrome parameters. Patients were randomized to receive 1500, 1800, or 2000 cal diets according to sex, age, and height. Because natural fructose might be differently absorbed compared with fructose from added sugars, we randomized obese subjects to either a low-fructose diet (<20 g/d) or a moderate-fructose diet with natural fruit supplements (50-70 g/d) and compared the effects of both diets on the primary outcome of weight loss in a 6-week follow-up period. Blood pressure, lipid profile, serum glucose, insulin resistance, uric acid, soluble intercellular adhesion molecule-1, and quality of life scores were included as secondary outcomes. One hundred two (78%) of the 131 participants were women, mean age was 38.8 ± 8.8 years, and the mean body mass index was 32.4 ± 4.5 kg/m(2). Each intervention diet was associated with significant weight loss compared with baseline. Weight loss was higher in the moderate natural fructose group (4.19 ± 0.30 kg) than the low-fructose group (2.83 ± 0.29 kg) (P = .0016). Compared with baseline, each intervention diet was associated with significant improvement in secondary outcomes. Reduction of energy and added fructose intake may represent an important therapeutic target to reduce the frequency of obesity and diabetes. For weight loss achievement, an energy-restricted moderate natural fructose diet was superior to a low-fructose diet. Copyright © 2011 Elsevier Inc. All rights reserved.
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-2134
mTOR and cancer therapy.
Proteins regulating the mammalian target of rapamycin (mTOR), as well as some of the targets of the mTOR kinase, are overexpressed or mutated in cancer. Rapamycin, the naturally occurring inhibitor of mTOR, along with a number of recently developed rapamycin analogs (rapalogs) consisting of synthetically derived compounds containing minor chemical modifications to the parent structure, inhibit the growth of cell lines derived from multiple tumor types in vitro, and tumor models in vivo. Results from clinical trials indicate that the rapalogs may be useful for the treatment of subsets of certain types of cancer. The sporadic responses from the initial clinical trials, based on the hypothesis of general translation inhibition of cancer cells are now beginning to be understood owing to a more complete understanding of the dynamics of mTOR regulation and the function of mTOR in the tumor microenvironment. This review will summarize the preclinical and clinical data and recent discoveries of the function of mTOR in cancer and growth regulation.
MED-3127
Study on soy isoflavone consumption and risk of breast cancer and survival.
AIM: Isoflavones in soy foods are part of a larger class of flayonoid compounds that have have been demonstrated to be potent dietary anti-cancer agents, and the effect of soy intake on the survival of ovarian cancer is conflicting. Therefore, we aimed to explore the whether soy intake is related to the risk of death of breast cancer. METHODS: A prospective study was conducted. A total of 256 patients included in this study had breast cancer and were recruited between January 2004 and January 2006. All of them were followed up from since January 2011. A univariate Cox's regression analysis was used to assess the association between soy intake and survival. RESULTS: The education level, menopausal status, ER/PR status and TNM stage were significant difference in the survival of breast cancer. The highest soy isoflavone was associated with a decreased death risk of breast cancer (OR=0.25, 95% CI=0.09-0.54). Moreover, the higher consumption of soy protein also presented a trend decreased breast cancer risk, and the highest consumption significantly reduced the cancer risk compared with the lowest consumption (OR=0.38, 95% CI=0.17-0.86). CONCLUSION: The present study suggests soy intake is associated with a significant reduced death risk of breast cancer in Chinese population. Further large sample studies are warranted to confirm the inverse association of soy consumption and breast cancer survival by menopausal status.
MED-3806
Toxicology of nutmeg abuse.
BACKGROUND: Unpleasant and frightening side effects associated with the abuse of nutmeg occasionally generate emergency department referrals. We report a young patient's first-time experience with nutmeg and review the mechanisms of its toxicity. CASE REPORT: A 13-year-old female ingested 15-24 g of nutmeg over a 3-hour period and smoked and shared 2 joints of marijuana. To facilitate ingestion, the nutmeg was put into 00-000 gelatin capsules. Bizarre behavior and visual, auditory, and tactile hallucinations developed. She also experienced nausea, gagging, hot/cold sensations, and blurred vision followed by numbness, double, and "triple" vision, headache, and drowsiness. Nystagmus, muscle weakness, and ataxia were present. Her vital signs and laboratory tests were normal. She received 50 g of activated charcoal and except for complaints of dizziness and visual changes, her 2-day admission was uneventful. The central nervous system activity of nutmeg is often postulated to result from biotransformation of its chemical components to amphetamine-like compounds, but this has not been proven. Nutmeg contains several compounds with structural similarities to substances with known central nervous system neuromodulatory activity.
MED-4463
Phenethyl isothiocyanate sensitizes human cervical cancer cells to apoptosis induced by cisplatin
Naturally-occurring chemopreventive agent phenethyl isothiocyanate (PEITC), derived primarily from watercress, has been shown to inhibit cell growth and induce apoptosis in cancer cells. In this study, we examined the potential of PEITC in enhancing cisplatin-induced apoptosis in cervical cancer cells. HeLa cells were exposed to PEITC, cisplatin or both. Pretreatment of cells with PEITC strongly enhanced cisplatin-induced cytotoxicity. PEITC activated the mitogen-activated protein kinases, including JNK, ERK, and p38. The synergistic induction of apoptosis was significantly attenuated by MEK1/2 inhibitor U0126, but not by JNK or p38 inhibitor, suggesting that ERK activation is responsible for the synergistic effect. We found that NF-κB signaling pathway is not involved in the synergistic effect. Sulforaphane and benzyl isothiocyanate, two other members of the isothiocyanate family, also sensitize HeLa cells to apoptosis induced by cisplatin. Furthermore, we found that the synergistic effect was not seen in normal cells. Finally, we demonstrated that Noxa induction was associated with apoptosis induced by PEITC plus cisplatin. Taken together, this study shows that PEITC can sensitize cancer cells to apoptosis induced by cisplatin and this effect is mediated through ERK activation, suggesting the potential of PEITC to be used as an adjuvant with cisplatin in combination therapeutic treatments.
MED-4671
Saffron in the treatment of patients with mild to moderate Alzheimer's disease: a 16-week, randomized and placebo-controlled trial.
WHAT IS KNOWN: Herbal medicines have been used in the treatment of behavioural and psychological symptoms of dementia but with variable response. Crocus sativus (saffron) may inhibit the aggregation and deposition of amyloid β in the human brain and may therefore be useful in Alzheimer's disease (AD). OBJECTIVE: The goal of this study was to assess the efficacy of saffron in the treatment of mild to moderate AD. METHODS: Forty-six patients with probable AD were screened for a 16-week, double-blind study of parallel groups of patients with mild to moderate AD. The psychometric measures, which included AD assessment scale-cognitive subscale (ADAS-cog), and clinical dementia rating scale-sums of boxes, were performed to monitor the global cognitive and clinical profiles of the patients. Patients were randomly assigned to receive capsule saffron 30 mg/day (15 mg twice per day) (Group A) or capsule placebo (two capsules per day) for a 16-week study. RESULTS: After 16 weeks, saffron produced a significantly better outcome on cognitive function than placebo (ADAS-cog: F=4·12, d.f.=1, P=0·04; CDR: F=4·12, d.f.=1, P=0·04). There were no significant differences in the two groups in terms of observed adverse events. WHAT IS NEW AND CONCLUSION: This double-blind, placebo-controlled study suggests that at least in the short-term, saffron is both safe and effective in mild to moderate AD. Larger confirmatory randomized controlled trials are called for. Copyright © 2010 The Authors. JCPT © 2010 Blackwell Publishing Ltd.
MED-5071
Identification of anthocyanins in the liver, eye, and brain of blueberry-fed pigs.
Dietary intervention with anthocyanins may confer benefits in brain function, including vision. Research to date indicates that animals have only a limited capacity to absorb anthocyanins, compared to other types of flavonoids. Pigs, which are a suitable model for human digestive absorption, were used to examine the deposition of anthocyanins in tissues including the liver, eye, and brain tissue. Pigs were fed diets supplemented with 0, 1, 2, or 4% w/w blueberries ( Vaccinium corymbosum L. 'Jersey') for 4 weeks. Prior to euthanasia, pigs were fasted for 18-21 h. Although no anthocyanins were detected in the plasma or urine of the fasted animals, intact anthocyanins were detected in all tissues where they were sought. LC-MS/MS results are presented for the relative concentration of 11 intact anthocyanins in the liver, eye, cortex, and cerebellum. The results suggest that anthocyanins can accumulate in tissues, including tissues beyond the blood-brain barrier.
MED-5110
Applying morphologic techniques to evaluate hotdogs: what is in the hotdogs we eat?
Americans consume billions of hotdogs per year resulting in more than a billion dollars in retail sales. Package labels typically list some type of meat as the primary ingredient. The purpose of this study is to assess the meat and water content of several hotdog brands to determine if the package labels are accurate. Eight brands of hotdogs were evaluated for water content by weight. A variety of routine techniques in surgical pathology including routine light microscopy with hematoxylin-eosin-stained sections, special staining, immunohistochemistry, and electron microscopy were used to assess for meat content and for other recognizable components. Package labels indicated that the top-listed ingredient in all 8 brands was meat; the second listed ingredient was water (n = 6) and another type of meat (n = 2). Water comprised 44% to 69% (median, 57%) of the total weight. Meat content determined by microscopic cross-section analysis ranged from 2.9% to 21.2% (median, 5.7%). The cost per hotdog ($0.12-$0.42) roughly correlated with meat content. A variety of tissues were observed besides skeletal muscle including bone (n = 8), collagen (n = 8), blood vessels (n = 8), plant material (n = 8), peripheral nerve (n = 7), adipose (n = 5), cartilage (n = 4), and skin (n = 1). Glial fibrillary acidic protein immunostaining was not observed in any of the hotdogs. Lipid content on oil red O staining was graded as moderate in 3 hotdogs and marked in 5 hotdogs. Electron microscopy showed recognizable skeletal muscle with evidence of degenerative changes. In conclusion, hotdog ingredient labels are misleading; most brands are more than 50% water by weight. The amount of meat (skeletal muscle) in most brands comprised less than 10% of the cross-sectional surface area. More expensive brands generally had more meat. All hotdogs contained other tissue types (bone and cartilage) not related to skeletal muscle; brain tissue was not present.
MED-3598
A prospective study of intake of trans-fatty acids from ruminant fat, partially hydrogenated vegetable oils, and marine oils and mortality from CVD.
Trans-fatty acids (TFA) have adverse effects on blood lipids, but whether TFA from different sources are associated with risk of CVD remains unresolved. The objective of the present study was to evaluate the association between TFA intake from partially hydrogenated vegetable oils (PHVO), partially hydrogenated fish oils (PHFO) and ruminant fat (rTFA) and risks of death of CVD, CHD, cerebrovascular diseases and sudden death in the Norwegian Counties Study, a population-based cohort study. Between 1974 and 1988, participants were examined for up to three times. Fat intake was assessed with a semi-quantitative FFQ. A total of 71,464 men and women were followed up through 2007. Hazard ratios (HR) and 95 % CI were estimated with Cox regression. Energy from TFA was compared to energy from all other sources, carbohydrates or unsaturated cis-fatty acids with different multivariable models. During follow-up, 3870 subjects died of CVD, 2383 of CHD, 732 of cerebrovascular diseases and 243 of sudden death. Significant risks, comparing highest to lowest intake category, were found for: TFA from PHVO and CHD (HR 1.23 (95 % CI 1.00, 1.50)) and cerebrovascular diseases (HR 0.65 (95 % CI 0.45, 0.94)); TFA from PHFO and CVD (HR 1.14 (95 % CI 1.03, 1.26)) and cerebrovascular diseases (HR 1.32 (95 % CI 1.04, 1.69)); and rTFA intake and CVD (HR 1.30 (95 % CI 1.05, 1.61)), CHD (HR 1.50 (95 % CI 1.11, 2.03)) and sudden death (HR 2.73 (95 % CI 1.19, 6.25)) in women. These associations with rTFA intake were not significant in men (P interaction ≥ 0.01). The present study supports that TFA intake, irrespective of source, increases CVD risk. Whether TFA from PHVO decreases risk of cerebrovascular diseases warrants further investigation.
MED-5360
Fruit, Vegetable and Antioxidant Intakes are Lower in Older Adults with Depression
Studies have shown an association between depression and both antioxidant levels and oxidant stress, but generally have not included intakes of antioxidants and antioxidant-rich fruits and vegetables. The present study examined the cross-sectional associations between clinically-diagnosed depression and intakes of antioxidants, fruits and vegetables in a cohort of older adults. Antioxidant, fruit and vegetable intakes were assessed in 278 elderly participants (144 with depression, 134 without depression) using a Block 1998 food frequency questionnaire, which was administered between 1999 and 2007. All participants were age 60 years or over. Vitamin C, lutein and cryptoxanthin intakes were significantly lower among depressed individuals than in comparison participants (p<0.05). In addition, fruit and vegetable consumption, a primary determinant of antioxidant intake, was lower in depressed individuals. In multivariable models, controlling for age, sex, education, vascular comorbidity score, body mass index, total dietary fat, and alcohol, vitamin C, cryptoxanthin, fruits and vegetables remained significant. Antioxidants from dietary supplements were not associated with depression. Antioxidant, fruit and vegetable intakes were lower in individuals with late-life depression than in comparison participants. These associations may partially explain the elevated risk of cardiovascular disease among older depressed individuals. In addition, these findings point to the importance of antioxidant food sources rather than dietary supplements.
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-1593
Oestrogen levels in serum and urine of premenopausal women eating low and high amounts of meat.
