bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and Histologic Spectrum of Nonalcoholic Fatty Liver Disease Associated With Normal Alt Values
Authors: Mofrad Pouneh , Contos Melissa J. , Haque Mahmadul , Sargeant Carol , Fisher Robert A. , Luketic Velimir A. , Sterling Richard K. , Shiffman Mitchell L. , Stravitz Richard T. , Sanyal Arun J.
Published: May 2003

A retrospective study was performed to (1) characterize the clinical and histologic features of those with nonalcoholic fatty liver disease (NAFLD) and normal alanine aminotransferase (ALT) values, (2) compare the spectrum of NAFLD associated with normal versus elevated ALT levels, and (3) determine whether there were differences in the clinical or histologic spectrum of NAFLD between those with a low normal versus high normal ALT value. A total of 51 subjects with NAFLD and normal ALT were identified and compared with 50 consecutive subjects with NAFLD and elevated ALT. The major indications for liver biopsy in those with normal ALT were unexplained hepatomegaly (n = 21) and evaluation as a potential donor for living donor liver transplantation (n = 16). The 2 groups were comparable with respect to age, gender distribution, and ethnicity. Approximately 80% of cases in both groups had at least 1 feature of the metabolic syndrome, the major risk factor for NAFLD. The 2 groups were also comparable with respect to the grade of the individual histologic parameters of NAFLD. A total of 12 subjects with normal ALT levels had bridging fibrosis, whereas 6 had cirrhosis. Diabetes was the only factor independently associated with an increased risk of advanced fibrosis (bridging fibrosis or cirrhosis) by multivariate analysis (relative risk: 2.3, P < .01). The mean steatosis (1.6 vs. 2.16, P < .04) and perisinusoidal fibrosis scores (0.35 vs. 0.9, P < .049) were lower in those with low normal (<30 IU/L) ALT versus high normal ALT. However, the prevalence of advanced fibrosis was similar (5 of 15 vs. 13 of 36, respectively). In conclusion, (1) the entire histologic spectrum of NAFLD can be seen in individuals with normal ALT values, (2) the histologic spectrum in these individuals is not significantly different from those with elevated ALT levels, and (3) a low normal ALT value does not guarantee freedom from underlying steatohepatitis with advanced fibrosis.
Mechanisms for Sensitization to Tnf–Induced Apoptosis by Acute Glutathione Depletion in Murine Hepatocytes
Authors: Matsumaru Katsuhiko , Ji Cheng , Kaplowitz Neil
Published: May 2003

We previously reported that depletion of glutathione in murine hepatocytes by diethylmaleate (DEM) or acetaminophen (APAP) leads to oxidative stress—dependent necrosis and sensitizes to tumor necrosis factor (TNF)–induced apoptosis in an oxidative stress—independent fashion, which could not be explained by interference with nuclear factor κB (NF–κB) nuclear translocation. The present report explores the mechanisms of these effects. We observed that DEM led to necrosis when both mitochondrial and cytosol glutathione were depleted profoundly but sensitized to TNF–induced apoptosis when cytosol glutathione was depleted selectively. DEM and APAP lead to a significant decrease in reduced glutathione (GSH)/glutathione disulfide (GSSG) ratio. Glutathione depletion by DEM or APAP was associated with inhibition of TNF–induced NF–κB transactivation of anti–apoptotic genes, including inducible nitric oxide synthase (i–NOS). Provision of exogenous NO partially abrogated the sensitization to TNF in response to glutathione depletion. Glutathione depletion alone led to sustained increase in phospho–jun levels and c–Jun–N–terminal kinase (JNK) activity. JNK inhibitor partially blocked the sensitization to TNF–induced apoptosis accompanying glutathione depletion. In conclusion, these findings suggest that extramitochondrial glutathione depletion alters the thiol–disulfide redox state, leading to inhibition of NF–κB transactivation of survival genes and to sustained activation of JNK, both of which contribute to the sensitization to TNF–induced apoptosis.
Oxidant–Induced Hepatocyte Injury From Menadione Is Regulated by Erk and Ap–1 Signaling
Authors: Czaja Mark J. , Liu Hailing , Wang Yongjun
Published: May 2003

Oxidative stress has been implicated as a mechanism for a variety of forms of liver injury. Although reactive oxygen species (ROS) may damage cellular macromolecules directly, oxidant–induced cell death may result from redox effects on signal transduction pathways. To understand the mechanisms of hepatocyte death from oxidative stress, the functions of the mitogen–activated protein kinases (MAPKs) were determined during oxidant–induced hepatocyte injury from menadione. Low, nontoxic, and high toxic concentrations of the superoxide generator menadione were established in the RALA255–10G rat hepatocyte cell line. Death from menadione was blocked by catalase and ebselen, indicating that death was secondary to oxidant generation and not arylation. Treatment with a nontoxic menadione concentration resulted in a brief activation of extracellular signal–regulated kinase (ERK) and c–Jun N–terminal kinase (JNK). In contrast, treatment with a toxic menadione concentration induced a prolonged activation of both ERK and JNK. Chemical inhibition of ERK function sensitized RALA hepatocytes to death from previously nontoxic menadione concentrations in association with sustained JNK activation. Adenoviral expression of a dominant–negative protein for c–Jun, a downstream substrate for JNK, blocked death from menadione. The pro–apoptotic effect of c–Jun was not mediated through the mitochondrial death pathway. In conclusion, RALA hepatocyte resistance to oxidant–induced death from menadione is dependent on ERK, whereas cell death is mediated by AP–1 activation. These findings identify signaling pathways that may be therapeutic targets in the prevention or treatment of oxidant–induced liver injury.
A Multicenter Study of Recombinant Human Interleukin 12 for the Treatment of Chronic Hepatitis C Virus Infection in Patients Nonresponsive to Previous Therapy
Authors: Pockros Paul J. , Patel Keyvr , O'Brien Christopher , Tong Myron , Smith Coleman , Rustgi Vinod , Carithers Robert L. , McHutchison John G. , Olek Elizabeth , DeBruin Michael F.
Published: May 2003

