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M E Coates

Publications and source records attributed to M E Coates.

At least 19 recordsLinked to original sources
PubMed1996

Effect of dietary arginine on urinary nitrate excretion in germ-free rats.

The effect of dietary arginine on the endogenous synthesis of nitrate in germ-free rats was investigated. The animals were fed, for up to 18 days, purified diets containing either casein or lactalbumin (proteins differing in arginine content) with or without additional free arginine. Urine was collected from all animals for 4 days, and the animals were then dosed ip with Escherichia coli lipopolysaccharide (LPS) to stimulate nitrate synthesis and urine collected for a further 4 days. The urine samples were analysed for nitrate by ion chromatography. Although the excretion of nitrate was markedly stimulated by LPS treatment, there were no significant effects of protein source or arginine supplementation of the diet.

Administration, Oral↗
PubMed1996

Microbial amino acid synthesis and utilization in rats: incorporation of 15N from 15NH4Cl into lysine in the tissues of germ-free and conventional rats.

The absorption of lysine synthesised by the gastrointestinal microflora was estimated by comparing the 15N incorporated into body lysine in four germ-free (15N-GF) and four conventional (15N-CV) rats. They were fed for 10 d on a protein-free diet containing fermentable carbohydrates and 15NH4Cl; another four conventional rats (control), fed on the same diet but with unlabelled NH4Cl, were used to estimate the natural abundance of 15N. The eviscerated carcass of each rat was homogenized and a sample hydrolysed. Lysine was isolated by ion-exchange chromatography and its 15N enrichment was measured by isotoperatio mass spectrometry. The 15N-CV rats significantly incorporated 15N into their body lysine. The 15N-GF rats had a statistically significant, although small, incorporation of 15N into their body lysine, probably arising from a measurement artifact. It was concluded, therefore, that all [15N]lysine was of microbial origin. The total lysine content in the body and the 15N enrichment of lysine in the microbial fraction of the faeces of the 15N-CV rats were also determined. The amount of microbial lysine absorbed by the 15N-CV rats was estimated by dividing the total amount of [15N]lysine in the body by the enrichment of microbial lysine. It was estimated that the daily absorption of microbial lysine by the conventional rats was 21.3 (SE 2.04) mg/kg body weight0.75.

Amino Acids↗
PubMed1996

A study of low-nutrient diets used for aging studies in the rat.

The effects of diets of low caloric value on rats used in aging studies were investigated. Groups of 85 Sprague-Dawley rats were fed ad libitum from 3 months of age on three different diets containing 8 or 10 Megajoule (MJ) of metabolizable energy and 80 or 100 g of crude protein/kg. Body weights, food consumption, and morphological and biochemical parameters were monitored throughout life. Kidneys were examined histologically. Rats given the diet with highest energy and protein ate less food, attained greater weights, and had larger abdominal fat deposits than those on the lower energy diets. They had a raised proteinuria, and nearly half developed glomerulosclerosis and tubulo-interstitial damage by 26 months. There was no significant difference in mortality between the groups, and no other serious abnormalities were observed. It is concluded that rats can be maintained into old age with no signs of nutritional inadequacy on diets with lower energy and protein contents than those in general use.

Abdomen↗
PubMed1995

Lectins and also bacteria modify the glycosylation of gut surface receptors in the rat.

Oral exposure to lectins or the presence or absence of bacteria in the rat small intestine were shown by histological methods using anti-lectin antibodies or digoxigenin-labelled lectins to have major effects on the state of glycosylation of lumenal membranes and cytoplasmic glycoconjugates of epithelial cells. Taken together with the dramatic effects of exposure to lectins on gut function, metabolism and bacterial ecology, this can be used as a basis for new perspectives of biomedical manipulations to improve health.

Administration, Oral↗
PubMed1992

A comparison of indomethacin with ibuprofen on gastrointestinal mucosal integrity in conventional and germ-free rats.

