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Biomedical subjects

A Steward

Publications and source records attributed to A Steward.

11 recordsLinked to original sources
PubMed1992

Effects of androgens in models of rheumatoid arthritis.

Testosterone and its metabolite 5 alpha-dihydrotestosterone (DHT) were compared with dexamethasone 21-acetate in two different animal models of arthritis and found to have effects on cartilage breakdown and inflammation. In the mouse air pouch, at the three dose levels used, significant effects were obtained with DHT and were more pronounced on cartilage breakdown than on inflammation. At the lowest dose of 0.3 mg kg-1 there was a 64% inhibition of collagen breakdown and 18% inhibition of glycosaminoglycans (GAGs) breakdown. In the antigen-induced arthritis mouse model testosterone had significant inhibitory effects on inflammation (synovial hyperplasia) and cartilage erosion.

Animals↗
PubMed1988

A modified mouse air pouch model for evaluating the effects of compounds on granuloma induced cartilage degradation.

1. Employing rat femoral head cartilage implanted in a 6 day old mouse air pouch, the effects of inflammatory stimuli (i.e. cotton pellets, carrageenan, zymosan) on the loss of proteoglycan and collagen and granuloma formation have been studied. 2. Wrapping of the cartilage in cotton resulted in granuloma formation with accelerated loss of proteoglycan and collagen over the 14 day implantation period. The amount of loss increased with increasing weight of cotton. 3. The effects of different classes of anti-rheumatic drugs on granuloma formation and proteoglycan and collagen loss from cotton wrapped femoral head cartilage in the mouse air pouch have been studied. 4. Non-steroidal anti-inflammatory drugs (NSAIDs) had no influence on granuloma formation, but in general accelerated the rates of proteoglycan and collagen loss. 5. Dexamethasone and prednisolone significantly reduced granuloma formation and had a marked protective effect on cartilage breakdown. 6. Of the slow acting anti-rheumatic drugs examined, only gold sodium thiomalate (GSTM) and dapsone significantly decreased cartilage loss, with an accompanying modest decrease in granuloma formation. 7. The immunosuppressants cyclophosphamide and methotrexate, but not azathioprine, reduced cartilage degradation, but had no effect on granuloma formation. 8. The results for the different classes of anti-inflammatory and anti-rheumatic drugs are discussed in relation to their effects in other animal models and their reported therapeutic activities in man. It is concluded that the mouse air pouch method as described offers advantages as an animal model over existing procedures to predict therapeutic efficacy in man.

Animals↗
PubMed1988

Proteoglycan biosynthesis as a determinant of patella damage in the murine antigen-induced arthritis model.

The incorporation of 35SO4 into cartilage proteoglycan has been employed as a measure of patella damage in the murine antigen-induced arthritis model. In a preliminary set of experiments, where both the proteoglycan concentration and 35SO4 incorporation were determined in control and arthritic patella over a 2 day to 6 day week period, the arthritic joint contained significantly higher levels of radioactivity compared with the controls. A subsequent study over an extended period of 10 weeks confirmed the earlier results, and indicated that the 6 week samples showed the greatest difference (71%) in 35SO4 incorporation between the arthritic and control patella.

Animals↗
PubMed1988

The serum amyloid P response in the mouse air pouch.

Levels of the acute phase reactant serum amyloid P (SAP) have been measured in the mouse pouch model of rheumatoid arthritis. Implantation of cartilage resulted in a significant and rapid elevation in the SAP concentration, which remained high for the duration of the experiment (14 days). Initial studies with several clinically employed antirheumatic drugs indicated that dexamethasone and cyclosporin A had a marked inhibitory effect.

Air↗
PubMed1986

The determination of receptor constants for histamine H2-agonists in the guinea-pig isolated right atrium using an irreversible H2-antagonist.

From measurements of chronotropy in the guinea-pig isolated right atrium, a compound (E1309) was found which behaved as an irreversible antagonist at the histamine H2 receptor. E1309 was used to block irreversibly a proportion of the H2 receptors and the dissociation constants, relative efficacies and receptor reserves of four H2-agonists were determined. The calculated dissociation constants were similar to the Ki values reported from H2-radioligand binding studies but different from the observed EC50 values. The order of potency for the four H2-agonists was impromidine much greater than histamine greater than dimaprit greater than 4-methylhistamine. The order of relative efficacy was 4-methylhistamine greater than dimaprit greater than histamine greater than impromidine, the natural agonist not being the most efficacious. This atypical finding is discussed in relation to other receptor classes.