Recombinant human interleukin 12 (IL–12) is an immunomodulatory cytokine that is active against several viruses. Treatment options in patients with chronic hepatitis C with nonresponse to interferon (IFN)–based therapy are limited. Prior dose–ranging studies have indicated drug tolerability and transient suppression of hepatitis C virus (HCV) RNA by IL–12. The aim of this study was to determine the safety and efficacy of prolonged IL–12 therapy in patients who have failed treatment with IFN–α ± ribavirin. A total of 225 patients at 21 U.S. sites who had a history of nonresponse to IFN–α or combination IFN–α plus ribavirin for treatment of HCV were randomized to 500 ng/kg IL–12 or placebo subcutaneously twice weekly for 12 weeks. The groups were then unblinded; patients receiving IL–12 continued for another 36 weeks, and the placebo group received 48 weeks of treatment with IL–12 in an open–label fashion. HCV RNA, serum alanine aminotransferase (ALT) level, and a repeat liver biopsy were assessed at 24 weeks following therapy. Approximately 1% (2 of 160) of nonresponsive patients enrolled for treatment had a sustained virologic response to IL–12 therapy, but 3% (7 of 225) developed severe adverse events probably related to treatment, resulting in early termination of the trial. Common adverse effects reported by most patients included chills, fever, fatigue, headache, and arthralgia. At termination of the study, 160 patients had received at least 8 weeks of treatment with IL–12. Paired liver biopsy specimens were available for evaluation in 54 patients, but there were no significant changes in Knodell fibrosis or histologic activity index (HAI) scores. In conclusion, IL–12 as monotherapy at the doses used in this trial for chronic hepatitis C has low efficacy, was poorly tolerated, and is unlikely to provide an alternative to conventional IFN–based therapy.
Sources of semiochemicals mediating host finding inCallosobruchus chinensis(Coleoptera: Bruchidae)
Authors: Babu A. , Hern A. , Dorn S.
Published: May 2003

Bruchid pests such asCallosobruchus chinensis(Linnaeus) endanger stored legume seeds throughout the tropical belt. The chemical composition of the headspace volatiles from healthy and fourth instar larvae-infested cowpea seeds were identified, characterized, and compared using gas chromatography–mass spectrometry. Y-tube olfactometer bioassays were performed to evaluate the effect of these chemicals on the orientation of conspecific adult females. Analysis of volatiles released from healthy and infested seeds revealed qualitative differences for three out of the 17 compounds identified. Dimethyl disulphide, isobutenyl methyl ketone and methyl trisulphide were found only in the blend emitted from infested but not from healthy seeds. Quantitative differences were apparent for tridecane which was released in larger amounts from infested seeds. While volatiles collected from healthy seeds were attractive to female bruchids, volatiles collected from infested seeds were repellent. To test the hypothesis that the qualitative differences in the chemical composition found may be due to insect-derived components, the volatiles from frass and fourth instar larvae combined were analysed. These volatiles contained both of the sulphides emitted from infested seed but not from healthy seeds. Although a limited induction of volatiles from cowpea seeds cannot be excluded, it is postulated that behavioural differences of the female weevils are largely due to insect-derived semiochemicals. The potential use of such semiochemicals as part of an integrated pest management strategy is discussed.
Diving beetles (Dytiscidae) as predators of mosquito larvae (Culicidae) in field experiments and in laboratory tests of prey preference
Authors: Lundkvist E. , Landin J. , Jackson M. , Svensson C.
Published: May 2003

Field experiments were performed in artificial ponds to evaluate how the density of predatory diving beetles (Dytiscidae) would affect the population levels of mosquito larvae (Culicidae). Mosquitoes colonizing the ponds were predominantly species of the genus Culex. In 2000, most of the dytiscids colonizing the ponds were small (Hydroporus spp.), and these predators had no impact on the size of larval mosquito populations, not even in ponds with added dytiscids. In 2001, larger beetles (Ilybius, Rhantus, and Agabus spp.) were more common, and there were significantly fewer mosquito larvae in ponds with the highest numbers of dytiscids. There was a negative correlation between numbers of diving beetles in the ponds and the mean body length of mosquito larvae. In neither year could dytiscid densities be maintained above a certain level owing to emigration. In laboratory tests, there were marked differences between three common dytiscid species in regard to preferences for Daphnia and Culex species as prey: Colymbetes paykulli Erichson chose mosquito larvae more often, whereas both Ilybius ater (De Geer) and I. fuliginosus (Fabricius) preferred Daphnia spp. All of the tested dytiscids consumed large numbers of prey. Since some dytiscid species can efficiently decrease populations of mosquito larvae, they are probably important in the natural control of these dipterans.
The active fraction of psyllium seed husk
Authors: Marlett Judith A. , Fischer Milton H.
Published: May 2003

