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Biomedical subjects

J M Rawlings

Publications and source records attributed to J M Rawlings.

30 records · Page 2Linked to original sources
PubMed1996

The role of tooth-brushing and diet in the maintenance of periodontal health in dogs.

Tooth-brushing every other day did not maintain clinically healthy gingivae in dogs. The daily addition of a dental hygiene chew to a regimen of tooth brushing every other day reduced the gingivitis scores and reduced the accumulation of dental deposits (plaque, calculus and stain). Daily tooth-brushing should be the recommendation to the dog owner irrespective of dietary regimen. Providing a dental hygiene chew daily seems to give an added health benefit when tooth-brushing is less frequent, and provides the pet owner with a useful adjunct for homecare.

Analysis of Variance↗
PubMed1994

Evidence for redox cycling of diquat in rat small intestine.

It has previously been established that acute diquat (1,1'-ethylene, 2,2'-bipyridilium) toxicity in the rat is associated with stimulation of net fluid secretion into the gastrointestinal tract. We have examined the possibility that the mechanism of diquat toxicity in the small intestine involves redox cycling of the bipyridyl leading to a disturbance of biochemical function and oxidative stress. Experiments performed in vitro showed that diquat (10 microM to 1 mM) produced an increase in activity of the pentose phosphate pathway in rat small intestinal tissue slices, suggesting that there was oxidation of NADPH even at concentrations of diquat which do not cause intestinal fluid secretion in anaesthetized rats. When the effect of diquat on pentose phosphate activity was measured in rats in situ at a dose which causes maximal fluid secretion [50 mM diquat dibromide (DQBr2)], production of 14CO2 from [1-14C]-glucose increased by 278 +/- 28% (N = 4) within 1 hr of exposure to diquat. Under these same conditions, the tissue content of NADPH in the proximal small intestine was significantly depleted, though there was no corresponding increase in NADP+ concentration. Diquat had no effect on tissue concentrations of either the reduced or oxidized forms of NAD. It is likely that NADPH oxidation at low diquat concentrations can be adequately compensated for by mechanisms within the tissue which protect against oxidative stress. However, the data also suggest that diquat-induced fluid secretion in the rat small intestine is associated with redox cycling of bipyridyl leading to depletion of NADPH.

Animals↗
PubMed1994

Effect of dosing vehicle on the dermal absorption of fluazifop-butyl and fomesafen in rats in vivo.

One important factor which may influence the extent and rate of percutaneous absorption is the dosing vehicle. The purpose of the experiments described was to compare the effect of dosing vehicles of different polarities on the absorption of two herbicides across rat skin in vivo. Rats were dosed dermally with either fluazifop-butyl (logP(oct) 4.5) or fomesafen sodium salt (logP(oct) -1.2) in propylene glycol (PG), octanol (OCT), or ethyl decanoate (ED), and the amount of radioactivity excreted in urine was determined. Absorption rates were estimated from the urinary excretion data and from blood kinetic data derived from intravenously dosed rats. For fluazifop-butyl the average rate of absorption (x10(-2) micrograms/hr-1 +/- SE) was not greatly influenced by the dosing vehicle (OCT, 2.94 +/- 0.08; ED, 3.66 +/- 0.10; PG, 3.95 +/- 0.32) despite relatively large differences in solubility (PG, 38 mg/ml; OCT, and ED, > 600 mg/ml). These results were consistent with the finding that there was at most only a twofold difference in the epidermal membrane:vehicle partition coefficients (km). In contrast, the absorption rate of fomesafen from PG (1.98 +/- 0.04) was approximately half that of ED (3.98 +/- 0.06) and OCT (4.49 +/- 0.08) for the first 30 hr after application and was in keeping with solubility data (PG, 638 mg/ml; OCT, 12 mg/ml; ED, < 10 mg/ml). At later time points the absorption of fomesafen from PG increased; this is discussed in relation to the penetration-enhancing properties of PG.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1994

Comparison of two methods for determining the toxicokinetics of fluazifop-butyl after intravenous dosing in rats.

