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Biomedical subjects

J M Rawlings

Publications and source records attributed to J M Rawlings.

At least 19 recordsLinked to original sources

Bioconcentration and toxicity of dodecylbenzene sulfonate (C12LAS) to aquatic organisms exposed in experimental streams.

Fish, mollusks, and crustaceans were caged in the tail pool of streams during a C(12)LAS (dodecyl benzene sulfonate) model ecosystem experimental program. Bioconcentration of total C(12)LAS and individual isomers and acute and chronic toxicity were investigated during this study. Toxicity endpoints were based on water and tissue (i.e., body burden) concentrations at which adverse effects were observed. At 32 days, total C(12)LAS bioconcentration factors (BCFs) for the fathead minnow and three invertebrate species ranged from 9 to 116. In general, bioconcentration was affected by isomer position, exposure concentration, and species. BCF values tended to decrease as isomer position moved from external (e.g., 2-phenyl) to internal (e.g., 5,6-phenyl). BCFs also decreased as exposure concentration increased. Mean acute 4-d LC(50) values ranged from 1.5 to >3.0 mg/L for the six species tested. Lethal body burdens associated with 50% mortality (LBB(50)) varied from 0.21 to 0.60 mmole/kg (wet weight). During the 32-day chronic exposures, the EC(20) values were 0.27 (0.204-0.352), 0.95 (0.597-1.29), and approximately 1.0 mg/L for Corbicula (length), Hyalella (survival), and fathead minnow (survival), respectively. At these EC(20) values, C(12)LAS body burdens were 0.035, 0.23, and 0.19 mmoles/kg wet weight in Corbicula, Hyalella, and fathead minnow, respectively. Fish exposed to wastewater treatment plant effluent had total C(12)LAS tissue concentrations ranging from 0.0005 to 0.0039 mmoles/kg wet weight. These concentrations are approximately 45-360 times below the tissue concentration associated with subtle effects in the model ecosystem stream exposures. Total C(12)LAS body burdens in feral and caged Corbicula exposed to WWTP effluents were approximately 0.0013 mmoles/kg; approximately 25-fold below concentrations associated with effects in stream exposures.

Animals↗

Localization of alkaline phosphatase and Ca2+-ATPase in the cat placenta.

We localized alkaline phosphatase and plasma membrane calcium-ATPase (PMCA) in the cat placental syncytiotrophoblast to address their polarized distribution and their potential as markers for specific plasma membrane purification. We used enzyme- (alkaline phosphatase) and immuno- (PMCA) histochemistry and, for alkaline phosphatase, compared data to observations on the human placenta. Alkaline phosphatase activity in the cat was localized to the decidual cell membranes, to within the associated interstitial space and on the subjacent apical (maternal facing) plasma membrane of the syncytiotrophoblast. Occasional maternal capillaries were positive on their basal surface and there was focal staining within the syncytiotrophoblast. This widespread distribution is less specific than in the human placenta where alkaline phosphatase was restricted to the apical and basal plasma syncytiotrophoblast membranes, with much greater density on the apical membrane. Expression of PMCA in the cat was restricted to the basal membrane of the syncytiotrophoblast only. This specific localization of PMCA is identical to the human placenta and all other species in which its placental localization has been studied. We conclude that the plasma membranes of the cat syncytiotrophoblast show a broadly similar functional polarization to the human and that PMCA would prove a useful marker in isolation of the cat syncytiotrophoblast basal plasma membrane.

Adult↗

Influence of a high fibre diet on glycaemic control and quality of life in dogs with diabetes mellitus.

A study was undertaken to evaluate a high fibre diet used in the management of 10 dogs with naturally occurring insulin-dependent diabetes mellitus. Following baseline measurements of health and glycaemic control, the dogs were fed a canned diet containing a blend of insoluble and soluble dietary fibres and were monitored during the ensuing four months. Switching to the high fibre diet was associated with significantly lower mean 24-hour and postprandial plasma glucose concentrations, which were maintained over the study period. The high fibre diet was also associated with significant reductions in plasma concentrations of fructosamine, glycated haemoglobin, free glycerol and cholesterol, and there were significant improvements in dog activity and demeanour. Bodyweight declined during the fourth month of feeding the diet, which is likely to have resulted from underfeeding relative to increased activity. The results indicate that a high fibre diet can significantly improve glycaemic control and quality of life in dogs with diabetes mellitus.

