Debbie Bush

Effect of intragastric acid stability of fat emulsions on gastric emptying, plasma lipid profile and postprandial satiety

Fat is often included in common foods as an emulsion of dispersed oil droplets to enhance the organoleptic quality and stability. The intragastric acid stability of emulsified fat may impact on gastric emptying, satiety and plasma lipid absorption. The aim of the present study was to investigate whether, compared with an acid-unstable emulsion, an acid-stable fat emulsion would empty from the stomach more slowly, cause more rapid plasma lipid absorption and cause greater satiety. Eleven healthy male volunteers received on two separate occasions 500 ml of 15 % (w/w) [13C]palmitate-enriched olive oil-in-water emulsion meals which were either stable or unstable in the acid gastric environment. MRI was used to measure gastric emptying and the intragastric oil fraction of the meals. Blood sampling was used to measure plasma lipids and visual analogue scales were used to assess satiety. The acid-unstable fat emulsion broke and rapidly layered in the stomach. Gastric emptying of meal volume was slower for the acid-stable fat emulsion (P < 0.0001; two-way ANOVA). The rate of energy delivery of fat from the stomach to the duodenum was not different up to t = 110 min. The acid-stable emulsion induced increased fullness (P < 0.05), decreased hunger (P < 0.0002), decreased appetite (P < 0.0001) and increased the concentration of palmitic acid tracer in the chylomicron fraction (P < 0.04). This shows that it is possible to delay gastric emptying and increase satiety by stabilising the intragastric distribution of fat emulsions against the gastric acid environment. This could have implications for the design of novel foods.

Determination of baseline human nasal pH and the effect of intranasally administered buffers.

The nose is becoming a common route of drug administration, however, little is known about the pH of the human nasal cavity. Local pH may have a direct effect on the rate and extent of absorption of ionizable compounds and hence this study was performed to investigate normal pH values and whether pH could be manipulated by various buffers. Twelve healthy volunteers participated in a study to measure pH in the anterior and posterior sites of the nasal cavity. Miniature pH electrodes were placed 3 cm apart in the nasal cavity and a baseline was recorded for 30 min once the pH had stabilized. One hundred microlitres of isotonic solution was sprayed into the nostril and the pH was measured for 4 h post-dose. The following five formulations were tested: formulation A--sodium chloride (0.9%) at pH 7.2; formulation B--sodium chloride (0.9%) at pH 5.8; formulation C--Sorensens phosphate buffer (0.06 M) at pH 5. 8; formulation D--Sorensens phosphate buffer (0.13 M) at pH 5.8 and formulation E--formulation as (c) but adjusted to pH 5.0. Each formulation also contained saccharin sodium (0.5%) as a taste marker for nasal clearance. The time at which each subject detected the taste of saccharin was noted. The 30-minute baseline recording prior to administration of the nasal spray formulation demonstrates that there was both considerable intersubject and intrasubject variation in nasal pH. The average pH in the anterior of the nose was 6.40 (+0. 11, -0.15 S.D.) when calculated from H(+) values. The pH in the posterior of the nasal cavity was 6.27 (+0.13, -0.18 S.D.). The overall range in pH was 5.17-8.13 for anterior pH and 5.20-8.00 for posterior pH. Formulation A caused the pH in the anterior part of the nasal cavity to reach a maximum of 7.06 in 11.25 min from the baseline of pH 6.14 (P<0.05). The mean baseline pH was 6.5 for the posterior part of the nose which did not change over the recording period. Formulation B caused the anterior pH to increase from pH 6. 60 to 7.25 within the first minute. This fell back to a mean pH of 7.07 over the first hour which was still significantly above the baseline. It remained at this value for the remainder of the recording period. The initial average posterior pH was 6.32 and again this did not significantly change over the recording period. Formulation C produced a sustained increase in anterior nasal pH from a baseline pH of 6.57-7.12. A small transient decrease was observed in the pH in the posterior of the nose but baseline pH of 6. 6 was re-established within 15 min post dose. Formulation D significantly reduced anterior nasal pH from 6.30 to 5.87 by 30 min reaching a pH of 5.95 by 90 min where it remained for the remainder of the recording period. The posterior baseline pH was 6.3 and introduction of the pH 5.8 buffer caused a slow increase over 90 min to pH 6.6. Formulation E increased anterior pH from 6.1 to 6.7 for the remainder of the recording period. It had an insignificant effect on posterior nasal pH. The mean (+/-S.D.) time to taste saccharin for formulations A to E was 13.42+/-10.21, 14.67+/-8.37, 11.67+/-8.08, 10.08+/-7.6, 9.80+/-6.73 min, respectively. There was no significant difference between the clearance times for the different formulations. In conclusion, average baseline human nasal pH is approximately 6.3. Nasal anterior pH can be decreased when buffers of 0.13 M and above are used. Mildly acidic solutions produce an increase in pH presumably due to reflux bicarbonate secretion. Posterior nasal pH was not altered by administration of any buffer except the 0.13 M buffer at pH 5.8. This produced a rise in posterior pH.