1. We have described and compared the use of two blood sampling techniques to measure the kinetics of fluazifop-butyl, a selective herbicide. Following intravenous administration of radiolabelled compound, blood samples were collected from female rats either by tail vein puncture or from chronically implanted catheters inserted in tethered rats. Urine samples were also collected from tethered animals. 2. Both techniques indicate that fluazifop-butyl is rapidly eliminated from blood into urine (t(1/2)3-4.5 h) and the overall blood concentration profiles were comparable between the two methods. However, by using cannulated rats, kinetic data were obtained from individual animals, providing evidence of inter-animal variation and allowing compartmental and statistical analysis. 3. The tethered rat technique is relatively simple and reliable. Compared to tail vein bleeding, results obtained from cannulated animals are more informative, providing comprehensive data from a small number of rats. It is therefore the preferred method for our kinetic based research studies using compounds known to exhibit multicompartmental elimination kinetics.

Animals↗
PubMed1992

Diquat-induced intestinal secretion in the anaesthetized rat.

1. Diquat (1,1'-ethylene-2,2'-bipyridilium) is a non-selective desiccant herbicide which, when administered orally to mammalian species, causes significant secretion of fluid into the lumen of the gastrointestinal tract. In order to characterize this secretory response in more detail the effect of sublethal doses of diquat dibromide (DQBr2) on intestinal secretion was investigated in vivo in the jejunum of anaesthetized rats. 2. Ligated segments of jejunum (10 cm) which were prepared in groups of up to five animals were filled with 500 microliters of isosmotic DQBr2 solutions with concentrations ranging from 1-100 mM and maintained in the anaesthetized rat for 1, 2 or 3 h; in control experiments a solution of 100 mM NaBr was used. 3. It was found that while all of the fluid instilled into the segments was absorbed in the control experiments, there was both a dose- and time-dependent secretory response to DQBr2. Maximal fluid secretion occurred after treatment with 50 mM DQBr2 for 3 h. 4. Histological assessment of the jejunum revealed an increase in cell exfoliation and evidence of luminal distension after incubation with DQBr2. However, no structural damage to the mucosa could be seen to account for the fluid secretion. 5. The model described provides a quantitative means of evaluating intestinal secretion and may be used for elucidating the mechanism by which diquat alters fluid transport processes.

Animals↗
PubMed1991

The effect of E. coli STa enterotoxin on the absorption of weakly dissociable anti-malarial drugs from rat intestine in vivo.

1. The effect of E. coli heat stable (STa) enterotoxin on the absorption of radiolabelled anti-malarial weak bases and their appearance in peripheral blood was assessed in vivo by a recirculation procedure in rat intestinal loops. 2. Enterotoxin increased the jejunal disappearance of quinine (P less than 0.05), trimethoprim (P less than 0.05), proguanil (P less than 0.05) and chloroquine (P less than 0.001) and left pyrimethamine disappearance unaltered. Peripheral blood levels of trimethoprim (P less than 0.02) and proguanil (P less than 0.05) were higher after STa exposure. 3. In the ileum, enterotoxin increased the luminal disappearance (P less than 0.05) and peripheral blood appearance (P less than 0.001) of chloroquine. The luminal disappearance rate of trimethoprim was reduced (P less than 0.05) and that of pyrimethamine unchanged. 4. The increased jejunal absorption of the anti-malarial drugs occurred despite STa causing a reduction in the amount of net fluid absorption. It seems likely that the enhanced absorption with STa exposure is related to the effect of STa on the microclimate pH. An elevation in the microclimate pH would increase the amount of undissociated weak base available for non-ionic diffusion. 5. The favourable elevation of microclimate pH by STa seemed to be outweighted by the reduced fluid absorption in the ileum. Only chloroquine still showed enhanced absorption in the ileum and this may have been because unlike the other antimalarial drugs, chloroquine has two dissociable groups likely to be affected by the mucosal surface pH changes.

Acid-Base Equilibrium↗
PubMed1990

Water permeability of acinar cell membranes in the isolated perfused rabbit mandibular salivary gland.

