query: Boosting Good Bacteria in the Colon Without Probiotics

positive: Propionate. Anti-obesity and satiety enhancing factor? Propionate is produced along with acetate and butyrate as a result of fermentative activity of gut microflora on dietary fiber. It has long been known to exhibit hypophagic effects in ruminants, however, its potential physiological roles in non-ruminants as well as humans remained unnoticed over the years. In view of various studies pointing towards the hypophagic as well as hypocholesterolemic effects of propionate in humans, it may act as an important factor in amelioration of obesity, a lifestyle disease arising due to energy imbalance and growing at a startling rate globally. Short chain fatty acids have recently been ascribed as ligands to G-protein coupled receptors (GPRs) 41 and 43. Thus, propionate along with acetate may also be involved in the regulation of adipogenesis and adipokine release mediated via GPRs. The present review summarizes the evidence which collectively raise the possibility of propionate as a dietary factor to depress appetite and combat the obesity epidemic. Copyright © 2011 Elsevier Ltd. All rights reserved.

positive: Butyrate and other short-chain fatty acids as modulators of immunity: what relevance for health? PURPOSE OF REVIEW: High-fiber diets have been shown to reduce plasma concentrations of inflammation markers. Increased production of fermentation-derived short-chain fatty acids (SCFAs) is one of the factors that could exert these positive effects. This review examines the effects of SCFAs on immune cells and discusses the relevance of their effects on systemic inflammation, as frequently seen in obesity. RECENT FINDINGS: SCFAs have been shown to reduce chemotaxis and cell adhesion; this effect is dependent on type and concentration of SCFA. In spite of conflicting results, especially butyrate seems to have an anti-inflammatory effect, mediated by signaling pathways like nuclear factor-κB and inhibition of histone deacetylase. The discrepancies in the results could be explained by differences in cell types used and their proliferative and differentiation status. SUMMARY: SCFAs show anti-inflammatory effects and seem to have the potency to prevent infiltration of immune cells from the bloodstream in, for example, the adipose tissue. In addition, their ability to inhibit the proliferation and activation of T cells and to prevent adhesion of antigen-presenting cells could be important as it recently has been shown that obesity-associated inflammation might be antigen-dependent. More studies with concentrations in micromolar range are needed to approach more physiological concentrations.

positive: Quantification of butyryl CoA:acetate CoA-transferase genes reveals different butyrate production capacity in individuals according to diet and age. The gastrointestinal microbiota produces short-chain fatty acids, especially butyrate, which affect colonic health, immune function and epigenetic regulation. To assess the effects of nutrition and aging on the production of butyrate, the butyryl-CoA:acetate CoA-transferase gene and population shifts of Clostridium clusters lV and XlVa, the main butyrate producers, were analysed. Faecal samples of young healthy omnivores (24 ± 2.5 years), vegetarians (26 ± 5 years) and elderly (86 ± 8 years) omnivores were evaluated. Diet and lifestyle were assessed in questionnaire-based interviews. The elderly had significantly fewer copies of the butyryl-CoA:acetate CoA-transferase gene than young omnivores (P=0.014), while vegetarians showed the highest number of copies (P=0.048). The thermal denaturation of the butyryl-CoA:acetate CoA-transferase gene variant melting curve related to Roseburia/Eubacterium rectale spp. was significantly more variable in the vegetarians than in the elderly. The Clostridium cluster XIVa was more abundant in vegetarians (P=0.049) and in omnivores (P<0.01) than in the elderly group. Gastrointestinal microbiota of the elderly is characterized by decreased butyrate production capacity, reflecting increased risk of degenerative diseases. These results suggest that the butyryl-CoA:acetate CoA-transferase gene is a valuable marker for gastrointestinal microbiota function. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

positive: Mechanisms of primary cancer prevention by butyrate and other products formed during gut flora-mediated fermentation of dietary fibre. Dietary fibres are indigestible food ingredients that reach the colon and are then fermented by colonic bacteria, resulting mainly in the formation of short-chain fatty acids (SCFA) such as acetate, propionate, and butyrate. Those SCFA, especially butyrate, are recognised for their potential to act on secondary chemoprevention by slowing growth and activating apoptosis in colon cancer cells. Additionally, SCFA can also act on primary prevention by activation of different drug metabolising enzymes. This can reduce the burden of carcinogens and, therefore, decrease the number of mutations, reducing cancer risk. Activation of GSTs by butyrate has been studied on mRNA, protein, and enzyme activity level by real-time RT-PCR, cDNA microarrays, Western blotting, or photometrical approaches, respectively. Butyrate had differential effects in colon cells of different stages of cancer development. In HT29 tumour cells, e.g., mRNA GSTA4, GSTP1, GSTM2, and GSTT2 were induced. In LT97 adenoma cells, GSTM3, GSTT2, and MGST3 were induced, whereas GSTA2, GSTT2, and catalase (CAT) were elevated in primary colon cells. Colon cells of different stages of carcinogenesis differed in post-transcriptional regulatory mechanisms because butyrate increased protein levels of different GST isoforms and total GST enzyme activity in HT29 cells, whereas in LT97 cells, GST protein levels and activity were slightly reduced. Because butyrate increased histone acetylation and phosphorylation of ERK in HT29 cells, inhibition of histone deacetylases and the influence on MAPK signalling are possible mechanisms of GST activation by butyrate. Functional consequences of this activation include a reduction of DNA damage caused by carcinogens like hydrogen peroxide or 4-hydroxynonenal (HNE) in butyrate-treated colon cells. Treatment of colon cells with the supernatant from an in vitro fermentation of inulin increased GST activity and decreased HNE-induced DNA damage in HT29 cells. Additional animal and human studies are needed to define the exact role of dietary fibre and butyrate in inducing GST activity and reducing the risk of colon cancer.

positive: Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis Intestinal microbiota metabolism of choline/phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). Herein we demonstrate that intestinal microbiota metabolism of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis. Omnivorous subjects are shown to produce significantly more TMAO than vegans/vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. Specific bacterial taxa in human feces are shown to associate with both plasma TMAO and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predict increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (MI, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice significantly altered cecal microbial composition, markedly enhanced synthesis of TMA/TMAO, and increased atherosclerosis, but not following suppression of intestinal microbiota. Dietary supplementation of TMAO, or either carnitine or choline in mice with intact intestinal microbiota, significantly reduced reverse cholesterol transport in vivo. Intestinal microbiota may thus participate in the well-established link between increased red meat consumption and CVD risk.

positive: Infectobesity: obesity of infectious origin. The rapid increase in obesity and the associated health care costs have prompted a search for better approaches for its prevention and management. Such efforts may be facilitated by better understanding the etiology of obesity. Of the several etiological factors, infection, an unusual causative factor, has recently started receiving greater attention. In the last two decades, 10 adipogenic pathogens were reported, including human and nonhuman viruses, scrapie agents, bacteria, and gut microflora. Some of these pathogens are associated with human obesity, but their causative role in human obesity has not been established. This chapter presents information about the natural hosts, signs and symptoms, and pathogenesis of the adipogenic microorganisms. If relevant to humans, "Infectobesity" would be a relatively novel, yet extremely significant concept. A new perspective about the infectious etiology of obesity may stimulate additional research to assess the contribution of hitherto unknown pathogens to human obesity and possibly to prevent or treat obesity of infectious origins.

positive: A vegetarian dietary pattern as a nutrient-dense approach to weight management: an analysis of the national health and nutrition examination survey... BACKGROUND: Population-based studies have shown that vegetarians have lower body mass index than nonvegetarians, suggesting that vegetarian diet plans may be an approach for weight management. However, a perception exists that vegetarian diets are deficient in certain nutrients. OBJECTIVE: To compare dietary quality of vegetarians, nonvegetarians, and dieters, and to test the hypothesis that a vegetarian diet would not compromise nutrient intake when used to manage body weight. DESIGN: Cross-sectional analysis of National Health and Nutrition Examination Survey (1999-2004) dietary and anthropometric data. Diet quality was determined using United States Department of Agriculture's Healthy Eating Index 2005. Participants included adults aged 19 years and older, excluding pregnant and lactating women (N = 13,292). Lacto-ovo vegetarian diets were portrayed by intakes of participants who did not eat meat, poultry, or fish on the day of the survey (n = 851). Weight-loss diets were portrayed by intakes of participants who consumed 500 kcal less than their estimated energy requirements (n = 4,635). Mean nutrient intakes and body mass indexes were adjusted for energy, sex, and ethnicity. Using analysis of variance, all vegetarians were compared to all nonvegetarians, dieting vegetarians to dieting nonvegetarians, and nondieting vegetarians to nondieting nonvegetarians. RESULTS: Mean intakes of fiber, vitamins A, C, and E, thiamin, riboflavin, folate, calcium, magnesium, and iron were higher for all vegetarians than for all nonvegetarians. Although vegetarian intakes of vitamin E, vitamin A, and magnesium exceeded that of nonvegetarians (8.3 ± 0.3 vs 7.0 ± 0.1 mg; 718 ± 28 vs 603 ± 10 μg; 322 ± 5 vs 281 ± 2 mg), both groups had intakes that were less than desired. The Healthy Eating Index score did not differ for all vegetarians compared to all nonvegetarians (50.5 ± 0.88 vs 50.1 ± 0.33, P = 0.6). CONCLUSIONS: These findings suggest that vegetarian diets are nutrient dense, consistent with dietary guidelines, and could be recommended for weight management without compromising diet quality. Copyright © 2011 American Dietetic Association. Published by Elsevier Inc. All rights reserved.