OBJECTIVE: Based on the hypothesis that high-meat diets may increase breast cancer risk through hormonal pathways, the present analysis compared oestrogens in serum and urine by meat-eating status. DESIGN: Intervention with repeated measures. SETTING: Two randomized soya trials (BEAN1 and BEAN2) among premenopausal healthy women. SUBJECTS: BEAN1 participants completed seven unannounced 24 h dietary recalls and donated five blood and urine samples over 2 years. BEAN2 women provided seven recalls and three samples over 13 months. Serum samples were analysed for oestrone (E₁) and oestradiol (E₂) using RIA. Nine oestrogen metabolites were measured in urine by LC-MS. Semi-vegetarians included women who reported consuming <30 g of red meat, poultry and fish daily, and pescatarians those who reported consuming <20 g of meat/poultry but >10 g of fish daily. All other women were classified as non-vegetarians. We applied mixed models to compute least-square means by vegetarian status adjusted for potential confounders. RESULTS: The mean age of the 272 participants was 41·9 (SD 4·5) years. Serum E₁ (85 v. 100 pg/ml, P = 0·04) and E₂ (140 v. 154 pg/ml, P = 0·04) levels were lower in the thirty-seven semi-vegetarians than in the 235 non-vegetarians. The sum of the nine urinary oestrogen metabolites (183 v. 200 pmol/mg creatinine, P = 0·27) and the proportions of individual oestrogens and pathways did not differ by meat-eating status. Restricting the models to the samples collected during the luteal phase strengthened the associations. CONCLUSIONS: Given the limitations of the study, the lower levels of serum oestrogens in semi-vegetarians than non-vegetarians need confirmation in larger populations.
MED-4876
Cyanobacterial neurotoxin BMAA in ALS and Alzheimer's disease.
OBJECTIVE: The aim of this study was to screen for and quantify the neurotoxic amino acid beta-N-methylamino-L-alanine (BMAA) in a cohort of autopsy specimens taken from Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and non-neurological controls. BMAA is produced by cyanobacteria found in a variety of freshwater, marine, and terrestrial habitats. The possibility of geographically broad human exposure to BMAA had been suggested by the discovery of BMAA in brain tissues of Chamorro patients with ALS/Parkinsonism dementia complex from Guam and more recently in AD patients from North America. These observations warranted an independent study of possible BMAA exposures outside of the Guam ecosystem. METHODS: Postmortem brain specimens were taken from neuropathologically confirmed cases of 13 ALS, 12 AD, 8 HD patients, and 12 age-matched non-neurological controls. BMAA was quantified using a validated fluorescent HPLC method previously used to detect BMAA in patients from Guam. Tandem mass spectrometric (MS) analysis was carried out to confirm the identification of BMAA in neurological specimens. RESULTS: We detected and quantified BMAA in neuroproteins from postmortem brain tissue of patients from the United States who died with sporadic AD and ALS but not HD. Incidental detections observed in two out of the 24 regions were analyzed from the controls. The concentrations of BMAA were below what had been reported previously in Chamarro ALS/ Parkinsonism dementia complex patients, but demonstrated a twofold range across disease and regional brain area comparisons. The presence of BMAA in these patients was confirmed by triple quadrupole liquid chromatography/mass spectrometry/mass spectrometry. CONCLUSIONS: The occurrence of BMAA in North American ALS and AD patients suggests the possibility of a gene/environment interaction, with BMAA triggering neurodegeneration in vulnerable individuals. (c) 2009 The Authors Journal compilation (c) 2009 Blackwell Munksgaard.
MED-5003
Genistein inhibits differentiation of primary human adipocytes.
Genistein, a major soy isoflavone, has been reported to exhibit antiadipogenic and proapoptotic potential in vivo and in vitro. It is also a phytoestrogen which has high affinity to estrogen receptor beta. In this study, we determined the effect of genistein on adipogenesis and estrogen receptor (ER) alpha and beta expression during differentiation in primary human preadipocytes. Genistein inhibited lipid accumulation in a dose-dependent manner at concentrations of 6.25 microM and higher, with 50 microM genistein inhibiting lipid accumulation almost completely. Low concentrations of genistein (3.25 microM) increased cell viability and higher concentrations (25 and 50 microM) decreased it by 16.48+/-1.35% (P<.0001) and 50.68+/-1.34% (P<.0001). Oil Red O staining was used to confirm the effects on lipid accumulation. The inhibition of lipid accumulation was associated with inhibition of glycerol-3-phosphate dehydrogenase activity and down-regulation of expression of adipocyte-specific genes, including peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding protein alpha, glycerol-3-phosphate dehydrogenase, adipocyte fatty acid binding protein, fatty acid synthase, sterol regulatory element-binding protein 1, perilipin, leptin, lipoprotein lipase and hormone-sensitive lipase. These effects of genistein during the differentiation period were associated with down-regulation of ERalpha and ERbeta expression. This study adds to the elucidation of the molecular pathways involved in the inhibition of adipogenesis by phytoestrogens.
MED-4935
Polychlorinated naphthalenes in human adipose tissue from New York, USA.
Polychlorinated naphthalenes (PCNs) are persistent, bioaccumulative, and toxic contaminants. Prior to this study, the occurrence of PCNs in human adipose tissues from the USA has not been analyzed. Here, we have measured concentrations of PCNs in human adipose tissue samples collected in New York City during 2003-2005. Concentrations of PCNs were in the range of 61-2500pg/g lipid wt. in males and 21-910pg/g lipid wt. in females. PCN congeners 52/60 (1,2,3,5,7/1,2,4,6,7) and 66/67 (1,2,3,4,6,7/1,2,3,5,6,7) were predominant, collectively accounting for 66% of the total PCN concentrations. Concentrations of PCNs in human adipose tissues were 2-3 orders of magnitude lower than the previously reported concentrations of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). Concentrations of PCNs were not correlated with PCB concentrations. The contribution of PCNs to dioxin-like toxic equivalents (TEQs) in human adipose tissues was estimated to be <1% of the polychlorinated dibenzo-p-dioxin/dibenzofuran (PCDD/F)-TEQs.
MED-2658
Alkylphenols--potential modulators of the allergic response.
The prevalence of allergic diseases has increased in recent decades. Allergic diseases, particularly asthma, are complex diseases with strong gene-environment interactions. Epidemiological studies have identified a variety of risk factors for the development of allergic diseases. Among them, endocrine-disrupting chemicals (EDCs) play an important role in triggering or exacerbating these diseases. 4-Nonylphenol (NP) and 4-octylphenol (OP)--two major alkylphenols--have been recognized as common toxic and xenobiotic endocrine disrupters. Due to their low solubility, high hydrophobicity, and low estrogenic activity, they tend to accumulate in the human body and may be associated with the adverse effects of allergic diseases. Recently, new evidence has supported the importance of alkylphenols in the in vitro allergic response. This review focuses on the effects of alkylphenols on several key cell types in the context of allergic inflammation. Copyright © 2012. Published by Elsevier B.V.
MED-4890
Effect of diet and exercise intervention on the growth of prostate epithelial cells.
Epidemiological studies suggest a positive association between nutrient intake, hyperinsulinemia and risk of Benign prostatic hyperplasis (BPH). This study tests the hypothesis that a low-fat, high-fiber diet and daily exercise would lower serum insulin and reduce the growth of serum-stimulated primary prostate epithelial cells in culture. Serum samples were obtained from eight overweight men before and after the Pritikin residential, 2-week diet and exercise intervention and from seven men who were long-term followers of the low-fat, high-fiber diet and regular exercise lifestyle. The serum was used to stimulate primary prostate epithelial cells in culture. Growth was measured after 48 and 96 h and apoptosis after 96 h. At 48 h there was no significant difference in growth within the Pre, 2-week or Long-Term groups. At 96 h growth was significantly reduced in the 2-week (13%) and in the Long-Term (14%) groups compared to the Pre data. At 96 h, apoptosis was not significantly different among the three groups. Fasting insulin was reduced by 30% in the 2-week group and by 52% in the Long-Term group compared to the Pre data. Testosterone was unchanged in the 2-week group. The results of this study indicate that a low-fat, high-fiber diet and daily exercise lowers insulin and reduces growth of prostate primary epithelial cells and suggests that lifestyle may be an important factor in the development or progression of BPH. Future prospective trials should address the effects of this lifestyle modification on BPH symptomatology and progression.
MED-4439
A case of fatal caffeine poisoning.
Caffeine is a natural alkaloid methylxanthine that is found in various plants such as coffee or tea. Symptoms of a severe overdose may present with hypokalemia, hyponatremia, ventricular arrhythmias, hypertension followed by hypotension, respiratory failure, seizures, rhabdomyolysis, ventricular fibrillation and finally circulatory collapse. A 21-year-old woman called for the ambulance herself soon after the ingestion of about 10,000 mg of caffeine. At the arrival of the ambulance, the patient went into cardiac arrest almost immediately. After a total resuscitation period of 34 min including seven counter-shocks and 2 mg epinephrine, the patient was stable enough to be transferred to the hospital. The patient soon went into VF again and received two more counter-shocks and 1 mg epinephrine and finally an intravenous bolus dose of 300 mg amiodarone. The initial arterial blood gas showed pH at 6.47, lactate at 33 mmol/l and potassium level at 2.3 mmol/l. Unfortunately, no blood samples for caffeine analysis were taken. Three days after hospital admission, the patient developed myoclonus, which did not respond to medical treatment. Excessive intake of caffeine may produce arrhythmias and pronounced hypokalemia and ensuing ventricular fibrillation. In case of counter-shock-resistant VF, it can be necessary to give an early loading dose of amiodarone. Furthermore, it may be beneficial to replace the potassium as early as possible. Epinephrine and buffer solutions used during resuscitation may further decrease blood potassium levels and should be administrated cautiously. Epinephrine can be replaced by other vasopressor drugs, such as vasopressin without effects on beta-receptors.
MED-2513
Insights into the beneficial effect of caloric/ dietary restriction for a healthy and prolonged life
Over the last several years, new evidence has kept pouring in about the remarkable effect of caloric restriction (CR) on the conspicuous bedfellows- aging and cancer. Through the use of various animal models, it is now well established that by reducing calorie intake one can not only increase life span but, also, lower the risk of various age related diseases such as cancer. Cancer cells are believed to be more dependent on glycolysis for their energy requirements than normal cells and, therefore, can be easily targeted by alteration in the energy-metabolic pathways, a hallmark of CR. Apart from inhibiting the growth of transplantable tumors, CR has been also shown to inhibit the development of spontaneous, radiation, and chemically induced tumors. The question regarding the potentiality of the anti-tumor effect of CR in humans has been in part answered by the resistance of a cohort of women, who had suffered from anorexia in their early life, to breast cancer. However, human research on the beneficial effect of CR is still at an early stage and needs further validation. Though the complete mechanism of the anti-tumor effect of CR is far from clear, the plausible involvement of nutrient sensing pathways or IGF-1 pathways proposed for its anti-aging action cannot be overruled. In fact, cancer cell lines, mutant for proteins involved in IGF-1 pathways, failed to respond to CR. In addition, CR decreases the levels of many growth factors, anabolic hormones, inflammatory cytokines, and oxidative markers that are deregulated in several cancers. In this review, we discuss the anti-tumor effect of CR, describing experiments done in vitro in tumor models and in vivo in mouse models in which the tumor was induced by means of radiation or chemical exposure, expressing oncogenes or deleting tumor suppression genes. We also discuss the proposed mechanisms of CR anti-tumor action. Lastly, we argue the necessity of gene expression studies in cancerous versus normal cells upon CR.
MED-3792
Serum prolactin and oestradiol levels in women with cyclical mastalgia.
Basal serum prolactin and serum oestradiol-17-beta concentrations were measured four times during one menstrual cycle in 20 women with severe cyclical mastalgia and normal to slightly fibroadenotic breasts. A group of 10 normal women who had never experienced mastalgia served as controls. Basal serum prolactin was significantly elevated in patients compared to normals, although within the normal range. Serum oestradiol concentrations did not differ in the two groups and were also within the normal range. A significant positive correlation between oestradiol and prolactin was found in patients and normals, but with larger prolactin levels in patients. The results point towards a prolactin secretory hypersensitivity for oestradiol in patients with cyclical mastalgia. Prolactin is considered a central factor in the eliciting of cyclical mastalgia.
MED-2100
Cytological abnormalities in nipple aspirates of breast fluid from women with severe constipation.
The relation between epithelial dysplasia in nipple aspirates of breast fluid and frequency of bowel movements was studied in 1481 white women. There was a significant positive association with dysplasia (risk ratio 4.5; 95% confidence interval 1.9-11.9) in women reporting severe constipation, i.e., two or fewer bowel movements weekly, which was not seen in women reporting more than one bowel movement daily. Women who had one bowel movement daily or one every other day had increased risk ratios. Cytological abnormalities in breast epithelium associated with severe constipation may be relevant to studies of diet and breast disease since the intestinal flora has been reported to metabolism bile salts and oestrogens secreted by the liver into the gastrointestinal tract-a process which may be enhanced by severe constipation.
MED-3508
Gastrointestinal infections and the development of irritable bowel syndrome.
