Dietary aspects of a health strategy for England.
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Diet↗
Biomedical subjects
S Bingham
Publications and source records attributed to S Bingham.
Synthesis and anthelmintic activity of 3'-benzoylurea derivatives of 6-phenyl-2,3,5,6-tetrahydroimidazo[2,1-b]thiazole.
Reaction of 3-amino derivatives of the nematocides tetramisole and levamisole with variously substituted benzoylisocyanates gave a series of benzoylureas I which were tested for activity against helminths and ectoparasites. Compounds bearing 2,6-difluoro and 4-trifluoromethyl substituents had potent nematocidal activity in both mice and sheep. No antiectoparasitic activity was observed.
Animals↗
Synthesis and biological activity of a series of diaryl-substituted alpha-cyano-beta-hydroxypropenamides, a new class of anthelmintic agents.
A series of alpha-cyano-beta-hydroxypropenamides was prepared and tested for anthelmintic activity. alpha-Cyano-beta-hydroxy-N-[4- (trifluoromethyl)phenyl]-3-[4-(trifluoromethyl)phenyl]propenamide (1) showed good activity against the nematode Nematospirodes dubius in a mixed parasite infection in mice; several of the analogues were also effective against the cestode Hymenolepis nana. In sheep trials, 1 caused 100% reduction of the hematophagous nematode Haemonchus contortus after a single dose of 20 mg/kg but did not show satisfactory control of Trichostrongylus colubriformis or Ostertagia circumcincta. Against the liver fluke Fasciola hepatica, 1 suppressed egg production but only temporarily, suggesting that the adult flukes were not eliminated. Mechanism of action studies on 1 using Ascaris mitochondria showed it to be an uncoupler of oxidative phosphorylation.
Amides↗
Modulating effects in human diets of dietary fibre and beef, and of time and dose on the reactive microcapsule trapping of benzo[a]pyrene metabolites in the rat gastrointestinal tract.
Trapping by magnetic polyethyleneimine (PEI) microcapsules was utilized to investigate the influence in male rats of dose, human dietary composition and time-dependence on reactive metabolites of benzo[a]pyrene (B[a]P) in the gastrointestinal (GI) tract; also, PEI microcapsules modified with copper phthalocyanine tetrasulphonic acid (CPTS) were tested in vivo for trapping of endogenous mutagens having planar molecular structure. In a preliminary experiment the PEI microcapsules were administered by gavage at 0, 24 and 48 h, with [14C]B[a]P at 2 h to chow-fed BDVI rats; microcapsules were recovered from faeces collected at 24, 48 and 72 h, and then subjected to an extraction sequence showing that the trapped B[a]P metabolites were inconsistent with B[a]P diol epoxide trapping (as previously found) and unaltered by elapsed time or 5-fold dose alteration of B[a]P. Then five groups of F344 rats were fed isocalorically either one of four low-fat human diets or rat chow; in order to investigate influences of diet both on B[a]P and endogenous mutagens, half of each group was tested at 2 weeks with this PEI microcapsule/[14C]B[a]P protocol and then at 3 weeks, PEI-CPTS microcapsules (two gavages). So as to provide a cross-over comparison, the other half of each group was first tested with PEI-CPTS microcapsules followed by PEI microcapsules/[14C]B[a]P 1 week later. The human diets were prepared from cooked British foods so as to simulate the adequate intake of all nutrients required by humans; but with 3-fold differences in intake levels of beef and dietary fibre non-starch polysaccharide (NSP), while ensuring the same intake of available energy, protein, fat and calcium. They gave very similar body-weight gains in the four groups but greatly reduced faecal weight, protein and total faecal enzyme activity compared with chow; the extraction pattern of microcapsule-trapped B[a]P metabolite radioactivity was not significantly altered. However, human diet consumption caused a 2- to 6-fold increase in B[a]P metabolite binding to microcapsules and reductions in microcapsule recovery, net 70-h B[a]P excretion, faecal protein and total activities for beta-glucuronidase and beta-galactosidase; these effects were more pronounced after 3 weeks, presumably due to prolonged dietary adaptation. Increased NSP in human diets significantly increased the B[a]P metabolite excretion and marginally reduced the microcapsule binding. The increase in microcapsule binding of B[a]P metabolites, interpreted as reflecting an increased amount of reactive metabolites encountered, was related to the dietary intake weight ratio of beef/NSP.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Systematic modulation by human diet levels of dietary fibre and beef on metabolism and disposition of benzo[a]pyrene in the gastrointestinal tract of Fischer F344 rats.