A series of experiments and evaluations of fractions isolated from psyllium seed husk (PSH) were used to test the overall hypothesis that a gel-forming component of PSH is not fermented and that it is this component that is responsible for the laxative and cholesterol-lowering properties of PSH. A gel is isolated from human stools collected during a controlled diet study when PSH is consumed but not when the control diet only is consumed. Evaluations of three fractions isolated from PSH suggest that gel-forming fraction B, which is about 55% of PSH, is poorly fermented and is the component that increases stool moisture and faecal bile acid excretion, the latter leading to lower blood cholesterol levels. Fraction C, representing <15% of PSH, is viscous, but is rapidly fermented. Fraction A is alkali-insoluble material that is not fermented. In concentrations comparable with their presence in PSH, fractions A and C do not alter moisture and bile acid output. The active fraction of PSH is a highly-branched arabinoxylan consisting of a xylose backbone and arabinose- and xylose-containing side chains. In contrast to arabinoxylans in cereal grains that are extensively fermented, PSH possesses a structural feature, as yet unidentified, that hinders its fermentation by typical colonic microflora.
Dietary fibre analysis
Authors: McCleary Barry V.
Published: May 2003

The 'gold standard' method for the measurement of total dietary fibre is that of the Association of Official Analytical Chemists (2000; method 985.29). This procedure has been modified to allow measurement of soluble and insoluble dietary fibre, and buffers employed have been improved. However, the recognition of the fact that non-digestible oligosaccharides and resistant starch also behave physiologically as dietaryfibre has necessitated a re-examination of the definition of dietary fibre, and in turn, a re-evaluation of the dietary fibre methods of the Association of Official Analytical Chemists. With this realisation, the American Association of Cereal Chemists appointed a scientific review committee and charged it with the task of reviewing and, if necessary, updating the definition of dietary fibre. It organised various workshops and acceptedcomments from interested parties worldwide through an interactive website. More recently, the (US) Food and Nutrition Board of the Institute of Health, National Academy of Sciences, under the oversight of the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, assembled a panel to develop a proposed definition(s) of dietary fibre. Various elements of these definitions were in agreement, but not all. What was clear from both reviews is that there is an immediate need to re-evaluate the methods that are used for dietary fibre measurement and to make appropriate changes where required, and to find new methods to fill gaps. In this presentation, the 'state of the art' in measurement of total dietary fibre and dietary fibre components will be described and discussed, together with suggestions for future research.
Colonic mucin: methods of measuring mucus thickness
Authors: Strugala Vicki , Allen Adrian , Dettmar Peter W. , Pearson Jeffrey P.
Published: May 2003

Mucus is a water-insoluble gel secreted by the gastrointestinal tract. It exists as a protective gel layer adherent to the epithelial surface of the stomach, small intestine and colon. The mucus gel is composed of 1–10% (w/v) mucin glycoprotein in a plasma-like fluid. Since the mucus gel is predominantly water, standard histological techniques dehydrate the mucus, making visualisation of the functional barrier difficult. Specialist techniques have been developed to enable visualisation of the intact mucus layer. A simple histological method using snap-frozen tissue, sectioned with a cryostat and stained with modified periodic acid-Schiff s/Alcian blue in mucus-preserving conditions will be described. A second powerfulin vivoanimal model is described which enables measurement of mucus secretion over time. The use of these two methods has allowed the characterisation of the normal mucus layer in the colon and the determination of how it is affected by disease and dietary intervention, in particular the effect of dietary fibre, and evidence that fibre deficiency results in colonic mucosal fragility is presented.
Regulation of short-chain fatty acid production
Authors: Macfarlane Sandra , Macfarlane George T.
Published: May 2003

Short-chain fatty acid (SCFA) formation by intestinal bacteria is regulated by many different host, environmental, dietary and microbiological factors. In broad terms, however, substrate availability, bacterial species composition of the microbiota and intestinal transit time largely determine the amounts and types of SCFA that are produced in healthy individuals. The majority of SCFA in the gut are derived from bacterial breakdown of complex carbohydrates, especially in the proximal bowel, but digestion of proteins and peptides makes an increasing contribution to SCFA production as food residues pass through the bowel. Bacterial hydrogen metabolism also affects the way in which SCFA are made. This outcome can be seen through the effects of inorganic electron acceptors (nitrate, sulfate) on fermentation processes, where they facilitate the formation of more oxidised SCFA such as acetate, at the expense of more reduced fatty acids, such as butyrate. Chemostat studies using pure cultures of saccharolytic gut micro-organisms demonstrate that C availability and growth rate strongly affect the outcome of fermentation. For example, acetate and formate are the major bifidobacterial fermentation products formed during growth under C limitation, whereas acetate and lactate are produced when carbohydrate is in excess. Lactate is also used as an electron sink inClostridium perfringensand, to a lesser extent, inBacteroides fragilis. In the latter organism acetate and succinate are the major fermentation products when substrate is abundant, whereas succinate is decarboxylated to produce propionate when C and energy sources are limiting.
Dietary fibre intake and clinical indices in the French Supplementation en Vitamines et Minéraux AntioXydants (SU.VI.MAX) adult cohort
Authors: Lairon Denis , Bertrais Sandrine , Vincent Stephanie , Arnault Nathalie , Galan Pilar , Boutron Marie-Christine , Hercberg Serge
Published: May 2003