Visceral hypersensitivity in symptomatic diverticular disease and the role of neuropeptides and low grade inflammation.

Background  Recurrent abdominal pain is reported by a third of patients with diverticulosis, particularly those with previous episodes of acute diverticulitis. The current understanding of the etiology of this pain is poor. Our aim was to assess visceral sensitivity in patients with diverticular disease and its association with markers of previous inflammation and neuropeptides.

Improved methods for fMRI studies of combined taste and aroma stimuli.

Previous neuroimaging studies of the cortical representation of gustatory and olfactory stimuli have often delivered tastants to the mouth in very small quantities or stimulated olfaction orthonasally. In studies of retro-nasal olfaction, swallowing was generally delayed to reduce head motion artefacts. The present fMRI study aims to improve upon such methodological limitations to allow investigation of the cortical representation of flavour (taste and aroma combination) as it typically occurs during the consumption of liquid foods. For this purpose we used (1) a novel, automated, sprayed stimulus delivery system and a larger volume of liquid sample (containing sweet tastants and banana/pear aroma volatiles) to achieve more extensive stimulation of the oral cavity taste receptors, (2) a pseudo-natural delivery paradigm that included prompt swallowing after each sample delivery to obtain physiological retro-nasal olfactory stimulation, (3) fMRI acquisition with wide brain coverage and double-echo EPI to improve sensitivity. We validated our paradigm for the delivery of volatiles using atmospheric pressure chemical ionisation mass spectrometry. This showed that the main retro-nasal delivery of volatiles in the paradigm occurs immediately after the swallow. Several brain areas were found to be activated, including the insula, frontal operculum, rolandic operculum/parietal lobe, piriform, dorsolateral prefrontal cortex, anterior cingulate cortex, ventro-medial thalamus, hippocampus and medial orbitofrontal cortex.

Non-invasive quantification of small bowel water content by MRI: a validation study

Substantial water fluxes across the small intestine occur during digestion of food, but so far measuring these has required invasive intubation techniques. This paper describes a non-invasive magnetic resonance imaging (MRI) technique for measuring small bowel water content which has been validated using naso-duodenal infusion. Eighteen healthy volunteers were intubated, with the tube position being verified by MRI. After a baseline MRI scan, each volunteer had eight 40 ml boluses of a non-absorbable mannitol and saline solution infused into their proximal small bowel with an MRI scan being acquired after each bolus. The MRI sequence used was an adapted magnetic resonance cholangiopancreatography sequence. The image data were thresholded to allow for intra- and inter-subject signal variations. The MRI measured volumes were then compared to the known infused volumes. This MRI technique gave excellent images of the small bowel, which closely resemble those obtained using conventional radiology with barium contrast. The mean difference between the measured MRI volumes and infused volumes was 2% with a standard deviation of 10%. The maximum 95% limits of agreement between observers were -15% to +17% while measurements by the same operator on separate occasions differed by only 4%. This new technique can now be applied to study alterations in small bowel fluid absorption and secretion due to gastrointestinal disease or drug intervention.

Dual pH probe monitoring versus single pH probe monitoring in infants on milk feeds : the impact on diagnosis

OBJECTIVES Oesophageal pH monitoring is the gold standard technique for the detection of gastro-oesophageal reflux in adults and children. A standard parameter used to define “abnormal” reflux is the percentage of recording time for which the gastric pH is < 4. This study investigated the relevance of this measure in infants on regular milk feeds whose gastric contents and refluxate will be neutral for most of the recording time. METHODS Simultaneous oesophageal and gastric pH monitoring was carried out on all infants who were milk fed exclusively and admitted to hospital for suspected gastro-oesophageal reflux. In vitro studies were performed to establish the buffering capacities of the fruit juice, Dioralyte (a glucose electrolyte solution), breast milk, and milk formula feeds available on the paediatric wards. RESULTS Complete sets of data were obtained from 30 babies with a mean age of 4 months. Gastric pH was ⩽ 4 for a mean (SEM) of 42.4 (4.9)% of the recording time. The mean (SEM) percentage time that oesophageal pH was < 4 for the total recording period was 6.89 (0.92)%. Recalculation of the percentage of time that the gastric pH was > 4 increased this value to 17.81 (2.46)%. Using a cut off point of 10%, 11 of the 30 babies would have been diagnosed positive for reflux using the conventional method; however, recalculation by ignoring the time for which gastric pH was high doubled this to 22 positive for reflux. CONCLUSION Combined oesophageal and gastric pH monitoring greatly increases the number of positive results from tests in infants on regular milk feeds. Key messages Reflux of neutral feeds is not easily detectable by conventional pH monitoring procedures Conventional pH monitoring may severely underestimate the incidence of gastro-oesophageal reflux in babies A dual probe approach, which monitors gastric acid and oesophageal pH, leads to a significantly higher diagnosis rate