Groups of male Fischer F344 rats isocalorically consuming cooked, low-fat human diets were given magnetic polyethyleneimine (PEI) microcapsules and [14C]benzo[a]pyrene (B[a]P) by gavage in order to determine the effects of 3-fold changes in levels of dietary fibre non-starch polysaccharide (NSP) and beef protein during gastrointestinal transit on microcapsule trapping and associated parameters. Total 14C trapped by microcapsules during 70 h was decreased by fibre and increased by beef with significant effects (P = 0.03) for dietary mass ratio beef/fibre and compared to controls eating chow. Total B[a]P excreted in faeces and the ration for faeces/urine were increased by fibre and not by beef; the distribution of B[a]P metabolites between liquid and solids of faeces was increased by both factors but there was a net decrease by fibre when allowing for its influence on faecal mass. The distribution of binding between microcapsules and faecal solids was increased significantly by beef, but fibre had no effect when mass-normalized. B[a]P metabolites were extracted from microcapsules by methanol-ammonia and HPLC assay showed mainly benzo[a]pyrene-3,6-dione (B[a]P 3,6-dione), benzo[a]pyrene-1,6-dione (B[a]P 1,6-dione), an unidentified metabolite and substances consistent with tetraols; the beef (P = 0.02) and beef/fibre ratio (P = 0.01) significantly increased B[a]P-1,6-dione trapped and released. In vitro, B[a]P 3,6-semidione (dione reduced form) was bound by PEI microcapsules; the extent of extraction/hydrolysis was much lower than for B[a]P e,6-dione or B[a]P 7,8-diol 9.10-epoxide. Urinary excretion of B[a]P metabolites was decreased by fibre but not by beef. Nearly all the above parameters were different in a control group consuming rat chow. Taken together, these results are consistent with the following conclusions; (i) dietary fibre NSP overall decreases the availability of B[a]P metabolites to contact microcapsules and intestinal mucosa through static bulking rather than absorption; (ii) beef protein increases binding to microcapsules, and enhances free radical activation of B[a]P to its 6-yl radical form; (iii) a systematic set of concordant relationships for B[a]P disposition were found between faecal solids, faecal liquids, microcapsules and urine; and (iv) rat chow produced effects quite unrepresentative of the range for human diets prepared to be in the norm for human use. Endogenous UV-absorbing substances trapped by microcapsules or excreted in urine were also altered by dietary beef levels and were different from those of chow-consuming animals. It is generally concluded that human diets can and should be used in studying carcinogen metabolism and disposition.
Animals↗
Adaptation of the mechanisms controlling gastric motility following chronic vagotomy in the ferret.
Changes in gastric motility were studied in the urethane-anaesthetized ferret following acute or chronic (3 weeks) vagotomy. The stomach was divided into the corpus and antrum and the effects of vagotomy on tone, frequency and contraction amplitude were investigated separately in the two gastric regions. In the corpus tone is kept at low levels by vagal activation of nonadrenergic, non-cholinergic (NANC) inhibitory neurones and also tonic sympathetic inhibition of intramural cholinergic activity. Frequency of contractions is also low due to tonic inhibition of cholinergic neurones by the vagus but not the sympathetic nervous system. There appears to be little vagal involvement in contraction amplitude but there is sympathetic inhibition of this parameter again via inhibition of cholinergic neurones. In the antrum there is no vagally driven inhibition of tone but a sympathetic inhibition of cholinergic neurones tends to reduce tone in the intact animal. Frequency of contractions does not appear to be extrinsically modulated. The vagus is tonically excitatory with regard to contraction amplitude in the antrum whereas the sympathetic nervous system is inhibitory, again via inhibition of cholinergic neurones. After chronic vagotomy some adaptation appears to take place within the surviving control systems in both the corpus and the antrum. Changes in cholinergic function have been suggested previously and are corroborated in this study. In addition novel alterations in intrinsic NANC systems and the remaining sympathetic innervation have been demonstrated in both regions of the stomach which tended to reduce the effects of vagotomy and return values for the parameters measured toward those observed in intact animals. The contribution of the cholinergic, adrenergic and NANC neurotransmitter systems to the post-vagotomy motility patterns differed in the corpus and antrum.
Adaptation, Physiological↗
The abdominal visceral innervation and the emetic reflex: pathways, pharmacology, and plasticity.