The aim of our study was to investigate the relationship between dietary fibre intake and some clinical indices, blood biochemical variables and the incidence of cardiovascular disease and cancers in France, taking advantage of an ongoing cohort, the Supplementation en Vitamines et Minéraux AntioXydants (SU.VI.MAX) intervention study. This preliminary report provides data on dietary fibre intake in this French adult population group of 4080 subjects (2168 men and 1912 women) aged 45–65 years at inclusion. The data obtained for fibre intake indicate that most men and women have low to moderate intakes of total dietary fibre (mean 21·0 and 17·1 g/d respectively), with only 21% of the men and 7% of the women having total dietary fibre intakes at the recommended level (i.e. >25 g/d) and soluble fibre accounting for 19% of the total dietary fibre intake for both genders. The main food sources of dietary fibre are cereals (30–35% total), vegetables (20–24% total) and fruit (19–22% total). No marked regional differences were observed within France. The highest dietary fibre intakes have been found to be associated with a lower BMI, blood systolic pressure, plasma triacylglycerols and plasma glucose in men and lower BMI in women. Overall, these data support the concept of a beneficial effect of a high dietary fibre intake on cardiovascular disease risk.
New insight into butyrate metabolism
Authors: Knudsen Knud Erik Bach , Serena Anja , Canibe Nuria , Juntunen Katri S.
Published: May 2003

Butyrate is a C4acid produced by microbial fermentation of carbohydrates and protein in the large intestine of all animal species. The factor of prime importance for the production rate of butyrate in the lower gut is type and levels of non-digestible carbohydrates entering the large intestine. It was previously believed that 85–90% of the butyrate produced in the gut was cleared when passing the gut epithelium, but recent studies with catheterised pigs have shown that the concentration of butyrate in the portal vein is strongly influenced by the production rate in the large intestine. Increased gut production of butyrate further raises the circulating level of butyrate. For good reason it is not possible with current technologies to perform direct measurements of the variation in the butyrate concentration in the portal vein of human subjects, but short-chain fatty acid levels in portal blood from sudden-death victims, subjects undergoing emergency surgery or planned surgery have indicated a higher gut production and absolute and relative concentration of butyrate in non-fasted as compared with fasted human subjects. However, despite an expected higher gut production of butyrate when feeding a high-fibre rye-bread-based diet as compared with a low-fibre wheat-bread-based diet, there was no difference in absolute or relative levels of butyrate in the peripheral blood of human subjects.
Motor effects of short-chain fatty acids and lactate in the gastrointestinal tract
Authors: Cherbut Christine
Published: May 2003

Short-chain fatty acids (SCFA) affect local and remote motility of the gastrointestinal tract by mechanisms that are not completely understood. In the large intestine where they are produced, they inhibit peristaltic activity and may stimulate tonic activity. When present in the terminal ileum as a result of reflux of colon contents, they elicit propulsive contractions. These local motor effects could involve a neuro-hormonal sensory mechanism located in the mucosa of the terminal ileum and proximal colon. Finally, through a humoral pathway probably involving polypeptide YY release, ileal and colonic SCFA modify upper motility by inducing relaxation of the proximal stomach and lower oesophageal sphincter and reducing gastric emptying. One characteristic feature of the SCFA effects is the dose-dependency of the gastrointestinal motor responses. Indeed, the effects occur only below or above a threshold of SCFA concentration in lumen contents. One putative physiological role of the motor effects of SCFA might be to maintain the physico-chemical balance of the lumen environment in the terminal ileum and proximal colon. Another role might be to co-regulate motility of the upper intestine. The clinical relevance of these effects is unclear. However, some recent findings suggest that excessive SCFA concentrations might induce adverse effects on gastrointestinal and colonic motility and sensitivity in certain diseases such as inflammatory bowel disease and gastro-oesophageal reflux disease.
Molecular analysis of the effect of short-chain fatty acids on intestinal cell proliferation
Authors: Blottiere Herve M. , Buecher Bruno , Galmiche Jean-Paul , Cherbut Christine
Published: May 2003

Short-chain fatty acids (SCFA), particularly butyrate, were shown to regulate cell proliferationin vitroandin vivo. Indeed, butyrate is the major fuel for colonic epithelial cells, and it can influence cell proliferation through the release of growth factors or gastrointestinal peptides such as gastrin, or through modulation of mucosal blood flow. Lastly, SCFA can act directly on genes regulating cell proliferation, and butyrate is the main SCFA to display such an effect. Butyrate inhibits histone deacetylase, which will allow histone hyperacetylation. Such hyperacetylation leads to transcription of several genes, including p21/Cipl. Moreover, it will allow cyclin D3 hyper-expression by inhibiting its degradation. The induction of the cyclin-dependent kinase inhibitory protein p21/Cipl accounts for cell arrest in the Gl phase of the cell cycle. However, in the absence of p21 other mechanisms are initiated, leading to inhibition of cell proliferation.
Process-induced changes on bioactive compounds in whole grain rye
Authors: Liukkonen Kirsi-Helena , Katina Kati , Wilhelmsson Annika , Myllymaki Olavi , Lampi Anna-Maija , Kariluoto Susanna , Piironen Vieno , Heinonen Satu-Maarit , Nurmi Tarja , Adlercreutz Herman , Peltoketo Anna , Pihlava Juha-Matti , Hietaniemi Veil , Poutanen Kaisa
Published: May 2003