PURPOSE OF REVIEW: Approximately 10% of the millions of persons with functional gastrointestinal disorders (FGDs) including irritable bowel syndrome (IBS) had their illness onset following an acute bout of infectious diarrhea and are referred to as having postinfectious (PI) FGD or PI-IBS. Recent studies have helped to identify the pathogenesis and natural history of these disorders. RECENT FINDINGS: Groups of patients with acute diarrhea or dysentery (passage of grossly bloody stools) are being followed for development of PI-IBS. Persistent mucosal inflammation, air trapping in the gut, and alteration of intestinal motility contribute to the disease symptoms in genetically susceptible persons. The prognosis of postinfectious forms of IBS is more favorable compared with people with idiopathic forms of the disorder. SUMMARY: With full characterization of postdiarrhea forms of FGDs, we should be able to define the mechanisms of disease early in the course of chronic illness and to better understand the more common idiopathic forms of the disease. We are likely to identify specific alteration of gut pathophysiology in postinfectious FGDs and to then classify them not as a poorly characterized group of functional disorders but as specific gastrointestinal disorders.
MED-4160
Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized cont...
CONTEXT: Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain. OBJECTIVE: To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States. DESIGN: Estrogen plus progestin component of the Women's Health Initiative, a randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998. INTERVENTIONS: Participants received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102). MAIN OUTCOMES MEASURES: The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome. A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes. RESULTS: On May 31, 2002, after a mean of 5.2 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. This report includes data on the major clinical outcomes through April 30, 2002. Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total mortality, and 1.15 (1.03-1.28) for the global index. Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the global index was 19 per 10 000 person-years. CONCLUSIONS: Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women. All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.
MED-4860
Blueberry Supplementation Improves Memory in Older Adults
The prevalence of dementia is increasing with expansion of the older adult population. In the absence of effective therapy, preventive approaches are essential to address this public health problem. Blueberries contain polyphenolic compounds, most prominently anthocyanins, which have antioxidant and anti-inflammatory effects. In addition, anthocyanins have been associated with increased neuronal signaling in brain centers mediating memory function as well as improved glucose disposal, benefits that would be expected to mitigate neurodegeneration. We investigated the effects of daily consumption of wild blueberry juice in a sample of nine older adults with early memory changes. At 12 weeks, we observed improved paired associate learning (p = 0.009) and word list recall (p = 0.04). In addition, there were trends suggesting reduced depressive symptoms (p = 0.08) and lower glucose levels (p = 0.10). We also compared the memory performances of the blueberry subjects with a demographically-matched sample who consumed a berry placebo beverage in a companion trial of identical design and observed comparable results for paired associate learning. The findings of this preliminary study suggest that moderate-term blueberry supplementation can confer neurocognitive benefit and establish a basis for more comprehensive human trials to study preventive potential and neuronal mechanisms.
MED-4778
Inhibitory effect of tea polyphenols on local tissue damage induced by snake venoms.
The methanolic extract of fresh tea leaves of Camellia sinensis L. (Theaceae) (CS) was assayed for its potential to inhibit enzymes with hydrolytic activity in Naja naja kaouthia Lesson (Elapidae) and Calloselasma rhodostoma Kuhl (Viperidae) venoms. These snake venom enzymes are responsible for the early effects of envenomation, such as local tissue damage and inflammation. The CS extract inhibited phospholipase A(2), proteases, hyaluronidase and L-amino acid oxidase in both venoms by in vitro neutralization and inhibited the hemorrhagic and the dermonecrotic activities of the venoms in vivo. It is suggested that the inhibitory potential of the CS extract against local tissue damage induced by snake venoms may be attributed to complexation and chelation between the venom proteins and the phenolic contents of the extract.
MED-2097
Nutritional intervention in patients with periodontal disease: clinical, immunological and microbiological variables during 12 months.
The role of nutrition in onset, progression and treatment of periodontitis has not been thoroughly evaluated. In the present prospective clinical study, we investigated the influence of a nutritional intervention on changes in clinical, microbiological and immunological periodontal variables during a period of 12 months in patients with the metabolic syndrome and chronic periodontitis. Twenty female subjects with the metabolic syndrome and mild to moderate chronic periodontitis participated in a guided nutritional intervention programme. Examinations were assessed before, and at 2 weeks, 3, 6 and 12 months after intervention. Clinical measurements included probing depth, Löe and Silness gingival index and Quigley-Hein plaque index. In gingival crevicular fluid, periodontopathogens, levels of IL-1beta and IL-6 as well as the activity of granulocyte elastase were determined. In stimulated saliva, antioxidative and oxidative variables were measured. After 12 months the following significant changes could be observed: reduction of clinical probing depth (2.40 v. 2.20 mm; P < 0.001), reduction of gingival inflammation (gingival index 1.13 v. 0.9; P < 0.001), reduced concentrations of IL-1beta (4.63 v. 1.10 pg/ml per site; P < 0.001) as well as IL-6 (1.85 v. 0.34 pg/ml per site; P = 0.022) in gingival crevicular fluid. Bacterial counts in gingival crevicular fluid as well as oxidative and antioxidative variables in saliva showed no significant changes. Only salivary catalase showed a tendency to lower values. These findings indicate that in patients with the metabolic syndrome wholesome nutrition might reduce inflammatory variables of periodontal disease and promote periodontal health.
MED-4173
Chronic disease and infant nutrition: is it significant to public health?
OBJECTIVE: To assess the public health significance of premature weaning of infants from breast milk on later-life risk of chronic illness. DESIGN: A review and summary of recent meta-analyses of studies linking premature weaning from breast milk with later-life chronic disease risk is presented followed by an estimation of the approximate exposure in a developed Western country, based on historical breast-feeding prevalence data for Australia since 1927. The population-attributable proportion of chronic disease associated with current patterns of artificial feeding in infancy is estimated. RESULTS: After adjustment for major confounding variables, current research suggests that the risks of chronic disease are 30-200 % higher in those who were not breast-fed compared to those who were breast-fed in infancy. Exposure to premature weaning ranges from 20 % to 90 % in post-World War II age cohorts. Overall, the attributable proportion of chronic disease in the population is estimated at 6-24 % for a 30 % exposure to premature weaning. CONCLUSIONS: Breast-feeding is of public health significance in preventing chronic disease. There is a small but consistent effect of premature weaning from breast milk in increasing later-life chronic disease risk. Risk exposure in the Australian population is substantial. Approximately 90 % of current 35-45-year-olds were weaned from breast-feeding by 6 months of age. Encouraging greater duration and exclusivity of breast-feeding is a potential avenue for reducing future chronic disease burden and health system costs.
MED-5249
Coffee and its consumption: benefits and risks.
Coffee is the leading worldwide beverage after water and its trade exceeds US $10 billion worldwide. Controversies regarding its benefits and risks still exist as reliable evidence is becoming available supporting its health promoting potential; however, some researchers have argued about the association of coffee consumption with cardiovascular complications and cancer insurgence. The health-promoting properties of coffee are often attributed to its rich phytochemistry, including caffeine, chlorogenic acid, caffeic acid, hydroxyhydroquinone (HHQ), etc. Many research investigations, epidemiological studies, and meta-analyses regarding coffee consumption revealed its inverse correlation with that of diabetes mellitus, various cancer lines, Parkinsonism, and Alzheimer's disease. Moreover, it ameliorates oxidative stress because of its ability to induce mRNA and protein expression, and mediates Nrf2-ARE pathway stimulation. Furthermore, caffeine and its metabolites help in proper cognitive functionality. Coffee lipid fraction containing cafestol and kahweol act as a safeguard against some malignant cells by modulating the detoxifying enzymes. On the other hand, their higher levels raise serum cholesterol, posing a possible threat to coronary health, for example, myocardial and cerebral infarction, insomnia, and cardiovascular complications. Caffeine also affects adenosine receptors and its withdrawal is accompanied with muscle fatigue and allied problems in those addicted to coffee. An array of evidence showed that pregnant women or those with postmenopausal problems should avoid excessive consumption of coffee because of its interference with oral contraceptives or postmenopausal hormones. This review article is an attempt to disseminate general information, health claims, and obviously the risk factors associated with coffee consumption to scientists, allied stakeholders, and certainly readers. © Taylor and Francis Group, LLC
MED-4901
Antioxidant status in humans after consumption of blackberry (Rubus fruticosus L.) juices with and without defatted milk.
The present study was designed to evaluate the possible effect of the consumption of blackberry juices (BJ) prepared with water (BJW) and defatted milk (BJM) on the plasma antioxidant capacity and the enzymatic and nonenzymatic antioxidants. A significant (p < 0.05) increase in the ascorbic acid content in the plasma was observed after intake of both BJs. However, no changes were observed in the plasma urate and alpha-tocopherol levels. An increase on the plasma antioxidant capacity, by ORAC assay, was observed only after consumption of BJW but not statistically significant. Plasma antioxidant capacity had a good positive correlation with ascorbic acid (r = 0.93) and a negative correlation with urate level (r = -0.79). No correlation was observed between antioxidant capacity and total cyanidin or total ellagic acid contents. Further, it was observed that plasma catalase increased following intake of BJ's. No change was observed on the plasma and erythrocyte CAT and glutathione peroxidase activities. A significant decrease (p < 0.05) in the urinary antioxidant capacity between 1 and 4 h after intake of both BJs was observed. A good correlation was observed between total antioxidant capacity and urate and total cyanidin levels. These results suggested association between anthocyanin levels and CAT and a good correlation between antioxidant capacity and ascorbic acid in the human plasma after intake of BJs. Follow-up studies investigating the antioxidant properties and health benefits are necessary to demonstrate the health benefits of polyphenols.
MED-4733
Mercury in human hair as an indicator of the fish consumption.
OBJECTIVES: Mercury and most of its compounds are extremely toxic and should be handled with care. It can be inhaled and absorbed through the skin and mucous membranes. The most toxic forms of mercury are its organic compounds such as dimethylmercury and methylmercury. Fish have a natural tendency to accumulate mercury. Methylmercury is produced by microbial methylation of inorganic mercury in water sediment then it infiltrates the food chain and it consequently accumulates in fish. Fish are the main source of methylmercury in human food. Mercury is transferred into a hair; and this can be than used to monitor the long-term exposure to mercury. The content of mercury in hair depends on the frequency of fish consumption. The aim of our study was to compare mercury content in the hair of children that had various amounts of fish consumption (increased or reduced). DESIGN: Total mercury content in hair was determined by direct method of cold vapors using an AMA 245 analyzer. A total of 174 hair samples from the children (9-17 years old) were analyzed. In this study, the following localities were compared: Neratovice (n=42), Jeseníky (n=44), Prague (n=59) in Czech Republic and Olsztyn in Poland (n=29). Every sample was accompanied with questionnaire about age, gender, regions, amalgam fillings and fish consumption. RESULTS: We did not find a correlation between the content of mercury in hair with age, gender or amalgam fillings. We did find a correlation between fish consumption and the amount of mercury found in the hair samples. CONCLUSION: The amount of mercury in hair increases with more frequent consumption of freshwater and marine fish.
MED-2570
In vitro investigations of the potential health benefits of Australian-grown faba beans (Vicia faba L.): chemopreventative capacity and inhibitory ...
The functional properties, including antioxidant and chemopreventative capacities as well as the inhibitory effects on angiotensin-converting enzyme (ACE), α-glucosidase and pancreatic lipase, of three Australian-grown faba bean genotypes (Nura, Rossa and TF(Ic*As)*483/13) were investigated using an array of in vitro assays. Chromatograms of on-line post column derivatisation assay coupled with HPLC revealed the existence of active phenolics (hump) in the coloured genotypes, which was lacking in the white-coloured breeding line, TF(Ic*As)*483/13. Roasting reduced the phenolic content, and diminished antioxidant activity by 10-40 % as measured by the reagent-based assays (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and oxygen radical absorbance capacity) in all genotypes. Cell culture-based antioxidant activity assay (cellular antioxidant activity) showed an increase of activity in the coloured genotypes after roasting. Faba bean extracts demonstrated cellular protection ability against H₂O₂-induced DNA damage (assessed using RAW264.7 cells), and inhibited the proliferation of all human cancer cell lines (BL13, AGS, Hep G2 and HT-29) evaluated. However, the effect of faba bean extracts on the non-transformed human cells (CCD-18Co) was negligible. Flow cytometric analyses showed that faba bean extracts successfully induced apoptosis of HL-60 (acute promyelocytic leukaemia) cells. The faba bean extracts also exhibited ACE, α-glucosidase and pancreatic lipase inhibitory activities. Overall, extracts from Nura (buff-coloured) and Rossa (red-coloured) were comparable, while TF(Ic*As)*483/13 (white-coloured) contained the lowest phenolic content and exhibited the least antioxidant and enzyme inhibition activities. These results are important to promote the utilisation of faba beans in human diets for various health benefits.
MED-3822
Cellulite: nature and aetiopathogenesis.
Only a limited number of studies on cellulite have been published in the international literature and many of them reach somewhat antithetical conclusions. Consequently, it is not yet possible to reconcile the extreme differences of opinion which have lingered on for years concerning the nature of this disorder, as well as its origin and even the most basic aspects of its histopathological classification. It does not even have a recognized name: in fact, the term 'cellulitis' is used in scientific English to indicate a spreading gangrenous infection of the subcutaneous cellular tissue. The other terms used from time to time [panniculitis, lipodystrophy, edematofibrosclerotic panniculitis (EFP), liposclerosis, lipoedema, etc.] have quite different morphological and pathogenetic connotations in general. Over the last few decades, three major conflicting theories have emerged in relation to the ethiopathogenesis of cellulite. These indicate, respectively, the following causes: 1. Oedema caused by excessive hydrophilia of the intercellular matrix. 2. A homeostatic alteration on a regional microcirculatory level; this pathogenetic theory is summarized in a synthetic and self-explanatory denomination: EFP. 3. A peculiar anatomical conformation of the subcutaneous tissue of women, different from male morphology. These theories must all now be updated in the light of recent advances on the sophisticated and composite physiopathology of the adipose organ - which acts not only as a control device which regulates the systematic equilibrium of energy and modulates the food intake and the metabolism of other tissue substrate through a multiple glandular secretion of hormones and parahormones.