1. The diffusive water permeability of epithelial cell membranes in the perfused rabbit mandibular salivary gland was measured at 37 degrees C by a 1H nuclear magnetic resonance relaxation method using an extracellular relaxation reagent, gadolinium diethylenetriaminepentaacetic acid (Gd(DTPA)). 2. In glands perfused with a HEPES-buffered solution containing 10 mmol l-1 Gd(DTPA), the spin-lattice (T1) relaxation of the water protons showed two exponential components. The water compartment responsible for the slower component corresponded in magnitude to 71 +/- 5% of the wet weight of the gland, and was attributed to the exchangeable intracellular water of the acinar cells. 3. The rate constant for water efflux from the cells was estimated to be 4.1 +/- 0.1 s-1 which would be consistent with a diffusive membrane permeability (Pd) of approximately 3 x 10(-3) cm s-1. Stimulation with acetylcholine (10(-6) mol l-1) did not cause any detectable change in membrane water permeability. 4. Since the basolateral membrane probably provides the main pathway for water efflux, the osmotic water permeability of this barrier (expressed per gland) was estimated to be less than 6.2 cm3 s-1. This would be insufficient to account for the generation of a near-isosmotic fluid at the flow rates observed during secretion, and suggests that a substantial fraction of the flow of water occurs via a paracellular route.

Acetylcholine↗
PubMed1987

Electrodes for 24 hours pH monitoring--a comparative study.

Three pH electrodes in clinical use were examined--(1) antimony electrode with remote reference electrode (Synectics 0011), (2) glass electrode with remote reference electrode (Microelectrodes Inc. MI 506) and (3) combined glass electrode with integral reference electrode (Radiometer GK2801C). In vitro studies showed that both glass electrodes were similar and superior to the antimony electrode with respect to response time, drift, and sensitivity. The effect of the siting of the reference electrode on the recorded pH was examined in five human volunteers. The pH reading using a remote skin reference electrode was higher by a mean of 0.3 pH units (range 0.0-0.6) in the stomach, lower by 0.65 pH units (0.5-0.8) in the duodenum and lower by 0.3 pH units (0.0-0.6) in the oesophagus than that simultaneously obtained with an intraluminal reference electrode. Buccal reference electrodes gave similar readings to skin. Combined reference and glass pH electrodes are recommended for 24-hour ambulatory pH monitoring.

Antimony↗
PubMed1987

Measurement of jejunal surface pH in situ by plastic pH electrode in patients with coeliac disease.

Attaching plastic pH electrodes to a Crosby capsule provides a means of measuring mucosal surface pH in the small intestine during jejunal biopsy. Plastic electrodes, with operating characteristics comparable to glass electrodes within the physiological pH range, were selected because of their mechanical flexibility. The sensing tip can be placed close to the capsule aperture to facilitate contact with the intestinal mucosa. Using this system, the jejunal mucosal surface pH was found to be 5.97 +/- 0.07 in 15 control subjects. In contrast, 13 coeliac patients had a significantly (p less than 0.001) higher jejunal surface pH of 6.73 +/- 0.15, subdivisible into 4 untreated patients with a mean value of 6.95 +/- 0.33 and 9 patients on a gluten-free diet with a mean value of 6.63 +/- 0.15, both higher (p less than 0.01, p less than 0.005) than the control value. An elevated jejunal surface pH in coeliac disease was associated with partial or subtotal villous atrophy and with low brush border enzyme activities. Confirming previous in vitro findings, the elevated surface pH in coeliac jejunum may affect digestive and absorptive processes occurring at the brush border.

Adolescent↗
PubMed1985

Plastic pH electrodes for the measurement of gastrointestinal pH.

Plastic electrodes have been developed for measuring pH in the human gastrointestinal tract. The electrodes have a plastic hydrogen ion sensitive membrane sealed to a length of fluid filled PVC tubing. Two recently developed hydrogen ion sensitive ligands have been examined. Their operational characteristics have been described. These electrodes have an electrical response of 52 to 58 mV/pH unit change in the range pH 4-9, with a diminished response outwith this range. They have a low resistance value and a fast response time of one second to reach 90% of their maximum response. The electrodes can be passed down the biopsy channel of an endoscope to obtain mucosal pH readings under direct vision. Readings obtained in this way using plastic electrodes are comparable to those obtained with glass electrodes. Alternatively, these electrodes can be joined to a Crosby capsule, allowing continuous recording of mucosal pH through to the jejunum during jejunal biopsy procedures. These electrodes can be used repeatedly or may be acceptable as inexpensive disposable items for sterile clinical use.

Amines↗