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Biomedical subjects

S J Jackson

Publications and source records attributed to S J Jackson.

At least 19 recordsLinked to original sources
PubMed2006

Frequent feeding delays the gastric emptying of a subsequent meal.

To assess the suitability of the 13C-octanoic acid breath test for measuring gastric emptying in circumstances other than the post-absorptive state, a preliminary study was performed where 6 hourly spaced isoenergetic meals preceded the determination of gastric emptying of a subsequent 2 MJ meal. Emptying was measured in three individuals on four separate occasions, with a reproducibility of 8%. A crossover study was then conducted to test the hypothesis that meal frequency can modulate the gastric emptying of a subsequent meal, with the potential to influence appetite regulation. Sixteen subjects were fed to energy balance, receiving food either as 2 isoenergetic meals 3 h apart or 6 isoenergetic meals fed hourly. Gastric emptying of a subsequent 2 MJ meal was investigated. Visual analogue scales were used throughout to assess appetite. The maximum rate of gastric emptying was unchanged but the onset of emptying was delayed by the more frequent feeding pattern. There was no significant difference in subjective appetite before or after the test meal. In conclusion, short-term increases in feeding frequency delayed the gastric emptying of a subsequent meal, but significant effects on post-meal appetite could not be demonstrated.

Adult↗
PubMed2005

Cannabinoid-receptor 1 null mice are susceptible to neurofilament damage and caspase 3 activation.

Administered cannabinoids have been shown to ameliorate signs of CNS inflammatory disease in a number of animal models, including allergic encephalomyelitis. More recently, neuroprotective actions have been attributed to activation of the cannabinoid 1 receptor in a number of in vitro and in vivo models. One of these, chronic relapsing experimental allergic encephalomyelitis, is considered a robust analog of multiple sclerosis. In this study, spinal cord tissue from cannabinoid receptor 1 knockout mice was analyzed for neurofilament H and myelin basic protein content, as markers of neurons/axons and myelin respectively, during the course of chronic relapsing experimental allergic encephalomyelitis. Dephosphorylation of a neurofilament H epitope, immunoreactive to the SMI32 antibody, was assessed as a marker of axonal damage and levels of the endpoint cell death mediator caspase 3 were evaluated. It was found that both neurofilament and myelin basic protein levels decrease over the course of disease, indicating concomitant neuronal/axonal loss and demyelination. Loss of each marker was more severe in cannabinoid receptor 1 knockout animals. Increased SMI32 reactivity was observed as disease progressed. SMI32 reactivity was significantly increased in knockout animals over wildtype counterparts, an indication of greater axonal dephosphorylation and injury. Active caspase 3 levels were increased in all animals during disease, with knockout animals displaying highest levels, even in knockout animals prior to disease induction. These results indicate that lack of the cannabinoid receptor 1 is associated with increased caspase activation and greater loss and/or compromise of myelin and axonal/neuronal proteins. The increase of caspase 3 in knockout mice prior to disease induction indicates a latent physiological effect of the missing receptor. The data presented further strengthen the hypothesis of neuroprotection elicited via cannabinoid receptor 1 signaling.

Animals↗
PubMed2004

Delayed gastric emptying in the obese: an assessment using the non-invasive (13)C-octanoic acid breath test.

AIM: Much of the controversy surrounding the correlation between obesity and gastric emptying lies in the inconsistency of methodology and analysis. This study was designed to overcome some of the discrepancies encountered in previous studies and to test the hypothesis that obese individuals have altered gastric emptying compared to lean individuals. METHODS: Gastric emptying was measured using the (13)C-octanoic acid breath test in 16 lean and 16 obese women pair-matched for age. Following an overnight fast, subjects were given a standard 2 MJ egg meal labelled with 100 microl of [1-(13)C]-octanoic acid. Breath samples were collected at regular intervals over a 6-h period. (13)C-isotopic enrichment in the breath was analysed using isotope ratio mass spectrometry and the data fitted to the established gastric emptying model. The lag times (t(lag)), half excretion times (t(1/2)), latency phase (t(lat)) and ascension times (t(asc)) were calculated. RESULTS: The mean t(1/2)-values (+/-standard error of the mean) were 3.67 +/- 0.14 h and 4.23 +/- 0.18 h for lean and obese respectively, indicating significantly delayed gastric emptying in the obese (p = 0.019). The obese group also showed a significantly slower lag time (t(lag), p = 0.005) and latency phase (t(lat), p = 0.005), but no significant difference was found in the ascension time (t(asc), p = 0.154). Within groups, no correlation was found between half excretion times and body weight or half excretion times and body mass index. CONCLUSIONS: The present study demonstrated a prolonged lag phase and delayed gastric emptying in obese women when compared to lean women. This delay may be as a consequence of high-fat diets, a sedentary lifestyle and increased gastric distension associated with obesity, or a contributing factor in the pathogenesis of obesity resulting from the inactivation of gastrointestinal satiety signals and in an increase in food intake.