The effects of indomethacin and ibuprofen on gastrointestinal mucosal integrity were studied in conventional and germ-free rats. Only ibuprofen induced significant gastric erosion formation in both conventional and germ-free animals, demonstrating that the presence of micro-organisms is not required in this form of damage. Both indomethacin and ibuprofen caused significant intestinal damage and blood loss in germ-free animals. However, in the conventional counterparts, damage due to indomethacin was enhanced whereas that induced by ibuprofen was not. The results from the present work would suggest that non-steroidal anti-inflammatory drugs such as indomethacin, which are secreted largely in the bile, unlike ibuprofen, may act in concert with bacteria and the constituents of bile to induce, in part, intestinal damage and blood loss.

Animals↗
PubMed1991

Influence of dietary protein and gut microflora on endogenous synthesis of nitrate induced by bacterial endotoxin in the rat.

Germ-free (GF) rats were maintained on a diet marginally adequate in protein, with and without a supplement of NH4Cl. Their urinary excretion of total nitrogen, nitrate, urea and creatinine was measured before and for 4 days after injection of Escherichia coli endotoxin (lipopolysaccharide; LPS). Although more nitrogen was excreted by rats on the diet supplemented with NH4Cl, nitrate excretion was increased to a similar extent in rats on both diets. This suggests that oxidation of ammonia released by deamination of amino acids is an unlikely pathway of nitrate synthesis. In a second experiment, nitrate excretion before and after injection of LPS was measured in GF and conventional (CV) rats given high- or low-protein diets. Urinary 3-methylhistidine (3MH) was measured as an index of breakdown of tissue protein. In both environments, nitrate excretion was significantly greater, before and after LPS administration, by rats on the high-protein diet than by their counterparts on the low-protein diet, and was generally greater by GF than by CV rats. Since only small, non-significant rises in urinary 3MH were observed after LPS treatment, it was concluded that the bulk of the nitrogen required for nitrate synthesis in response to endotoxin is derived from dietary protein rather than from nitrogenous products of tissue breakdown.

Administration, Oral↗
PubMed1991

Achlorhydria-induced hypergastrinaemia: the role of bacteria.

1. Studies of Helicobacter pylori show that microbes can alter gastrin release. Lack of gastric acid (achlorhydria) causes hypergastrinaemia and allows bacteria to grow within the stomach. We speculated that the bacteria contribute to the rise in gastrin seen after acid inhibition, and tested the idea by comparing plasma gastrin levels during inhibition of acid secretion between germ-free and conventional rats. 2. Matched germ-free and conventional rats (n = 8 per group) received either vehicle (saline) or one of two doses of the histamine-H2-receptor antagonist loxtidine for 1 week. Gastrin was measured in cardiac blood by a specific r.i.a. 3. Plasma gastrin concentrations in germ-free and conventional rats were 59 +/- 11 pmol/l (mean +/- SEM) and 36 +/- 8 pmol/l, respectively, after vehicle, and 153 +/- 30 pmol/l and 181 +/- 27 pmol/l, respectively, after loxtidine at a dose of 10 mg day -1 kg -1, which partially inhibits acid secretion. Administration of loxtidine at a dose of 70 mg day -1 kg-1, which completely inhibits acid secretion, did not produce a significant extra rise in plasma gastrin concentration in germ-free rats (178 +/- 11 pmol/l), but further elevated plasma gastrin concentrations to 278 +/- 26 pmol/l in conventional rats (P less than 0.005 compared with germ-free rats). 4. Loxtidine produced a dose-dependent rise in the number of eosinophils in the gastric mucosa of conventional rats. 5. We conclude that partial inhibition of gastric acid secretion increases gastrin release independently of bacteria, but that bacteria are involved in the further rise in gastrin which occurs on more profound inhibition of gastric acid secretion.

Achlorhydria↗
PubMed1991

Urinary but not brain isatin levels are reduced in germ-free rats.