MED-3559
Antioxidant-induced changes of the AP-1 transcription complex are paralleled by a selective suppression of human papillomavirus transcription.
Considering the involvement of a redox-regulatory pathway in the expression of human papillomaviruses (HPVs), HPV type 16 (HPV-16)-immortalized human keratinocytes were treated with the antioxidant pyrrolidine-dithiocarbamate (PDTC). PDTC induces elevated binding of the transcription factor AP-1 to its cognate recognition site within the viral regulatory region. Despite of increased AP-1 binding, normally indispensable for efficient HPV-16 transcription, viral gene expression was selectively suppressed at the level of initiation of transcription. Electrophoretic mobility supershift assays showed that the composition of the AP-1 complex, predominantly consisting of Jun homodimers in untreated cells, was altered. Irrespective of enhanced c-fos expression, c-jun was phosphorylated and became primarily heterodimerized with fra-1, which was also induced after PDTC incubation. Additionally, there was also an increased complex formation between c-jun and junB. Because both fra-1 and junB overexpression negatively interferes with c-jun/c-fos trans-activation of AP-1-responsive genes, our results suggest that the observed block in viral transcription is mainly the consequence of an antioxidant-induced reconstitution of the AP-1 transcription complex. Since expression of the c-jun/c-fos gene family is tightly regulated during cellular differentiation, defined reorganization of a central viral transcription factor may represent a novel mechanism controlling the transcription of pathogenic HPVs during keratinocyte differentiation and in the progression to cervical cancer.
MED-2596
Association of Nut Consumption with Total and Cause-Specific Mortality
BACKGROUND Increased nut consumption has been associated with a reduced risk of major chronic diseases, including cardiovascular disease and type 2 diabetes mellitus. However, the association between nut consumption and mortality remains unclear. METHODS We examined the association between nut consumption and subsequent total and cause-specific mortality among 76,464 women in the Nurses’ Health Study (1980–2010) and 42,498 men in the Health Professionals Follow-up Study (1986–2010). Participants with a history of cancer, heart disease, or stroke were excluded. Nut consumption was assessed at baseline and updated every 2 to 4 years. RESULTS During 3,038,853 person-years of follow-up, 16,200 women and 11,229 men died. Nut consumption was inversely associated with total mortality among both women and men, after adjustment for other known or suspected risk factors. The pooled multivariate hazard ratios for death among participants who ate nuts, as compared with those who did not, were 0.93 (95% confidence interval [CI], 0.90 to 0.96) for the consumption of nuts less than once per week, 0.89 (95% CI, 0.86 to 0.93) for once per week, 0.87 (95% CI, 0.83 to 0.90) for two to four times per week, 0.85 (95% CI, 0.79 to 0.91) for five or six times per week, and 0.80 (95% CI, 0.73 to 0.86) for seven or more times per week (P<0.001 for trend). Significant inverse associations were also observed between nut consumption and deaths due to cancer, heart disease, and respiratory disease. CONCLUSIONS In two large, independent cohorts of nurses and other health professionals, the frequency of nut consumption was inversely associated with total and cause-specific mortality, independently of other predictors of death. (Funded by the National Institutes of Health and the International Tree Nut Council Nutrition Research and Education Foundation.)
MED-706
The aqueous extract of Hibiscus sabdariffa calices modulates the production of monocyte chemoattractant protein-1 in humans.
Diet supplementation and/or modulation is an important strategy to significantly improve human health. The search of plants as additional sources of bioactive phenolic compounds is relevant in this context. The aqueous extract of Hibiscus sabdariffa is rich in anthocyanins and other phenolic compounds including hydroxycitric and chlorogenic acids. Using this extract we have shown an effective protection of cultured peripheral blood mononuclear cells from the cellular death induced by H(2)O(2) and a significant role in the production of inflammatory cytokines. In vitro, the extract promotes the production of IL-6 and IL-8 and decreases the concentration of MCP-1 in supernatants in a dose-dependent manner. In humans, the ingestion of an acute dose of the extract (10g) was well tolerated and decreased plasma MCP-1 concentrations significantly without further effects on other cytokines. This effect was not due to a concomitant increase in the antioxidant capacity of plasma. Instead, its mechanisms probably involve a direct inhibition of inflammatory and/or metabolic pathways responsible for MCP-1 production, and may be relevant in inflammatory and chronic conditions in which the role of MCP-1 is well established. If beneficial effects are confirmed in patients, Hibiscus sabdariffa could be considered a valuable traditional herbal medicine for the treatment of chronic inflammatory diseases with the advantage of being devoid of caloric value or potential alcohol toxicity. Copyright 2009 Elsevier GmbH. All rights reserved.
MED-4707
Prospective study of nut consumption, long-term weight change, and obesity risk in women
Background: Data concerning the long-term association between nut consumption and weight change in a free-living population are sparse. Objective: The objective was to determine the relation between nut consumption and long-term weight change. Design: The participants were 51,188 women in the Nurses' Health Study II aged 20–45 y, who had no cardiovascular disease, diabetes, or cancer. We prospectively evaluated the dietary intake of nuts and subsequent weight changes from 1991 to 1999. Results: Women who reported eating nuts ≥2 times/wk had slightly less mean (± SE) weight gain (5.04 ± 0.12 kg) than did women who rarely ate nuts (5.55 ± 0.04 kg) (P for trend < 0.001). For the same comparison, when total nut consumption was subdivided into peanuts and tree nuts, the results were similar (ie, less weight gain in women eating either peanuts or tree nuts ≥2 times/wk). The results were similar in normal-weight, overweight, and obese participants. In multivariate analyses in which lifestyle and other dietary factors were controlled for, we found that greater nut consumption (≥2 times/wk compared with never/almost never) was associated with a slightly lower risk of obesity (hazard ratio: 0.77; 95% CI: 0.57, 1.02; P for trend = 0.003). Conclusions: Higher nut consumption was not associated with greater body weight gain during 8 y of follow-up in healthy middle-aged women. Instead, it was associated with a slightly lower risk of weight gain and obesity. The results of this study suggest that incorporating nuts into diets does not lead to greater weight gain and may help weight control.
MED-4838
Cholesterol gallstone disease.
With a prevalence of 10-15% in adults in Europe and the USA, gallstones are the most common digestive disease needing admission to hospital in the West. The interplay between interprandial and postprandial physiological responses to endogenous and dietary lipids underscores the importance of coordinated hepatobiliary and gastrointestinal functions to prevent crystallisation and precipitation of excess biliary cholesterol. Indeed, identifying the metabolic and transcriptional pathways that drive the regulation of biliary lipid secretion has been a major achievement in the field. We highlight scientific advances in protein and gene regulation of cholesterol absorption, synthesis, and catabolism, and biliary lipid secretion with respect to the pathogenesis of cholesterol gallstone disease. We discuss the physical-chemical mechanisms of gallstone formation in bile and the active role of the gallbladder and the intestine. We also discuss gaps in our knowledge of the pathogenesis of gallstone formation and the potential for gene targeting in therapy.
MED-5054
The potential toxicity of artificial sweeteners.
Since their discovery, the safety of artificial sweeteners has been controversial. Artificial sweeteners provide the sweetness of sugar without the calories. As public health attention has turned to reversing the obesity epidemic in the United States, more individuals of all ages are choosing to use these products. These choices may be beneficial for those who cannot tolerate sugar in their diets (e.g., diabetics). However, scientists disagree about the relationships between sweeteners and lymphomas, leukemias, cancers of the bladder and brain, chronic fatigue syndrome, Parkinson's disease, Alzheimer's disease, multiple sclerosis, autism, and systemic lupus. Recently these substances have received increased attention due to their effects on glucose regulation. Occupational health nurses need accurate and timely information to counsel individuals regarding the use of these substances. This article provides an overview of types of artificial sweeteners, sweetener history, chemical structure, biological fate, physiological effects, published animal and human studies, and current standards and regulations.
MED-4174
Perfluorooctanesulfonate and related fluorochemicals in human blood from several countries.
Perfluorooctanesulfonyl fluoride based compounds have been used in a wide variety of consumer products, such as carpets, upholstery, and textiles. These compounds degrade to perfluorooctanesulfonate (PFOS), a persistent metabolite that accumulates in tissues of humans and wildlife. Previous studies have reported the occurrence of PFOS, perfluorohexanesulfonate (PFHxS), perfluorooctanoate (PFOA), and perfluorooctanesulfonamide (PFOSA) in human sera collected from the United States. In this study, concentrations of PFOS, PFHxS, PFOA, and PFOSA were measured in 473 human blood/serum/plasma samples collected from the United States, Colombia, Brazil, Belgium, Italy, Poland, India, Malaysia, and Korea. Among the four perfluorochemicals measured, PFOS was the predominant compound found in blood. Concentrations of PFOS were the highest in the samples collected from the United States and Poland (>30 ng/mL); moderate in Korea, Belgium, Malaysia, Brazil, Italy, and Colombia (3 to 29 ng/mL); and lowest in India (<3 ng/mL). PFOA was the next most abundant perfluorochemical in blood samples, although the frequency of occurrence of this compound was relatively low. No age- or gender-related differences in the concentrations of PFOS and PFOA were found in serum samples. The degree of association between the concentrations of four perfluorochemicals varied, depending on the origin of the samples. These results suggested the existence of sources with varying levels and compositions of perfluorochemicals, and differences in exposure patterns to these chemicals, in various countries. In addition to the four target fluorochemicals measured, qualitative analysis of selected blood samples showed the presence of other perfluorochemicals such as perfluorodecanesulfonate (PFDS), perfluoroheptanoic acid (PFHpA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorododecanoic acid (PFDoA), and perfluoroundecanoic acid (PFUnDA) in serum samples, at concentrations approximately 5- to 10-fold lower than the concentration of PFOS. Further studies should focus on identifying sources and pathways of human exposure to perfluorochemicals.
MED-4830
Statin therapy induces ultrastructural damage in skeletal muscle in patients without myalgia.
Muscle pain and weakness are frequent complaints in patients receiving 3-hydroxymethylglutaryl coenzymeA (HMG CoA) reductase inhibitors (statins). Many patients with myalgia have creatine kinase levels that are either normal or only marginally elevated, and no obvious structural defects have been reported in patients with myalgia only. To investigate further the mechanism that mediates statin-induced skeletal muscle damage, skeletal muscle biopsies from statin-treated and non-statin-treated patients were examined using both electron microscopy and biochemical approaches. The present paper reports clear evidence of skeletal muscle damage in statin-treated patients, despite their being asymptomatic. Though the degree of overall damage is slight, it has a characteristic pattern that includes breakdown of the T-tubular system and subsarcolemmal rupture. These characteristic structural abnormalities observed in the statin-treated patients were reproduced by extraction of cholesterol from skeletal muscle fibres in vitro. These findings support the hypothesis that statin-induced cholesterol lowering per se contributes to myocyte damage and suggest further that it is the specific lipid/protein organization of the skeletal muscle cell itself that renders it particularly vulnerable. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
MED-1778
Dairy intake and semen quality among men attending a fertility clinic
Objective To examine the relationship between dairy food intake and semen parameters Design Longitudinal study Setting Men attending academic medical center fertility clinic in Boston, MA Patients 155 men Interventions None Main Outcome Measures total sperm count, sperm concentration, progressive motility, and morphology Results Low-fat dairy intake was positively related to sperm concentration and progressive motility. On average, men in the highest quartile of intake (1.22–3.54 servings/day) had 33% (95% confidence interval (CI) 1, 55) higher sperm concentration and 9.3 (95%CI 1.4, 17.2) percentage units higher sperm motility than men in the lowest quartile of intake (≤0.28 servings/day). These associations were primarily explained by intake of low-fat milk. The corresponding results for low-fat milk were 30% (95%CI 1,51) higher sperm concentration and 8.7 (95%CI 3.0, 14.4) percentage units higher sperm motility. Cheese intake was associated with lower sperm concentration among ever smokers. In this group, men in the highest tertile of intake (0.82–2.43 servings/day) had 53.2% (95%CI 9.7, 75.7) lower sperm concentration than men in the lowest tertile of cheese intake (<0.43 servings/day). Conclusions Our findings suggest that low-fat dairy intake, particularly low-fat milk, is related to higher sperm concentration and progressive motility, while cheese intake to lower sperm concentration among past or current smokers.
MED-2092
Cytotoxicity of Mouthrinses on Epithelial Cells by Micronucleus Test
Objectives To determine the cytotoxicity of three commercial mouthrinses Klorhex, Andorex and Tanflex on buccal epithelial cells using micronucleus (MN) test. Materials and Methods 28 patients with aged 16–24 undergone three mouthrinses’ application were analyzed before and after one week exposure. Physiologic saline was used for the control group. The MN incidence was scored in the buccal epithelial of each participants. The difference in pre- and post-treatment after one week incidence of MN and plaque (PI) and gingival indices (GI) was compared by non-parametric statistical tests. Results The micronuclei incidence increased in Klorhex, Tanflex and Andorex groups after exposure to mouth rinses (P<.05). But when compared with the control group, there was not any difference between Andorex and control group (P>.05). In the other study groups, MN incidence was significantly increased after 7 days treatment (P<.05). GI scores of all groups were decreased significantly (P<.05). PI scores were decreased only in the Klorhex group (P<.05). Conclusions Our primary findings support the presence of possible cytotoxic effects of the mouthrinses on gingival epithelial cells.