Adult↗
PubMed2001

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.

Acrylic Resins↗
PubMed2001

In vitro assessment of the mucoadhesion of cholestyramine to porcine and human gastric mucosa.

Previous in vivo studies have suggested that the extended gastric residence and uniform intragastric distribution of cholestyramine may be due to mucoadherent properties. This series of in vitro investigations explored the possibility of the anion exchange resin exhibiting bioadhesive behaviour, and investigated the characteristics, such as particle size and surface charge, that may affect it. Tensile strength measurements were carried out to determine the mucoadhesion of cholestyramine and other test materials (resin particulates, polymers and hydrogels) with varying adhesive properties, to isolated porcine and human gastric mucosa. Optimal instrumental parameters for the system were determined initially and used; all procedures were carried out at room temperature (22 degrees C). The particle size of cholestyramine did not affect mucoadhesion to either porcine or human gastric mucosa (P=0.673, porcine; P=0.969, human), whilst anionic exchangers were found to provide better mucoadhesion than cationic exchangers (P=0.0002, porcine; P=0.0009, human). In some instances, it was found that the detachment forces recorded were lower with human gastric mucosa than with porcine gastric mucosa, although this was not consistently statistically significant. A rank order of mucoadhesion was constructed from a comparison of cholestyramine with eight other test materials. Cholestyramine produced the second highest degree of mucoadhesion, with Carbopol producing the greatest adhesion. Dextran and polyethylene glycol did not display good mucoadhesion under these conditions. From the findings presented here, we have found that cholestyramine demonstrates good mucoadhesion to both porcine and human gastric mucosa when compared to other known bioadhesives. It is suggested that particle size does not contribute to this mucoadherent behaviour but the surface charge of the resin has a significant part to play.

Adhesiveness↗
PubMed2000

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.

Adolescent↗
PubMed2000

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.

Administration, Intranasal↗
PubMed2000

The effect of nasal patency on the clearance of radiolabeled saline in healthy volunteers.

PURPOSE: The objective of this study was to investigate the effect of nasal cavity patency on the penetration, deposition, and clearance of an aqueous isotonic saline solution. METHODS: The study was carried out as a single center, open, randomized, 2-way cross-over in healthy volunteers. Nasal patency was assessed using misting patterns on a cold metal surface at the beginning and end of study. 100 microl of technetium-99m radiolabeled saline solution was introduced into either the most or least patent nasal cavity using a purpose designed spray device. The distribution and residence time of the radiolabel was followed for 2 hours using gamma scintigraphy. RESULTS: The mean times to 50% clearance were 34+/-7 and 28+/-12 minutes (+/- s.d.) for the side view of the least and most patent nasal cavity respectively. Total clearance of the radiolabelled saline from the nose was not affected by patency. Between 7 and 35% of the radiolabelled saline solution remained in the nasal cavity at the end of imaging. Using endoscopy to track the clearance of an aqueous solution of food dye using the same delivery procedure, identified this region as hair in the nasal vestibule. The dye was seen to dry in this region along with the mucus. CONCLUSIONS: Nasal patency affects the initial, but not total clearance of solutions, however, the remaining solution may not be available for drug delivery.

Adolescent↗
PubMed2000

In vitro cytotoxicity of norviburtinal and isopinnatal from Kigelia pinnata against cancer cell lines.

Crude dichloromethane extracts of Kigelia pinnata stem bark and fruit showed cytotoxic activity in vitro against cultured melanoma and other cancer cell lines using the Sulphorhodamine B assay, which was used for bioassay-guided fractionation. Thin layer chromatography (TLC) examination of the most active fractions of both stem bark and fruits showed the presence of the same major components which were found to be norviburtinal and beta-sitosterol. Norviburtinal was found to be the most active compound but had little selectivity for melanoma cell lines whilst isopinnatal also showed some cytotoxic activity. beta-Sitosterol was found to be comparatively inactive. HPLC analysis of the crude extract showed that the amount of norviburtinal present in the plant material did not account for all of the activity of the total extracts.

Anthraquinones↗
PubMed1999

Twenty-four hour ambulatory nasal pH monitoring.