positive: EPIC-Oxford: lifestyle characteristics and nutrient intakes in a cohort of 33 883 meat-eaters and 31 546 non meat-eaters in the UK. OBJECTIVE: To describe the lifestyle characteristics and nutrient intakes of the Oxford cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN: Cohort of men and women recruited through general practices or by post to include a high proportion of non meat-eaters. Dietary, anthropometric and lifestyle data were collected at baseline and four diet groups were defined. SETTING: United Kingdom. PARTICIPANTS: In total, 65 429 men and women aged 20 to 97 years, comprising 33 883 meat-eaters, 10 110 fish-eaters, 18 840 lacto-ovo vegetarians and 2596 vegans. RESULTS: Nutrient intakes and lifestyle factors differed across the diet groups, with striking differences between meat-eaters and vegans, and fish-eaters and vegetarians usually having intermediate values. Mean fat intake in each diet group was below the UK dietary reference value of 33% of total energy intake. The mean intake of saturated fatty acids in vegans was approximately 5% of energy, less than half the mean intake among meat-eaters (10-11%). Vegans had the highest intakes of fibre, vitamin B1, folate, vitamin C, vitamin E, magnesium and iron, and the lowest intakes of retinol, vitamin B12, vitamin D, calcium and zinc. CONCLUSIONS: The EPIC-Oxford cohort includes 31 546 non meat-eaters and is one of the largest studies of vegetarians in the world. The average nutrient intakes in the whole cohort are close to those currently recommended for good health. Comparisons of the diet groups show wide ranges in the intakes of major nutrients such as saturated fat and dietary fibre. Such variation should increase the ability of the study to detect associations of diet with major cancers and causes of death.

positive: Kiwifruit improves bowel function in patients with irritable bowel syndrome with constipation. Irritable bowel syndrome (IBS) is a common functional disorder of the gastrointestinal system, and is characterized by abdominal pain, diarrhea (IBS/D), constipation (IBS/C), and alternating diarrhea and constipation (IBSC/A). The purpose of this study was to examine the impact of a four week kiwifruit intervention on bowel function in patients diagnosed with IBS/C. Fifty-four patients with IBS/C and 16 healthy adults participated in this study. All subjects participated in the 6 week, three phase study, which included a baseline phase (1 week), a dietary intervention period (4 weeks), and a post-intervention phase (1 week). Forty-one IBS/C patients and all healthy adults consumed two Hayward green (Actinida deliciosa var) kiwifruits per day for 4 weeks. Thirteen IBS/C patients in the control group took two placebo capsules per day for 4 weeks. Colon transit time was measured immediately prior to and following the intervention period. All subjects completed daily defecation records. After the 4-week intervention, weekly defecation frequency significantly increased in the IBS/C group of participants who consumed kiwifruit (p<0.05). Colon transit time significantly decreased (p=0.026) in the IBS/C group that consumed kiwi fruit. These findings suggest that kiwifruit consumption for 4 weeks shortens colon transit time, increases defecation frequency, and improves bowel function in adults diagnosed with IBS/C.

positive: The intestinal microbiome: a separate organ inside the body with the metabolic potential to influence the bioactivity of botanicals. For many years, it was believed that the main function of the large intestine was the resorption of water and salt and the facilitated disposal of waste materials. However, this task definition was far from complete, as it did not consider the activity of the microbial content of the large intestine. Nowadays it is clear that the complex microbial ecosystem in our intestines should be considered as a separate organ within the body, with a metabolic capacity which exceeds the liver with a factor 100. The intestinal microbiome is therefore closely involved in the first-pass metabolism of dietary compounds. This is especially true for botanical supplements, which are now marketed for various health applications. Being of natural origin, their structural building blocks, such as polyphenols, are often highly recognized by the human and especially the intestinal microbial metabolism machinery. Intensive metabolism results in often low circulating levels of the original products, with the consequence that final health effects of botanicals are often related to specific active metabolites which are produced in the body rather than being related to the product's original composition. Understanding how such metabolic processes contribute to the in situ exposure is therefore crucial for the proper interpretation of biological responses. A multidisciplinary approach, characterizing the food and phytochemical intake as well as the metabolic potency of the gut microbiota, while measuring biomarkers of both exposure and response in target tissues, is therefore of critical importance. With polyphenol metabolism as example, this review describes how the incorporation of microbial metabolism as an important variable in the evaluation of the final bioactivity of botanicals strongly increases the relevance and predictive value of the outcome. Moreover, knowledge about intestinal processes may offer innovative strategies for targeted product development. Copyright © 2010 Elsevier B.V. All rights reserved.

positive: Flaxseed: a potential source of food, feed and fiber. Flaxseed is one of the most important oilseed crops for industrial as well as food, feed, and fiber purposes. Almost every part of the flaxseed plant is utilized commercially, either directly or after processing. The stem yields good quality fiber having high strength and durability. The seed provides oil rich in omega-3, digestible proteins, and lignans. In addition to being one of the richest sources of α-linolenic acid oil and lignans, flaxseed is an essential source of high quality protein and soluble fiber and has considerable potential as a source of phenolic compounds. Flaxseed is emerging as an important functional food ingredient because of its rich contents of α-linolenic acid (ALA), lignans, and fiber. Lignans appear to be anti-carcinogenic compounds. The omega-3s and lignan phytoestrogens of flaxseed are in focus for their benefits for a wide range of health conditions and may possess chemo-protective properties in animals and humans. This paper presents a review of literature on the nutritional composition of flaxseed, its health benefits, and disease-prevention qualities, utilization of flaxseed for food, feed, and fiber, and processing of flaxseed.

positive: Bowel function measurements of individuals with different eating patterns. Bowel function was assessed in 51 subjects: 10 women and seven men who habitually consumed an omnivorous, vegetarian, or vegan diet. The subjects on these diets had a mean intake of fibre of 23 g, 37 g, and 47 g respectively. Mean transit times were variable and not significantly different between the groups. Vegans, however, had a greater frequency of defecation and passed softer stools. All measurements of bowel function were significantly correlated with total dietary fibre. As dietary fibre increased mean transit time decreased, stool frequency increased and the stools became softer. Men produced a greater quantity of softer, less formed faeces than women. During the luteal phase of the menstrual cycle women excreted harder stools and had a significantly longer mean transit time. The finding that mean transit time was more highly correlated with faecal form than any of the other bowel function measurements could be of practical importance.

negative: The intestinal microflora in allergic Estonian and Swedish 2-year-old children. BACKGROUND: The prevalence of allergic diseases seems to have increased particularly over the past 35-40 years. Furthermore, allergic disease is less common among children in the formerly socialist countries of central and Eastern Europe as compared with Western Europe. It has been suggested that a reduced microbial stimulation during infancy and early childhood would result in a slower postnatal maturation of the immune system and development of an optimal balance between TH1- and TH2-like immunity. AIMS: To test the hypothesis that allergic disease among children may be associated with differences in their intestinal microflora in two countries with a low (Estonia) and a high (Sweden) prevalence of allergy. METHODS: From a prospective study of the development of allergy in relation to environmental factors, 29 Estonian and 33 Swedish 2-year-old children were selected. They were either nonallergic (n = 36) or had a confirmed diagnosis of allergy (n = 27) as verified by typical history and at least one positive skin prick test to egg or cow's milk. Weighed samples of faeces were serially diluted (10-2-10-9) and grown under anaerobic conditions. The counts of the various genera and species were calculated for each child. In addition, the relative amounts of the particular microbes were expressed as a proportion of the total count. RESULTS: The allergic children in Estonia and Sweden were less often colonized with lactobacilli (P < 0.01), as compared with the nonallergic children in the two countries. In contrast, the allergic children harboured higher counts of aerobic micro-organisms (P < 0. 05), particularly coliforms (P < 0.01) and Staphylococcus aureus (P < 0.05). The proportions of aerobic bacteria of the intestinal flora were also higher in the allergic children (P < 0.05), while the opposite was true for anaerobes (P < 0.05). Similarly, in the allergic children the proportions of coliforms were higher (P < 0. 05) and bacteroides lower (P < 0.05) than in the nonallergic children. CONCLUSIONS: Differences in the indigenous intestinal flora might affect the development and priming of the immune system in early childhood, similar to what has been shown in rodents. The role of intestinal microflora in relation to the development of infant immunity and the possible consequences for allergic diseases later in life requires further study, particularly as it would be readily available for intervention as a means for primary prevention of allergy by the administration of probiotic bacteria.

