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Biomedical subjects

J C Mathers

Publications and source records attributed to J C Mathers.

At least 37 records · Page 2Linked to original sources
PubMed2000

Dietary strategies to reduce the burden of cancer and cardiovascular disease in the UK.

The importance attributed to dietary change as a means of helping to achieve the major goals of the UK's public health policy as articulated in the Health of the Nation White paper (Department of Health, 1992) is less apparent in the most recent strategy document (Department of Health, 1999). Greater emphasis is given to amelioration of the socio-economic circumstances that are believed to contribute to inequalities in health. Better understanding of the elements of foods and diets which help protect health together with better evidence of effective dietary interventions are essential if the opportunities to use diet to reduce the burden of non-communicable diseases are to be realised. This is likely to need new research strategies that take advantage of emerging information from genomics and proteomics to produce evidence of safety, efficacy and applicability. Ethical exploitation of the rapid growth in interest in 'functional foods' by the food industry will require a level of investment in biomedical research unusual in the past.

Adult↗
PubMed2000

Effect of oral antibiotics on intestinal production of propionic acid.

BACKGROUND: Propionic acid derived from colonic bacterial fermentation contributes substantially to overall propionate load in children with disorders of propionate metabolism, and its reduction is important for adequate metabolic control. AIMS: To evaluate the in vitro and in vivo effects of antibiotic treatment on propionate production by colonic bacteria, and plasma propionate concentrations in a child with propionic acidaemia. METHODS: In vitro fermentation techniques were used to study the effects of addition of antibiotics (metronidazole, clindamycin, erythromycin, and vancomycin) on net faecal production of short chain fatty acids including propionic acid. Courses of oral antibiotics of 7 days duration were used to assess the in vivo effects on faecal propionate production and metabolic control including plasma propionate concentrations. RESULTS: Metronidazole produced the largest and most consistent reduction (77-84%) in the production in vitro of propionate from faecal homogenates. Oral administration of metronidazole reduced faecal propionate production by 43% within 24 hours of treatment; a 7 day course virtually eliminated it for the next 3 weeks. These reductions were accompanied by substantially lowered plasma propionate concentrations during the same period. CONCLUSIONS: Intermittent courses of oral metronidazole might be as effective as continuous treatment in reducing gut propionate production in children with disorders of propionate metabolism.

Amino Acid Metabolism, Inborn Errors↗
PubMed2000

Evidence for altered control of glucose disposal after total colectomy.

Colonic fermentation of organic matter to short-chain fatty acids has been implicated in the improvement in insulin sensitivity achieved by feeding diets rich in complex carbohydrates. The present study assessed the potential role of the colon in determining postprandial glucose kinetics. Metabolic responses to a complex-carbohydrate test meal were determined in conjunction with a primed continuous infusion of D-[6,6-2H]glucose in a group of ileostomists and sex-matched controls. Glucose disposal (GD) was computed using Steele's (1959) non-steady-state kinetics on a single compartment model. Insulin sensitivity was derived using cumulative GD as the dependent variable, and time and the integrated insulin concentration as independent variables. The ileostomist group had a significantly higher postprandial plasma insulin concentration ( P = 0.034) compared with the control group, but no difference in the plasma glucose concentration. Total GD was similar in each group, although the insulin-dependent GD was substantially lower in the ileostomists (0.46 v. 0.13 mg glucose/min per pmol, P = 0.015). The ileostomist group also showed a 50% lower rate of glucose oxidation in the postprandial period (p = 0.005), although the rate of non-oxidative GD was not significantly affected. The present study indicates that loss of the colon is associated with several characteristics of the insulin resistance syndrome, and favours a view that the colon has a role in the control of postprandial glucose.

Adult↗
PubMed1999

Intestinal tumorigenesis in the Apc1638N mouse treated with aspirin and resistant starch for up to 5 months.

