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Biomedical subjects

S A Barker

Publications and source records attributed to S A Barker.

At least 37 records · Page 2Linked to original sources
PubMed1995

Wortmannin blocks lipid and protein kinase activities associated with PI 3-kinase and inhibits a subset of responses induced by Fc epsilon R1 cross-linking.

We have investigated the effects of wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI 3-kinase), on antigen-mediated signaling in the RBL-2H3 mast cell model. In RBL-2H3 cells, the cross-linking of high affinity IgE receptors (Fc epsilon R1) activates at least two cytoplasmic protein tyrosine kinases, Lyn and Syk, and stimulates secretion, membrane ruffling, spreading, pinocytosis, and the formation of actin plaques implicated in increased cell-substrate adhesion. In addition, Fc epsilon R1 cross-linking activates PI 3-kinase. It was previously shown that wortmannin causes a dose-dependent inhibition of PI 3-kinase activity and also inhibits antigen-stimulated degranulation. We report that the antigen-induced synthesis of inositol(1,4,5)P3 is also markedly inhibited by wortmannin. Consistent with evidence in other cell systems implicating phosphatidylinositol(3,4,5)P3 in ruffling, pretreatment of RBL-2H3 cells with wortmannin inhibits membrane ruffling and fluid pinocytosis in response to Fc epsilon R1 cross-linking. However, wortmannin does not inhibit antigen-induced actin polymerization, receptor internalization, or the actin-dependent processes of spreading and adhesion plaque formation that follow antigen stimulation in adherent cells. Wortmannin also fails to inhibit either of the Fc epsilon R1-coupled tyrosine kinases, Lyn or Syk, or the activation of mitogen-activated protein kinase as measured by in vitro kinase assays. Strikingly, there is substantial in vitro serine/threonine kinase activity in immunoprecipitates prepared from Fc epsilon R1-activated cells using antisera to the p85 subunit of PI 3-kinase. This activity is inhibited by pretreatment of the cells with wortmannin or by the direct addition of wortmannin to the kinase assay, suggesting that PI 3-kinase itself is capable of acting as a protein kinase. We conclude that Fc epsilon R1 cross-linking activates both lipid and protein kinase activities of PI 3-kinase and that inhibiting these activities with wortmannin results in the selective block of a subset of Fc epsilon R1-mediated signaling responses.

Actins↗
PubMed1995

Pharmacokinetics of ketoprofen in healthy horses and horses with acute synovitis.

The pharmacokinetic properties of a single intravenous dose of ketoprofen (2.2 mg/kg) in plasma and synovial fluid were compared in four healthy animals and four horses with experimentally induced acute synovitis. Synovitis was induced by the injection of a 1% solution of sterile carrageenan into the left intercarpal joint. Ketoprofen was administered at the same time as carrageenan infection. The plasma disposition followed a biexponential equation or a two-compartment model in most horses. The plasma harmonic mean half-life in healthy horses (0.88 h) was longer than in horses with synovitis (0.55 h). Synovial fluid concentrations of ketoprofen in healthy horses approximated those in plasma by 3 h post-dose. In horses with synovitis, synovial fluid concentrations approximated plasma concentrations by 1 h. Synovial fluid concentrations of ketoprofen in horses with synovitis were 6.5 times higher than those in healthy horses at 1 h. The area under the synovial fluid concentration curve for horses with synovitis was greater than in healthy horses. These data suggest that the inflamed joint serves as a site of sequestration for ketoprofen. Furthermore, these results indicate that plasma pharmacokinetics may be altered by inflammation in a peripheral compartments such as the joint.

Acute Disease↗
PubMed1995

Plasma/muscle ratios of sulfadimethoxine residues in channel catfish (Ictalurus punctatus).

Channel catfish (n = 84) maintained at a water temperature of 27 degrees C were used in a feeding study to determine the plasma to muscle concentration ratios of sulfadimethoxine (SDM) and 4-N-acetylsulfadimethoxine residues. Sulfadimethoxine medicated feed was provided free choice at 42 mg SDM/kg body weight once daily for 5 days and the plasma and muscle concentrations of SDM were determined at selected withdrawal times (6, 12, 24, 48, 72, and 96 hours) following the last dose. Considerable variation in total SDM tissue concentration among fish within a sampling period was observed. For fish (n = 12) at six hours post-dose, total SDM concentrations ranged from 1.4-24.8 micrograms/mL and 0.6-12.6 micrograms/g, with mean total SDM concentrations of 9.1 micrograms/mL and 5.3 micrograms/g for plasma and muscle, respectively. However, a mean plasma:muscle concentration ratio of 1.8:1 +/- 0.3:1 was obtained over all concentrations and sampling periods. The plasma:muscle 95% t distribution interval for individual fish was 1.2:1 to 2.4:1. A correlation coefficient of 0.967 was obtained for the relationship between plasma and muscle total SDM concentration among individual fish (n = 25). Results of this study indicate that plasma total SDM concentration may be used to identify samples containing violative SDM muscle residue. No fish contained total SDM muscle residues greater than the FDA tolerance (0.1 microgram/g) by 48 hours following the final dose.