negative: Hydrogen sulfide induces direct radical-associated DNA damage. Hydrogen sulfide (H(2)S) is produced by indigenous sulfate-reducing bacteria in the large intestine and represents an environmental insult to the colonic epithelium. Clinical studies have linked the presence of either sulfate-reducing bacteria or H(2)S in the colon with chronic disorders such as ulcerative colitis and colorectal cancer, although at this point, the evidence is circumstantial and underlying mechanisms remain undefined. We showed previously that sulfide at concentrations similar to those found in the human colon induced genomic DNA damage in mammalian cells. The present study addressed the nature of the DNA damage by determining if sulfide is directly genotoxic or if genotoxicity requires cellular metabolism. We also questioned if sulfide genotoxicity is mediated by free radicals and if DNA base oxidation is involved. Naked nuclei from untreated Chinese hamster ovary cells were treated with sulfide; DNA damage was induced by concentrations as low as 1 micromol/L. This damage was effectively quenched by cotreatment with butylhydroxyanisole. Furthermore, sulfide treatment increased the number of oxidized bases recognized by formamidopyrimidine [fapy]-DNA glycosylase. These results confirm the genotoxicity of sulfide and strongly implicate that this genotoxicity is mediated by free radicals. These observations highlight the possible role of sulfide as an environmental insult that, given a predisposing genetic background, may lead to genomic instability or the cumulative mutations characteristic of colorectal cancer.

negative: Detection of fecal residue on poultry carcasses by laser-induced fluorescence imaging. Feasibility of fluorescence imaging technique for the detection of diluted fecal matters from various parts of the digestive tract, including colon, ceca, small intestine, and duodenum, on poultry carcasses was investigated. One of the challenges for using fluorescence imaging for inspection of agricultural material is the low fluorescence yield in that fluorescence can be masked by ambient light. A laser-induced fluorescence imaging system (LIFIS) developed by our group allowed acquisition of fluorescence from feces-contaminated poultry carcasses in ambient light. Fluorescence emission images at 630 nm were captured with 415-nm laser excitation. Image processing algorithms including threshold and image erosion were used to identify fecal spots diluted up to 1: 10 by weight with double distilled water. Feces spots on the carcasses, without dilution and up to 1: 5 dilutions, could be detected with 100% accuracy regardless of feces type. Detection accuracy for fecal matters diluted up to 1: 10 was 96.6%. The results demonstrated good potential of the LIFIS for detection of diluted poultry fecal matter, which can harbor pathogens, on poultry carcasses.

negative: Cephalic phase of colonic pressure response to food. A cephalic phase of colonic pressure response to food was sought in five normal subjects (mean age (22.6) years, 22-24), studied on six separate occasions by recording intraluminal pressures in the unprepared sigmoid colon. Gastric acid secretion was measured simultaneously by continuous aspiration through a nasogastric tube. After a 60 minute basal period, one of five 30 minute food related cephalic stimuli, or a control stimulus was given in random order; records were continued for a further 120 minutes. The cephalic stimuli were: food discussion, sight and smell of food without taste, smell of food without sight or taste, sight of food without smell or taste, and modified sham feeding; the control stimulus was a discussion of neutral topics. Colonic pressures were expressed as study segment activity index (area under curve, mm Hg.min) derived by fully automated computer analysis. Gastric acid output was expressed as mmol/30 min. Food discussion significantly (p < 0.02, Wilcoxon's rank sum test) increased colonic pressure activity compared with control or basal activity. Smell of food without sight or taste also significantly (p < 0.03) increased the colonic pressure activity compared with control and basal periods. Sham feeding and sight and smell of food without taste significantly (p < 0.02 and p < 0.03) increased colonic pressures compared with control but not basal activity. The increase in colonic activity after sight of food without smell or taste was not significantly different from control or basal activity (p = 0.44 and p = 0.34). Food discussion was the strongest colonic stimulus tested. Food discussion and sham feeding significantly (p<0.02) stimulated gastric acid output above control and basal values. Sight and smell of food without taste significantly (p<0.02) increased acid output above basal. Smell of food without sight or taste and sight of food without smell or taste did not significantly (p=0.06, p=0.34) increase acid output. In contrast with the effect on colonic pressures, sham feeding was the best stimulus of acid output. Increased colonic pressure activity after food discussion correlated significantly (r=0.45, p<0.02) with gastric acid output. There was no correlation (r=-0.1, p>0.5) between colonic pressure activity and gastric acid output in the control study. These data show that there is a cephalic phase of the colonic response to food.