The Apc1638N mouse model, which carries a targeted mutant allele within the adenomatous polyposis (Apc) gene and develops intestinal tumours spontaneously, predominantly in the small bowel, was used to investigate the effects of two potential chemopreventive agents, aspirin and alpha-amylase resistant starch (RS). Heterozygous Apc+/Apc1638N mice were fed semi-purified diets rich in animal fat, animal proteins and sucrose and low in dietary fibre (Western style diets) from approximately 6 weeks up to 6 months of age. Two of the diets contained aspirin (300 mg/kg diet) and two RS (1:1 mixture of raw potato starch: Hylon VII at 200 g/kg diet) in a 2 x 2 factorial design. A fifth treatment group were fed a conventional rodent chow diet. The mice fed the Western style diets became almost three times as fat as the chow-fed mice but this did not affect tumour yield. Treatment with RS resulted in significantly more intestinal tumours whereas aspirin alone had no effect. However, there was a significant aspirin x RS interaction, which suggests that aspirin could prevent the small intestine tumour-enhancing effects of RS in this Apc-driven tumorigenesis model. The possibility that large amounts of purified forms of resistant starch may have adverse effects within the small bowel is a novel observation that requires further investigation since greater intakes of starchy foods (and of RS) are being encouraged as a public health measure in compensation for reduced dietary fat intake. However, it remains possible that any increased risk is restricted to carriers of germline mutations in APC.

Adenocarcinoma↗
PubMed1999

Nutrition in cancer prevention.

Although variation in diet may account for approximately one third of the variation in cancer incidence worldwide, epidemiologic studies have proven to be a blunt instrument for identifying causal relationships between intakes of specific food constituents and cancer risk at specific sites. Diets rich in fruits and vegetables seem to be protective, but the adverse effects of beta carotene supplementation trials on lung cancer incidence in smokers caution against the attribution of benefit to single substances. Important diet-gene interactions may exist, as illustrated by differential responses to variation in folate status in those with methylenetetrahydrofolate reductase polymorphisms. Targeting initial intervention studies in those with explicit genetic predisposition to cancer may have both greater cost-effectiveness and fewer ethical difficulties than do similar studies in the general public.

Diet↗
PubMed1999

The influence of the colon on postprandial glucagon-like peptide 1 (7-36) amide concentration in man.

Glucagon-like peptide (7-36) amide (GLP-1) is an incretin hormone of the enteroinsular axis released rapidly after meals despite the fact that GLP-1 secreting cells (L-cells) occur predominantly in the distal gut. The importance of these colonic L-cells for postprandial GLP-1 was determined in healthy control subjects and in ileostomy patients with minimal small bowel resection (<5 cm). Subjects were fed a high complex carbohydrate test meal (15.3 g starch) followed by two carbohydrate-free, high fat test meals (25 g and 48.7 g fat respectively). Circulating levels of glucose, insulin, glucagon, glucose insulinotrophic peptide (GIP) and GLP-1 were measured over a 9-h postprandial period. For both subject groups the complex carbohydrate test meal failed to elicit a rise in either GIP or GLP-1. However, both hormones were elevated after the fat load although the GLP-1 concentration was significantly reduced in the ileostomist group when compared with controls (P=0.02). Associated with this reduction in circulating GLP-1 was an elevation in glucagon concentration (P=0.012) and a secondary rise in the plasma glucose concentration (P=0.006). These results suggest that the loss of colonic endocrine tissue is an important determinant in the postprandial GLP-1 concentration. Ileostomists should not be assumed to have normal enteroinsular function as the colon appears to have an important role in postprandial metabolism.

Analysis of Variance↗
PubMed1998

Acute effects on insulin sensitivity and diurnal metabolic profiles of a high-sucrose compared with a high-starch diet.