Manufacturing of healthy whole-grain foods demands knowledge of process-induced changes in macro-, micro- and non-nutrients. The high content of dietary fibre is a challenge in relation to good product texture and sensory quality. The stability and bioavailability of bioactive compounds have a marked influence on the health effects of cereal foods. It was confirmed that sterols, folates, tocopherols and tocotrienols, alkylresorcinols, lignans, phenolic acids and total phenolics are concentrated in the bran layers of the rye grain, and are only present at low levels in the flour endosperm. The levels of folate and easily-extractable phenolic compounds increase in germination and sourdough baking, but there are negligible changes in the levels of sterols, lignans and alk(en)ylresorcinols. The levels of tocopherols and tocotrienols are reduced during the sourdough fermentation. In conclusion, many of the bioactive compounds in whole-grain rye are stable during food processing, and their levels can even be increased with suitable processing.
Who consumes whole grains, and how much?
Authors: Lang Rebecca , Jebb Susan A.
Published: May 2003

Regular consumption of whole grain foods has been associated with a reduction in the incidence of cardiovascular disease and diabetes, reductions in cancer mortality at certain sites and an overall reduction in premature death. Although benefits are observed at relatively low levels of intake (between two and three servings per d), the consumption of whole grain foods in some Western countries is less than one serving per d. The main sources of whole grain are wholemeal and rye breads and whole grain breakfast cereals. Typical consumers of whole-grain foods tend to be older, from a high socio-economic group, are less likely to smoke and are more likely to exercise than non-consumers. Some of these attributes may contribute to the observed health benefits. However whole grain foods are an important source of a range of nutrients as part of a healthy eating plan. There is considerable scope for strategies to promote increased consumption of whole grain foods to reduce the risk of a variety of chronic diseases
Whole grains protect against atherosclerotic cardiovascular disease
Authors: Anderson James W.
Published: May 2003

Atherosclerotic cardiovascular disease (ASCVD) is the most common cause of death in most Western countries. Nutrition factors contribute importantly to this high risk for ASCVD. Favourable alterations in diet can reduce six of the nine major risk factors for ASCVD, i.e. high serum LDL-cholesterol levels, high fasting serum triacylglycerol levels, low HDL-cholesterol levels, hypertension, diabetes and obesity. Wholegrain foods may be one the healthiest choices individuals can make to lower the risk for ASCVD. Epidemiological studies indicate that individuals with higher levels (in the highest quintile) of whole-grain intake have a 29% lower risk for ASCVD than individuals with lower levels (lowest quintile) of whole-grain intake. It is of interest that neither the highest levels of cereal fibre nor the highest levels of refined cereals provide appreciable protection against ASCVD. Generous intake of whole grains also provides protection from development of diabetes and obesity. Diets rich in whole-grain foods tend to decrease serum LDL-cholesterol and triacylglycerol levels as well as blood pressure while increasing serum HDL-cholesterol levels. Whole-grain intake may also favourably alter antioxidant status, serum homocysteine levels, vascular reactivity and the inflammatory state. Whole-grain components that appear to make major contributions to these protective effects are: dietary fibre; vitamins; minerals; antioxidants; phytosterols; other phytochemicals. Three servings of whole grains daily are recommended to provide these health benefits.
Epidemiological support for the protection of whole grains against diabetes
Authors: Murtaugh Maureen A. , Jacobs David R. , Jacob Brenda , Steffen Lyn M. , Marquart Leonard
Published: May 2003

The epidemic of type 2 diabetes among children, adolescents and adults is increasing along with the increasing prevalence of overweight and obesity. Overweight is the most powerful modifiable risk factor for type 2 diabetes. Intake of whole-grain foods may reduce diabetes risk. Three prospective studies in 160 000 men and women examined the relationship of whole-grain or cereal-fibre intake with the risk of type 2 diabetes. Each study used a mailed Willett food-frequency questionnaire and similar methods of quantifying whole-grain foods and cereal fibre. The self-reported incident diabetes outcome was more reliably determined in the two studies of health-care professionals than in the study of Iowa women. Risk for incident type 2 diabetes was 21–27% lower for those in the highest quintile of whole-grain intake, and 30–36% lower in the highest quintile of cereal-fibre intake, each compared with the lowest quintile. Risk reduction persisted after adjustment for the healthier lifestyle found among habitual whole-grain consumers. Observations in non-diabetic individuals support an inverse relationship between whole-grain consumption and fasting insulin levels. In feeding studies in non-diabetic individuals insulin resistance was reduced using whole grains or diets rich in whole grains. Glucose control improved with diets rich in whole grains in feeding studies of subjects with type 2 diabetes. There is accumulating evidence to support the hypothesis that whole-grain consumption is associated with a reduced risk of incident type 2 diabetes; it may also improve glucose control in diabetic individuals.
Resistant starch as a prebiotic and synbiotic: state of the art
Authors: Topping David L. , Fukushima Michihiro , Bird Anthony R.
Published: May 2003