negative: Faecal retention: a common cause in functional bowel disorders, appendicitis and haemorrhoids--with medical and surgical therapy. The present studies explored whether faecal retention in the colon is a causative factor in functional bowel disease, appendicitis, and haemorrhoids. Faecal retention was characterized by colon transit time (CTT) after radio-opaque marker ingestion and estimation of faecal loading on abdominal radiographs at 48 h and 96 h. Specific hypotheses were tested in patients (n = 251 plus 281) and in healthy random controls (n = 44). A questionnaire was completed for each patient, covering abdominal and anorectal symptoms and without a priori grouping. Patients with functional bowel disorders, predominantly women, had a significantly increased CTT and faecal load compared to controls. The CTT was significantly and positively correlated with segmental and total faecal loading. The faecal load was equal at 48 h and 96 h, mirroring the presence of permanent faecal reservoirs. In these first clinical studies to correlate bowel symptoms with CTT and colon faecal loading, abdominal bloating was significantly correlated with faecal loading in the right colon, total faecal load, and CTT. Abdominal pain was significantly and positively correlated to distal faecal loading and significantly associated with bloating. A new phenomenon with a high faecal load and a normal CTT was observed in a subset of patients (n = 90), proving faecal retention as hidden constipation. The CTT and faecal load were significantly higher in the right-side compared to the left and distal segments. Within the control group of healthy persons, the right-sided faecal load was significantly greater than the left and distal load. The CTT and faecal load significantly positively correlated with a palpable mass in the left iliac fossa and meteorism. Cluster analysis revealed that CTT and faecal load positively correlated with a symptom factor consisting of bloating, proctalgia and infrequent defecation of solid faeces. On the other hand, CTT and faecal load negatively correlated with a symptom factor comprising frequent easy defecations, repetitiveness, and incompleteness with solid or liquid faeces. The majority of patients with a heavy faecal load but normal CTT had repetitive daily defecation, mostly with ease and with altering faecal consistence. Flue-like episodes co-existed in symptom factors with abdominal pain and meteorism, and these symptoms together with a palpable right iliac fossa mass and tenderness, and in other factors with seldom and difficult defecation, and with epigastric discomfort and halitosis. Patients with seldom and difficult defecation of solid faeces experienced abdominal pain significantly more often and presented a palpable mass in the right iliac fossa with tenderness and meteorism. The CTT was significantly prolonged and faecal load significantly increased. In patients with a normal CTT and increased faecal load, only patients with abdominal pain had a significant correlation between faecal loading and bloating. CTT and faecal load were shown for the first time to increase significantly with the number of colonic redundancies (colon length), which also resulted in significantly increased bloating and pain. Intervention with a bowel stimulation regimen combining a fibre-rich diet, fluid, physical activity, and a prokinetic drug was essential to proving that abdominal symptoms and defecation disorders are caused by faecal retention, with or without a prolonged CTT. The CTT was significantly reduced, as was faecal load. Bloating and pain were reduced significantly. The defecation became easy with solid faeces, towards one per day and with significant reductions in incompleteness and repetitiveness. Proctalgia and flue-like episodes were significantly reduced. The intervention significantly reduced the presence of a tender palpable mass in the right fossa and rectal constipation. In patients with a normal CTT but increased faecal load, the intervention did not significantly change the CTT or load, but bloating and pain were significantly reduced, just as defecation improved overall. The novel knowledge of faecal retention in the patients does not explain why faecal retention occurs. However, it may be inferred from the present results that a constipated or irritable bowel may belong to the same underlying disease dimension, where faecal retention is a common factor. Thus, measuring CTT and faecal load is suggested as a guide to a positive functional diagnosis of bowel disorders compared to the constellation of symptoms alone. Thirty-five patients underwent surgery after being refractory to the conservative treatment for constipation. They had a significantly prolonged CTT and heavy faecal loading, which was responsible for the aggravated abdominal and defaecatory symptoms. The operated patients presented with a redundant colon (dolichocolon) significantly more often. These patients also had an extremely high rate of previous appendectomy. Twenty-one patients underwent hemicolectomy, and 11 patients had a subtotal colectomy with an ileosigmoidal anastomosis; three patients received a stoma. However, some patients had to have the initial segmental colectomy converted to a final subtotal colectomy because of persisting symptoms. Six more subtotal colectomies have been performed and the leakage rate of all colectomies is then 4.9 % (one patient died). After a mean follow-up of 5 years, the vast majority of patients were without abdominal pain and bloating, having two to four defecations daily with control and their quality of life had increased considerably. A faecalith is often located in the appendix, the occlusion of which is responsible for many cases of acute appendicitis, which is infrequent in all except white populations. An effort to trace the origin of the faecalith to faecal retention in the colon was made in a case control study (56 patients and 44 random controls). The CTT was longer and faecal load greater in patients with appendicitis compared to controls, though the difference was not significant. Power calculations showed that more patients were needed to reach statistical significance for these parameters. The presence of a faecalith was most often associated with a gangrenous or perforated appendix. No significant differences were found between the CTT and faecal load of patients who had or did not have a faecalith. However, the right-sided faecal load was significantly higher than the left and distal load. Haemorrhoids are often a consequence of constipation and defaecatory disorders and were found in every second patient with functional bowel disorders. The present studies are the first Danish reports of a novel operation to cure this disease, stapled haemorrhoidopexy (n = 40 and 258 patients). The majority of patients had prolapsed haemorrhoids, and the durability of procedure was confirmed with a follow-up of up to 5 years, meaning a normal anus. The operation time was short, post-operative pain was low, and recovery was rapid. No incontinence was observed, and patient satisfaction was high and significantly correlated with the appearance of a normal anus without prolapse. The cumulative risk of re-operation was greatest in the first 2 years after the stapled haemorrhoidopexy. Patients with persisting haemorrhoidal prolapse had the procedure repeated with results as good as those obtained in the rest of the patients. It was shown in a statistical model that the preoperative severity of haemorrhoidal disease and the immediate postoperative result contributed significantly to predicting the outcome that is the durability of the operation. The most frequent post-operative complication was bleeding requiring surgical haemostasis. One serious complication occurred after an anastomotic leak from a highly placed anastomosis, resulting in retro rectal, retro- and intra-peritoneal, and mediastinal gas. The patient recovered after conservative treatment and without surgical intervention. The stapling technique now used has revolutionized the surgical treatment of prolapsing haemorrhoids. Finally, a common cause may be suspected for diseases constantly associated with one another. Epidemiological evidence has recognized that constipation, diverticulosis and IBS increase the risk of colon cancer (and adenomas), diseases exceedingly rare in communities exempt from appendicitis. Haemorrhoids are a colonic co-morbidity as well. Notably, the patients with a functional bowel disorder had a much higher rate of a previous appendectomy than the background population. In addition, the patients who had previously had an appendectomy had a significantly longer CTT compared to patients, who had not. The data points to the involvement of faecal retention in the origin of faecaliths and, thus, acute appendicitis. Faecal reservoirs were shown in the right and left colon segments in both patients and controls, which are the same areas bearing the highest incidences of adenomateous polyps and malignancies. Familial colorectal cancer occurred significantly more often in patients who had a higher faecal load than the controls. Four malignancies and 25 adenomas were identified. An increased faecal load in the colon with or without delayed transit will increase bacterial counts and create a chronic inflammation of the colonic mucosa, which is a risk factor for cancer onset. A functional bowel disorder is then likely to occur with gradually transition from a primary functional disease into specific organic diseases. A diet rich in fibre and regular physical activity have a therapeutic and preventive effect on colorectal diseases associated with faecal retention.

negative: Starting at the beginning: new perspectives on the biology of mucosal T cells. The gastrointestinal tract is the central organ for uptake of fluids and nutrients, and at the same time it forms the main protective barrier between the sterile environment of the body and the outside world. In mammals, the intestine has further evolved to harbor a vast load of commensal bacteria that have important functions for the host. Discrimination by the host defense system of nonself from self can prevent invasion of pathogens, but equivalent responses to dietary or colonizing bacteria can lead to devastating consequences for the organism. This dilemma imposed by the gut environment has probably contributed significantly to the evolutionary drive that has led to sophisticated mechanisms and diversification of the immune system to allow for protection while maintaining the integrity of the mucosal barrier. The immense expansion and specialization of the immune system is particularly mirrored in the phylogeny, ontogeny, organization, and regulation of the adaptive intraepithelial lymphocytes, or IEL, which are key players in the unique intestinal defense mechanisms that have evolved in mammals.

negative: Dose-response efficacy of a proprietary probiotic formula of Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R for antibiotic-associa... OBJECTIVES: Standard therapies for antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) have limited efficacy. Probiotic prophylaxis is a promising alternative for reduction of AAD and CDAD incidence. METHODS: In this single-center, randomized, double-blind, placebo-controlled dose-ranging study, we randomized 255 adult inpatients to one of three groups: two probiotic capsules per day (Pro-2, n=86), one probiotic capsule and one placebo capsule per day (Pro-1, n=85), or two placebo capsules per day (n=84). Each probiotic capsule contained 50 billion c.f.u. of live organisms (Lactobacillus acidophilus CL1285 +Lactobacillus casei LBC80R Bio-K+ CL1285). Probiotic prophylaxis began within 36 h of initial antibiotic administration, continued for 5 days after the last antibiotic dose, and patients were followed for an additional 21 days. RESULTS: Pro-2 (15.5%) had a lower AAD incidence vs. Pro-1 (28.2%). Each probiotic group had a lower AAD incidence vs. placebo (44.1%). In patients who acquired AAD, Pro-2 (2.8 days) and Pro-1 (4.1 days) had shorter symptom duration vs. placebo (6.4 days). Similarly, Pro-2 (1.2%) had a lower CDAD incidence vs. Pro-1 (9.4%). Each treatment group had a lower CDAD incidence vs. placebo (23.8%). Gastrointestinal symptoms were less common in the treatment groups vs. placebo and in Pro-2 vs. Pro-1. CONCLUSIONS: The proprietary probiotic blend used in this study was well tolerated and effective for reducing risk of AAD and, in particular, CDAD in hospitalized patients on antibiotics. A dose-ranging effect was shown with 100 billion c.f.u., yielding superior outcomes and fewer gastrointestinal events compared to 50 billion c.f.u. (ClinicalTrials.gov number NCT00958308).

negative: Probiotics for preventing acute upper respiratory tract infections. BACKGROUND: Probiotics may improve a person's health by regulating their immune function. Some studies show that probiotic strains can prevent respiratory infections. However, no evidence of the benefits of probiotics for acute upper respiratory tract infections (URTIs) and related potential adverse effects has been published. OBJECTIVES: To assess the effectiveness and safety of probiotics for preventing acute URTIs. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (Ovid) (1950 to May week 1, 2011), EMBASE (1974 to May 2011), Web of Science which includes Science Citation Index (from 1900 to May 2011) and Conference Proceedings Citation Index (from 1991 to May 2011), the Chinese Biomedical Literature Database, which includes the China Biological Medicine Database (from 1978 to May 2011), the Chinese Medicine Popular Science Literature Database (from 2000 to May 2011) and the Masters Degree Dissertation of Beijing Union Medical College Database (from 1981 to May 2011). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing probiotics with placebo to prevent acute URTIs. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility, quality of trials and extracted data. MAIN RESULTS: We included 14 RCTs, although we could only extract available data to meta-analyse in 10 trials which involved 3451 participants. We found that probiotics were better than placebo when measuring the number of participants experiencing episodes of acute URTI: at least one episode: odds ratio (OR) 0.58; 95% confidence interval (CI) 0.36 to 0.92; at least three episodes: OR 0.53; 95% CI 0.36 to 0.80; rate ratio of episodes of acute URTI: rate ratio 0.88; 95% CI 0.81 to 0.96; and reduced antibiotic prescription rates for acute URTIs: OR 0.67; 95% CI 0.45 to 0.98. Probiotics and placebo were similar when measuring the mean duration (MD) of an episode of acute URTI: MD -0.29; 95% CI -3.71 to 3.13 and adverse events: OR 0.92; 95% CI 0.37 to 2.28. Side effects of probiotics were minor and gastrointestinal symptoms were the most common. We found that some subgroups had a high level of heterogeneity when conducting pooled analyses. AUTHORS' CONCLUSIONS: Probiotics were better than placebo in reducing the number of participants experiencing episodes of acute URTIs, the rate ratio of episodes of acute URTI and reducing antibiotic use. This indicates that probiotics may be more beneficial than placebo for preventing acute URTIs. However, the results have some limitations and there were no data for older people.

