Biomedical subjects
R C Cottrell
Publications and source records attributed to R C Cottrell.
Guidelines for sugar consumption in Europe: is a quantitative approach justified?
OBJECTIVES: There is incongruity between the sugar consumption guidelines set in different European countries. A number have adopted maximum limits ranging from 10-25% energy, while others have no quantitative recommendations at all. This raises the question whether or not there should be a common European guideline for sugar consumption. DESIGN: This paper examines if such a goal for sugar is merited and reviews the published literature on associations between sugar consumption and dental caries, obesity and micronutrient dilution. RESULTS: Evidence showed that higher intakes of sugar were related to leanness, not obesity, and had no detrimental effects on micronutrient intakes in most people. In the case of dental caries, there was a relationship between frequency of sugar intake and the incidence of decay. However, in populations where fluoride use was adequate, associations between sugar intake and caries rarely reached statistical significance. CONCLUSIONS: The available evidence does not justify a common quantitative recommendation for sugar. It is suggested that dental caries merits a more integrated public health approach where advice on the frequency of foods containing fermentable-carbohydrates is placed in context alongside oral hygiene.
Introduction: nutritional aspects of palm oil.
The production, composition, and food uses of palm oil are outlined in this introduction to a detailed appraisal of the nutritional and health implications of the use of palm oil in the food supply. The putative role of dietary fats and oils in general, and of palm oil in particular, in the etiology of coronary heart disease and cancer is critically assessed. It is concluded that the evidence available is difficult to interpret unambiguously. Some evidence to suggest that the minor components of palm oil might have useful biological effects is also discussed.
Dietary patterns and cancer.
The possible role of dietary habits in the aetiology of cancers, and in the differences observed in the prevalence of this group of diseases between populations, should be considered in the context of the competing theories of cancer causation. This paper briefly reviews the historical context in which the contemporary emphasis on nutritional influences in cancer causation is placed and outlines the scope of the evidence currently available.
Has the science of nutrition benefited from the food industry?
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Fish oils--their significance to human health.
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Short-term toxicity study of Green S in rats.
Groups of 15 rats of each sex were fed Green S at dietary concentrations to provide dose levels of 0 (control), 250, 500 or 1500 mg/kg body weight/day for 13 wk. Additional groups of five animals of each sex were given the same treatments for 2 or 6 wk. There was a marked excretion of green colour in the faeces and some green colouring of the urine, although the latter may have been due to contamination. The males showed increased water and food intakes associated, particularly at the highest dose, with a higher rate of body-weight gain. Haematological examination revealed a transitory mild anaemia at the highest dose level, whilst no findings indicative of a toxic effect were found in the renal concentration tests or the serum analyses. With a dose of 1500 mg Green S/kg a greater proportion of the rats showed higher urinary protein, protein casts, increased caecal weight, thyroid degeneration in female animals and enlargement of the lymph nodes in the intestine wall. The no-effect dose level for Green S in this study was considered to be 500 mg/kg.
Adverse effects of toxins and drugs on the surfactant systems.
Various inhaled or administered compounds have adverse effects on the surfactant system. In experimental animals quartz inhalation induces alveolar proteinosis. This condition may also be induced by amphiphilic drugs or through increases in surfactant apoproteins. In one experimental model, damage to Clara cells by a methyl-furan derivative led to an increase in extracellular surfactant levels without a change in whole lung pool size. A comparative study of the effects of nitrogen dioxide in the rat and hamster demonstrated differing effects on Clara cells, type II and surfactant levels. These and other studies demonstrate that the effects of chemicals and drugs on cells involved in surfactant synthesis, secretion and catabolism provide a sensitive indicator of incipient toxic effects in the lung.
The role of DNA-repair processes in N-nitrosopyrrolidine-induced mutagenesis.
The cytotoxic and mutagenic effects of increasing concentrations of N-nitrosopyrrolidine (NPYR) were studied using various DNA repair mutants of Escherichia coli together with rat-liver S9 activation system. Irrespective of which strain was used, the cytotoxic effects of NPYR were similar to those observed in the parent strain. Mutagenicity studies revealed that the uvrA- derivative was more mutable than its repair proficient parent. These observations suggest that NPYR reacts with DNA to generate bulky lesions, which although potentially mutagenic, do not contribute significantly to cell-killing. Subsequent experiments with the metabolic inhibitor SKF 525A revealed that this compound only partially inhibited the mutagenic activity of NPYR, suggesting that although hepatic mixed function oxidase enzymes may participate in NPYR activation other pathways of metabolism are also involved.
The role of oral nitrate in the nitrosation of [14C]proline by conventional microflora and germ-free rats.