Decreased insulin sensitivity is associated with diabetes mellitus, ischemic heart disease, and hypertension, both independently and in association as what is called the metabolic syndrome. Although the negative effects of obesity, sedentary lifestyles, and high-fat diets on insulin sensitivity are well established, the influence of type and quantity of dietary carbohydrate is more controversial. This study aimed to assess the acute (24 h) effects of a high-sucrose compared with a high-starch diet on insulin sensitivity and to identify changes in blood metabolites that might lead to altered insulin sensitivity. Eight healthy adults consumed high-sucrose or high-starch diets (50% of dietary energy) in a randomized, crossover trial. Insulin sensitivity was assessed by a short insulin tolerance test the following morning. No differences were detected in insulin sensitivity, either for glucose metabolism [Kitt(glucose) (the rate constant for the decline in blood glucose concentrations) for sucrose diet = 3.86%/min, for starch diet = 3.72%/min; pooled SEM = 0.23] or for lipid metabolism [Kitt(NEFA) (the rate constant for the decline in blood fatty acid concentrations) for sucrose diet = 12.9%/min, for starch diet = 11.4%/min; pooled SEM = 1.18]. Profiles for blood glucose and serum insulin concentrations revealed higher peaks and lower troughs with the high-sucrose diet whereas area under the curve for glucose was higher with the high-starch diet (6780 +/- 245 mmol x L/min) than with the high-sucrose diet (6290 +/- 283 mmol x L/min) (P < 0.001). Plasma fatty acid concentrations showed a late postprandial rise with the sucrose-rich diet relative to the starch-rich diet, which was mirrored with a fractionally later peak in triacylglycerol concentrations.

Adult↗
PubMed1998

Dietary carbohydrates and insulin sensitivity.

This review considers recent findings and ideas on the impact of dietary carbohydrates on insulin sensitivity in the context of the prevention of diabetes and cardiovascular disease. We assess the evidence for benefits in insulin sensitivity following high starch as distinct from high sucrose intakes when the diet is low in fat. We consider relationships between obesity, leptin and carbohydrate intake. We conclude that reducing the rate of carbohydrate digestion in the small bowel may be the key stage at which to intervene to reduce insulinaemia and so prevent downregulation of insulin receptors and insulin resistance.

Animals↗
PubMed1998

Colonic epithelial cell proliferation in hereditary non-polyposis colorectal cancer.

BACKGROUND: Despite the recent discovery of four genes responsible for up to 90% of all cases of hereditary non-polyposis colorectal cancer (HNPCC), there will still be families in whom predictive testing is not possible. A phenotypic biomarker would therefore be useful. An upwards shift of the proliferative compartment in colonic crypts is reported to be one of the earliest changes in premalignant mucosa. AIMS: To assess the role of crypt cell proliferation as a phenotypic biomarker in HNPCC. PATIENTS: Thirty five patients at 50% risk of carrying the HNPCC gene (21 of whom subsequently underwent predictive testing and hence gene carrier status was known) and 18 controls. METHODS: Crypt cell proliferation was measured at five sites in the colon using two different techniques. Labelling index was determined using the monoclonal antibody MIB1 and whole crypt mitotic index was measured using the microdissection and crypt squash technique. The distribution of proliferating cells within the crypts was also assessed. RESULTS: There were no significant differences in the total labelling index or mean number of mitoses per crypt, nor in the distribution of proliferating cells within the crypt, between the study and control groups at any site. When the 21 patients in whom gene carrier status was known were analysed separately there were no significant differences in the measured indices of proliferation between the HNPCC gene carriers and non-gene carriers. CONCLUSION: Crypt cell proliferation is not a discriminative marker of gene carriage in HNPCC.

Adolescent↗
PubMed1997

Dietary carbohydrates and insulin sensitivity: a review of the evidence and clinical implications.

