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Biomedical subjects

J B Taylor

Publications and source records attributed to J B Taylor.

At least 55 records · Page 3Linked to original sources
PubMed1988

The glutathione transferase activity and tissue distribution of a cloned Mr28K protective antigen of Schistosoma mansoni.

A protective Mr28K antigen of Schistosoma mansoni, expressed from its cDNA, has been purified in a single step and shown to possess glutathione (GSH) transferase activity as predicted from sequence homologies with two mammalian GSH transferase multigene families. It is notable for its high 1-chloro-2,4-dinitrobenzene GSH transferase and linoleic acid hydroperoxide GSH peroxidase activities. The major GSH transferase of S. mansoni has been purified and its subunit is identical to this Mr28K antigen by criteria of Mr, immunochemistry, substrate specificity and peptide sequence analysis. In the parasite, the antigen is present in the tegument, protonephridial cells and subtegumental parenchymal cells. No significant immunological cross-reactivity between the S.mansoni and mammalian (human and rat) GSH transferases was observed.

Amino Acid Sequence↗
PubMed1988

In vitro and in vivo binding of phenylbutazone and related drugs to equine feeds and digesta.

In vitro and in vivo studies of phenylbutazone binding to equine ingesta and digesta were undertaken. In vitro binding to chopped hay and powdered pony nuts in buffer solutions at 37 degrees C was found to be time-, concentration- and pH-dependent. Percentage binding generally increased with time, decreased with concentration and varied with buffer pH in an unpredictable manner. Other non-steroidal anti-inflammatory drugs (NSAIDs) also bound to hay, the degree of binding being less for meclofenamate and least for flunixin in comparison with phenylbutazone. Phenylbutazone became bound to digesta collected from eight regions of the gastrointestinal tract when they were spiked with a concentration of 1 mg.10 g-1 digesta, the amounts ranging from 80.0 per cent (duodenum) to 99.6 per cent (stomach). Binding also occurred to equine digesta following the oral administration of phenylbutazone (4.4 mg.kg-1) to three ponies. It was concluded that drug uptake by and release from equine ingesta and digesta were probably adsorptive and desorptive processes. The clinical significance of the findings for the use of NSAIDs in equine medicine was considered.

Animal Feed↗
PubMed1988

Pharmacokinetics, metabolism and excretion of phenylbutazone in cattle following intravenous, intramuscular and oral administration.

The absorption, metabolism and urinary excretion of phenylbutazone were investigated in six adult cattle in a cross-over study involving administration intravenously, intramuscularly and orally at a dose rate of 4.4 mg kg-1. Following intravenous injection plasma disposition was described by a three compartment open model with mean elimination half-life (t1/2 beta) and clearance (ClB) values of 35.9 hours and 2.77 ml kg-1 h-1, respectively. Somewhat longer t1/2 beta values were obtained after oral and intramuscular dosing and these may have resulted from sequestration within and slow absorption from the gastrointestinal tract and continual uptake from intramuscular sites following precipitation as a depot. Absorption was more complete after intramuscular than after oral dosing; area under curve values were almost twice as high for the intramuscular route. Double peaks in the plasma concentration time curves after oral dosing were recorded in some cows. These may have resulted from drug adsorption on to and subsequent desorption from hay or as a consequence of enterohepatic shunting. There was no evidence for opening of the oesophageal groove and direct passage of the drug into the abomasum. Two hydroxylated metabolites of phenylbutazone, oxyphenbutazone and gamma-hydroxyphenylbutazone were detected in trace amounts in plasma for 72 hours and in much higher concentrations in urine for 168 hours. Approximate urine:plasma (U/P) concentration ratios for the metabolites approached and occasionally exceeded the U/P ratio for endogenous creatinine, indicating poor reabsorption and, possibly, tubular secretion. Cumulative urinary excretion data indicated that the hydroxylated derivatives of phenylbutazone are probably formed more slowly in cattle than in horses.

Administration, Oral↗
PubMed1987

Measurement of flunixin in equine inflammatory exudate and plasma by high performance liquid chromatography.

An accurate and reliable method for the separation of flunixin from, and measurement in, equine inflammatory exudate and plasma by high performance liquid chromatography has been developed. Flunixin can be detected in concentrations as low as 0.05 micrograms/ml using an ultraviolet spectrophotometric detector at 285 nm. Samples were acidified with 2M hydrochloric acid and extracted with dichloromethane. The extract was evaporated and reconstituted in acetonitrile. Iminodibenzyl was used as internal standard. The mean recovery of flunixin from plasma was 97.6 +/- 3.9 per cent. Particular advantages of the method are the short analysis time and ease of sample preparation. Data were obtained on the distribution of flunixin between plasma and acute inflammatory exudate following administration of a single intravenous dose of 1.1 mg/kg bodyweight flunixin meglumine. The drug was cleared more slowly from exudate than from plasma.