MED-2166
Blood Harmane (1-methyl-9h-pyrido[3,4-b]indole) Concentrations in Essential Tremor: Repeat Observation in Cases and Controls in New York
Essential tremor (ET) is a widespread late-life neurological disease. Genetic and environmental factors are likely to play important etiological roles. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing neurotoxin. Previously, elevated blood harmane concentrations were demonstrated in ET cases compared to controls, but these observations were all been cross-sectional, assessing each subject at only one time point. Thus, no one has ever repeat-assayed blood harmane in the same subjects twice. Whether the observed case-control difference persists at a second time point, years later, is unknown. The current goal was to re-assess a sample of our ET cases and controls to determine whether blood harmane concentration remained elevated in ET at a second time point. Blood harmane concentrations were quantified by a well-established high performance liquid chromatography method in 63 ET cases and 70 controls. A mean of approximately 6 years elapsed between the initial and this subsequent blood harmane determination. The mean log blood harmane concentration was significantly higher in cases than controls (0.30 ± 0.61 g−10/ml vs. 0.08 ± 0.55 g−10/ml), and the median value in cases was double that of controls: 0.22 g−10/ml vs. 0.11 g−10/ml. The log blood harmane concentration was highest in cases with a family history of ET. Blood harmane concentration was elevated in ET cases compared to controls when re-assessed at a second time point several years later, indicating what seems to be a stable association between this environmental toxin and ET.
MED-717
Fructose intake at current levels in the United States may cause gastrointestinal distress in normal adults.
OBJECTIVE: Fructose intake has increased considerably in the United States, primarily as a result of increased consumption of high-fructose corn syrup, fruits and juices, and crystalline fructose. The purpose was to determine how often fructose, in amounts commonly consumed, would result in malabsorption and/or symptoms in healthy persons. DESIGN: Fructose absorption was measured using 3-hour breath hydrogen tests and symptom scores were used to rate subjective responses for gas, borborygmus, abdominal pain, and loose stools. SUBJECTS/SETTING: The study included 15 normal, free-living volunteers from a medical center community and was performed in a gastrointestinal specialty clinic. INTERVENTION: Subjects consumed 25- and 50-g doses of crystalline fructose with water after an overnight fast on separate test days. MAIN OUTCOME MEASURES: Mean peak breath hydrogen, time of peak, area under the curve (AUC) for breath hydrogen and gastrointestinal symptoms were measured during a 3-hour period after subjects consumed both 25- and 50-g doses of fructose. STATISTICAL ANALYSES: Differences in mean breath hydrogen, AUC, and symptom scores between doses were analyzed using paired t tests. Correlations among peak breath hydrogen, AUC, and symptoms were also evaluated. RESULTS: More than half of the 15 adults tested showed evidence of fructose malabsorption after 25 g fructose and greater than two thirds showed malabsorption after 50 g fructose. AUC, representing overall breath hydrogen response, was significantly greater after the 50-g dose. Overall symptom scores were significantly greater than baseline after each dose, but scores were only marginally greater after 50 g than 25 g. Peak hydrogen levels and AUC were highly correlated, but neither was significantly related to symptoms. CONCLUSIONS: Fructose, in amounts commonly consumed, may result in mild gastrointestinal distress in normal people. Additional study is warranted to evaluate the response to fructose-glucose mixtures (as in high-fructose corn syrup) and fructose taken with food in both normal people and those with gastrointestinal dysfunction. Because breath hydrogen peaks occurred at 90 to 114 minutes and were highly correlated with 180-minute breath hydrogen AUC, the use of peak hydrogen measures may be considered to shorten the duration of the exam.
MED-4417
Glycated haemoglobin and blood pressure-lowering effect of cinnamon in multi-ethnic Type 2 diabetic patients in the UK: a randomized, placebo-contr...
AIMS: To determine the blood glucose lowering effect of cinnamon on HbA1c, blood pressure and lipid profiles in people with type 2 diabetes. METHODS: 58 type 2 diabetic patients (25 males and 33 females), aged 54.9 ± 9.8, treated only with hypoglycemic agents and with an HbA1c more than 7% were randomly assigned to receive either 2g of cinnamon or placebo daily for 12 weeks. RESULTS: After intervention, the mean HbA1c was significantly decreased (P<0.005) in the cinnamon group (8.22% to 7.86%) compared with placebo group (8.55% to 8.68%). Mean systolic and diastolic blood pressures (SBP and DBP) were also significantly reduced (P<0.001) after 12 weeks in the cinnamon group (SBP: 132.6 to 129.2 mmHg and DBP: 85.2 to 80.2 mmHg) compared with the placebo group (SBP: 134.5 to 134.9 mmHg and DBP: 86.8 to 86.1 mmHg). A significant reduction in fasting plasma glucose (FPG), waist circumference and body mass index (BMI) was observed at week 12 compared to baseline in the cinnamon group, however, the changes were not significant when compared to placebo group. There were no significant differences in serum lipid profiles of total cholesterol, triglycerides, HDL and LDL cholesterols neither between nor within the groups. CONCLUSIONS: Intake of 2g of cinnamon for 12 weeks significantly reduces the HbA1c, SBP and DBP among poorly controlled type 2 diabetes patients. Cinnamon supplementation could be considered as an additional dietary supplement option to regulate blood glucose and blood pressure levels along with conventional medications to treat type 2 diabetes mellitus. © 2010 The Authors. Diabetic Medicine © 2010 Diabetes UK.
MED-3664
A randomized, placebo-controlled trial of acetaminophen for treatment of migraine headache.
OBJECTIVE: To evaluate the efficacy and safety of acetaminophen 1000 mg for the treatment of episodic migraine headache. BACKGROUND: While acetaminophen is commonly used to treat migraine, there have been limited published clinical trial efficacy results. DESIGN/METHODS: Ten investigators at 13 private, ambulatory, primary care sites in the United States enrolled and treated 346 outpatient adults 18-72 years of age with migraine headache of moderate to severe intensity into a randomized, placebo-controlled, double-blind clinical trial of 6 hours duration. Each patient was randomly assigned to a single dose of study medication of acetaminophen 1000 mg (n = 177) or placebo (n = 169). The percentage of patients with a reduction in baseline headache pain intensity from severe or moderate to mild or none 2 hours after treatment and the headache pain intensity difference from baseline at 2 hours were the primary efficacy measures. Other measures of pain relief, severity differences from baseline for migraine-associated symptoms of nausea, photophobia, phonophobia, and functional disability, and percentage of patients with migraine-associated symptoms reduced to none were also assessed. RESULTS: Significantly (P = .001) more patients treated with acetaminophen 1000 mg reported mild to no pain after 2 hours (52.0%) compared with those treated with placebo (32.0%). The mean pain intensity difference from baseline measured at 2 hours was significantly (P < .001) greater for patients treated with acetaminophen 1000 mg (0.82) compared with those treated with placebo (0.46). A significant difference in favor of acetaminophen 1000 mg over placebo was also observed at 1 hour after treatment for the percentage of patients with mild to no pain and for mean pain intensity difference from baseline. Acetaminophen 1000 mg was significantly more effective than placebo for all but 1 (pain reduced to none at 2 hours) clinically important secondary pain relief outcomes. Mean severity changes from baseline in migraine-associated symptoms of nausea, photophobia, phonophobia, and functional disability at 2 and 6 hours were significantly (P < .001) in favor of acetaminophen over placebo; the percentage of patients with no symptoms at 2 and 6 hours statistically significantly favored acetaminophen in 6 of 8 comparisons. Adverse events, overall, and specifically for nausea, were reported more frequently in the placebo group. CONCLUSIONS: Acetaminophen 1000 mg, a nonprescription drug, is an effective and well-tolerated treatment for episodic and moderate migraine headache. In addition, acetaminophen generally provided a beneficial effect on associated symptoms of migraine including nausea, photophobia, phonophobia, and functional disability.
MED-3436
How to save a life during a clinic visit for erectile dysfunction by modifying cardiovascular risk factors.
Erectile dysfunction (ED) is an early marker for systemic atherosclerosis and is a predictor for coronary artery disease and cardiac events. The aim of this paper is to convey the importance of addressing cardiovascular risk factors in patients with ED and to inform urologists as well as other physicians who are not specialized in cardiology how to carry out a basic cardiovascular evaluation, including history, physical examination and objective data. We review the evidence and pathophysiology linking ED to cardiovascular disease, and then describe how to carry out a basic cardiovascular evaluation. We present data from the literature showing that appropriate use of lifestyle modifications and medical therapy has a positive effect on mortality, on numerous cardiovascular end points and on ED. Suggestions of when to refer the ED patient to an internist or cardiologist are provided. Identifying and treating cardiovascular risk factors may not only benefit the patient's ED, but it might also save the patient's life.
MED-4250
Short-term effects of a snack including dried prunes on energy intake and satiety in normal-weight individuals.
The purpose of this study was to test the hypothesis that a preload including dried prunes consumed as a snack before a meal, compared to an isoenergetic and equal weighed bread product preload would: (a) have greater short-term effect on satiety measured by subsequent ad libitum meal intake, (b) induce greater satiety as assessed by visual analogue scales (VAS), and (c) reduce appetite for dessert offered shortly after lunch. Forty-five healthy, normal-weight subjects participated in this randomised within-subject crossover study. Statistical analysis of the results showed that when subjects consumed the preload that included dried prunes, also consumed less amount of dessert and had lower total energy intake at meal. Additionally, subjects' feeling of hunger, desire and motivation to eat, as assessed with the use of VAS, were lower at all time points between snack and meal. Since macronutrients content of both preloads were similar, the satiating power of prunes could be due to their relatively high fiber content. Identifying meal patterns and foods that promote satiety without increasing considerably the overall energy intake is very important. The addition of dried prunes to a snack seems to promote satiety besides providing valuable nutrients. 2010 Elsevier Ltd. All rights reserved.
MED-1377
Higher Diet Quality Is Associated with Decreased Risk of All-Cause, Cardiovascular Disease, and Cancer Mortality among Older Adults
Increased attention in dietary research and guidance has been focused on dietary patterns, rather than on single nutrients or food groups, because dietary components are consumed in combination and correlated with one another. However, the collective body of research on the topic has been hampered by the lack of consistency in methods used. We examined the relationships between 4 indices—the Healthy Eating Index–2010 (HEI-2010), the Alternative Healthy Eating Index–2010 (AHEI-2010), the alternate Mediterranean Diet (aMED), and Dietary Approaches to Stop Hypertension (DASH)—and all-cause, cardiovascular disease (CVD), and cancer mortality in the NIH-AARP Diet and Health Study (n = 492,823). Data from a 124-item food-frequency questionnaire were used to calculate scores; adjusted HRs and 95% CIs were estimated. We documented 86,419 deaths, including 23,502 CVD- and 29,415 cancer-specific deaths, during 15 y of follow-up. Higher index scores were associated with a 12–28% decreased risk of all-cause, CVD, and cancer mortality. Specifically, comparing the highest with the lowest quintile scores, adjusted HRs for all-cause mortality for men were as follows: HEI-2010 HR: 0.78 (95% CI: 0.76, 0.80), AHEI-2010 HR: 0.76 (95% CI: 0.74, 0.78), aMED HR: 0.77 (95% CI: 0.75, 0.79), and DASH HR: 0.83 (95% CI: 0.80, 0.85); for women, these were HEI-2010 HR: 0.77 (95% CI: 0.74, 0.80), AHEI-2010 HR: 0.76 (95% CI: 0.74, 0.79), aMED HR: 0.76 (95% CI: 0.73, 0.79), and DASH HR: 0.78 (95% CI: 0.75, 0.81). Similarly, high adherence on each index was protective for CVD and cancer mortality examined separately. These findings indicate that multiple scores reflect core tenets of a healthy diet that may lower the risk of mortality outcomes, including federal guidance as operationalized in the HEI-2010, Harvard’s Healthy Eating Plate as captured in the AHEI-2010, a Mediterranean diet as adapted in an Americanized aMED, and the DASH Eating Plan as included in the DASH score.
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-5343
Managing medical mistakes: ideology, insularity and accountability among internists-in-training.
By the end of graduate medical training, novice internists (collectively known as the housestaff) were initiated into the experience of either having done something to a patient which had a deleterious consequence or else having witnessed colleagues do the same. When these events occurred, the housestaff engaged in social-psychological processes, utilizing a variety of coping mechanisms and in-group practices to manage these mishaps. Three major mechanisms were utilized by the housestaff for defining and defending the various mishaps which frequently occurred: denial, discounting and distancing. Denial consisted of three components: the negation of the concept of error by defining the practice of medicine as an art with 'gray areas', the repression of actual mistakes by forgetting them and the redefinition of mistakes to non-mistakes. Discounting included those defenses which externalized the blame; namely mistakes which were due to circumstances beyond their control. These included: blaming the bureaucratic system outside of medicine; blaming superiors or subordinates within internal medicine; blaming the disease and blaming the patient. When they could not longer deny or discount a mistake because of its magnitude, they utilized distancing techniques. Not withstanding this shared elaborate repertoire of denial, discounting and distancing, it was found that profound doubts and even guilt remained for many housestaff. These troublesome feelings neither easily nor automatically resolved themselves. Interspersed among their defenses were fundamental questions of culpability and responsibility as they vacillated between self and other blame. For many 'the case was never closed', even as they terminated formal training, a point neglected in the medical and sociological literature. Little in their 3 year graduate program allowed them to work through the attendant vulnerability and ambiguity accompanying the managing of mistakes. Hence, there were maladaptive aspects of the collectively acquired defense mechanisms. The whole system of accountability during graduate medical specialty training was found to be a variable, and at times, contradictory process. The housestaff ultimately sees itself as the sole arbiter of mistakes and their adjudication. Housestaffers come to feel that nobody can judge them or their decisions, least of all their patients. As they progress through training even internal accountability cohorts--the Department of Medicine, teaching faculty and peers--are discounted to varying degrees. They have developed a strong ideology justifying their jealously guarded autonomy.(ABSTRACT TRUNCATED AT 400 WORDS)
MED-2099
In vitro binding capacities of three dietary fibers and their mixture for four toxic elements, cholesterol, and bile acid.