Comparative scintigraphic assessment of the intragastric distribution and residence of cholestyramine, Carbopol 934P and sucralfate

It has been demonstrated that orally administered cholestyramine is distributed throughout the stomach and provides prolonged gastric residence via mucoadhesion. Gamma scintigraphy was used to compare the gastric emptying and residence of this resin with two formulations known to exhibit retentive or bioadhesive properties, Carbopol 934P and sucralfate. Fasted normal subjects received a single radiolabelled dose and gastrointestinal transit was monitored for 6 h. The subjects were fed after 4 h to determine the effects of inducing a fed pattern of motility on the retention of the formulations. Initial gastric emptying was similar (Mean T50+/-S.E.M.: cholestyramine=66.93+/-9.39 min; Carbopol=56.57+/-11.96 min; sucralfate=48.33+/-11.07 min; P=0.548: n=10), however, the emptying of cholestyramine slowed beyond 2 h. This resulted in greater residence for cholestyramine (Mean AUC0-6+/-S.E.M. (relative units)=11516+/-686 versus 7657+/-1170 versus 6170+/-998; cholestyramine versus Carbopol versus sucralfate; P=0.004: n=10), with approximately 25% remaining in the stomach at 6 h compared to 3.84 and 2.65% of Carbopol and sucralfate, respectively. Cholestyramine was also distributed widely throughout the stomach whereas Carbopol and sucralfate were concentrated in the body and antrum. Thus, as cholestyramine had a comparable emptying time to Carbopol and sucralfate but greater gastric residence and wider distribution, it could provide a potential mucoadhesive drug delivery system targeting the gastric mucosa for treatment of conditions such as Helicobacter pylori infection.

Monitoring of Gallbladder and Gastric Coordination by EPI

To assess for the first time the potential of echo‐planar magnetic resonance imaging (EPI) for measuring simultaneously both gallbladder and gastric emptying.

fMRI and MEG analysis of visceral pain in healthy volunteers.

Background  Although many studies of painful rectal stimulation have found activation in the insula, cingulate, somatosensory, prefrontal cortices and thalamus, there is considerable variability when comparing functional magnetic resonance imaging (fMRI) results. Multiple factors may be responsible, including the model used in fMRI data analysis. Here, we assess the temporal response of activity to rectal barostat distension using novel fMRI and magnetoencephalography (MEG) analysis.

Effect of resin surface charge on gastric mucoadhesion and residence of cholestyramine

Previous studies performed on excised gastric tissue and in healthy volunteers revealed that the ion exchange resin, cholestyramine, exhibits mucoadherent behaviour. This study was designed to elucidate whether surface charge affected this behaviour. Gamma scintigraphy was performed on fasted normal subjects following oral administration of cholestyramine or the cationic exchanger Amberlite(R) IRP-69, either uncoated or polymer-coated to mask their charge. Subjects were fed after 4 h. The initial gastric emptying of all formulations was similar (T(50) values (mean+/-S.E.M.): cholestyramine=85.86+/-9.16 min; IRP-69=76.09+/-9.23 min; polymer-coated cholestyramine=72.0+/-12.64 min; polymer-coated IRP-69=70.25+/-10.57 min: P=0.724). However, after 3 h the emptying pattern of cholestyramine was slower than that of IRP-69. This resulted in greater retention times than IRP-69 (AUC(0-6) values (relative units)=15,200+/-1093 versus 9452+/-811; cholestyramine versus IRP-69: P=0.0004). This effect was reduced by polymer-coating the cholestyramine. Serial images showed that cholestyramine was trapped in the oropharyngeal region and subsequently displaced by the meal, resulting in higher levels of activity remaining at 6 h. Thus, cholestyramine exhibited prolonged gastric residence via mucoadhesion and was distributed throughout the stomach. The surface charge of the resin was found to have a contributory role. These materials may have potential for the delivery of drugs in the topical treatment of the gastric mucosa, for example in the eradication of Helicobacter pylori.