In recent years the role of the area postrema in the emetic reflex has been predominant and the involvement of the abdominal visceral innervation has tended to be overlooked. This paper attempts to redress the balance reflex by reviewing aspects of the existing literature and complementing this with original studies from the ferret. In view of the widespread use of the ferret in studies of emesis and particularly in the characterization of the antiemetic actions of 5-HT3 receptor antagonist, the opportunity is taken to assess the suitability of this species for studies of emesis. It is concluded that the ferret is sensitive to a wide range of emetic stimuli including intragastric irritants, opiate and dopamine receptor agonists, many cytotoxic drugs, and radiation. For several stimuli it is more sensitive than other species and for radiation on the basis of its ED100 it appears to be the most sensitive of the laboratory animals studied. Using electrical stimulation of the central end of the dorsal vagal trunk in the abdomen in conscious and anaesthetized animals, the vagal afferents were shown to be capable of eliciting emesis. Using lesioning studies an involvement of the vagus in the emetic response to a number of cytotoxic drugs (e.g., cisplatinum, cyclophosphamide, mustine) and radiation was demonstrated, although the magnitude of the effect varied with the different stimuli. An attempt is made to reconcile these observations with previous studies of area postrema ablation. The problems of interpreting the effects of nerve lesions are critically discussed in light of preliminary evidence presented here that there may be a degree of plasticity in the emetic pathway following such lesions. The range of antiemetic effects of 5-HT3 receptor antagonists is reviewed and an attempt is made to identify the site(s) at which these agents act. Results are presented that suggest a link between the vagus and 5-HT3 receptor antagonism. These studies are discussed together with others and lead us to propose that (in the ferret) 5-HT3 receptor antagonists have their main antiemetic effect by acting on vagal afferent terminals in the wall of the upper gut with an additional minor site either in the nucleus tractus solitarius or presynaptically on the vagal afferent terminals in the medulla where binding sites for 5-HT3 receptor ligands have recently been demonstrated in this species.
Abdomen↗
Recoverable, semipermeable, microencapsulated DNA surrogates for monitoring the colorectal cavity; in-situ effects of fibre and meat in human diets on benzo[a]pyrene and possible endogenous cross-linking agents.
Semipermeable magnetic microcapsules containing polyethyleneimine (PEI) as a DNA surrogate are shown to trap 14C-benzo[a]pyrene and hitherto unknown, endogenous, putative cross-linking agent(s) within the gut of male Fischer rats. Trapping is substantially modulated by complete, cooked human diets fed isocalorically and varied three-fold in either beef, fat or bran fibre nonstarch polysaccharide within the normal human intake levels. Preliminary results indicate that the crosslinking agent(s) are derived from microflora. Using metabolized benzo[a]pyrene as a model DNA damaging agent within the gut, beef and decreased bran fibre were found to increase its availability, paralleling risk alterations found in nutritional epidemiology. These novel microcapsules are capable of intercepting a range of substances relevant to DNA damage.
Animals↗
Definitions and intakes of dietary fiber.
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Dietary Fiber↗
Modulation of the vagal drive to the intramural cholinergic and non-cholinergic neurones in the ferret stomach by baclofen.
1. In the urethane-anaesthetized ferret vagotomy (cervical and abdominal) and hexamethonium both produced an increase in gastric corpus pressure after treatment with atropine and guanethidine, section of the greater splanchnic nerves and adrenalectomy. 2. The pressure increase was due to an interruption of a tonic vagal drive to the intramural non-adrenergic, non-cholinergic inhibitory neurones. 3. The GABAB receptor agonist baclofen (8 mg/kg s.c.) produced an increase in gastric pressure and enhanced the amplitude of the rhythmic contractions. Baclofen was without effect in vagotomized animals. 4. In the presence of atropine, guanethidine, adrenalectomy and section of the greater splanchnic nerves, baclofen produced only a slight enhancement of rhythmic contractions but the large increase in gastric pressure was still present. Under the above conditions the effects of baclofen on the whole stomach were virtually identical to those observed in the corpus region alone. 5. Baclofen was without effect on the magnitude of the corpus relaxation produced by the submaximal vagal efferent stimulation in the presence of atropine. 6. These results demonstrate that the GABAB agonist baclofen, probably acting at a central site, enhanced rhythmic gastric activity by increasing the vagal drive to the intramural cholinergic neurones. Simultaneously gastric pressure was increased primarily by a reduction in the tonic vagal drive to the intramural non-adrenergic, non-cholinergic inhibitory neurones in the corpus region. The results of both the baclofen and vagotomy studies further demonstrate the importance of the vagal innervation of the non-adrenergic, non-cholinergic inhibitory neurones in the regulation of gastric pressure.
Adrenalectomy↗
Average portion weights of foods consumed by a randomly selected British population sample.
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Diet Surveys↗
Reduction of infarct size with intracoronary perfluorochemical in a canine preparation of reperfusion.