Water-soluble dietary fibers from apple peels and water-insoluble dietary fibers from wheat bran and soybean-seed hull were used to evaluate their binding capacities for four toxic elements (Pb, Hg, Cd, and As), lard, cholesterol, and bile acids. The water-soluble dietary fibers showed a higher binding capacity for three toxic cations, cholesterol, and sodium cholate; and a lower binding capacity for lard, compared to the water-insoluble ones. A mixture of the dietary fibers from all samples - apple peels, wheat bran, and soybean-seed hull - in the ratio 2:4:4 (w/w) significantly increased the binding capacity of water-insoluble dietary fibers for the three toxic cations, cholesterol, and sodium cholate; moreover, the mixture could lower the concentrations of Pb(2+) and Cd(+) in the tested solutions to levels lower than those occurring in rice and vegetables grown in polluted soils. However, all the tested fibers showed a low binding capacity for the toxic anion, AsO(3)(3-). Copyright © 2010. Published by Elsevier B.V.
MED-5112
Legume and soy food intake and the incidence of type 2 diabetes in the Shanghai Women’s Health Study
Background It has been postulated that a diet high in legumes may be beneficial for the prevention of type 2 diabetes mellitus (type 2 DM). However, data linking type 2 DM risk and legume intake are limited. Objective The objective of the study was to examine the association between legume and soy food consumption and self-reported type 2 DM. Design The study was conducted in a population-based prospective cohort of middle-aged Chinese women. We followed 64 227 women with no history of type 2 DM, cancer, or cardiovascular disease at study recruitment for an average of 4.6 y. Participants completed in-person interviews that collected information on diabetes risk factors, including dietary intake and physical activity in adulthood. Anthropometric measurements were taken. Dietary intake was assessed with a validated food-frequency questionnaire at the baseline survey and at the first follow-up survey administered 2–3 y after study recruitment. Results We observed an inverse association between quintiles of total legume intake and 3 mutually exclusive legume groups (peanuts, soybeans, and other legumes) and type 2 DM incidence. The multivariate-adjusted relative risk of type 2 DM for the upper quintile compared with the lower quintile was 0.62 (95% CI: 0.51, 0.74) for total legumes and 0.53 (95% CI: 0.45, 0.62) for soybeans. The association between soy products (other than soy milk) and soy protein consumption (protein derived from soy beans and their products) with type 2 DM was not significant. Conclusions Consumption of legumes, soybeans in particular, was inversely associated with the risk type 2 DM.
MED-1143
Risk perceptions and food choice: an exploratory analysis of organic- versus conventional-produce buyers.
Consumer choice between organically (without pesticides) and conventionally grown produce is examined. Exploratory focus-group discussions and questionnaires (N = 43) suggest that individuals who purchase organically grown produce believe it is substantially less hazardous than the conventional alternative and are willing to pay significant premiums to obtain it (a median 50% above the cost of conventional produce). The value of risk reduction implied by this incremental willingness to pay is not high relative to estimates for other risks, since the perceived risk reduction is relatively large. Organic-produce consumers also appear more likely than conventional-produce consumers to mitigate other ingestion-related risks (e.g., contaminated drinking water) but less likely to use automobile seatbelts.
MED-4837
Prevalence of different types of gallstone in the patients with cholelithiasis at Kathmandu Medical College, Nepal.
BACKGROUND: Gallstone disease known as cholelithiasis is the most common digestive surgical disorder and account for an important part of health care expenditure. Attempt was made to analyse the gallstone for typing depending upon the composition. AIMS & OBJECTIVES: The main objective of this study was to see the prevalence of different types of gallstone in Nepal and to correlate them with the clinical findings. MATERIALS & METHODS: Gallstones of 80 different patients who underwent cholecystectomy for cholelithiasis were collected from 20th January 2005 to 16th May 2006 in Department of Pathology, Kathmandu Medical College Teaching Hospital. Detailed history was taken. Stones were analyzed with chemical and enzymatic methods using clinical spectrophotometer. RESULTS & CONCLUSION: The most commonly involved age group for cholelithiasis (32.5%) is found to be 30-39 years with a female predominance (M: F=1:3.2). Cholelithiasis was found more commonly among non-vegetarian with the vegetarian: non-vegetarian ratio 1:9. Mixed type stone was found to be the most common type of stone comprising 78.75%, followed by cholesterol stone 12.5%, Brown pigment stone 7.5% and Black pigment stone 1.25%.
MED-1770
Possible health impact of animal oestrogens in food.
Oestrogens govern reproductive functions in vertebrates, and are present in all animal tissues. The theoretical maximum daily intake (TMDI) of oestradiol-17beta by consumption of cattle meat is calculated to be 4.3 ng. Following the use of oestradiol-containing growth-promoting agents, TMDI is increased by a factor of 4.6 to 20 ng oestradiol-17beta, assuming that single dosage and 'good animal husbandry' are observed. Pork and poultry probably contain similar amounts of oestrogens as untreated cattle. The mean concentration of oestradiol-17beta in whole milk is estimated at 6.4 pg/ml. Scarce data available on eggs report up to 200 pg/g oestradiol-17beta. The risk evaluation of oestrogenic growth-promoting agents is limited by analytical uncertainties. Residues of oestradiol-17alpha and the importance of oestrogen conjugates are widely unknown. The performance of mass spectrometry still needs to be improved for confirmation of oestrogen concentrations in most food. At present, the potential relevance of oestradiol acyl esters, the actual daily production rate of oestradiol in prepubertal children, and the role of oestradiol metabolites in cancer are obscure. The presence of different cytoplasmic oestrogen receptor subtypes and potential oestradiol effects in non-reproductive functions require further examination.
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-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-2898
Macular pigment and risk for age-related macular degeneration in subjects from a Northern European population.
PURPOSE: Age and advanced disease in the fellow eye are the two most important risk factors for age-related macular degeneration (AMD). In this study, the authors investigated the relationship between these variables and the optical density of macular pigment (MP) in a group of subjects from a northern European population. METHODS: The optical density of MP was measured psychophysically in 46 subjects ranging in age from 21 to 81 years with healthy maculae and in 9 healthy eyes known to be at high-risk of AMD because of advanced disease in the fellow eye. Each eye in the latter group was matched with a control eye on the basis of variables believed to be associated with the optical density of MP (iris color, gender, smoking habits, age, and lens density). RESULTS: There was an age-related decline in the optical density of macular pigment among volunteers with no ocular disease (right eye: r(2) = 0.29, P = 0.0006; left eye: r(2) = 0.29, P < 0.0001). Healthy eyes predisposed to AMD had significantly less MP than healthy eyes at no such risk (Wilcoxon's signed rank test: P = 0.015). CONCLUSIONS: The two most important risk factors for AMD are associated with a relative absence of MP. These findings are consistent with the hypothesis that supplemental lutein and zeaxanthin may delay, avert, or modify the course of this disease.
MED-853
Hydrogen peroxide 3% exposures.
OBJECTIVE: To present a child who developed gastric ulcers and duodenal erosions after ingestion of hydrogen peroxide 3% and delineate the epidemiology, medical outcomes, and toxicity of exposures to this agent managed by a poison control center. METHODS: A retrospective chart review of exposures to hydrogen peroxide 3% reported to the Long Island Regional Poison Control Center from January 1992 to April 1995 was conducted. Data extracted included age, route of exposure, amount of agent, symptoms, therapy, and medical outcome. RESULTS: There were 670 exposures to hydrogen peroxide 3% of 81,126 total exposures reported during the 40 months. Most exposures were by oral route (77%), occurred in children < 17 years old (67%), and were asymptomatic (85.6%). All but one exposure resulted in a benign outcome. One child, who presented with bloody emesis, developed multiple gastric ulcers and duodenal erosions after ingestion of hydrogen peroxide 2-4 oz. CONCLUSIONS: Exposure to hydrogen peroxide 3% is usually benign, however, severe gastric injury may occur following small ingestions in children. Patients who report persistent vomiting or bloody emesis require medical evaluation and consideration of endoscopy to evaluate gastrointestinal injury.
MED-4662
Iodine-induced neonatal hypothyroidism secondary to maternal seaweed consumption: a common practice in some Asian cultures to promote breast milk s...
Mild iodine deficiency is a recognised problem in Australia and New Zealand. However, iodine excess can cause hypothyroidism in some infants. We highlight two cases which illustrate the risks of excess dietary iodine intake during pregnancy and breastfeeding. They also describe a cultural practice of consuming seaweed soup to promote breast milk supply. Although most attention recently has been on the inadequacy of iodine in Australian diets, the reverse situation should not be overlooked. Neither feast nor famine is desirable. © 2011 The Authors. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians).
MED-1649
Consumption of a boiled Greek type of coffee is associated with improved endothelial function: the Ikaria study.
OBJECTIVE: The association of coffee consumption with cardiovascular disease remains controversial. Endothelial function is associated with cardiovascular risk. We examined the association between chronic coffee consumption and endothelium function in elderly inhabitants of the island of Ikaria. METHODS: The analysis was conducted on 142 elderly subjects (aged 66-91 years) of the Ikaria Study. Endothelial function was evaluated by ultrasound measurement of flow-mediated dilation (FMD). Coffee consumption was evaluated based on a food frequency questionnaire and was categorized as 'low' (< 200 ml/day), 'moderate' (200-450 ml/day), or 'high' (> 450 ml/day). RESULTS: From the subjects included in the study, 87% consumed a boiled Greek type of coffee. Moreover, 40% had a 'low', 48% a 'moderate' and 13% a 'high' daily coffee consumption. There was a linear increase in FMD according to coffee consumption ('low': 4.33 ± 2.51% vs 'moderate': 5.39 ± 3.09% vs 'high': 6.47 ± 2.72%; p = 0.032). Moreover, subjects consuming mainly a boiled Greek type of coffee had a significantly higher FMD compared with those consuming other types of coffee beverages (p = 0.035). CONCLUSIONS: Chronic coffee consumption is associated with improved endothelial function in elderly subjects, providing a new connection between nutrition and vascular health.
MED-1312
Inhibitory effect of oatmeal extract oligomer on vasoactive intestinal peptide-induced inflammation in surviving human skin.
The aim of this study was to evaluate the antiinflammatory effect of oatmeal extract oligomer on skin fragments stimulated by a neuromediator, vasoactive intestinal peptide (VIP). Skin fragments (from plastic surgery) were maintained in survival conditions for 6 h. To induce inflammation, VIP was placed in contact with dermis by culture medium. Histological analysis was then performed on hematoxylin- and eosin-stained slides. Edema was evaluated with semiquantitative scores. Vasodilation was studied by quantifying the percentage of dilated vessels according to scores and by measuring their surface by morphometrical image analysis. TNF-alpha dosage was made on culture supernatants. Vasodilation was significantly increased after application of VIP. After treatment with oatmeal extract oligomer, the mean surface of dilated vessels and edema were significantly decreased compared with VIP-treated skin. Moreover, treatment with this extract decreased TNF-alpha.
MED-4981
One-year study on the variation of carotenoid antioxidant substances in living human skin: influence of dietary supplementation and stress factors.
Variation in the level of the carotenoid antioxidant substances beta-carotene and lycopene in the human skin of ten healthy volunteers was measured with resonance Raman spectroscopy in an in vivo experiment over the course of 12 months. Information on the lifestyle of the volunteers concerning dietary supplementation and stress factors was obtained daily by the completion of questionnaires. The results showed individual variations in the levels of carotenoid antioxidant substances in the skin of the volunteers, which strongly correlated to specific lifestyles, such as the intake of dietary supplementations rich in carotenoids, and the influence of stress factors. A carotenoid-rich nutrition, based on large amounts of fruit and vegetables, increased the measured carotenoid levels of skin, while stress factors such as fatigue, illness, smoking, and alcohol consumption gave rise to a decrease in carotenoid levels of the skin. These decreases occurred relatively quickly over the course of one day, while the subsequent increases lasted for up to 3 days. During the summer and autumn months, an increase in the level of carotenoids in the skin was measured for all volunteers. The average "seasonal increase" of the carotenoid content in the skin was determined to be 1.26-fold.
MED-4740
Evaluation of background exposures of Americans to dioxin-like compounds in the 1990s and the 2000s.
The US Environmental Protection Agency's 2004 Dioxin Reassessment included a characterization of background exposures to dioxin-like compounds, including an estimate of an average background intake dose and an average background body burden. These quantities were derived from data generated in the mid-1990s. Studies conducted in the 2000s were gathered in an attempt to update the estimates generated by the Reassessment. While these studies suggest declines in the average background dose and body burden, a precise quantification of this decline, much less a conclusion that a decline has indeed occurred, cannot be made because of the inconsistency of study design and data sources, and the treatment of non-detects in the generation of congener average concentrations. The average background intake of the Reassessment was 61.0 pg TEQ/day, and using more current data, the average background intake was 40.6 pg TEQ/day. The average body burden from the surveys in the mid-1990s was 22.9 pg TEQ/g lipid weight (pg/g lwt). More recent blood concentration data, from NHANES 2001/2, suggest an adult average at 21.7 pg/g TEQ lwt. These TEQ values include the 17 dioxin and furan congeners and 3 coplanar PCBs, and were generated substituting ND=(1/2)DL or ND=DL/sq rt (2). Results are provided for ND=0 and analyses conducted to evaluate the impacts of this substitution. A more detailed examination of beef and pork data from similarly designed national statistical surveys show that declines in pork are statistically significant while the beef concentrations appeared to have remained constant between the time periods.