Insulin resistance is associated with diabetes mellitus, ischemic heart disease, and hypertension both independently and as part of syndrome X. Environmental influences on SI are incompletely understood. Exercise has a strong beneficial effect and obesity a strong adverse effect. The balance of evidence suggests that a high-fat diet is likely to reduce insulin sensitivity but the effects of dietary carbohydrates are more controversial. Extensive studies in animals showed a detrimental effect of diets very high in fructose or sucrose, particularly in association with induction of hypertriglyceridemia. The more limited studies in humans had conflicting results, partly because of heterogeneity of design. Certain groups of subjects may be more sensitive to adverse effects of high intakes of dietary sucrose or fructose. More carefully controlled studies in humans are needed to provide evidence on which to base public health policies with respect to dietary carbohydrates and SI.

Animals↗
PubMed1997

Dose-response effects of raw potato starch on small-intestinal escape, large-bowel fermentation and gut transit time in the rat.

This study was designed to quantify starch digestion within the small and large bowels separately when raw potato starch (RPS) was included at 0-240 g/kg in diets fed to growing male Wistar rats. RPS was incorporated in the diets at the expense of maize starch which was expected to be almost completely digested in the small bowel. The digestibility of the maize starch was 0.99 but only 0.28 of the RPS was digested before the terminal ileum so that with increasing intakes of RPS there was a progressive increase in starch supply to the large bowel (LB). Of this starch 0.77, 0.72 and 0.73 was fermented in the large bowel when RPS constituted 80, 160 and 240 g/kg diet respectively. With increasing RPS intake, there was a curvilinear response in molar proportion of butyrate in caecal contents with a maximum value at about 80 g RPS/kg diet. The molar proportion of acetate increased linearly, that of propionate was unchanged, whilst proportions of the minor short-chain fatty acids all declined markedly with increasing RPS intake. The novel marker Bacillus stearothermophilus spores (BSS) was compared with CrEDTA in estimation of whole-gut mean transit time (MTT) when given together in a single test meal. Whilst estimates of MTT for the two markers were strongly correlated within individual rats (r2 0.72), BSS produced estimates that were 13 h longer than those based on CrEDTA. Neither marker detected a change in MTT with increasing RPS intake but, with both, the rate constant (k1) for the 'largest mixing pool' declined significantly (P < 0.001) as dietary RPS concentration was changed from 0-240 g/kg.

Analysis of Variance↗
PubMed1996

Tissue hypertrophy and epithelial proliferation rate in the gut of rats fed on bread and haricot beans (Phaseolus vulgaris).

The present study was designed to test the hypothesis that increasing short-chain fatty acid (SCFA) production in the large bowel increases gut epithelial proliferation rate (EPR). Two experiments were carried out in which rats were fed on bread (wholemeal or white)-based diets containing graded amounts of cooked haricot (Phaseolus vulgaris) beans; the latter are a rich source of fermentable carbohydrates. Consumption of beans was associated with several-fold increases in SCFA production with the greatest relative increase being for butyrate. Despite the very large increase in SCFA production, there was no evidence that this had any effect on EPR in the duodenum. Where the basal diet contained wholemeal bread (Expt 1) there was no effect of enhanced SCFA supply on EPR in either the caecum or colon, but with the white bread-based diet (Expt 2) adding beans produced increments in both SCFA supply and EPR in the caecum. Evidence that SCFA are responsible for enhanced EPR above normal levels is not convincing. In those instances where enhanced SCFA supply is associated with increased EPR, the increase may be (1) from a hypoproliferative state towards normal, (2) a transient phenomenon accompanying tissue hypertrophy or (3) a homeostatic response to increased cell loss by cell sloughing or apoptosis. It is not likely that there is any direct link with risk of colon cancer.

Animals↗
PubMed1995

Estimation of the fermentability of dietary fibre in vitro: a European interlaboratory study.