Germ-free rats excreted considerably smaller amounts of the monoamine oxidase-inhibiting compound isatin than the substantially larger output by conventional animals of the same strain, although concentrations in brain and other tissues were similar in the two groups. Thus, isatin is likely to be elaborated both endogenously in rat tissues and "exogenously" by flora inhabiting the lumen of the alimentary tract.

Animals↗
PubMed1989

Influence of dietary protein and gut microflora on endogenous synthesis of nitrate and N-nitrosamines in the rat.

Groups of four germ-free (GF) and conventional (CV) rats were given purified diets containing either 50 or 200 g lactalbumin/kg for 2 wk and their urinary excretion of nitrate was measured. Urinary excretion of N-nitrosoproline was also measured in one of the three experiments. Both GF and CV rats given the high-protein diet excreted significantly more nitrate and N-nitrosoproline than those given the low-protein diet. On both diets GF rats excreted more nitrate than their CV counterparts but N-nitrosoproline excretion was not affected by environment. Groups of 11 GF and CV rats given diets containing sesame meal with or without a supplement of lysine-HCl for 2 wk, excreted similar amounts of nitrate on both diets, but more nitrate was excreted by GF rats than by their CV counterparts. N-nitrosoproline excretion by rats given the lysine supplement was higher in both environments. It is concluded that endogenous synthesis of nitrate is mediated by mammalian tissues rather than microflora and that dietary protein is an important source of nitrogen for the synthesis, although surplus amino acids from an imbalanced protein source do not act as precursors of endogenously formed nitrate. Some of the synthesized nitrate or its precursors appears to be metabolized by the microflora in the CV rat.

Animals↗
PubMed1987

Gnotobiotes in nutritional studies.

Studies with gnotobiotic animals have demonstrated extensive synthesis of vitamins, involvement in the metabolism of nitrogenous compounds and modification of lipids among the activities of the conventional microflora. The extent to which they affect the host depends on factors such as the structure of the gut, the position of the sites of bacterial proliferation and the host's nutritional status. Thus the findings in experimental animals may not always be applicable to man. Results so far indicate that in circumstances of dietary inadequacy bacterial activity may be detrimental or beneficial. However, these effects are small, and it seems reasonable to conclude that the influence of the indigenous microflora on the host's nutrition is of relatively minor importance compared with its role as a barrier against invasion by undesirable organisms.

Animal Nutritional Physiological Phenomena↗
PubMed1987

Dietary fat and N-nitrosation in the rat.

1. Groups of four conventional (CV) rats ate natural or purified diets either with or without 100 g fat/kg and drank 0.235 M-sodium nitrate. The fats tested were butterfat, coconut oil, olive oil, maize oil and safflower oil. 2. Decreased urinary excretion of N-nitrosoproline (NPRO) was observed in rats fed on fat-supplemented diets compared with those fed on low-fat diets, with butterfat having the greatest effect of the fats tested. 3. Reduced excretion of NPRO was not the result of inhibition of the intragastric N-nitrosation reaction or absorption of nitrosamine from the gastrointestinal tract. 4. The availability of nitrite in aqueous solution was decreased by the fat diets but the effect was similar in all the fats tested. 5. Nitrate reductase activity was present in the forestomach contents of CV rats at pH greater than 4 and was apparently inhibited by feeding a fat diet. No nitrate reductase activity was detected in stomach contents of germ-free rats. 6. Nitrate reductase activity in stomach and small intestinal tissue was not altered by feeding a fat diet. 7. It was concluded that nitrate reductase activity in stomach contents was of microbial origin and the decreased urinary excretion of NPRO on feeding the fat diets was mainly due to the inhibition of nitrate reductase activity in stomach contents.

Animals↗
PubMed1987

Gastrointestinal pH measurement in rats: influence of the microbial flora, diet and fasting.