Animals↗
PubMed1993

Disruption and fractionation of biological materials by matrix solid-phase dispersion.

The isolation of drug residues, environmental contaminants or naturally occurring component molecules from biological materials is often a complex undertaking. We report here the development and application of a simple approach to the disruption of biological samples that also allows for the rapid fractionation and isolation of the sample's natural components or incurred residues. This process, called matrix solid-phase dispersion (MSPD), combines the use of mechanical forces generated from the grinding of samples with irregular shaped particles (silica or polymer based solid supports) with the lipid solubilizing capacity of a support-bound polymer (octadecylsilyl or others) to produce a sample column material from which dispersed sample matrix components can be selectively isolated. The factors governing this process and examples of its various applications are presented.

Animals↗
PubMed1993

Isolation and partial characterization of glycolipid fractions from Mycobacterium avium serovar 2 (Mycobacterium paratuberculosis 18) that inhibit activated macrophages.

Glycolipid fractions from Mycobacterium avium serovar 2 (Mycobacterium paratuberculosis 18) inhibited the killing of Candida albicans by activated bovine peripheral-blood-derived macrophages. Fractions were derived by using the matrix solid-phase dispersion technique, which is a new method of simultaneous lysis and partial fractionation of components of bacterial cells. Further purification of active fractions was performed by concanavalin A affinity chromatography, centrifugal filtration, and differing solvent solubility. Three different fractions were isolated and partially characterized. Two of these fractions have characteristics typical of glycolipids, and the third fraction has characteristics compatible with a peptidoglycolipid. This peptidoglycolipid fraction has been purified and named MIF-A3.

Acetonitriles↗
PubMed1992

Chromatographic methods for tetracycline analysis in foods.

The tetracyclines have served for decades as an important class of antibiotics in food animal health and production. As such, they have also been a source of concern for residue monitoring authorities around the world. In response to this concern a number of microbial inhibition, immunoassay and bacterial receptor methods have evolved for the detection of this class of compounds in various foods of animal origin. However, these methods often lack specificity and are subject to false positive and false negative results. For these reasons a number of chromatographic methods for the separation and determination of the tetracyclines isolated from foods have been developed that are capable of identifying and quantifying individual tetracycline drugs. We present here an overview of tetracycline analytical methods, including microbial inhibition, immunoassay and receptor technologies for detection, techniques for isolation from food matrices, and thin-layer chromatographic, high-performance liquid chromatographic, gas chromatographic and mass spectrometric procedures for determination of this class of compounds. A discussion of the variables involved in such methodology and a review of method criteria are offered.

Animals↗
PubMed1992

Separation and spectral data of the six isomeric ozonides from methyl oleate.

The structures of the products obtained on ozonation of methyl oleate have been re-examined. The assignments for the six isomeric ozonides of methyl oleate have been made by 1H and 13C nuclear magnetic resonance (NMR), which were consistent with the retention times observed in high-performance liquid chromatography; the assignments were confirmed by mass and infrared spectroscopy. Two triplets for the ozonide ring protons of the cis and trans isomers in the normal (MOO1) and the two cross ozonides (MOO1 and MOO3) can be resolved by 400 MHz NMR. For MOO1 and MOO3, where the two ring carbons are equivalent, two peaks for the ring carbons of each cross ozonides are resolved in the 13C NMR spectra, one for the cis and one for the trans isomer. For MOO2, four peaks for the ring carbons are resolved in the 13C NMR spectra, two for the cis and two for the trans isomer.

Chromatography, High Pressure Liquid↗
PubMed1991

Lysis and fractionation of Mycobacterium paratuberculosis and Escherichia coli by matrix solid-phase dispersion.

A novel method for the lysis and subsequent fractionation of bacterial constituents from Mycobacterium paratuberculosis strain 19698 (M. paratuberculosis) and Escherichia coli strain DH5 alpha utilizing the technique of matrix solid-phase dispersion (MSPD) is described. Bacteria were blended with octadecylsilyl (C18) derivatized silica to obtain cellular lysis. The blended material was used to prepare a column which was sequentially eluted with solvents of increasing polarity. Fractionation of cellular components was confirmed by analysis of the solvent extracts. The possible applicability of the MSPD technique as a general method for the lysis and fractionation of bacterial components is proposed.

Bacteriological Techniques↗
PubMed1991

Carbohydrates and the chemical industry: achievements and prospects.