Animals↗
PubMed1987

Metabolism, excretion, pharmacokinetics and tissue residues of phenylbutazone in the horse.

The pharmacokinetics, metabolism, excretion and tissue residues of phenylbutazone (PBZ) in the horse were studied following both intravenous and oral administration of the drug at a dose rate of 4.4 mg/kg. A 72-hour blood sampling schedule failed to demonstrate a third exponential phase; the plasma disposition following intravenous injection being described by a two compartment open model, with the following elimination phase parameters: beta = 0.13h-1, t1/2 beta = 5.46h, Vdarea = 0.141 1/kg and C1B = 17.9 ml/kg/h. The hydroxylated metabolites oxyphenbutazone (OPBZ) and gamma-hydroxyphenylbutazone (OHPBZ) were present in detectable concentrations in plasma for 72 and 24 h, respectively. After 36 h OPBZ concentrations exceeded plasma PBZ concentrations. In urine the principal metabolites were OPBZ and OHPBZ but smaller concentrations of another compound, probably gamma-hydroxyoxyphenbutazone (OHOPBZ), were also detected. The percentages of the administered dose recovered from urine were 30.7, 39.0 and 40.3 after 24, 48 and 72 h from the time of injection. Recovery of PBZ and its metabolites from urine was significantly reduced in the first 24 h after oral dosing when the horses had free access to hay, probably as a result of markedly delayed absorption, but this did not occur in animals deprived of food for a few hours before and after dosing. Determination of approximate values of urine/plasma (U/P) concentration ratios for PBZ and its metabolites relative to endogenous creatinine U/P concentration ratio suggested that PBZ was filtered in small amounts only because of the high degree of plasma protein binding and then excreted by diffusion trapping in the alkaline urine. Much higher U/P ratios were obtained for the hydroxylated derivatives, and one at least (OHPBZ) was secreted into urine.

Animals↗
PubMed1986

Tissue distribution of rat glutathione transferase subunit 7, a hepatoma marker.

Polyadenylated RNA isolated from NN-dimethyl-4-aminoazobenzene-induced rat hepatoma was used to prepare a cDNA library in lambda gt10. Full-length clones complementary to mRNA coding for glutathione transferase subunit 7 were isolated and one of these clones (pGSTr7) was fully characterized. In Northern blot analysis, mRNA hybridizing to 32P-labelled pGSTr7 was found in poly(A)-containing RNA isolated from seven normal rat tissues but not from testis and liver. A similar hybridizing mRNA species was also detected in human placental mRNA. The same probe, used in a Southern blot analysis of genomic DNA, suggests the presence of a multigene family in the rat.

Animals↗
PubMed1986

Differential tissue expression of the glutathione transferase multigene family.

The content of GSH transferase mRNAs in poly(A)-containing RNA isolated from eight rat tissues was examined by immunoprecipitation of cell-free translation products and by Northern blotting. Considerable tissue-specific distribution and heterogeneity of immunoprecipitable GSH transferase subunits 1 and 2 synthesized in vitro was observed. These results were confirmed by Northern blotting using a 32P-labelled subunit 1 cDNA probe. The same probe, used in a Southern blot analysis of genomic DNA, provided confirmation that GSH transferase subunits 1 and 2 comprise a multigenic family in the rat. The results show that the selection of cDNA clones coding for chosen subunits can be made easier by making use of qualitative and quantitative tissue differences in GSH transferase mRNAs.

Animals↗
PubMed1986

Massive inguinal scrotal bladder hernias: a review of the literature with 2 new cases.

The bladder frequently is a component of inguinal hernias. However, massive bladder hernias into the scrotum are rare, with 73 cases having been reported previously in the literature. We report 2 additional successfully treated cases. From our experience, we believe that simple reduction of the hernia followed by inguinal herniorrhaphy is the treatment of choice.

Hernia, Inguinal↗
PubMed1986

Effects of dietary protein, fat and restriction on body composition and energy balance in lactating rats.

Isoenergetic diets formulated at three levels of dietary protein using 12,24 and 40% casein and at two levels of fat using 2.26 and 13.82% corn oil were fed at five levels of intake, ad libitum, 75, 62.5, 50 and 37.5% of average ad libitum intake, to 90 lactating rats from d 7 to 14 of lactation. Regression equations developed from lactating rats killed on d 7 of lactation were used to calculate initial body composition and energy of rats killed on d 14 of lactation. Changes in body weight and body water were significantly (P less than 0.05) affected by dietary fat and protein, but change in dry lean body mass was affected only by level of dietary fat, whereas body nitrogen and fat and lean body energy were not affected by level of dietary fat or protein. However, restricted intake significantly increased loss of all these. Likewise, restricted intake decreased milk production. Changes in weights of heart and liver were not affected by diet or intake, whereas intestinal weight decreased with intake restriction. Liver enzyme activities were markedly affected by intake restriction, whereas responses to dietary protein and fat were marginal.