Animals↗
PubMed1977

Halothane solubility in human blood.

In a study of the influence of nutritional state on halothane anaesthesia, results were obtained which showed how the blood/gas partition coefficient for halothane varied with blood chemistry in 20 patients undergoing elective surgery. For each patient the partition coefficient lambda was measured by equilibration at 37 degrees C of a blood sample with a 1% halothane in 5% carbon dioxide in air mixture, followed by chemical extraction and estimation of the halothane content by gas chromatography. The haematocrit and haemoglobin, serum albumin, total protein, triglyceride and cholesterol concentrations were measured by routine laboratory methods. Regressions were sought of lambda on each of these, and on the globulin concentration and the ratios of albumin: globulin and albumin: total protein, deduced from these determinations. The only statistically significant regression (P = 0.0004) was that of lambda on the serum triglyceride concentration (T) (mmol/litre): lambda = 1.83 + 0.424T. The dependence of lambda on haemoglobin concentration was not statistically significant, but the slope of the regression was consistent with those of previous investigators. The regressions of lambda, corrected to the mean triglyceride concentration, on the ratios of albumin: globulin and albumin: total protein were not statistically significant but were not significantly different from an earlier reported result.

Anesthesia, Inhalation↗
PubMed1976

Pharmacokinetics of halothane in the dog. Comparison of theory and measurement in individuals.

After surgical preparation under pentobarbitone anaesthesia seven dogs of mean body weight 31 kg were ventilated with 1% halothane for 80 min. At 1, 2, 5, 10, 20, 40 and 80 min after the start of the halothane administration blood samples were taken from the femoral artery and pulmonary artery and from a cerebral, a renal and a femoral vein. At 80 min a biopsy sample of skeletal muscle (psoas) was taken. The halothane tension in all samples was determined by extraction into carbon tetrachloride followed by gas chromatographic analysis using chloroform as an internal standard. The measured tensions were compared with tensions computed from a multi-compartment model of the uptake and distribution of halothane in the body. The model was quantified by measurements, in each individual, of total body mass, the masses of the major organs and the solubility of halothane in the major organs and tissues; by measurements of blood volume and solubility in blood at the start and finish of the halothane administration; and by repeated measurements of alveolar ventilation, cardiac output and body temperature. For the original version of the model, the computed tensions deviated from the measured tensions to an extent greater than could be attributed to experimental error and in a manner which could be attributed to metabolism of halothane and probably to direct diffusion of halothane from well-perfused organs and lean tissues into fat. Direct experimental evidence of diffusion into perirenal fat was obtained in supplementary experiments. With the quantitation of the model distorted to mimic the processes of metabolism and diffusion, measured arterial tensions could be predicted with a mean error of -0.2 mm Hg (SD 0.6 mm Hg). The mean measured arterial tension was 3.5 mm Hg.

Animals↗
PubMed1975

The solubility of halothane in canine blood and tissues.

In vitro measurements were made of the solubility of halothane (about 1%, carried in 5% carbon dioxide in air) in tissues taken from dogs, mostly Alsatians, and usually after about 8 hr anaesthesia with pentobarbitone and halothane. The mean Ostwald solubility coefficient lambda in atm- minus 1 at 37 degrees C, for seven to 21 animals, were: brain 6.03, gut 4.23, cardiac muscle 4.88, kidney 4.95, liver 6.64, skeletal muscle (psoas) 5.45. For the gracilis muscle solubilities up to 20 atm- minus 1 were obtained. Solubility in blood was shown to increase significantly with haematocrit and haemoglobin and to be significantly higher in blood from unanaesthetized than from anaesthetized animals. The best-estimate equations were lambda-2.38 + 0.042H for the unanaesthetized condition and lambda-1.69+0.049 H for the anaesthetized condition, where H is haematocrit %. Combining the present results with those for other species showed that the solubility of halothane increased fairly systematically from blood to kidney to brain to liver, and from ox to man to dog to rabbit.

Anesthesia↗
PubMed1975

Organ weights in the dog.

The masses of the major organs in eight large dogs, mostly of alsatian type, which had been subjected to about 8 h anaesthesia and surgery, were determined by post mortem weighing. The organ masses as percentage of the total body mass (29.6 +/- 6.0 kg, mean +/- sd) were: brain 0.28 +/- 0.05, gut 2.61 +/- 0.49, heart 0.73 +/- 0.04, kidneys 0.40 +/- 0.07, liver 2.36 +/- 0.38.

Animals↗