Carbohydrates are man's largest organic source of renewal energy both on land and in the sea. Whether consumed by man or animal, evolution has ensured that the enzymes in living cells use carbohydrates with conservation of that energy. Industries that make monomer carbohydrates dissipate the energy stored in its polymers. Prospects for future chemical and biochemical utilisation depend on remedying this tragedy and learning the lesson taught by nature.

Animals↗
PubMed1991

Pharmacokinetics and elimination of salicylic acid in rabbits.

Sodium salicylate was administered to rabbits in order to compare its disposition with that in other major and minor agricultural species. A dose of 44 mg/kg was given orally (p.o.) or intravenously (i.v.), and plasma and urine samples were collected for 36 h and 96 h, respectively. The majority of the drug was excreted as salicylic acid (SA) within 12 h. The major metabolites following an oral dose were salicyluric acid (SUA) and the glucuronide conjugates of SA and SUA. Following i.v. dosing, sulfate conjugates of both SA and SUA were also evident. Both SA and SUA were detected in plasma. Following i.v. administration, SA was distributed with a Vss of 0.249 +/- 0.082 l/kg and cleared at a rate of 0.0432 +/- 0.006 l/h/kg. The biological half-life, calculated from the terminal disposition-rate constant, was 4.3 h (i.v.) or 9.7 h (p.o.). The urinary elimination pattern of SA and metabolites in the rabbit was similar to that previously reported by our laboratories for cattle and goats, although total recovery of the administered dose was not as high as for the latter two species. However, the volume of distribution was larger than for cattle and goats, and rabbits cleared the drug more slowly than those species. As a consequence, the biological half-life was eight to ten times longer than in the ruminants studied previously.

Administration, Oral↗
PubMed1990

Method for the isolation and liquid chromatographic determination of eight sulfonamides in milk.

A method for the isolation and liquid chromatographic determination of eight sulfonamides in milk is presented. Fortified or blank milk samples (0.5 ml) were blended with octadecylsilyl (C18T) derivatized silica (2 g). A column made from the sample C18T matrix was first washed with hexane (8 ml) following which the sulfonamides were eluted with methylene chloride (8 ml). The eluate contained sulfonamide analytes which were free from interferences when analyzed by high-performance liquid chromatography (HPLC) utilizing UV detection (270 nm, photodiode array). Standard curve correlation coefficients (range, 0.998 +/- 0.002 to 0.999 +/- 0.001), average percentage recoveries (73.1 +/- 7.4 to 93.7 +/- 2.7%), and the inter-(3.9-9.6%) and intra-assay (2.2-6.7%) variabilities, were determined for the concentration range examined (62.5-2000 ng/ml) and resulted in a minimal detectable limit of 1.25 ng on column (62.5 ng/ml, 20 microliters injection from a final sample volume of 0.5 ml). Savings in terms of time and solvent make this procedure attractive when compared to classical isolation techniques for sulfonamides.

Animals↗
PubMed1990

Pharmacokinetics and metabolism of fenbendazole in channel catfish.

Fenbendazole (FBZ) was administered intravenously (1 mg/kg) and orally (5 mg/kg) to catheterized, confined channel catfish. Blood samples were collected for 72 h, and resulting FBZ plasma concentrations were pharmacokinetically modelled. Following intravenous administration t 1/2 alpha was 0.51 h, t 1/2 beta was 16.8 h, body clearance (C1B) was 0.0598 L/kg/h, and Vd (area) was 1.45 L/kg. After oral administration the t 1/2 (abs) was 1.47 h, the t 1/2 beta was 20.1 h, and the tlag was 0.1 h. Following oral administration of 5 mg FBZ/kg body weight, the following tissues and body fluids were sampled for concentrations of FBZ, oxfendazole (FBZ-SO), sulphone metabolite (FBZ-SO2) and hydroxy metabolite (FBZ-OH): liver, posterior kidney, fat, muscle, bowel contents and urine. Fenbendazole was detected in the highest concentrations in abdominal fat, whereas oxfendazole was found primarily in the kidney, liver and abdominal fat. The sulphone metabolite was detected only in urine and bowel contents, while the hydroxy metabolite was found most often in the liver and abdominal fat samples.

Absorption↗
PubMed1990

Immobilization of lipase from Candida cylindraceae and its use in the synthesis of menthol esters by transesterification.

Lipase (EC 3.1.1.3) from Candida cylindraceae has been immobilized by the cellulose-titanium chloride method, and on EP-400 polyethylene, with and without glutaraldehyde crosslinking, to give active preparations when assessed by their ability to catalyse the hydrolysis of tributyrin. In both cases, the use of glutaraldehyde crosslinking was shown to improve the stability of the preparations for repeated use. The lipase immobilized on EP-400 polyethylene was found to be effective in transesterification using tributyrin or triacetin as acyl donors with l-menthol as acceptor. The production of methyl butanoate and of methyl acetate using this immobilized preparation was in each case enhanced in the presence of Amberlite IR 47 Anion exchange resin (OH form).