The effect of low-dose (15 ml/kg) intracoronary perfluorochemical (Fluosol-DA) on infarct size, regional myocardial blood flow, and ventricular function was studied in 20 anesthetized closed-chest dogs subjected to 11/2 hr of proximal left anterior descending occlusion. In this preparation reperfusion was simulated with fibrinolytic therapy. The animals were randomly assigned one of two treatment groups and given 15 ml/kg of either oxygenated intracoronary perfluorochemical (n = 9) or saline (n = 11). Contrast ventriculograms were obtained at baseline, 1 hr after occlusion, and at 24 hr after reperfusion and were analyzed with a radial fractional shortening method. Regional myocardial blood flow was measured with radioactive microspheres. At 24 hr the area at risk was defined in vivo with monastryl blue staining and the area of necrosis was estimated after incubation of left ventricular slices with triphenyltetrazolium chloride. No significant changes were noted in heart rate, blood pressure, pulmonary capillary wedge pressure, or dP/dt during the experimental protocol. Infarct size was significantly reduced (p less than .02) in the perfluorochemical-treated group, both when expressed as a percentage of the total left ventricular mass (7.9 +/- 1.7% vs 14.7 +/- 2.5%) and as a percentage of the area at risk (20.1 +/- 5.0% vs 46.8 +/- 8.5%). This was associated with significant improvement in fractional shortening in the jeopardized zone at 24 hr after reperfusion. Although endocardial blood flow was significantly greater in the central ischemic zone and lateral region at risk immediately after reperfusion in the perfluorochemical-treated group, no difference was found 1 hr after reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The use of 4-aminobenzoic acid as a marker to validate the completeness of 24 h urine collections in man.
1. At the present time there is no method whereby the completeness of 24 h urine collections can be accurately assessed when clinical studies are undertaken. The suitability of 4-aminobenzoic acid (PAB) given with meals as a marker for completeness of urine collections was therefore investigated. 2. When a single dose of 80 mg of PAB was given to four volunteers 93% was recovered in the urine in 5 h. 3. Eight volunteers living in a calorimeter, where complete urine collection could be guaranteed, were given various doses of PAB divided up throughout the day. 88 +/- 5% was excreted in the urine over a 24 h period. Urine excretion and oral dose were directly related. 4. Thirty-three reliable free-living volunteers eating their normal diet took 80 mg of PAB with meals (240 mg/day). Mean urine recovery over the 24 h period was 223 +/- 9 mg, or 93 +/- 4% of the administered dose. The range in individual recovery from maximum to minimum was 15%, compared with 75% for creatinine excretion per kg fat-free mass. 5. PAB is a safe marker of the completeness of 24 h urine collections. Any collection containing less than 205 out of 240 mg (85%) of PAB, given as 80 mg with each of three meals, is probably incomplete.
4-Aminobenzoic Acid↗
Dietary fibre intake in Japan.
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Colonic Neoplasms↗
Diet and health of people with an ileostomy. 1. Dietary assessment.
1. People with an ileostomy experience digestive problems with some foods. Why those foods are avoided is not known nor is it certain whether this interferes with the nutritional adequacy of their diet. 2. A detailed dietary assessment has therefore been made of thirty-seven subjects with ileostomies and a similar number of age- and sex-matched healthy controls. All food and drink eaten over 1 week was weighed and recorded. In addition. A larger group of seventy-nine ileostomy subjects and seventy matched controls answered a questionnaire designed to identify foods which upset them and which they avoided. 3. Total nutrient and energy intakes were similar in the two groups but the subjects with an ileostomy ate less dietary fibre (g/d; mean + SD: ileostomy subjects 18.0 +/- 5.9, controls 20.9 +/- 5.5; P less than 0.05) mainly due to lower fruit and vegetable intakes. Iron and vitamins A and C intakes were also less. 4. A majority of ileostomy subjects had a pattern of food intake different from the controls, taking more of their energy in the morning and less at night. A variety of food items upset more than half of them including nuts, pips, seeds, skins, onions, beetroot, lettuce, raw cabbage and carrot, peas, sweetcorn, mushrooms and dried fruit. 5. On the basis of the results it is possible to formulate general dietary advice for people with an ileostomy.
Adult↗
Diet and health of people with an ileostomy. 2. Ileostomy function and nutritional state.
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Adult↗
Methods and validity of dietary assessments in four Scandinavian populations.
Average intakes of nonstarch polysaccharides (dietary fiber), foods, and nutrients were measured in representative samples of 30 men aged 50-59 in 4 Scandinavian populations with a 3-4 fold difference in risk for large bowel cancer. The assessment technique, a 4-day weighed record of food consumed and duplicate collections of all food eaten, was validated by chemical analysis of the duplicates, by measuring 24-hour urine and fecal nitrogen excretion, and by comparing the constituents of the urine samples collected during the survey with similar collections 1-2 weeks later. There were good agreements between estimates of fat and protein intake obtained by food-table calculations of the 4-day weighed record and the chemically analyzed duplicates. Urinary plus fecal nitrogen excretion was equal to estimated nitrogen intake during the survey, and no discernable changes in urinary output occurred after the survey, thereby implying that dietary habits had not changed as a result of the investigative technique. It is concluded that the dietary data are indicative of current patterns of food consumption and are sufficiently valid for comparison with data on cancer risk in the 4 areas.
Colonic Neoplasms↗