Non-infectious diseases such as CHD and certain cancers have become major causes of death and disability in affluent countries. Probiotics (principally lactic acid bacteria; LAB) may assist in lowering the risk of these diseases. Experimental studies with probiotics have given generally inconclusive outcomes for infectious disease and for biomarkers for non-infectious disease. In part this situation may reflect their inability to colonise the adult human gut effectively. Prebiotics can assist in promoting colonisation, and resistant starch (RS), as a high-amylose starch, is a prebiotic and synbiotic. This starch exerts its synbiotic action through adhesion of the bacteria to the granule surface. Consumption of RS assists in recovery from infectious diarrhoea in man and animals. A rice porridge, high in RS, appears to modify the autochthonous porcine large-bowel microflora favourably through lowering Escherichia coli and coliform numbers. Many of the beneficial effects of RS on large-bowel function appear to beexerted through short-chain fatty acids (SCFA) formed by bacterial fermentation. In man LAB are found in relatively highest numbers in milk-fed infants where theprofile of fermentation products differs quite markedly from that in adults. It appearsunlikely that ingestion of current probiotics will alter either total SCFA or the proportions of the major acids. More emphasis needs to be given to the investigation of the effects of complex carbohydrates, including RS, on the autochthonous microflora of the human large bowel.
Wholegrain health claims in Europe
Authors: Richardson David P.
Published: May 2003

Wholegrain foods are important sources of nutrients and phyto-protective components, which are in short supply in many member states of the EU, including the UK. Encouraging the public to increase consumption of whole-grain foods is a positive health message that has critical public health implications. In February 2002 the UK Joint Health Claims Initiative (JHCI) published its authoritative endorsement that whole-grain foods are associated with a healthy heart (Joint Health Claims Initiative, 2002). This new health claim reflects a similar one in the USA based on the accumulation of epidemiological evidence between 1996 and 2001 from several very large cohort studies in the USA, Finland and Norway, which show a consistent protective effect of whole grain and reduced risk of CHD. The JHCI code of practice on health claims requires that the claimed benefit must be scientifically valid, with evidence supporting efficacy of the food in human consumers, under typical conditions of use. The evidence-based approach consists of the identification of studies, an evaluation of individual references, a critical evaluation of the totality of the evidence and a statement that there is significant scientific agreement to establish the validity of the claim. The studies suggest that an intake of three servings per d may have an important cardio-protective effect. The development of a process for the substantiation of health claims in the UK and in the EU is important to underpin regulatory developments, which should protect the consumer, promote fair trade and encourage innovation in the food industry. The present paper sets out the format of the scientific dossier that was presented to the JHCI and includes a call to promote further research to identify the important protective components in the whole grain ‘package’ and the biological mechanisms behind the observed beneficial effects on health. The major sources of whole grain in the UK are bread and breakfast cereals, and >90% of adults in the UK consume less than three servings per d. Increasing the variety and availability of acceptable whole-grain foods could lead to greater consumption levels, which has important public health implications and offers an attractive and food-based dietary strategy for targeting the whole population.
Dietary fibre and prebiotics in infant formulas
Authors: Ghisolfi Jacques
Published: May 2003

Prebiotics have the potential to promote immediate and long-term effects on the health and well-being of infants. They have been added to infant formulas in Japan for 20 years and have only recently been used in Europe. The objective is to change the intestinal microflora in order to mimic the bacteriological effect and, thus, the functional effects of human milk. There is, however, a potential risk of long-term effects of the use of these infant formulas. The consequences of using prebiotics in infants, during the first months of life, on the composition and development of the intestinal microflora, and on the resulting bacterial–bacterial and bacterial–host interactions are not known. Attempts have been made to improve infant and follow-on formulas by prebiotic supplementation, but intervention studies are needed to evaluate their immediate and long-term beneficial effects and demonstrate the absence of harmful consequences from their use.
Rye, lignans and human health
Authors: Hallmans Göran , Zhang Jie-Xian , Lundin Eva , Stattin PäR , Johansson Anders , Johansson Ingegerd , Hultén Kerstin , Winkvist Anna , Lenner Per , Åman Per , Adlercreutz Herman
Published: May 2003

Rye bran contains a high content not only of dietary fibre, but also of plant lignans and other bioactive compounds in the so-called dietary fibre complex. Blood concentrations of lignans such as enterolactone have been used as biomarkers of intake of lignan-rich plant food. At present, evidence from studies in human subjects does not warrant the conclusion that rye, whole grains or phyto-oestrogens protect against cancer. Some studies, however, have pointed in that direction, especially in relation to cancers of the upper digestive tract. A number of prospective epidemiological studies have clearly shown a protective effect of whole-grain cereals against myocardial infarctions. A corresponding protective effect against diabetes and ischaemic stroke (brain infarct) has also been demonstrated. It seems reasonable to assume that these protective effects are associated with one or more factors in the dietary fibre complex.
Anti-cancer effects of butyrate: use of micro-array technology to investigate mechanisms
Authors: Williams Elizabeth A. , Coxhead Jonathan M. , Mathers John C.
Published: May 2003