The pH of the rat intestinal tract was decreased by the presence of a microbial flora, but its influence in the forestomach is less clear. Stomach pH values varied according to the amount of food present at the time of measurement. Fasting increased the pH of the gastrointestinal tract in conventional rats but had little effect in germfree rats. In the conventional rat, feeding a purified diet compared with a commercial diet resulted in a lower pH in the forestomach and a higher pH in the caecal contents. Magnesium trisilicate promoted gastric emptying in conventional rats and its antacid effect was observed only in the caecum and colon.

Animals↗
PubMed1986

Nitrate reduction, gastro-intestinal pH and N-nitrosation in gnotobiotic and conventional rats.

The reduction of nitrate in germ-free, gnotobiotic and conventional rats was investigated using blood methaemoglobin values as indicative of nitrite formation. Nitrate reduction was found to occur in the absence of a microbial flora, and throughout the experiment the blood content of methaemoglobin was higher in germ-free than in conventional rats. In vitro incubations of the gastric and small-intestinal mucosae of germ-free rats confirmed the presence of a heat-labile nitrate-reducing system. Measurement of the gastro-intestinal pH of germ-free and conventional rats revealed a generally higher pH value throughout the germ-free gastro-intestinal tract, with highly significant differences in the luminal pH of the forestomach, jejunum/ileum and caecum and a significant difference in the pH of the glandular stomach. Although some formation of N-nitrosoproline from proline and nitrate occurred in germ-free and gnotobiotic rats, nitrosation proceeded more readily in conventional rats. This effect may have been due to the lower gastric pH in the conventional rats although a more direct role for the flora cannot be discounted.

Animals↗
PubMed1986

Gordon memorial lecture. The biologists' debt to the domestic fowl.

Although it is highly desirable to reduce the need for experiments with animals, in vitro methods cannot entirely supplant them. Observations made in simple systems must be checked in a live subject if they are to be relevant to man or other higher animals. Young growing chicks are very susceptible to vitamin deficiencies. Biological assays in chicks have been used to check the validity of chemical and microbiological methods of measuring vitamins in foods. Experiments with chicks and chick embryos deprived of vitamin B12 have served to predict the likely clinical effects of analogues of the vitamin. The discovery of the growth-promoting properties of dietary antibiotics stimulated research into the influence of the gut microflora on its host. Studies in germ-free and gnotobiotic chicks have implicated Streptococcus faecium as one of the organisms responsible for the growth depression reversed by antibiotics. In general the growth of conventional chicks given adequate diets is slightly less good than that of their germ-free counterparts, although small beneficial effects of the microflora have been observed in special circumstances. The most important function of the indigenous microflora appears to be as a barrier against invasion by pathogens. To sustain this protective barrier may incur a small cost to the host in terms of dietary energy and other nutrients.

Animals↗
PubMed1985

Protein turnover of breast muscle in germ-free and conventional chicks.

The effect of the gut microflora on protein turnover in pectoral muscle (M. pectoralis profundus) was studied by means of dietary infusion of L-[U-14C]phenylalanine and of massive dose injection of L-[4-3H]phenylalanine in chicks fed on a semi-purified casein-gelatin (SCG) diet until 19 d of age, and in those subsequently given either a nitrogen-free (NF) diet or NF supplemented with methionine and arginine (MA) for a further 9 d. Time-course changes in radioactivity released in expired carbon dioxide during the 8 h infusion period showed that isotopic equilibrium was reached in 4 h with the SCG diet and in 5 h with the MA diet. However, with the protein-deprived chicks given the NF diet, isotopic equilibrium was not achieved since radioactivity in CO2 increased linearly throughout. On feeding the NF diet, fractional protein synthesis rate and the absolute amount of protein synthesized in chick breast muscle were reduced. These reductions were partially alleviated by supplementing the NF diet with methionine and arginine. The fractional degradation rate of breast muscle was increased in chicks given the NF diet, while the absolute amount of protein degraded was decreased. The addition of methionine and arginine counteracted these changes brought about by protein starvation. Generally speaking, the presence of the gut microflora had little, if any, effect on protein turnover rate in chick-breast muscle.

Animals↗