The urinary excretion of N-nitroso-L-[U-14C]proline by conventional microflora and germ free rats was used to assess the role of the gut bacteria and oral nitrate in the endogenous formation of N-nitroso compounds. The formation of nitrosoproline was qualitatively similar in conventional and germfree rats (equivalent to nitrosation of approximately 0.01-0.05% of the initial dose of [U-14C]proline) suggesting no involvement of the intestinal flora in this reaction. Furthermore, nitrosamino acid production was similar following the administration of nitrate and [U-14C]proline or [U-14C]proline alone, demonstrating no involvement of exogenous nitrate under the conditions of the experiment. Dietary contamination with nitrate/nitrite was negligible. The results are consistent with the suggestion that nitrate/nitrite reserves in the body are important in the formation of nitrosoproline in vivo.
A comparative study of the pulmonary effects of NO2 in the rat and hamster.
A study of the response of rat and hamster to nitrogen dioxide (NO2) under identical conditions has been undertaken. Exposure to 20 parts/IO6 NO2 for 24 h produced a mild cytotoxic effect on the terminal bronchiole and proximal alveoli in the rat, whereas the hamster developed a moderate to severe bronchiolitis and alveolitis. Electron microscopic examination of tissue sections showed accumulation of surfactant in lamellar bodies of the alveolar type II cell in the rat but not in the hamster, whereas in the hamster Clara cells were observed in mitosis. Increased levels of surfactant isolated from whole lung homogenates by sucrose gradient centrifugation were found in both rat and hamster. In contrast surfactant isolated from bronchiolo-alveolar lavage was increased only in the hamster. The results suggest that caution must be exercised in the choice of animal model in investigations aimed at the understanding of the toxicological effects of nitrogen dioxide in man.
The 1984 COMA report--a new approach?
This paper argues that the 1984 COMA report marks a new departure in recommending dietary changes to individuals rather than to the population en masse. The consequences of this approach include the necessity of providing members of the public with accurate and intelligible information on foods and a reliable means of assessing their dietary intake of fat.
Replacement of surfactant in hyaline membrane disease.
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The Clara cell and pulmonary surfactant: a study using selective chemical ablation.
Administration of 3-hydroxymethylfuran-N-ethylcarbamate (HFC) to female hamsters via the jugular vein under pentobarbitone anaesthetic at 20 mg per kg body weight produced pronounced necrosis of the Clara cells without apparent morphological effect on other cell types as judged by transmission electron microscope examination. The surfactant material recoverable by minimal lavage followed by purification by sucrose gradient ultracentrifugation increased, reaching a maximum around 48 h after treatment. At this time static pressure/volume measurements on isolated lungs indicated an increase in airway surface compliance. Lavageable surfactant phospholipid composition was examined by 31P nuclear magnetic resonance (n.m.r.). The distribution of phospholipids between the various classes was unchanged by HFC treatment. No change in the total lung surfactant pool size was seen. These results are discussed in relation to the possible roles of the Clara cell in influencing airway surfactant levels.
Nitrosoproline formation in control and antibiotic-treated rats given nitrate and proline.
The role of the gastrointestinal microflora in the nitrate-dependent formation of nitrosoproline was assessed in control and antibiotic-treated rats. Urinary nitrosoproline excretion as an index of in vivo nitrosamine formation was shown to be unaffected by bacterial decontamination of the alimentary tract, and proceeded in the absence of detectable nitrate reductase activity in the intestinal contents. These observations suggest that the gut microflora are not required for the formation of nitrosamino acid from nitrate and proline.
Direct determination of D-[U-14C] glucaric acid in urine by ion-exchange high-performance liquid chromatography.
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Phospholipid and protein analysis of pulmonary surfactant.
Quantitative analysis of the phospholipid composition of pulmonary surfactant preparations has been achieved by a modification of the phosphorus-31 nuclear magnetic resonance method of E London and G Feigenson (J. Lipid Res. 20, 408-412, 1979). Resolution of the protein components by a 2-dimensional isoelectric-focussing-SDS/polyacrylamide-gel-electrophoresis technique is reported for the first time.
Studies of the metabolic bioactivation of n-nitrosopyrrolidine in the rat.
The metabolism of N-nitrosopyrrolidine (NPYR) to 4-hydroxybutanal (4-HB) (the first stable product of the putative alpha-hydroxylation pathway) and its bioactivation in the Ames bacterial mutagenicity test system were examined in the presence of a number of inhibitors. Both SKF 525A and piperonyl butoxide were found to be potent inhibitors of the production of 4-HB by rat liver microsomal preparations but were ineffective in the mutagenicity model with liver S-9 from either untreated or Aroclor 1254 pretreated rats. In addition two inhibitors of the mutagenic activity of N-nitrosodimethylamine (NDMA) in this system, 2-phenylethylamine and benzimidazole failed to reduce the activity of NPYR. These results suggest that the bioactivation of NPYR may proceed by processes other than the cytochrome P-450 dependent route generating 4-HB and the amine oxidase catalysed route implicated in NDMA activation. Evidence was also obtained of a second cytosol dependent bioactivation step involving a microsome generated pre-mutagen. This activity may be responsible, at least in part, for the enhancement by cytosol of the mutagen producing activity of liver microsomes from Aroclor 1254 pretreated (but not control) rats.