MED-876
Adherence to Mediterranean diet and intake of antioxidants influence spontaneous conversion of atrial fibrillation.
BACKGROUND AND AIM: The Mediterranean diet (MedD) has long been associated with lower incidence of cardiovascular disease. Little information is available on association between MedD, vitamins intake and arrhythmias. We sought to investigate the relationship between adherence to MedD, antioxidants intake and spontaneous conversion of atrial fibrillation (AF). METHODS AND RESULTS: A group of 800 subjects was included in a case-control study; 400 of them had a first detected episode of AF. Nutritional parameters were assessed by a self-administered food frequency validated questionnaire and completed by an interviewer-administered 7 days diet recall. Adherence to MedD was evaluated using the Mediterranean Score and intake of antioxidants from food was calculated. Adherence to the Med Diet was lower in patients that developed AF compared to control (mean Med Score: 22.3 ± 3.1 vs 27.9 ± 5.6; p < 0.001). The median value was 23.5 (Q1-Q3 range 23-30) in patients with AF and 27.4 (Q1-Q3 range 26-33). The estimated intake of total antioxidants was lower in patients with AF (13.5 ± 8.3 vs 18.2 ± 9.4 mmol/d; p < 0.001). Patients in the highest quartile of Mediterranean Score had higher probability of spontaneous conversion of atrial fibrillation (OR1.9; 95%CI 1.58-2.81). High levels of antioxidants intake were also associated with an increasing probability of spontaneous conversion of arrhythmia (O.R. 1.8; 95%CI 1.56-2.99; P < 0.01). CONCLUSIONS: Patients with atrial fibrillation had lower adherence to MedD and lower antioxidant intake compared to control population. Moreover patients with arrhythmia showing a higher Med Score had more probability of a spontaneous conversion of atrial fibrillation. Copyright © 2011 Elsevier B.V. All rights reserved.
MED-4448
Construction of a flavonoid database for assessing intake in a population-based sample of women on Long Island, New York.
Flavonoids have been hypothesized to reduce cancer risk. Previous epidemiological studies conducted to evaluate this hypothesis have not assessed all flavonoids, including classes that could contribute to intake among Americans, which would result in an underestimation of intake. This misclassification could mask variability among individuals, resulting in attenuated effect estimates for the association between flavonoids and cancer. To augment flavonoid and lignan intake estimates, we developed a database that can be used in conjunction with a food-frequency questionnaire (FFQ). Coupling information derived from the available literature with the U.S. Department of Agriculture databases, we estimated content of 6 flavonoid classes and lignans for 50 food group items. We combined these estimates with responses from a modified Block FFQ that was self-completed in 1996-1997 by a population-based sample of women without breast cancer on Long Island, New York (n = 1,500). Total flavonoid and lignan content of food items ranged from 0 to 129 mg/100 g, and the richest sources were tea, cherries, and grapefruit. Individual intake estimates, from highest to lowest, were flavan-3-ols, flavanones, flavonols, lignans, isoflavones, anthocyanidins, and flavones. Each class of flavonoids and lignans exhibited a wide range of intake levels. This database is useful to quantify flavonoid and lignan intake for other observational studies conducted in the United States that utilize the Block FFQ.
MED-5096
Very low n-3 long-chain polyunsaturated fatty acid status in Austrian vegetarians and vegans.
BACKGROUND/AIMS: The objective of the study was to collect data on dietary fat intake of omnivores, vegetarians, vegans and semi-omnivores as well as its impact on n-3 and n-6 fatty acids in long-term markers such as sphingolipids, phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylethanolamine (PE) as well as the calculated sphingo- and phospholipids (SPL) of erythrocytes. METHOD: The present observational study included 98 Austrian adult volunteers of both genders, of which 23 were omnivores, 25 vegetarians, 37 vegans, and 13 semi-omnivores. Information on anthropometry using measured body weight and height was obtained. The amount and composition of ingested fat were calculated from 24-hour recalls and the fatty acid pattern in the phospholipids was assessed using gas chromatography. RESULTS: The unbalanced n-6/n-3 ratio and the limited dietary sources of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in vegans and vegetarians led to reductions in C20:5n-3, C22:5n-3, C22:6n-3 and total n-3 fatty acids in SPL, PC, PS and PE compared with omnivores and semi-omnivores. The total content of polyunsaturated fatty acids, monounsaturated fatty acids and saturated fatty acids remained unchanged. CONCLUSION: The vegetarian diet, with an average n-6/n-3 ratio of 10/1, promotes biochemical n-3 tissue decline. To ensure physical, mental and neurological health vegetarians have to reduce the n-6/n-3 ratio with an additional intake of direct sources of EPA and DHA, regardless of age and gender. (c) 2008 S. Karger AG, Basel.
MED-2105
Recent Perspectives on the Relations between Fecal Mutagenicity, Genotoxicity, and Diet
DNA damage is an essential component of the genesis of colonic cancer. Gut microbial products and food components are thought to be principally responsible for the damage that initiates disease progression. Modified Ames tests and Comet assays have been developed for measuring mutagenicity and genotoxicity. Their relevance to oncogenesis remains to be confirmed, as does the relative importance of different mutagenic and genotoxic compounds present in fecal water and the bacteria involved in their metabolism. Dietary intervention studies provide clues to the likely risks of oncogenesis. High-protein diets lead to increases in N-nitroso compounds in fecal water and greater DNA damage as measured by the Comet assay, for example. Other dietary interventions, such as non-digestible carbohydrates and probiotics, may lead to lower fecal genotoxicity. In order to make recommendations to the general public, we must develop a better understanding of how genotoxic compounds are formed in the colon, how accurate the Ames and Comet assays are, and how diet affects genotoxicity.
MED-5125
Whole-grain consumption is associated with a reduced risk of noncardiovascular, noncancer death attributed to inflammatory diseases in the Iowa Wom...
BACKGROUND: It has recently been shown that oxidative stress, infection, and inflammation are predominant pathophysiologic factors for several major diseases. OBJECTIVE: We investigated the association of whole-grain intake with death attributed to noncardiovascular, noncancer inflammatory diseases. DESIGN: Postmenopausal women (n = 41 836) aged 55-69 y at baseline in 1986 were followed for 17 y. After exclusions for cardiovascular disease, cancer, diabetes, colitis, and liver cirrhosis at baseline, 27 312 participants remained, of whom 5552 died during the 17 y. A proportional hazards regression model was adjusted for age, smoking, adiposity, education, physical activity, and other dietary factors. RESULTS: Inflammation-related death was inversely associated with whole-grain intake. Compared with the hazard ratios in women who rarely or never ate whole-grain foods, the hazard ratio was 0.69 (95% CI: 0.57, 0.83) for those who consumed 4-7 servings/wk, 0.79 (0.66, 0.95) for 7.5-10.5 servings/wk, 0.64 (0.53, 0.79) for 11-18.5 servings/wk, and 0.66 (0.54, 0.81) for >or=19 servings/wk (P for trend = 0.01). Previously reported inverse associations of whole-grain intake with total and coronary heart disease mortality persisted after 17 y of follow-up. CONCLUSIONS: The reduction in inflammatory mortality associated with habitual whole-grain intake was larger than that previously reported for coronary heart disease and diabetes. Because a variety of phytochemicals are found in whole grains that may directly or indirectly inhibit oxidative stress, and because oxidative stress is an inevitable consequence of inflammation, we suggest that oxidative stress reduction by constituents of whole grain is a likely mechanism for the protective effect.
MED-4369
Interventions for nausea and vomiting in early pregnancy
Background Nausea, retching and vomiting are very commonly experienced by women in early pregnancy. There are considerable physical and psychological effects on women who experience these symptoms. This is an update of a review of interventions for nausea and vomiting in early pregnancy previously published in 2003. Objectives To assess the effectiveness and safety of all interventions for nausea, vomiting and retching in early pregnancy, up to 20 weeks’ gestation. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (28 May 2010). Selection criteria All randomised controlled trials of any intervention for nausea, vomiting and retching in early pregnancy. We excluded trials of interventions for hyperemesis gravidarum which are covered by another review. We also excluded quasi-randomised trials and trials using a crossover design. Data collection and analysis Four review authors, in pairs, reviewed the eligibility of trials and independently evaluated the risk of bias and extracted the data for included trials. Main results Twenty-seven trials, with 4041 women, met the inclusion criteria. These trials covered many interventions, including acupressure, acustimulation, acupuncture, ginger, vitamin B6 and several antiemetic drugs. We identified no studies of dietary or other lifestyle interventions. Evidence regarding the effectiveness of P6 acupressure, auricular (ear) acupressure and acustimulation of the P6 point was limited. Acupuncture (P6 or traditional) showed no significant benefit to women in pregnancy. The use of ginger products may be helpful to women, but the evidence of effectiveness was limited and not consistent. There was only limited evidence from trials to support the use of pharmacological agents including vitamin B6, and anti-emetic drugs to relieve mild or moderate nausea and vomiting. There was little information on maternal and fetal adverse outcomes and on psychological, social or economic outcomes. We were unable to pool findings from studies for most outcomes due to heterogeneity in study participants, interventions, comparison groups, and outcomes measured or reported. The methodological quality of the included studies was mixed. Authors’ conclusions Given the high prevalence of nausea and vomiting in early pregnancy, health professionals need to provide clear guidance to women, based on systematically reviewed evidence. There is a lack of high-quality evidence to support that advice. The difficulties in interpreting the results of the studies included in this review highlight the need for specific, consistent and clearly justified outcomes and approaches to measurement in research studies.
MED-4505
Dietary nitrate reduces maximal oxygen consumption while maintaining work performance in maximal exercise.
The anion nitrate-abundant in our diet-has recently emerged as a major pool of nitric oxide (NO) synthase-independent NO production. Nitrate is reduced stepwise in vivo to nitrite and then NO and possibly other bioactive nitrogen oxides. This reductive pathway is enhanced during low oxygen tension and acidosis. A recent study shows a reduction in oxygen consumption during submaximal exercise attributable to dietary nitrate. We went on to study the effects of dietary nitrate on various physiological and biochemical parameters during maximal exercise. Nine healthy, nonsmoking volunteers (age 30+/-2.3 years, VO(2max) 3.72+/-0.33 L/min) participated in this study, which had a randomized, double-blind crossover design. Subjects received dietary supplementation with sodium nitrate (0.1 mmol/kg/day) or placebo (NaCl) for 2 days before the test. This dose corresponds to the amount found in 100-300 g of a nitrate-rich vegetable such as spinach or beetroot. The maximal exercise tests consisted of an incremental exercise to exhaustion with combined arm and leg cranking on two separate ergometers. Dietary nitrate reduced VO(2max) from 3.72+/-0.33 to 3.62+/-0.31 L/min, P<0.05. Despite the reduction in VO(2max) the time to exhaustion trended to an increase after nitrate supplementation (524+/-31 vs 563+/-30 s, P=0.13). There was a correlation between the change in time to exhaustion and the change in VO(2max) (R(2)=0.47, P=0.04). A moderate dietary dose of nitrate significantly reduces VO(2max) during maximal exercise using a large active muscle mass. This reduction occurred with a trend toward increased time to exhaustion implying that two separate mechanisms are involved: one that reduces VO(2max) and another that improves the energetic function of the working muscles. Copyright 2009 Elsevier Inc. All rights reserved.
MED-2696
Dietary total antioxidant capacity and gastric cancer risk in the European prospective investigation into cancer and nutrition study.
A high intake of dietary antioxidant compounds has been hypothesized to be an appropriate strategy to reduce gastric cancer (GC) development. We investigated the effect of dietary total antioxidant capacity (TAC) in relation to GC in the European Prospective Investigation into Cancer (EPIC) study including 23 centers in 10 European countries. A total of 521,457 subjects (153,447 men) aged mostly 35-70 years old, were recruited largely between 1992 and 1998. Ferric reducing antioxidant potential (FRAP) and total radical-trapping antioxidant parameter (TRAP), measuring reducing and chain-breaking antioxidant capacity were used to measure dietary TAC from plant foods. Dietary antioxidant intake is associated with a reduction in the risk of GC for both FRAP (adjusted HR 0.66; 95%CI (0.46-0.95) and TRAP (adjusted HR 0.61; 95%CI (0.43-0.87) (highest vs. lowest quintile). The association was observed for both cardia and noncardia cancers. A clear effect was observed in smokers with a significant reduction in GC risk for the fifth quintile of intake for both assays (highest vs. lowest quintile: adjusted HR 0.41; 95%CI (0.22-0.76) p for trend <0.001 for FRAP; adjusted HR 0.52; 95%CI (0.28-0.97) p for trend <0.001 for TRAP) but not in nonsmokers. In former smokers, the association with FRAP intake was statistically significant (highest vs. lowest quintile: adjusted HR 0.4; 95%CI (0.21-0.75) p < 0.05); no association was observed for TRAP. Dietary antioxidant capacity intake from different sources of plant foods is associated with a reduction in the risk of GC. Copyright © 2011 UICC.
MED-2489
Agricultural policies, food and public health
A historical view on how our agricultural systems evolved and how they are contributing to obesity and disease.
MED-4323
Dehydroepiandrosterone and ageing.