negative: Probiotics for the prevention of pediatric antibiotic-associated diarrhea. BACKGROUND: Antibiotics alter the microbial balance within the gastrointestinal tract. Probiotics may prevent antibiotic-associated diarrhea (AAD) via restoration of the gut microflora. Antibiotics are prescribed frequently in children and AAD is common in this population. OBJECTIVES: To assess the efficacy and adverse effects of probiotics (any specified strain or dose) for the prevention of antibiotic-associated diarrhea in children. To assess adverse events associated with the use of probiotics when co-administered with antibiotics in children. SEARCH STRATEGY: MEDLINE, EMBASE, CENTRAL, CINAHL , AMED, and the Web of Science (inception to August 2006) were searched along with specialized registers including the Cochrane IBD/FBD Review Group, CISCOM, Chalmers PedCAM Research Register and trial registries from inception to 2005. Letters were sent to authors of included trials, nutra/pharmaceutical companies, and experts in the field requesting additional information on ongoing or unpublished trials. Conference proceedings, dissertation abstracts, and reference lists from included and relevant articles were hand searched. SELECTION CRITERIA: Randomized, parallel, controlled (placebo, active, or no treatment) trials comparing co-administered probiotics with antibiotics for the prevention of diarrhea secondary to antibiotic use in children (0 to 18 years). DATA COLLECTION AND ANALYSIS: Methodological quality assessment and data extraction were conducted independently by two authors (BCJ, AS). Dichotomous data (incidence of diarrhea, adverse events) were combined using pooled relative risks, and continuous data (mean duration of diarrhea, mean daily stool frequency) as weighted mean differences, along with their corresponding 95% confidence intervals. Adverse events were summarized using risk difference. For overall pooled results on the incidence of diarrhea, a priori sensitivity analyses included per protocol versus intention to treat, random versus fixed effects, and methodological quality criterion. Subgroup analysis were conducted on probiotic strain, dose, definition of antibiotic-associated diarrhea, and antibiotic agent. MAIN RESULTS: Ten studies met the inclusion criteria. Trials included treatment with either Lactobacilli spp., Bifidobacterium spp., Streptococcus spp., or Saccharomyces boulardii alone or in combination. Six studies used a single strain probiotic agent and four combined two probiotic strains. The per protocol analysis for 9/10 trials reporting on the incidence of diarrhea show statistically significant results favouring probiotics over active/non active controls (RR 0.49; 95% CI 0.32 to 0.74). However, intention to treat analysis showed non-significant results overall (RR 0.90; 95% CI 0.50 to 1.63). Five of ten trials monitored for adverse events (n = 647); none reported a serious adverse event. AUTHORS' CONCLUSIONS: Probiotics show promise for the prevention of pediatric AAD. While per protocol analysis yields treatment effect estimates that are both statistically and clinically significant, as does analysis of high quality studies, the estimate from the intention to treat analysis was not statistically significant. Future studies should involve probiotic strains and doses with the most promising evidence (e.g., Lactobacillus GG, Lactobacillus sporogenes, Saccharomyces boulardii at 5 to 40 billion colony forming units/day). Research done to date does not permit determination of the effect of age (e.g., infant versus older children) or antibiotic duration (e.g., 5 days versus 10 days). Future trials would benefit from a validated primary outcome measure for antibiotic-associated diarrhea that is sensitive to change and reflects what treatment effect clinicians, parents, and children consider important. The current data are promising, but it is premature to routinely recommend probiotics for the prevention of pediatric AAD.

negative: Probiotics, prebiotics infant formula use in preterm or low birth weight infants: a systematic review Background Previous reviews (2005 to 2009) on preterm infants given probiotics or prebiotics with breast milk or mixed feeds focused on prevention of Necrotizing Enterocolitis, sepsis and diarrhea. This review assessed if probiotics, prebiotics led to improved growth and clinical outcomes in formula fed preterm infants. Methods Cochrane methodology was followed using randomized controlled trials (RCTs) which compared preterm formula containing probiotic(s) or prebiotic(s) to conventional preterm formula in preterm infants. The mean difference (MD) and corresponding 95% confidence intervals (CI) were reported for continuous outcomes, risk ratio (RR) and corresponding 95% CI for dichotomous outcomes. Heterogeneity was assessed by visual inspection of forest plots and a chi2 test. An I2 test assessed inconsistencies across studies. I2> 50% represented substantial heterogeneity. Results Four probiotics studies (N=212), 4 prebiotics studies (N=126) were included. Probiotics: There were no significant differences in weight gain (MD 1.96, 95% CI: -2.64 to 6.56, 2 studies, n=34) or in maximal enteral feed (MD 35.20, 95% CI: -7.61 to 78.02, 2 studies, n=34), number of stools per day increased significantly in probiotic group (MD 1.60, 95% CI: 1.20 to 2.00, 1 study, n=20). Prebiotics: Galacto-oligosaccharide / Fructo-oligosaccharide (GOS/FOS) yielded no significant difference in weight gain (MD 0.04, 95% CI: -2.65 to 2.73, 2 studies, n=50), GOS/FOS yielded no significant differences in length gain (MD 0.01, 95% CI: -0.03 to 0.04, 2 studies, n=50). There were no significant differences in head growth (MD −0.01, 95% CI: -0.02 to 0.00, 2 studies, n=76) or age at full enteral feed (MD −0.79, 95% CI: -2.20 to 0.61, 2 studies, n=86). Stool frequency increased significantly in prebiotic group (MD 0.80, 95% CI: 0.48 to 1.1, 2 studies, n=86). GOS/FOS and FOS yielded higher bifidobacteria counts in prebiotics group (MD 2.10, 95% CI: 0.96 to 3.24, n=27) and (MD 0.48, 95% CI: 0.28 to 0.68, n=56). Conclusions There is not enough evidence to state that supplementation with probiotics or prebiotics results in improved growth and clinical outcomes in exclusively formula fed preterm infants.

negative: Good semen quality and life expectancy: a cohort study of 43,277 men. Fertility status may predict later mortality, but no studies have examined the effect of semen quality on subsequent mortality. Men referred to the Copenhagen Sperm Analysis Laboratory by general practitioners and urologists from 1963 to 2001 were, through a unique personal identification number, linked to the Danish central registers that hold information on all cases of cancer, causes of death, and number of children in the Danish population. The men were followed until December 31, 2001, death, or censoring, whichever occurred first, and the total mortality and cause-specific mortality of the cohort were compared with those of all age-standardized Danish men or according to semen characteristics. Among 43,277 men without azospermia referred for infertility problems, mortality decreased as the sperm concentration increased up to a threshold of 40 million/mL. As the percentages of motile and morphologically normal spermatozoa and semen volume increased, mortality decreased in a dose-response manner (P(trend) < 0.05). The decrease in mortality among men with good semen quality was due to a decrease in a wide range of diseases and was found among men both with and without children; therefore, the decrease in mortality could not be attributed solely to lifestyle and/or social factors. Semen quality may therefore be a fundamental biomarker of overall male health.