Five European laboratories tested a simple in vitro batch system for dietary fibre fermentation studies. The inoculum was composed of fresh human faeces mixed with a carbonate-phosphate buffer complex supplemented with trace elements and urea. Five dietary fibre sources (cellulose, sugarbeet fibre, soyabean fibre, maize bran and pectin) were used by each laboratory on three occasions to determine pH, residual non-starch polysaccharides (NSP) and short-chain fatty acid production during fermentation. Cellulose and maize bran degradabilities were very low (7.2(SE 10.8) and 6.2 (SE 9.1)% respectively after 24 h), whereas pectin and soyabean fibre were highly degraded (97.4 (SE 4.4) and 91.1 (SE 3.4)% respectively after 24 h). Sugarbeet fibre exhibited an intermediate level of degradability (59.5 (SE 14.9)%). Short-chain fatty acid production was closely related to NSP degradation (r 0.99). Although each variable was ranked similarly by all laboratories, some differences occurred with respect to absolute values. However, the adaptation of donors to the experimental substrates was not an influential factor. Interlaboratory differences could be reduced either by adding less substrate during incubations or using less-diluted inocula. In vitro fermentations with inocula made from human faeces and from rat caecal contents gave similar results. There was a close correspondence between the data obtained in the present experiment and those previously published in in vivo studies in the rat using the same fibres. The in vitro batch system tested during the present study provides a rapid means of obtaining quantitative estimates of the fermentation and the estimation of the energy content of new sources of dietary fibre.

Animals↗
PubMed1995

Digestive adaptations of rats given white bread and cooked haricot beans (Phaseolus vulgaris): large-bowel fermentation and digestion of complex carbohydrates.

Two experiments were carried out to examine the short (1-3 d) and medium (14 d) term adaptations of rat large-bowel (LB) fermentation to alterations in substrate supply brought about by including cooked haricot beans (Phaseolus vulgaris) in diets based on white bread. Changes in organic matter (OM) flow from the ileum occurred within 1 d and were stable for 14 d but the pattern of caecal short-chain fatty acids took much longer to stabilize with considerable increases in butyrate between 1 and 3 d and up to 14 d. This suggests that the metabolic activity of the LB microflora may take a considerable time to stabilize after an abrupt change in substrate supply. Despite an almost fourfold change in OM supply to the LB, the proportion of this OM apparently fermented in that organ (0.46) remained fairly constant. None of the apparent resistant starch measured in the diets could be detected in faeces. Dietary non-starch polysaccharides (NSP) were extensively fermented with similar values (0.82) for both bread and bean NSP and there was little indication of any interaction between the two diet components on NSP fermentation. An attempt was made to fractionate ileal and faecal OM to provide a basis for a quantitative model of LB stoichiometry.

Adaptation, Physiological↗
PubMed1995

Proliferative compartment deregulation in the non-neoplastic colonic epithelium of familial adenomatous polyposis.

Previous work has shown abnormalities in the proliferative activity of the colorectal mucosa in familial adenomatous polyposis (FAP). Some doubts remain about the validity of these findings because of difficulties in excluding adenomatous crypts, particularly in methods using tritiated thymidine, bromodeoxyuridine, and ornithine decarboxylase. The proliferative activity of the epithelium in colonic resections from 20 FAP patients was compared with that of age, sex, and site matched controls using a new monoclonal antibody MIB1 to assay the expression of Ki-67 antigen in routinely processed tissue. The labelling indices were very similar in the polyposis and control cases (25.5 (1.4)% and 26.7 (1.7)% respectively) but analysis of the distribution of labelled cells showed a significant shift of the proliferative compartment towards the luminal surface in the FAP group. Specifically, the labelling index was lower in the basal fifth of the polyposis crypts and higher in the two fifths at the luminal surface. These results show that analysis of proliferative activity in FAP is now achievable in routine histological material and indicate deregulation of proliferative control in the FAP colonic crypt. This may form a useful diagnostic adjunct to standard clinical and molecular genetic techniques, particularly in view of the current interest in dietary and pharmacological intervention in sporadic colorectal carcinoma.

Adenomatous Polyposis Coli↗