Candida↗
PubMed1990

Elimination of salicylic acid in goats and cattle.

Sodium salicylate was administered to cattle and goats IV and PO according to a crossover design. Total urinary excretion of SA and its metabolites was measured for 3 days after dosing. Salicyluric acid (SUA) was the only metabolite detected in urine of either species. Recovery of sodium salicylate and SUA in goats amounted to 67.9 and 34.6% of the dose, respectively, after IV administration. After oral dosing, total recoveries were 30.2% (sodium salicylate) and 71.7% (SUA) of dose. By comparison, cattle excreted significantly (P less than 0.05) less sodium salicylate (54.0%) and more SUA (49.9%) after IV dosing. The same pattern was observed after oral administration, wherein cattle excreted less than 12% as sodium salicylate and more than 99% as SUA. In both species, almost 90% of the drug excreted as sodium salicylate was found in urine within the first 12 hours after an IV dose and within 24 hours after oral dosing. The excretion of SUA was somewhat slower in both species, especially after oral administration. The data suggested that there were only quantitative differences in the metabolism and elimination of sodium salicylate between the 2 species, with cattle excreting a higher proportion of the drug as the glycine conjugate SUA.

Administration, Oral↗
PubMed1989

Isolation of drug residues from tissues by solid phase dispersion.

A new method based on solid phase dispersion of tissue for the subsequent isolation of drugs is reported. By blending tissues with a polymeric phase bound to a solid support one obtains a semi-dry material which can be used as a column packing material from which one can isolate drugs in a stepwise fashion based on the solubility characteristics of the drugs in this matrix. The applicability of this approach for multidrug residue extraction from a single sample is demonstrated for compounds representing the organophosphate, benzimidazole anthelmintic and beta-lactam antibiotic drug classes.

Animals↗
PubMed1989

The in vivo oxidative metabolism of 2,4- and 2,6-dimethylaniline in the dog and rat.

The xylidine 2,4-dimethylaniline (2,4-DMA) produces hepatic cholangiofibrosis, bile duct proliferation, and foci of cellular hyperplasia and degeneration in the rat. The same compound is relatively innocuous in the dog. 2,6-Dimethylaniline (2,6-DMA) does not produce hepatic lesions in the rat, except at high doses but is a potent inducer of fatty degeneration in the dog. The purpose of the present study was to examine pathways of in vivo metabolism of both isomers in the rat and dog. The major urinary metabolite of 2,4-DMA in the rat was N-acetyl-4-amino-3-methylbenzoic acid (AAMBA) while in the dog it was 6-hydroxy-2,4-dimethylaniline (6-HDMA). The dog also produced a smaller amount of unacetylated 4-amino-3-methylbenzoic acid (4-AMBA) and its glycine conjugate. 2,6-DMA was metabolized principally to 4-hydroxy-2,6-dimethylaniline (4-HDMA) in both species, but the dog also produced significant quantities of 2-amino-3-methylbenzoic acid (2-AMBA), along with trace amounts of the glycine conjugate of the latter and 2,6-dimethylnitrosobenzene. Trace levels of an unknown postulated to be 3,5-dimethyl-4-imino-quinone were also found in urine of dogs. In rats, repeated administration of either xylidine for 10 days failed to increase the appearance of metabolites, but 3-methylcholanthrene (3-MC) did increase the urinary concentration of AAMBA in 2,4-DMA dosed rats. The divergent pathways of metabolism in the 2 species could be responsible for species specific pathologies produced by these 2 xylidines.

Aniline Compounds↗
PubMed1988

The oxidative metabolism of fenbendazole: a comparative study.

The oxidative metabolism of fenbendazole (FBZ) was studied in hepatic fractions prepared from livers of cattle, sheep, goats, chickens, ducks, turkeys, rats, rabbits and catfish. All species produced the sulfoxide metabolite (oxfendazole; FBZ-SO), and p-hydroxyfenbendazole (FBZ-OH) was produced by all species except sheep. The product of demethoxycarbonylation, fenbendazole amine (FBZ-NH2), was not produced by liver preparations of any species. A fourth metabolite, resulting from the further oxidation of oxfendazole, fenbendazole sulfone (FBZ-SO2), was formed in all species but at highly varying rates. The chicken exhibited the highest overall rate of FBZ metabolism, followed by the duck, goat, sheep, steer, catfish, rat, rabbit, and turkey. Considerable variation was evident among avian species, the duck and turkey produced substantially less of the FBZ-OH and FBZ-SO2 metabolites than the chicken. Catfish liver preparations formed equivalent amounts of metabolite at 25 degrees C and 37 degrees C incubation temperatures. The formation of the sulfone metabolite (FBZ-SO2), however, was practically nonexistent in catfish.

Animals↗