negative: IELs: enforcing law and order in the court of the intestinal epithelium. The intestinal intraepithelial lymphocytes (IELs) are mostly T cells dispersed as single cells within the epithelial cell layer that surrounds the intestinal lumen. IELs are, therefore, strategically located at the interface between the antigen-rich outside world and the sterile core of the body. The intestine of higher vertebrates has further evolved to harbor numerous commensal bacteria that carry out important functions for the host, and while defensive immunity can effectively protect against the invasion of pathogens, similar immune reactions against food-derived antigens or harmless colonizing bacteria can result in unnecessary and sometimes damaging immune responses. Probably as a result of this unique dilemma imposed by the gut environment, multiple subsets of IEL have differentiated, which all display characteristics of 'activated yet resting' immune cells. Despite this common feature, IELs are heterogeneous with regard to their phenotype, ontogeny, and function. In this review, we discuss the different subtypes of IELs and highlight the distinct pathways they took that led to their unique differentiation into highly specialized effector memory T cells, which provide the most effective immune protection yet in a strictly regulated fashion to preserve the integrity and vital functions of the intestinal mucosal epithelium.

negative: Mechanisms of breast cancer bone metastasis. Bone, as well as liver and lung, is one of the most preferential metastatic target sites for cancers including breast, prostate, and lung cancers and the consequences are always devastating. Like other metastasis, breast cancer bone metastasis consists of several steps from the escape of primary site to the colonization in target site. This review focuses on several key steps including: 1. Invasion and escape from primary tumor site. 2. Target migration toward bone. 3. Specific adhesion and arrest in bone. 4. Establishment of metastasis in bone. The factors involved in this process will provide good targets for therapy. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

negative: High polyphenol, low probiotic diet for weight loss because of intestinal microbiota interaction. The relative proportion of Bacteroidetes to Firmicutes is decreased in obese people. This imbalance in gut microbiota generates signals controlling the expression of genes by the epithelial intestinal cells. Both dairy and non-dairy probiotics increase body weight, reportedly through Lactobacillus species growth in the gut. On the other hand, daily intake of some fruits and drinks such as three apples or three pears or grapefruit, or green tea, which all are rich in polyphenols, can significantly reduce body weight in obese people. Metabolism of polyphenols by microbiota involves the cleavage of glycosidic linkages. Glycans, which are the product of glycosidic cleavage, are necessary for survival of the intestinal microbiota as a nutrient foundation. There are two pivotal points: (i) Firmicutes possess a disproportionately smaller number of glycan-degrading enzymes than Bacteroidetes, (ii) Firmicutes are more repressed than the Bacteroidetes by phenolic compounds' antimicrobial properties. The Bacteroidetes community prevails following dietary polyphenol intake and its fermentation to phenolic compounds, due to having more glycan-degrading enzymes, so this may thus be a mechanism by which dietary polyphenols exert their weight lowering effect. I suggest that future studies utilize clone libraries and fingerprinting techniques enabling identification of the composition and community structure of the microbiota, and dot blot hybridization or fluorescent in situ hybridization to analyze abundance of particular taxa in obese and individuals. A supplementation with polyphenols with high bioavailability in obese individuals with higher Firmicutes/Bacteroides community ratio phenotype, when associated to a probiotic restricted diet, is proposed for weight loss; this hypothesis could have relevant implication in planning a successful dietary regimen and/or neutraceutical/pharmaceutical preparations for achieving and maintaining a normal body weight in obese individuals, especially including much more use of polyphenol-rich foodstuffs and/or polyphenol-rich syrups, and including low amounts of probiotic-rich foodstuffs like yogurt, soy yogurt, or as probiotic supplements. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

negative: 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.

negative: Initial contamination of chicken parts with Salmonella at retail and cross-contamination of cooked chicken with Salmonella from raw chicken during ... The current study was undertaken to acquire data on contamination of chicken parts with Salmonella at retail and to acquire data on cross-contamination of cooked chicken with Salmonella from raw chicken during meal preparation. Whole raw chickens (n = 31) were obtained from local retail stores and cut into two wings, two breasts without skin or bones, two thighs, and two drumsticks. Data for cross-contamination were obtained by cutting up a sterile, cooked chicken breast with the same board and knife used to cut up the raw chicken. The board, knife, and latex gloves used by the food handler were not rinsed or washed before cutting up the sterile, cooked chicken breast, thus providing a worst-case scenario for cross-contamination. Standard curves for the concentration of Salmonella bacteria in 400 ml of buffered peptone water after 6 h of incubation of chicken parts as a function of the initial log number of Salmonella bacteria inoculated onto chicken parts were developed and used to enumerate Salmonella bacteria. Standard curves were not affected by the type of chicken part but did differ (P < 0.05) among the five isolates of Salmonella examined. Consequently, Salmonella bacteria were enumerated on naturally contaminated chicken parts using a standard curve developed with the serotype of Salmonella that was isolated from the original sample. The prevalence of contamination was 3 % (4 of 132), whereas the incidence of cross-contamination was 1.8 % (1 of 57). The positive chicken parts were a thigh from chicken 4, which contained 3 CFU of Salmonella enterica serotype Kentucky, and both wings, one thigh, and one cooked breast portion from chicken 15, which all contained 1 CFU of serotype 8,20:-:z(6). These results indicated that the poultry industry is providing consumers in the studied area with chicken that has a low prevalence and low number of Salmonella bacteria at retail and that has a low incidence and low level of cross-contamination of cooked chicken with Salmonella from raw chicken during meal preparation under a worst-case scenario.

negative: Curcumin: a new paradigm and therapeutic opportunity for the treatment of osteoarthritis: curcumin for osteoarthritis management The management of osteoarthritis represents a real challenge. This complex and multi-factorial disease evolves over decades and requires not only the alleviation of symptoms, i.e. pain and joint function but also the preservation of articular structure without side effects. Nutraceuticals are good candidates for the management of OA due to their safety profile and potential efficacy. However, they are not part of the treatment guidelines and published recommendations. Curcumin is the yellow pigment isolated from the rhizomes of Curcuma longa, commonly known as turmeric. Curcumin is a highly pleiotropic molecule with an excellent safety profile. Strong molecular evidence has been published for its potency to target multiple inflammatory diseases. However, naturally occurring curcumin cannot achieve its optimum therapeutic outcomes due to its low solubility and poor bioavailability. Nevertheless, curcumin presents great potential for treating OA and has been categorized as having preclinical evidence of efficacy. This review aimed at gathering most of the available information to document the potential efficacy of curcumin based on the results obtained in in vitro models of cartilage and osteoarthritis and in other diseases.

negative: Mechanisms of antimicrobial resistance in bacteria. The treatment of bacterial infections is increasingly complicated by the ability of bacteria to develop resistance to antimicrobial agents. Antimicrobial agents are often categorized according to their principal mechanism of action. Mechanisms include interference with cell wall synthesis (e.g., beta-lactams and glycopeptide agents), inhibition of protein synthesis (macrolides and tetracyclines), interference with nucleic acid synthesis (fluoroquinolones and rifampin), inhibition of a metabolic pathway (trimethoprim-sulfamethoxazole), and disruption of bacterial membrane structure (polymyxins and daptomycin). Bacteria may be intrinsically resistant to > or =1 class of antimicrobial agents, or may acquire resistance by de novo mutation or via the acquisition of resistance genes from other organisms. Acquired resistance genes may enable a bacterium to produce enzymes that destroy the antibacterial drug, to express efflux systems that prevent the drug from reaching its intracellular target, to modify the drug's target site, or to produce an alternative metabolic pathway that bypasses the action of the drug. Acquisition of new genetic material by antimicrobial-susceptible bacteria from resistant strains of bacteria may occur through conjugation, transformation, or transduction, with transposons often facilitating the incorporation of the multiple resistance genes into the host's genome or plasmids. Use of antibacterial agents creates selective pressure for the emergence of resistant strains. Herein 3 case histories-one involving Escherichia coli resistance to third-generation cephalosporins, another focusing on the emergence of vancomycin-resistant Staphylococcus aureus, and a third detailing multidrug resistance in Pseudomonas aeruginosa--are reviewed to illustrate the varied ways in which resistant bacteria develop.

negative: The Prevalence of Phosphorus Containing Food Additives in Top Selling Foods in Grocery Stores Objective To determine the prevalence of phosphorus-containing food additives in best selling processed grocery products and to compare the phosphorus content of a subset of top selling foods with and without phosphorus additives. Design The labels of 2394 best selling branded grocery products in northeast Ohio were reviewed for phosphorus additives. The top 5 best selling products containing phosphorus additives from each food category were matched with similar products without phosphorus additives and analyzed for phosphorus content. Four days of sample meals consisting of foods with and without phosphorus additives were created and daily phosphorus and pricing differentials were computed. Setting Northeast Ohio Main outcome measures Presence of phosphorus-containing food additives, phosphorus content Results 44% of the best selling grocery items contained phosphorus additives. The additives were particularly common in prepared frozen foods (72%), dry food mixes (70%), packaged meat (65%), bread & baked goods (57%), soup (54%), and yogurt (51%) categories. Phosphorus additive containing foods averaged 67 mg phosphorus/100 gm more than matched non-additive containing foods (p=.03). Sample meals comprised mostly of phosphorus additive-containing foods had 736 mg more phosphorus per day compared to meals consisting of only additive-free foods. Phosphorus additive-free meals cost an average of $2.00 more per day. Conclusion Phosphorus additives are common in best selling processed groceries and contribute significantly to their phosphorus content. Moreover, phosphorus additive foods are less costly than phosphorus additive-free foods. As a result, persons with chronic kidney disease may purchase these popular low-cost groceries and unknowingly increase their intake of highly bioavailable phosphorus.