Epidemiological evidence suggests that a high intake of resistant starch and NSP protects against colo-rectal cancer. The mechanisms underlying this protection are thought to be mediated by the short-chain fatty acid butyrate, which is present in the colonic lumen in millimolar concentrations as a result of bacterial fermentation of carbohydrates that have resisted digestion in the small intestine.In vitrostudies have shown that butyrate displays a host of chemo-preventative properties including increased apoptosis, reduced proliferation, down regulation of angiogenesis, enhanced immunosurveillance and anti-inflammatory effects in colo-rectal cancer cell lines. However, the molecular mechanisms underlying the apparent chemo-preventative actions of butyrate are largely unknown. The evidence supporting the role of butyrate as an anti-cancer agent is reviewed, with particular emphasis on those studies that have attempted to elucidate the mechanism of action of butyrate. Our understanding of the mechanistic action of butyrate and its role in cancer prevention is likely to advance considerably in this post-genomic era with the application of genomic and proteomic technologies. Studies are described that have used gene array and proteomic techniques to investigate the response of colo-rectal cancer cells to butyrate. These pioneering studies illustrate the potential of these technologies to help characterise the molecular responses of the cancer cell to butyrate, and to define the role of butyrate (and other nutrients) in the prevention of colo-rectal cancer.
Colonic diverticula
Authors: Eastwood Martin
Published: May 2003

Diverticulosis is a condition that is associated with ageing. The older the individual the more likely they are to have diverticulosis, but this process is not necessarily inevitable. Diverticula are a herniation through the wall of the sigmoid colon and are likely to be a consequence of a weakness in the colonic wall or prolonged exposure to increased intracolonic pressure consequent on a low dietary fibre intake. The tensile strength of the colon declines with age and becomes least in the distal colon. Adult Africans living in Africa eat a high-fibre diet and are free from diverticulosis. Their colons are stronger, wider and thinner than those Scottish adults of the same age. The strength of the colon is in part dependent on collagen fibres and their diameter. The collagen fibrils on the left side of the colon are smaller and more tightly packed than those of the right side of the colon. Ageing and the presence of colonic diverticulosis are associated with smaller more-tightly-packed collagen fibrils. An animal model was established to investigate the effect of a lifelong high- and low-fibre diet on the development of colonic diverticulosis. The findings show that a high-fibre diet from birth, and preferably a maternal high-fibre diet, lessen the risk of diverticulosis with age.
On defining dietary fibre
Authors: DeVries Jonathan W.
Published: May 2003

Establishing a definition for dietary fibre has historically been a balance between nutrition knowledge and analytical method capabilities. While the most widely accepted physiologically-based definitions have generally been accurate in defining the dietary fibre in foods, scientists and regulators have tended, in practice, to rely on analytical procedures as the definitional basis in fact. As a result, incongruities between theory and practice have resulted in confusion regarding the components that make up dietary fibre. In November 1998 the president of the American Association of Cereal Chemists (AACC) appointed an expert scientific review committee and charged it with the task of reviewing and, if necessary, updating the definition of dietary fibre. The committee was further charged with assessing the state of analytical methodology and making recommendations relevant to the updated definition. After due deliberation, an updated definition of dietary fibre was delivered to the AACC Board of Directors for consideration and adoption (Anon, 2000; Jones 2000/7). The updated definition includes the same food components as the historical working definition used for approximately 30 years (a very important point, considering that the majority of the research of the past 30 years delineating the positive health effects of dietary fibre is based on that working definition). However, the updated definition more clearly delineates the make-up of dietary fibre and its physiological functionality. As a result, relatively few changes will be necessary in analytical methodology. Current methodologies, in particular AACC-approved method of analysis 32–05 (Grami, 2000), Association of Official Analytical Chemists' official method of analysis 985.29 (Horwitz, 2000a) or AACC 32–07 (Grami, 2000) Association of Official Analytical Chemists 991.43 (Horwitz, 2000a) will continue to be sufficient and used for most foods. A small number of additional methods will be necessary to quantify the dietary fibre levels in foods containing fibres such as fructans (polymers and oligomers of fructose, inulin), modified dextrins, and/or synthetic dietary fibre analogues.
Wholegrain cereals and cancer in Italy
Authors: Vecchia Carlo La , Chatenoud Liliane , Negri Eva , Franceschi Silvia
Published: May 2003

The relationship between frequency of consumption of whole-grain foods and cancer risk has been analysed using data from an updated series of case-control studies conducted in Northern Italy between 1983 and 1997. The overall dataset included the following incident histologically-confirmed neoplasms: oral cavity and pharynx 524, oesophagus 410, stomach 745, colon 955, rectum 625, liver 435, gallbladder 65, pancreas 402, larynx 388, soft tissue sarcomas 217, breast 3412, endometrium 750, ovary 971, prostate 127, bladder 431, kidney 190, thyroid 428, Hodgkin's disease 201, non-Hodgkin's lymphomas 529, multiple myelomas 185. Controls were 10 058 patients admitted to hospital for acute non-neoplastic conditions unrelated to long-term modifications in diet, tobacco or alcohol use. The multivariate odds ratios for the highest category of whole-grain cereal consumption were 0.3–0.5 for upper digestive tract and respiratory neoplasms and colon, 0.6 for rectum and liver, 0.4 for gallbladder, 0.8 for pancreas, 0.2 for soft tissue sarcomas, 0.9 for breast and endometrium, 0.7 for ovary, 0.7 for prostate, 0.4 for bladder and kidney, 1.1 for thyroid and about 0.5 for lymphomas and 0.6 for myelomas. In this population whole-grain food consumption is an indicator of reduced risk of several neoplasms.
Diet and cancer: where are we and where are we going?
Authors: Rennert Gad
Published: May 2003