Animals↗

The use of P-aminobenzoic acid and chromic oxide to confirm complete excreta collection in a carnivore, Felis silvestris catus.

Complete excreta collection is a pre-requisite for several protocols in protein metabolism, and lack of confidence in achieving this may be increased when working with carnivores. Recovery of p-aminobenzoic acid (PABA) as a check for complete urine collection and chromic oxide for complete faeces collection were assessed in the cat. A single oral dose of PABA (4 mg/kg BW) was excreted more slowly than has been reported in the human (82% recovery at 6 h). A daily dose of PABA proved a useful method for confirming complete urine collection in the cat, and was 99% excreted in 72 h. Chromic oxide (500 mg/cat) was administered orally and recovery of chromium in the faeces was 90% after 96 h. A HPLC method for the analysis of PABA in cat urine was developed, and from the application of the techniques to a nitrogen balance study, it was concluded that PABA and chromic oxide are useful checks for complete excreta collection in the cat.

4-Aminobenzoic Acid↗

Feline hypertension: clinical findings and response to antihypertensive treatment in 30 cases.

Systolic hypertension was diagnosed in 30 cats. At diagnosis, 16 of those were found to be in chronic renal failure only, while five were azotaemic and either receiving treatment for hyperthyroidism (four cases) or were untreated hyperthyroid cases (one case). Two cases were untreated hyperthyroid cases with no evidence of azotaemia and the remaining seven cases had no definitive diagnosis of the underlying cause of their hypertension. The successful treatment used for the majority of cases was amlodipine, which lowered systolic blood pressure from 202.5+/-16.8 to 153.2+/-21.6 mmHg (mean+/-SD; n=29) within the first 50 days. Each case was followed for at least three months, or to the end of its natural life, and each cat was re-examined every six to eight weeks. Systolic blood pressure was kept below a target value of 165 mmHg in 58 per cent of cases treated for three months or longer. At the time of writing, 19 of the cases had died or been euthanased with a median treatment time of 203 days, one case was lost to follow-up and 10 cases were still alive, nine of which had been treated for six months or more. Amlodipine can be used for long-term control of feline systemic hypertension.

Amlodipine↗

Survival of cats with naturally occurring chronic renal failure: effect of dietary management.

Fifty cats with naturally occurring stable chronic renal failure (CRF) were entered into a prospective study on the effect of feeding a veterinary diet restricted in phosphorus and protein with or without an intestinal phosphate binding agent on their survival from initial diagnosis. Twenty-nine cats accepted the veterinary diet, whereas compliance (due to limited intake by the cats or owner resistance to diet change) was not achieved in the remaining 21. At diagnosis, both groups of cats were matched in terms of age, bodyweight, plasma creatinine, phosphate, potassium and parathyroid hormone (PTH) concentrations, packed cell volume and urine specific gravity. Feeding the veterinary diet was associated with a reduction in plasma phosphate and urea concentrations and prevented the increase in plasma PTH concentrations seen in cats not receiving the diet. Cats fed the veterinary diet survived for longer when compared with those that were not (median survival times of 633 versus 264 days). These data suggest that feeding a diet specifically formulated to meet the needs of cats with CRF, together with phosphate binding drugs if required, controls hyperphosphataemia and secondary renal hyperparathyroidism, and is associated with an increased survival time.

Animals↗

Effect of dietary phosphate restriction on renal secondary hyperparathyroidism in the cat.