negative: Review of harmful gastrointestinal effects of carrageenan in animal experiments. In this article I review the association between exposure to carrageenan and the occurrence of colonic ulcerations and gastrointestinal neoplasms in animal models. Although the International Agency for Research on Cancer in 1982 identified sufficient evidence for the carcinogenicity of degraded carrageenan in animals to regard it as posing a carcinogenic risk to humans, carrageenan is still used widely as a thickener, stabilizer, and texturizer in a variety of processed foods prevalent in the Western diet. I reviewed experimental data pertaining to carrageenan's effects with particular attention to the occurrence of ulcerations and neoplasms in association with exposure to carrageenan. In addition, I reviewed from established sources mechanisms for production of degraded carrageenan from undegraded or native carrageenan and data with regard to carrageenan intake. Review of these data demonstrated that exposure to undegraded as well as to degraded carrageenan was associated with the occurrence of intestinal ulcerations and neoplasms. This association may be attributed to contamination of undegraded carrageenan by components of low molecular weight, spontaneous metabolism of undegraded carrageenan by acid hydrolysis under conditions of normal digestion, or the interactions with intestinal bacteria. Although in 1972, the U.S. Food and Drug Administration considered restricting dietary carrageenan to an average molecular weight > 100,000, this resolution did not prevail, and no subsequent regulation has restricted use. Because of the acknowledged carcinogenic properties of degraded carrageenan in animal models and the cancer-promoting effects of undegraded carrageenan in experimental models, the widespread use of carrageenan in the Western diet should be reconsidered.

negative: A comparative review of thermography as a breast cancer screening technique. Breast cancer is the most frequently diagnosed cancer of women in North America. Despite advances in treatment that have reduced mortality, breast cancer remains the second leading cause of cancer induced death. Several well established tools are used to screen for breast cancer including clinical breast exams, mammograms, and ultrasound. Thermography was first introduced as a screening tool in 1956 and was initially well accepted. However, after a 1977 study found thermography to lag behind other screening tools, the medical community lost interest in this diagnostic approach. This review discusses each screening tool with a focus brought to thermography. No single tool provides excellent predictability; however, a combination that incorporates thermography may boost both sensitivity and specificity. In light of technological advances and maturation of the thermographic industry, additional research is required to confirm the potential of this technology to provide an effective non-invasive, low risk adjunctive tool for the early detection of breast cancer.

negative: Globalization, diet, and health: an example from Tonga. The increased flow of goods, people, and ideas associated with globalization have contributed to an increase in noncommunicable diseases in much of the world. One response has been to encourage lifestyle changes with educational programmes, thus controlling the lifestyle-related disease. Key assumptions with this approach are that people's food preferences are linked to their consumption patterns, and that consumption patterns can be transformed through educational initiatives. To investigate these assumptions, and policies that derive from it, we undertook a broad-based survey of food-related issues in the Kingdom of Tonga using a questionnaire. Data on the relationships between food preferences, perception of nutritional value, and frequency of consumption were gathered for both traditional and imported foods. The results show that the consumption of health-compromising imported foods was unrelated either to food preferences or to perceptions of nutritional value, and suggests that diet-related diseases may not be amenable to interventions based on education campaigns. Given recent initiatives towards trade liberalization and the creation of the World Trade Organization, tariffs or import bans may not serve as alternative measures to control consumption. This presents significant challenges to health policy-makers serving economically marginal populations and suggests that some population health concerns cannot be adequately addressed without awareness of the effects of global trade.

negative: Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: An updated systematic evidence review for the U.S. ... BACKGROUND: Vitamin and mineral supplements are commonly used to prevent chronic diseases. PURPOSE: To systematically review evidence for the benefit and harms of vitamin and mineral supplements in community-dwelling, nutrient-sufficient adults for the primary prevention of cardiovascular disease (CVD) and cancer. DATA SOURCES: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Database of s of Reviews of Effects were searched from January 2005 to 29 January 2013, with manual searches of reference lists and gray literature. STUDY SELECTION: Two investigators independently selected and reviewed fair- and good-quality trials for benefit and fair- and good-quality trials and observational studies for harms. DATA EXTRACTION: Dual quality assessments and data abstraction. DATA SYNTHESIS: Two large trials (n = 27 658) reported lower cancer incidence in men taking a multivitamin for more than 10 years (pooled unadjusted relative risk, 0.93 [95% CI, 0.87 to 0.99]). The study that included women showed no effect in that group. High-quality studies (k = 24; n = 324 653) of single and paired nutrients (such as vitamins A, C, or D; folic acid; selenium; or calcium) were scant and heterogeneous and showed no clear evidence of benefit or harm. Neither vitamin E nor β-carotene prevented CVD or cancer, and β-carotene increased lung cancer risk in smokers. LIMITATIONS: The analysis included only primary prevention studies in adults without known nutritional deficiencies. Studies were conducted in older individuals and included various supplements and doses under the set upper tolerable limits. Duration of most studies was less than 10 years. CONCLUSION: Limited evidence supports any benefit from vitamin and mineral supplementation for the prevention of cancer or CVD. Two trials found a small, borderline-significant benefit from multivitamin supplements on cancer in men only and no effect on CVD. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

negative: Can nutrition limit exercise-induced immunodepression? Prolonged exercise and heavy training are associated with depressed immune cell function. To maintain immune function, athletes should eat a well-balanced diet sufficient to meet their energy, carbohydrate, protein, and micronutrient requirements. Consuming carbohydrate during prolonged strenuous exercise attenuates rises in stress hormones and appears to limit the degree of exercise-induced immune depression. Recent evidence suggests that antioxidant vitamin supplementation may also reduce exercise stress and impairment of leukocyte functions. Further research is needed to evaluate the effects of other antioxidants and dietary immunostimulants such as probiotics and echinacea on exercise-induced immune impairment.

negative: Antimicrobial Traits of Tea- and Cranberry-Derived Polyphenols against Streptococcus mutans There are over 750 species of bacteria that inhabit the human oral cavity, but only a small fraction of those are attributed to causing plaque-related diseases such as caries. Streptococcus mutans is accepted as the main cariogenic agent and there is substantial knowledge regarding the specific virulence factors that render the organism a pathogen. There has been rising interest in alternative, target-specific treatment options as opposed to nonspecific mechanical plaque removal or application of broad-spectrum antibacterials that are currently in use. The impact of diet on oral health is undeniable, and this is directly observable in populations that consume high quantities of polyphenol-rich foods or beverages. Such populations have low caries incidence and better overall oral health. Camellia sinensis, the plant from which various forms of tea are derived, and Vaccinium macrocarpon (American cranberry fruit) have received notable attention both for their prevalence in the human diet as well as for their unique composition of polyphenols. The biologically active constituents of these plants have demonstrated potent enzyme-inhibitory properties without being bactericidal, a key quality that is important in developing therapies that will not cause microorganisms to develop resistance. The aim of this review is to consider studies that have investigated the feasibility of tea, cranberry, and other select plant derivatives as a potential basis for alternative therapeutic agents against Streptococcus mutans and to evaluate their current and future clinical relevance.

negative: Several culinary and medicinal herbs are important sources of dietary antioxidants. We assessed the contribution of culinary and medicinal herbs to the total intake of dietary antioxidants. Our results demonstrate that there is more than a 1000-fold difference among antioxidant concentrations of various herbs. Of the dried culinary herbs tested, oregano, sage, peppermint, garden thyme, lemon balm, clove, allspice and cinnamon as well as the Chinese medicinal herbs Cinnamomi cortex and Scutellariae radix all contained very high concentrations of antioxidants (i.e., >75 mmol/100 g). In a normal diet, intake of herbs may therefore contribute significantly to the total intake of plant antioxidants, and be an even better source of dietary antioxidants than many other food groups such as fruits, berries, cereals and vegetables. In addition, the herbal drug, Stronger Neo-Minophagen C, a glycyrrhizin preparation used as an intravenous injection for the treatment of chronic hepatitis, boosts total antioxidant intake. It is tempting to speculate that several of the effects due to these herbs are mediated by their antioxidant activities.