Many studies have shown that overall dietary patterns, dietary components consumed, or mode of food preparation are all possibly relevant in either reducing or increasing the risk of cancer in animals or man. Yet, dietary intervention studies, stemming from laboratory and epidemiological observational studies have often failed to demonstrate the anticipated protection against cancer. One possible explanation for the discrepancy between the results of various observational and experimental chemo-prevention studies is the lack of control for biological diversity of the participants of these studies. It is suggested that future epidemiological studies provide evidence stratified by status of major metabolic polymorphisms pertinent to the study subject, and that future intervention studies take these differences into account in the design and analysis phases.
Dietary fibre and colon cancer: where do we go from here?
Authors: Hill Michael
Published: May 2003

The relationship between intake of dietary fibre and risk of colon cancer has been studied for 30 years and still the data are inconclusive. There are many possible reasons for this outcome, and they include a failure to consider exposure to dietary fibre separately by source, or colon cancers separately by subsite. These potential confounders have been known for at least 20 years. However, the disease is normally considered by epidemiologists as a single entity. More recently, it has become clear that colon cancer can arise via various histological pathways, and by various genetic pathways. There is no reason at all for assuming that risk factors for these possible pathways are the same. There is a need, therefore, for a more detailed approach to the study of diet and colon cancer, with fibre source and cancer subsite, genetic pathway and histological pathway taken into account.
The glycaemic index: importance of dietary fibre and other food properties
Authors: Björck Inger , Elmståhl Helena Liljeberg
Published: May 2003

An increasing body of evidence suggests that a low-glycaemic-index (GI) diet has a therapeutic as well as a preventive potential in relation to the insulin resistance syndrome. The implementation of a low-GI diet, however, will require an extended list of low-GI foods to be available on the market. The tailoring of low-GI bread products offers a particular challenge due to their generally high GI and abundance in the diet. Low-GI bread products can be tailored by, for example, enclosure of cereal kernels, sourdough fermentation and/or addition of organic acids, or use of cereal genotypes with elevated contents of amylose or β-glucans. Low-GI cereal foods appear to vary in effect on ‘second-meal’ glucose tolerance in healthy subjects. In addition to the slow release properties of such foods, the content of dietary fibre appears to play a role. The low glycaemia to starch in a pasta breakfast (GI 54) promoted a higher glucose tolerance and lowered triacylglycerol levels at a standardized lunch ingested 4 h later, compared with a white-wheat bread breakfast (GI 100). The metabolic benefits of the low GI properties per se have been demonstrated also in the longer term. Thus, a reduction in dietary GI improved glucose and lipid metabolism and normalized fibrinolytic activity in type 2 diabetics, while maintaining a similar amount and composition of dietary fibre. However, the higher dietary fibre content frequently associated with low-GI foods may add to the metabolic merits of a low-GI diet. Consequently, a low-GI barley meal rich in dietary fibre (GI 53) improved glucose tolerance from evening meal to breakfast, whereas an evening meal with pasta had no effect (GI 54). The exchange of common high-GI bread for low-GI high-fibre bread, as the only dietary modification, improved insulin economy in women at risk of type 2 diabetes. These results are in accordance with epidemiological evidence of a reduced risk of type 2 diabetes with a low-GI diet rich in cereal fibre. It is concluded that low-GI cereal foods developed should preferably be rich in dietary fibre.
Colonic mucus: secretion and turnover in relation to dietary fibre intake
Authors: Brownlee Iain A. , Havler Mike E. , Dettmar Peter W. , Allen Adrian , Pearson Jeffrey P.
Published: May 2003

The colon is subjected to a myriad of potentially damaging agents that may reside within the lumen for 1–2 d. Its first line of defence against these agents is the protective mucus bilayer that lines the entire colonic mucosa. This bilayer acts as a physical barrier to mucosal aggressors and also reduces shear stress to the mucosa. These actions are dependent on the unstimulated (‘resting’) colonic mucus thickness, and also on the rate that this layer can be replenished. The colonic mucus layer is altered in a number of colonic diseases that have been linked to a deficiency of fibre in the diet. The action of fibre intake on colonic mucus thickness and secretion is unknown. Using an in vivo rat model it has been demonstrated that: (1) fibre deficiency leads to a decreased protective potential of the mucus layer (e.g. the mean resting mucus thickness of the fibre-deficient group (429 μm) was significantly lower than its respective control (579 μm; P< 0.001), as was its total mucus secretion over 6 h (270 μm v. 541 μm; P<0.01); (2) specific fibre types in the diet alter the secretion dynamics of colonic mucus (e.g. a cellulose-based diet reduces total mucus secretion over 6 h compared with its control (175 μm v. 463 μm). Analysis of the diets suggested a necessity for both soluble and insoluble fibre types in the diet to increase mucosal protection.