Twenty-three cats with stable chronic renal failure (CRF) were examined in a prospective study of the effects of feeding a veterinary diet restricted in phosphorus and protein with or without an intestinal phosphate binding agent (aluminium hydroxide) on plasma phosphate and parathyroid hormone (PTH) concentrations. Fifteen cats accepted the veterinary diet; compliance was not achieved in the remaining eight (due to limited intake by the cats or owner resistance to diet change). Feeding the veterinary diet was associated with a significant fall in plasma phosphate and PTH concentrations by five months, with only two cats requiring aluminium hydroxide therapy. The maximum decrease in plasma PTH concentration was not associated with a significant change in plasma 1,25 dihydroxycholecalciferol concentration. Euparathyroidism was achieved in eight cats. Conversely, in cats with CRF fed proprietary diets over the same time period, mean plasma PTH concentrations did not change significantly; indeed, in seven of the eight cats, PTH concentrations increased. Dietary therapy alone or in combination with intestinal phosphate binders does reduce PTH concentrations in cats with CRF and, when effective control of phosphate intake is achieved, plasma PTH can be normalised.

Aluminum Hydroxide↗

Effect on canine oral health of adding chlorhexidine to a dental hygiene chew.

A study to compare the effect of a dental hygiene chew with or without 0.2% chlorhexidine on the development of gingivitis and the accumulation of dental deposits was performed using 11 small dogs. Confirming previous data, the daily addition of a standard chew to a dry diet resulted in significantly less gingivitis and calculus after 3 weeks compared with feeding the dry diet alone. Addition of chlorhexidine to the chew made no difference to the degree of gingivitis or the amount of calculus that accumulated, but did result in significantly less plaque accumulation after 3 weeks. The abrasiveness of the chew, rather than the antibacterial activity of chlorhexidine, is likely to have contributed the most to the maintenance of oral health in dogs with mild gingivitis.

Analysis of Variance↗

Oral malodor and its relevance to periodontal disease in the dog.

Oral malodor has been studied extensively in humans but very little work has been done in dogs where it constitutes a significant problem. In this article we review its causes, methods of detection, and strategies for preventing it. Oral malodor arises from microbial metabolism of exogenous and endogenous proteinaceous substrates in the oral cavity and is exacerbated by periodontal disease and poor oral hygiene. Gram negative bacteria found in plaque, in periodontal pockets, and on the dorsum of the tongue are primarily responsible for odor production. The volatile sulfur compounds (VSCs) hydrogen sulfide and methyl mercaptan, which are produced by these bacteria, are not only primarily responsible for the objectionable odor but have been implicated in the pathogenesis of periodontal disease. Assessment of malodor by portable sulfide monitors correlates well with organoleptic measurements. Reduction of microbial load in the oral cavity due to good oral hygiene practices (such as tooth-brushing) or by the use of appropriate diets or chews may reduce malodor formation.

Animals↗

Studies of oral malodor in the dog.

We compared currently used methods for assessing oral malodor and found a significant, positive correlation between the concentration of volatile sulfur compounds (VSCs) in breath and the human perception of malodor, but only within a limited range of VSC production. Daily tooth-brushing from an early age maintains a low and consistent level of oral malodor that does not differ significantly throughout the day. In contrast, dogs with elevated concentrations of VSC production suffer from the highest level of malodor early in the morning, prior to feeding and daily activities. Even in older dogs, periodontal therapy can result in a substantial reduction of oral malodor that remains significantly below pre-treatment values for up to 3 months after treatment.

Animals↗

Effect of two dietary regimens on gingivitis in the dog.

The effect of two commercially available dietary regimens on the development of gingivitis and the accumulation of dental plaque, calculus and stain in the dog were studied. One regimen consisted of feeding an oral hygiene chew and a standard dry diet. The other was based on a specifically designed oral care dry main meal. The study was conducted using 15 dogs in a two period, parallel cross-over design. Each period consisted of a one week pretest phase followed by a three week test phase. During the test phase, gingivitis and plaque were measured after one week and gingivitis, calculus, stain and plaque were measured after a further two weeks. Comparison of the two regimens showed that there were equal amounts of gingivitis, plaque and calculus by the end of the study. There was significantly more stain and significant loss in bodyweight when the main meal was fed. The role of dietary modification in the maintenance of periodontal health is discussed.

Animal Feed↗

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↗

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↗

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↗

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↗

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↗