Dehydroepiandrosterone (DHEA) is the major steroid produced by the adrenal zona reticularis and, in contrast to cortisol and aldosterone, its secretion declines with ageing. This has generated major interest in its putative role as an 'anti-ageing' hormone. However, it is not clear that the age-associated, physiological decline in DHEA secretion represents a harmful deficiency. DHEA exhibits its action mainly by conversion to sex steroids. In addition, DHEA has neurosteroidal properties and may exhibit direct action via specific binding sites on endothelial cells. There is convincing evidence for beneficial effects of DHEA in patients with adrenal insufficiency and future research will hopefully elucidate its role in patients receiving pharmacological glucocorticoid treatment. However, in healthy elderly subjects, current evidence from randomised, controlled trials does not justify the use of DHEA, with no major beneficial effects reported and, in addition, potentially adverse effects on sex steroid-dependent tumour growth need to be considered. Copyright 2004 Elsevier Ltd.
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-1612
Effect of protein ingestion on the glucose and insulin response to a standardized oral glucose load.
Type II diabetic subjects were given 50 g protein, 50 g glucose, or 50 g glucose with 50 g protein as a single meal in random sequence. The plasma glucose and insulin response was determined over the subsequent 5 h. The plasma glucose area above the baseline following a glucose meal was reduced 34% when protein was given with the glucose. When protein was given alone, the glucose concentration remained stable for 2 h and then declined. The insulin area following glucose was only modestly greater than with a protein meal (97 +/- 35, 83 +/- 19 microU X h/ml, respectively). When glucose was given with protein, the mean insulin area was considerably greater than when glucose or protein was given alone (247 +/- 33 microU X h/ml). When various amounts of protein were given with 50 g glucose, the insulin area response was essentially first order. Subsequently, subjects were given 50 g glucose or 50 g glucose with 50 g protein as two meals 4 h apart in random sequence. The insulin areas were not significantly different for each meal but were higher when protein + glucose was given. After the second glucose meal the plasma glucose area was 33% less than after the first meal. Following the second glucose + protein meal the plasma glucose area was markedly reduced, being only 7% as large as after the first meal. These data indicate that protein given with glucose will increase insulin secretion and reduce the plasma glucose rise in at least some type II diabetic persons.
MED-2240
Curcumin (diferuloylmethane) delivery methods: a review.
Curcumin interacts with a large number of extra- and intracellular targets in a biphasic dose-dependent manner. It controls inflammation, oxidative stress, cell survival, cell secretion, homeostasis, and proliferation. Its mechanisms of action are generally directed toward cells that exhibit disordered physiology or blatant mutation-based abnormal states. Optimizing preventative or therapeutic applications require delivering appropriate quantities of curcumin to lesioned cellular targets. Since diseased conditions anatomically are located from topical to systemic sites, efficient application of curcumin requires specific lesion-oriented delivery methods, representatives of which are here reviewed. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.
MED-2064
Anti-proliferative activity and chemoprotective effects towards DNA oxidative damage of fresh and cooked Brassicaceae.
Epidemiological evidence shows that regular consumption of Brassicaceae is associated with a reduced risk of cancer and heart disease. Cruciferous species are usually processed before eating and the real impact of cooking practices on their bioactive properties is not fully understood. We have evaluated the effect of common cooking practices (boiling, microwaving, and steaming) on the biological activities of broccoli, cauliflower and Brussels sprouts. Anti-proliferative and chemoprotective effects towards DNA oxidative damage of fresh and cooked vegetable extracts were evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium and Comet assays on HT-29 human colon carcinoma cells. The fresh vegetable extracts showed the highest anti-proliferative and antioxidant activities on HT-29 cells (broccoli>cauliflower = Brussels sprouts). No genotoxic activity was detected in any of the samples tested. The cooking methods that were applied influenced the anti-proliferative activity of Brassica extracts but did not alter considerably the antioxidant activity presented by the raw vegetables. Raw, microwaved, boiled (except broccoli) and steamed vegetable extracts, at different concentrations, presented a protective antioxidative action comparable with vitamin C (1 mm). These data provide new insight into the influence of domestic treatment on the quality of food, which could support the recent epidemiological studies suggesting that consumption of cruciferous vegetables, mainly cooked, may be related to a reduced risk of developing cancer.
MED-4186
Bisphenol A (BPA) in U.S. food.
Bisphenol A (BPA) is a chemical used for lining metal cans and in polycarbonate plastics, such as baby bottles. In rodents, BPA is associated with early sexual maturation, altered behavior, and effects on prostate and mammary glands. In humans, BPA is associated with cardiovascular disease, diabetes, and male sexual dysfunction in exposed workers. Food is a major exposure source. We know of no studies reporting BPA in U.S. fresh food, canned food, and food in plastic packaging in peer reviewed journals. We measured BPA levels in 105 fresh and canned foods, foods sold in plastic packaging, and in cat and dog foods in cans and plastic packaging. We detected BPA in 63 of 105 samples, including fresh turkey, canned green beans, and canned infant formula. Ninety-three of these samples were triplicates which had similar detected levels. Detected levels ranged from 0.23 to 65.0 ng/g ww and were not associated with type of food or packaging but did vary with pH. BPA levels were higher for foods of pH 5 compared to more acidic and alkaline foods. Detected levels were comparable to those found by others. Further research is indicated to determine BPA levels in U.S. food in larger, representative sampling.
MED-3729
Role of antioxidants in cancer therapy.
Oxidative stress is a key component in linking environmental toxicity to the multistage carcinogenic process. Reactive oxygen species (ROS) are generated in response to both endogenous and exogenous stimuli. To counterbalance ROS-mediated injury, an endogenous antioxidants defense system exists; however, when oxidation exceeds the control mechanisms, oxidative stress arises. Chronic and cumulative oxidative stress induces deleterious modifications to a variety of macromolecular components, such as DNA, lipids, and proteins. A primary mechanism of many chemotherapy drugs against cancer cells is the formation of ROS, or free radicals. Radiotherapy is based on the fact that ionizing radiation destroys tumor cells. Radiotherapy induces direct lesions in the DNA or biological molecules, which eventually affect DNA. Free radicals produced by oncology therapy are often a source of serious side effects as well. The objective of this review is to provide information about the effects of antioxidants during oncology treatments and to discuss the possible events and efficacy. Much debate has arisen about whether antioxidant supplementation alters the efficacy of cancer chemotherapy. There is still limited evidence in both quality and sample size, suggesting that certain antioxidant supplements may reduce adverse reactions and toxicities. Significant reductions in toxicity may alleviate dose-limiting toxicities so that more patients are able to complete prescribed chemotherapy regimens and thus, in turn, improve the potential for success in terms of tumor response and survival. Copyright © 2013 Elsevier Inc. All rights reserved.
MED-2223
Evaluation of Antiradical Activity of Different Cocoa and Chocolate Products: Relation with Lipid and Protein Composition
Chocolate antioxidant properties are often claimed; however, they are frequently different from the parent natural sources due to the industry or artisan transformation. In particular, antioxidant property of chocolate and cocoa are not adequately taken into consideration by consumers who normally make use of this food just for its flavor and taste properties. In this study, we have investigated the antioxidant capacity and total phenolic content of cocoa nibs, cocoa masses, and corresponding chocolate bars with different percentages of cocoa from different origins. The antioxidant capacity of the different samples was measured by two different assays [1,1-diphenyl-2-picryl-hydrazyl radical (DPPH) and ferric reducing antioxidant of potency (FRAP) tests]. The Folin–Ciocalteu reagent was used to assess the total phenolic content. The masses showed a higher antioxidant power than the nibs, and this has been attributed to the fact that in the nibs is still present the lipid part, which will form the cocoa butter. The influence of milk, whey, and soy proteins was also investigated. Our results showed that the extra dark cocoa bar, 100% cocoa chocolate, is the best in terms of total polyphenol content and in terms of antioxidant capacity according to the DPPH and FRAP tests. In addition, the bars of organic dark chocolate 80%, dark Tanzania 80%, and Trinidad 80% products are well performing in all respects. As highlighted by us, the antiradical properties of cocoa products are higher than many antioxidant supplements in tablets.
MED-4783
Childhood soy intake and breast cancer risk in Asian American women.
INTRODUCTION: Historically, breast cancer incidence has been substantially higher in the United States than in Asia. When Asian women migrate to the United States, their breast cancer risk increases over several generations and approaches that for U.S. Whites. Thus, modifiable factors, such as diet, may be responsible. METHODS: In this population-based case-control study of breast cancer among women of Chinese, Japanese, and Filipino descent, ages 20 to 55 years, and living in San Francisco-Oakland (California), Los Angeles (California) and Oahu (Hawaii), we interviewed 597 cases (70% of those eligible) and 966 controls (75%) about adolescent and adult diet and cultural practices. For subjects with mothers living in the United States (39% of participants), we interviewed mothers of 99 cases (43% of eligible) and 156 controls (40%) about the daughter's childhood exposures. Seventy-three percent of study participants were premenopausal at diagnosis. RESULTS: Comparing highest with lowest tertiles, the multivariate relative risks (95% confidence interval) for childhood, adolescent, and adult soy intake were 0.40 (0.18-0.83; P(trend) = 0.03), 0.80 (0.59-1.08; P(trend) = 0.12), and 0.76 (0.56-1.02; P(trend) = 0.04), respectively. Inverse associations with childhood intake were noted in all three races, all three study sites, and women born in Asia and the United States. Adjustment for measures of westernization attenuated the associations with adolescent and adult soy intake but did not affect the inverse relationship with childhood soy intake. DISCUSSION: Soy intake during childhood, adolescence, and adult life was associated with decreased breast cancer risk, with the strongest, most consistent effect for childhood intake. Soy may be a hormonally related, early-life exposure that influences breast cancer incidence.
MED-5036
Meta-analysis of long-term mobile phone use and the association with brain tumours.
We evaluated long-term use of mobile phones and the risk for brain tumours in case-control studies published so far on this issue. We identified ten studies on glioma and meta-analysis yielded OR = 0.9, 95% CI = 0.8-1.1. Latency period of > or =10-years gave OR = 1.2, 95% CI = 0.8-1.9 based on six studies, for ipsilateral use (same side as tumour) OR = 2.0, 95% CI = 1.2-3.4 (four studies), but contralateral use did not increase the risk significantly, OR = 1.1, 95% CI = 0.6-2.0. Meta-analysis of nine studies on acoustic neuroma gave OR = 0.9, 95% CI = 0.7-1.1 increasing to OR = 1.3, 95% CI = 0.6-2.8 using > or =10-years latency period (four studies). Ipsilateral use gave OR = 2.4, 95% CI = 1.1-5.3 and contra-lateral OR = 1.2, 95% CI = 0.7-2.2 in the > or =10-years latency period group (three studies). Seven studies gave results for meningioma yielding overall OR = 0.8, 95% CI = 0.7-0.99. Using > or =10-years latency period OR = 1.3, 95% CI = 0.9-1.8 was calculated (four studies) increasing to OR = 1.7, 95% CI = 0.99-3.1 for ipsilateral use and OR = 1.0, 95% CI = 0.3-3.1 for contralateral use (two studies). We conclude that this meta-analysis gave a consistent pattern of an association between mobile phone use and ipsilateral glioma and acoustic neuroma using > or =10-years latency period.
MED-2080
Platelets in atherosclerosis.
Beyond obvious functions in haemostasis and thrombosis, platelets are considered to be essential in proinflammatory surroundings such as atherosclerosis, allergy, rheumatoid arthritis and even cancer. In atherosclerosis, platelets facilitate the recruitment of inflammatory cells towards the lesion sites and release a plethora of inflammatory mediators, thereby enriching and boosting the inflammatory milieu. Platelets do so by interacting with endothelial cells, circulating leukocytes (monocytes, neutrophils, dendritic cells, T-cells) and progenitor cells. This cross-talk enforces leukocyte activation, adhesion and transmigration. Furthermore, platelets are known to function in innate host defense through the release of antimicrobial peptides and the expression of pattern recognition receptors. In severe sepsis, platelets are able to trigger the formation of neutrophil extracellular traps (NETs), which bind and clear pathogens. The present antiplatelet therapies that target key pathways of platelet activation and aggregation therefore hold the potential to modulate platelet-derived immune functions by reducing cellular interactions of platelets with other immune components and by reducing the secretion of inflammatory proteins into the milieu. The objective of this review is to update and discuss the current perceptions of the platelet immune constituents and their prospect as therapeutic targets in an atherosclerotic setting.
MED-2994
Carcinogenicity and regulation of caramel colorings.
2- and 4-methylimidazoles are present as contaminants in caramel colorings manufactured with ammonia catalysts. Both contaminants have been shown to induce cancer in animals and may be present in caramel colorings in amounts that exceed federal guidelines. California requires warning notices on products that could lead to consumption of more than 30 micrograms per day. The US Food and Drug Administration should bar the use of excessively contaminated caramel coloring in food.
MED-4180
Half-lives of serum PCB congener concentrations in environmentally exposed early adolescents.
The aim was to determine half-life of six most abundant PCB congeners in the body of early adolescents. In 304 environmentally exposed children, PCB serum concentration was determined at the age of 8 and 12years. Half-life was determined for each child assuming exponential decrease or for the whole cohort using multiple regression. Results obtained by both approaches were in agreement. PCB reuptakes corrupting half-life estimates for each child and each congener were evaluated. If one of the serum PCB concentration values fell below the level of detection (LOD) the pair was excluded and if PCB half-life value exceeded the arbitrary value of 30years. The following median half-lives in years 4.46, 10.59, 9.7, 4.7, 9.1 and 9.8 were obtained for PCB congeners 118, 138(+163), 153, 156(+171), 170 and 180, respectively. The elimination half-life values were not systematically related to PCB serum concentration at any examination age. Between half-life values, percentage of children with significant reuptakes and PCB congener abundance in serum were found significant associations. Copyright Â© 2010 Elsevier Ltd. All rights reserved.