Animals↗
PubMed1986

Absorption and pharmacokinetics of phenylbutazone in Welsh Mountain ponies.

The disposition of phenylbutazone (4.4 mg/kg), administered intravenously to six Welsh Mountain ponies, was described by a two-compartment open model. Pharmacokinetic parameters were not significantly different after morning dosing in comparison with afternoon dosing. When phenylbutazone (4.4 mg/kg) was administered orally to the same ponies, marked variations in time to peak concentrations were produced with different feeding schedules. When access to hay was permitted before and after dosing, the mean time to peak concentration was 13.2 +/- 1.2 h and double peaks in the plasma concentration-time curve were common. Double peaks were also encountered when phenylbutazone was given to ponies deprived of food prior to, and allowed access to hay after, dosing. In this circumstance, mean times to peak concentration were much shorter (3.8 +/- 1.3 h after morning dosing and 5.3 +/- 1.5 h followed afternoon dosing). Absorption was more regular and double peaks were less apparent when food was withheld both before and after dosing. In order to explain these findings, it is tentatively postulated that, whereas some of the administered dose of phenylbutazone may be absorbed quickly, some may become adsorbed on to the feed and subsequently released by fermentative digestion in the large intestine and/or caecum. The consequences of delayed absorption in fed animals for toxicity and clinical efficacy, and for the use of phenylbutazone in equestrian sports, are considered. Delayed absorption in ponies given access to hay was not accompanied by a significant reduction in total absorption. Bioavailability was estimated to be approximately 69% in fed and 78% in unfed ponies. Estimates of bioavailability gave similar values for morning (72%) and afternoon (71%) dosing.

Administration, Oral↗
PubMed1986

Phenylbutazone and oxyphenbutazone distribution into tissue fluids in the horse.

The clinically recommended dose rate of phenylbutazone (4.4 mg/kg) was administered intravenously as a single dose to five Welsh Mountain ponies. Distribution of phenylbutazone and its active metabolite oxyphenbutazone into body fluids was studied by measuring concentrations in plasma, tissue-cage fluid, peritoneal fluid and acute inflammatory exudate harvested from a polyester sponge model of inflammation. The ready penetration of phenylbutazone into inflammatory exudate was demonstrated by the relatively high mean value for Cmax of 12.4 micrograms/ml occurring at a time of 4.6 h and a mean AUC0-24 of 128 microgram X h/ml. A high mean exudate:plasma AUC0-24 ratio of 0.83 was recorded. Plasma:exudate concentration ratios for phenylbutazone were initially greater than and subsequently less than one; the slower clearance from exudate was indicated by approximate t1/2 beta) values of 4.8 and 24 h for plasma and exudate, respectively. These findings may help to explain the relatively long duration of action of phenylbutazone, in spite of a plasma elimination half-life of less than 5 h. Lower values of Cmax and AUC0-24 for phenylbutazone passage into peritoneal fluid (6.3 micrograms/ml and 45 micrograms X h/ml) were recorded, and a limited number of sampling times indicated a similar degree of penetration as into tissue cage fluid. Mean concentrations of oxyphenbutazone in all fluids were lower than phenylbutazone concentrations at all times, but ready penetration of the metabolite into body fluids, especially into inflammatory exudate, occurred suggesting that oxyphenbutazone may contribute to the anti-inflammatory effect. The hyperaemia of acute inflammation and the high protein levels in inflammatory exudate may both assist passage of phenylbutazone and oxyphenbutazone into exudate.

Animals↗
PubMed1985

Pharmacokinetics of phenylbutazone in two age groups of ponies: a preliminary study.

A clinical dose rate (4.4 mg/kg bodyweight) of phenylbutazone was administered intravenously and orally to six Welsh mountain ponies to provide data on the pharmacokinetics and bioavailability of the drug. In three, three-year-old ponies, clearance of the drug from plasma after intravenous administration was almost twice as rapid as in three ponies aged eight to 10 years. After oral administration, plasma phenylbutazone levels were greater in the older ponies, the area under the plasma concentration time curve being almost twice as high. This did not result from more efficient absorption but from slower plasma clearance. The fractional absorption of phenylbutazone was similar in young and older ponies, 0.78 and 0.75, respectively. The 24 hour urinary excretion of phenylbutazone and its hydroxylated metabolites, oxyphenbutazone and gamma-hydroxyphenylbutazone, accounted for approximately 25 per cent of the administered intravenous dose in both young and older ponies. The possible fate(s) of the remaining 75 per cent were considered.