negative: Dietary seaweed modifies estrogen and phytoestrogen metabolism in healthy postmenopausal women. Seaweed and soy foods are consumed daily in Japan, where breast cancer rates for postmenopausal women are significantly lower than in the West. Likely mechanisms include differences in diet, especially soy consumption, and estrogen metabolism. Fifteen healthy postmenopausal women participated in this double-blind trial of seaweed supplementation with soy challenge. Participants were randomized to 7 wk of either 5 g/d seaweed (Alaria) or placebo (maltodextrin). During wk 7, participants also consumed a daily soy protein isolate (2 mg isoflavones/kg body weight). After a 3-wk washout period, participants were crossed over to the alternate supplement schedule. There was an inverse correlation between seaweed dose (mg/kg body weight) and serum estradiol (E2) (seaweed-placebo = y = -2.29 x dose + 172.3; r = -0.70; P = 0.003), [corrected] which was linear across the range of weights. Soy supplementation increased urinary daidzein, glycitein, genistein, and O-desmethylangolensin (P = 0.0001) and decreased matairesinol and enterolactone (P < 0.05). Soy and seaweed plus soy (SeaSoy) increased urinary excretion of 2-hydroxyestrogen (2-OHE) (P = 0.0001) and the ratio of 2-OHE:16alpha-hydroxyestrone (16alphaOHE(1)) (P = 0.01). For the 5 equol excretors, soy increased urinary equol excretion (P = 0.0001); the combination of SeaSoy further increased equol excretion by 58% (P = 0.0001). Equol producers also had a 315% increase in 2:16 ratio (P = 0.001) with SeaSoy. Seaweed favorably alters estrogen and phytoestrogen metabolism and these changes likely include modulation of colonic bacteria.

negative: Long-term health and quality-of-life consequences of mass screening for childhood celiac disease: a 10-year follow-up study. OBJECTIVE: Mass screening for celiac disease is controversial. The objective of this study was to determine whether detection of childhood celiac disease by mass screening improves long-term health status and health-related quality of life. METHODS: We conducted a prospective 10-year follow-up study of 32 children who were aged 2 to 4 years, had celiac disease identified by mass screening, and had a gluten-free diet (19) or a normal gluten-containing diet (13). The follow-up included assessments of general health status, celiac disease-associated symptoms, celiac disease-associated serum antibodies, and health-related quality of life. RESULTS: Ten years after mass screening, 81% of the children were adhering to a gluten-free diet. The health status improved in 66% of the treated children: in 41% by early treatment and in 25% by prevention of the gluten-dependent symptoms that they developed after diagnosis. For 19% of the children, treatment after screening would not have improved their health status, because they had no symptoms at screening and have remained symptom-free while consuming gluten. The health-related quality of life of the children with symptoms improved significantly after 1 year of gluten-free diet. Ten years after screening, the health-related quality of life of the children with celiac disease was similar to that of the reference population. CONCLUSION: Identification by mass screening led 10 years later to health improvement in 66% of children without deterioration of generic health-related quality of life. There is a good compliance after mass screening. In a research setting, delaying treatment for children without symptoms seems to be an option after a positive screening test. Long-term follow-up studies are needed to assess possible long-term complications in untreated, nonsymptomatic celiac disease.

negative: Fibromyalgia and nutrition, what do we know? Many people suffer from fibromyalgia (FM) without an effective treatment. They do not have a good quality of life and cannot maintain normal daily activity. Among the different hypotheses for its ethiopathophysiology, oxidative stress is one of the possibilities. Non-scientific information addressed to patients regarding the benefits of nutrition is widely available, and they are used to trying non-evidenced strategies. The aim of this paper is to find out what we know right now from scientific studies regarding fibromyalgia disease and nutritional status, diets and food supplements. A systematic search has been performed on Medline with a wide range of terms about these nutritional issues. The search has been made during 2009, for articles published between 1998 and 2008. TARGET POPULATION: people suffering from FM. Vegetarian diets could have some beneficial effects probably due to the increase in antioxidant intake. There is a high prevalence of obesity and overweight in patients, and weight control seems to be an effective tool to improve the symptoms. Some nutritional deficiencies have been described, it is not clear whether they are directly related to this disease or not. About the usefulness of some food supplements we found very little data, and it seems that more studies are needed to prove which ones could be of help. Dietary advice is necessary to these patients to improve their diets and maintain normal weight. It would be interesting to investigate more in the field of nutrition and FM to reveal any possible relationships.

negative: Overview of antibacterial, antitoxin, antiviral, and antifungal activities of tea flavonoids and teas. Tea leaves produce organic compounds that may be involved in the defense of the plants against invading pathogens including insects, bacteria, fungi, and viruses. These metabolites include polyphenolic compounds, the six so-called catechins, and the methyl-xanthine alkaloids caffeine, theobromine, and theophylline. Postharvest inactivation of phenol oxidases in green tea leaves prevents oxidation of the catechins, whereas postharvest enzyme-catalyzed oxidation (fermentation) of catechins in tea leaves results in the formation of four theaflavins as well as polymeric thearubigins. These substances impart the black color to black teas. Black and partly fermented oolong teas contain both classes of phenolic compounds. A need exists to develop a better understanding of the roles of polyphenolic tea compounds in food and medical microbiology. This overview surveys and interprets our present knowledge of activities of tea flavonoids and teas against foodborne and other pathogenic bacteria, virulent protein toxins produced by some of the bacteria, virulent bacteriophages, pathogenic viruses and fungi. Also covered are synergistic, mechanistic, and bioavailability aspects of the antimicrobial effects. Further research is suggested for each of these categories. The herein described findings are not only of fundamental interest, but also have practical implications for nutrition, food safety, and animal and human health.

negative: A diet low in animal fat and rich in N-hexacosanol and fisetin is effective in reducing symptoms of Parkinson's disease. This study describes how foods rich in fisetin and hexacosanol added to a strict diet reversed most symptoms of Parkinson's disease (PD) in one patient. This is a case report involving outpatient care. The subject was a dietitian diagnosed with idiopathic PD in 2000 at the age of 53 years old, with a history of exposure to neurotoxins and no family history of PD. A basic diet started in 2000 consisted of predominantly fruits, vegetables, 100% whole grains, extra virgin olive oil, nuts, seeds, nonfat milk products, tea, coffee, spices, small amounts of dark chocolate, and less than 25 g of animal fat daily. The basic diet alone failed to prevent decline due to PD. In 2009, the basic diet was enhanced with a good dietary source of both fisetin and hexacosanol. Six months after the patient started the enhanced diet rich in fisetin and hexacosanol, a clinically significant improvement in symptoms was noted; the patient's attending neurologist reported that the clinical presentation of cogwheel rigidity, micrographia, bradykinesia, dystonia, constricted arm swing with gait, hypomimia, and retropulsion appeared to be resolved. The only worsening of symptoms occurred when the diet was not followed precisely. Little improvement in tremor or seborrhea was observed. The clinical improvement has persisted to date. To the best of our knowledge, this is the first case where adjunctive diet therapy resulted in a significant reduction of symptoms of PD without changing the type or increasing the amount of medications.

negative: Preventing and arresting coronary atherosclerosis. The good news about coronary atherosclerosis is that it takes an awful lot of plaque before symptoms of myocardial ischemia occur. The bad news is that despite the need for large quantities of plaque for symptoms to occur, nevertheless nearly half of us in the United States eventually have the necessary quantity. Atherosclerosis is infrequently hereditary in origin. Most of us get atherosclerosis because we consume too much fat, cholesterol, and calories. The consequence is an elevated ( > 150 mg/dl) serum total cholesterol level, and the higher the number is above 150, the greater is the quantity of plaque deposited in our arteries. If the serum total cholesterol level can be prevented from rising to more than 150 mg/dl, plaques are not laid down; if elevated levels are lowered to 150 mg/dl, further plaque does not form, and parts of those present may vanish. A fruit-vegetarian-starch diet is necessary as a rule to achieve the 150 mg/dl level in most adults. Lipid-lowering drugs are required in the patients with familial hypercholesterolemia and in most patients with atherosclerotic events. The best news about atherosclerosis is that it can be prevented in those without the hereditary form, and it can be arrested by lowering elevated serum total (and LDL) cholesterol to the 150 mg/dl level.