The nasal delivery of drugs, both for systemic and local use, is an expanding field with many drugs being delivered by this route. It is known that changes in pH can affect drug absorption but there is no data regarding intranasal pH over time. We present the results of 24-h ambulatory nasal pH monitoring in four subjects, each of whom had monitoring on two separate occasions. The apparatus consisted of a pH monitor with two electrodes, thus enabling us to take readings from 1 and 4 cm behind the anterior end of the inferior turbinate. Measurements were recorded every 6 s by the posterior electrode and every 30 s by the anterior electrode. The recording apparatus was worn around the subjects waist. Analysis of the results showed that there was no diurnal variation and no significant differences between the subjects. The mean pH from the anterior electrode was higher than that from the posterior (7.1 versus 6.6). The pH did not fluctuate with daily activities such as eating, drinking or sleeping. The results are interesting and may be of importance with regard to the design of formulations for nasal drug delivery systems.

Activities of Daily Living↗
PubMed1999

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.

Animals↗
PubMed1998

Patterns of food and acid reflux in patients with low-grade oesophagitis--the role of an anti-reflux agent.

BACKGROUND: Food and acid have been shown to be refluxed independently of each other in healthy volunteers, and anti-reflux agents decrease the reflux of both parameters. Until now this phenomenon had not been studied in patients with low-grade oesophagitis, who are the group most likely to use anti-reflux medication. AIM: To assess patterns of gastro-oesophageal reflux of acid and food in 12 ambulant patients with endoscopically proven oesophagitis of between grades I and II, but who were otherwise healthy. Also to assess the effectiveness of a single dose of an alginate-containing anti-reflux agent in controlling food and acid reflux in this patient group. METHODS: Oesophageal pH monitoring and external ambulatory gamma detection were used to study food and acid reflux. A pH electrode was positioned 5 cm above the cardia and the gamma detector was positioned externally over the pH electrode. The patients then received a technetium-99m labelled meal designed to provoke reflux. Thirty minutes later the patients were given a 20 ml dose of alginate (Liquid Gaviscon), or 20 ml of tap water. Incidence of reflux was monitored for approximately 4 h from the end of the meal. Allocation to treatment group was randomized, with patients receiving the alternative treatment on the second study day after approximately a 7-day washout period. RESULTS: The mean percentage time oesophageal pH remained below 4 was 16.3 min for the control group and 5.4 min for the treatment group (P = 0.03). Food reflux was detected 23.7% of the time in the control group compared to 12% of the time in the treatment group (P = 0.02). The anti-reflux agent was also successful in decreasing the number of events, but the duration of the reflux events was not significantly different. CONCLUSIONS: Patients with grades I and II oesophagitis reflux food and acid independently, and are predominantly either food refluxers or acid refluxers, but not both. Liquid alginate decreases the number of both food and acid reflux events, but does not change their duration.

Adult↗
PubMed1998

The villain as reference idol: selection frequencies and salient attributes among New Zealand teenagers.

Teenagers from all 11 high schools in Dunedin, New Zealand, responded to a questionnaire about their villains (i.e., public figures, real or fictional, living or deceased, whom they strongly disliked). A total of 917 villains from all walks of life were selected. The naming of a villain was unrelated to age, gender, or socioeconomic status. Nearly nine times more male than female public figures were selected as villains. Approximately 70% of the villains were either politicians, criminals, or athletes. In general, males disliked their villains because of negative personality traits, while females disliked their villains for "crimes committed against humanity." Not only were villains disliked, but findings regarding level of influence revealed that many students used their villains as avoidance role models to mold and shape attitudes, values, and behaviors. An interesting finding, given the fact that these villains have no sanctioning power, was how much influence these socially distant public others have.

Adolescent↗
PubMed1997

In at the deep end--an insight into scuba diving and related dental problems for the GDP.

Scuba diving is one of the fastest growing sports in the world. It is inevitable that the general dental practitioner (GDP) will have patients who participate in this sport and they should be aware of a number of problems that a diver can experience that are associated with the teeth and related structures. The aim of this article is to introduce the GDP to the dental problems associated with diving and make recommendations on dental care for scuba divers.

Barotrauma↗
PubMed1994

Activity of extracts of Kigelia pinnata against melanoma and renal carcinoma cell lines.

Serial dilutions of standardised water, ethanol, and dichloromethane extracts of the stembark and fruits of Kigelia pinnata were tested for their growth inhibitory effects against four melanoma cell lines and a renal cell carcinoma line (Caki-2) using two different (MTT and SRB) assays. Lapachol, a possible constituent of these extracts, together with known therapeutic antineoplastic agents, was also tested in the same way. The IC50 of each extract was measured after extracts were diluted to 100 micrograms/ml in 1% ethanol or water. Significant inhibitory activity was shown by the dichloromethane extract of the stembark and lapachol (continuous exposure). Moreover, activity was dose-dependent, the extract being less active after 1 h exposure. Chemosensitivity of the melanoma cell lines to the stembark was greater than that seen for the renal adenocarcinoma line. In marked contrast, sensitivity to lapachol was similar amongst the five cell lines. Lapachol was not detected in the stembark extract.

Antineoplastic Agents, Phytogenic↗