Administration, Oral↗
PubMed1984

Construction and characterization of a plasmid containing complementary DNA to mRNA encoding the N-terminal amino acid sequence of the rat glutathione transferase Ya subunit.

Free polyribosomal poly(A)-containing RNA isolated from normal rat liver was used to prepare a complementary DNA plasmid library in the Pst1 site of the plasmid pAT153 . A plasmid pGSTr155 complementary to mRNA coding for a glutathione transferase Ya subunit was selected by differential hybridization in situ and preliminary characterization was performed by hybrid-selected mRNA translation, immunoprecipitation and polyacrylamide-gel electrophoresis of the product synthesized in vitro. The nucleotide sequence of the complementary DNA contained within pGSTr155 was determined and shown to contain a single open reading frame corresponding to the first 129 amino acids of the N-terminus of the Ya subunit and a further 63 nucleotides upstream of the initiating methionine codon.

Amino Acid Sequence↗
PubMed1984

Influence of phenylbutazone on eicosanoid levels in equine acute inflammatory exudate.

In a two part cross-over experiment, acute inflammatory exudates were induced in 7 ponies by subcutaneous implantation of 3 sterile carrageenin-soaked polyester sponge strips. Treatment comprised a single therapeutic geenin-soaked polyester sponge strips. Treatment comprised a single therapeutic dose of 4.4 mg/kg phenylbutazone (PBZ) administered intravenously at the time of sponge implantation. Exudates were harvested at 6, 12 and 24 hours and examined for leukocyte and erythrocyte numbers using the improved Neubauer technique; for eicosanoids by radioimmunoassay and by high performance liquid chromatography for concentrations of PBZ and its principal metabolite oxyphenbutazone. Plasma PBZ and oxyphenbutazone levels were measured in treated animals at 6, 12 and 24 hours. The administration of PBZ produced, at 6 hours, highly significant (P less than 0.001) reductions in exudate levels of prostaglandin E2 (PGE2) and 6-keto-PGF1 alpha (the stable breakdown product of prostacyclin, PGI2). Significant (P less than 0.01) reductions in these eicosanoids were maintained in treated animals at 12 and 24 hours. Levels of thromboxane B2 (TXB2), the catabolite of TXA2, were reduced in treated animals at 6 and 12 hours but these changes were not significant. Leukocyte numbers were significantly (P less than 0.001) increased from 6-hour values at 12 and 24 hours in both control and PBZ-treated animals but differences between control and treated ponies were not significant. This is the first report in ponies of eicosanoid inhibition following the administration of a non-steroid anti-inflammatory drug (NSAID). It is proposed that the model of inflammation used in this study might provide a means of assessing the efficacy and duration of action of NSAIDs in the horse.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Evidence that the Yb subunits of hepatic glutathione transferases represent two different but related families of polypeptides.

Three soluble rat liver glutathione (GSH) transferases A, C and one referred to as 'D', all of which are dimers of Yb subunits [Bass et al. (1977) Biochim. Biophys. Acta, 492, 163-175], have been compared with respect to C-terminal amino acids and tryptic peptide maps. GSH transferases A and 'D' gave different tryptic peptide maps and different C-terminal amino acids, lysine and proline respectively. In each case the number of tryptic peptides is about half of that expected from their lysine and arginine content, and there are 2 mol C-terminal amino acid/mol enzyme. This indicates that GSH transferases A and 'D' represent two different Yb homodimers, which we refer to here as Y1bY1b and Y2bY2b respectively. GSH transferase C is the corresponding heterodimer Y1bY2b since it gives all the tryptic peptides which arise from GSH transferase A and GSH transferase 'D' and also contains both C-terminal lysine and proline. These results provide a structural basis to similar conclusions drawn by Mannervik and Jensson [(1980) J. Biol. Chem. 257, 9909-9912] based on enzymic and immunological comparisons. Tryptic peptide maps show that GSH transferases A and 'D' have considerable homology since there are 23 peptides common to both, 12 peptides unique to A and 8 peptides unique to 'D'. Even so GSH transferase A is selectively induced by a phenobarbitone regime. It is, therefore, concluded that Y1b and Y2b are derived from separate but related genes. A similar conclusion has been drawn concerning the Ya and Yc subunits [Beale et al. (1982) Eur. J. Biochem. 126, 459-463], and a comparison of amino acid compositions, presented here, further suggests a genetic relationship between both pairs of subunits.

Amino Acids↗