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T F Slater

Publications and source records attributed to T F Slater.

At least 109 records · Page 6Linked to original sources
PubMed1981

The metabolism of canrenone in vitro by rat liver preparations.

1. The metabolism of [1-3H]canrenone, a primary metabolite of spironolactone and potassium canrenoate, by rat liver preparations in vitro has been investigated. 2. Canrenone was metabolized by 3-oxo-delta 4-reduction to give 3 alpha-hydroxy-5 beta-spirolactones, and also by a number of O2 and NADPH-dependent microsomal hydroxylation reactions. 3. A major metabolic route requiring the presence of a microsomal fraction, but apparently independent of oxygen and NADPH, led to the formation of a number of compounds tentatively identified as trihydroxy-spirolactones.

Animals↗
PubMed1981

Electron spin resonance studies on normal human uterus and cervix and on benign and malignant uterine tumors.

Electron spin resonance (ESR) studies at -130 degrees have been made on frozen samples of normal human cervix and uterus and on frozen samples of various pathological conditions of the cervix and uterus including fibroleiomyoma and carcinoma. Fifty-five samples of normal cervix and endometrium, 40 samples of nonmalignant disturbances, 15 benign tumor samples, and 20 malignant samples were studied. Very strong ESR signals were seen in frozen powders and frozen intact samples of normal cervix and endometrium and in nonmalignant gynecological conditions. In many cases, the ESR signal was greatly decreased or even undetectable in cancer samples. The substance(s) responsible for the ESR signal in frozen intact tissue (g = 2.11 to 2.15) is decreased in concentration when the sample is ground to powder under liquid nitrogen, and an anisotropic signal (g = 2.002 to 2.035) then becomes much more evident. The ESR signals in intact and in powder samples are sensitive to temperature variations; the signals disappear around 0 degrees, and only the intact samples show significant recovery of signal on recooling. The anisotropic g values and temperature sensitivity in the powders may result from an organic peroxy radical that is more strongly associated with a metal ion in intact samples.

Adenocarcinoma↗
PubMed1980

Two rapid methods for the simultaneous gas-liquid chromatographic determination of carbon tetrachloride and chloroform in biological material and expired air.

Two simple gas-liquid chromatographic techniques were developed for the simultaneous determination of CCl4 and CHCl3 in biological material and expired air and principally for use in the well-known CCl4-induced hepatotoxicity model: a non-extractive head-space analysis by flame ionization detection (FID) and a single-step toluene extraction using electron-capture detection (ECD). For head-space analysis, blood or liver homogenate is incubated with buffer in sealed reaction vials and the head-space vapour sampled for FID determination. Absolute signal response to CCl4 and CHCl3 was used for calibration in the range 5-500 microgram per gram of biological material. The method is reasonably accurate, e.g. CCl4 in liver homogenate 98 +/- 21.8 (S.D.) %, in blood 94 +/- 13.3%, but the precision is poor (rel. S.D. 10-20%). Air samples in volumes of up to 2 ml may be determined by direct FID injection. The ECD sensitivity of to CCl4 and CHCl3 permits determination of microsamples (50-500 microliters) of blood and liver homogenate by extraction with buffer into toluene containing an internal standard (propyl iodide). The linear range of the detector allowed calibration by peak area ratio in the concentration range (10-1500 ng of CCl4 or CHCl3 per millilitre of toluene. The accuracy of the method is high, e.g. in blood CHCl3 101 +/- 9.5 (S.D.)%, CCl4 100 +/- 15.2%, as is the precision: rel. S.D. ca 5% for both CCl4 and CHCl3. For elimination studies, CCl4 and CHCl3 in air may be trapped in toluene and determined by ECD. Recovery of known amounts of CCl4 and CHCl3 from air chamber was high: 100 +/- 4.7 (S.D.)% and 111 +/- 10.9%, respectively, and reduction of CCl4 to CHCl3 by the trapping system negligible (less than 0.01%). Cross-checking of the methods and application to the commonly used CCl4 hepatotoxicity model is demonstrated.

Air↗
PubMed1980

Rapid, sensitive determination of unchanged promethazine in biological material using a nitrogen-selective flame ionization detector. Identification of metabolites by gas chromatography-mass spectrometry.

A rapid, sensitive method has been developed to study the kinetics of unchanged promethazine (PM) in biological material using a nitrogen-selective flame ionization detector (N-FID). Unchanged PM is distinguished from its desmethyl metabolite. Sample clean-up of several biological fluids (rat plasma, blood, urine, liver and kidney homogenates) was studied and gas chromatographic (GC) conditions optimized. Usually 50 microliters-1.0 ml samples are extracted into n-heptane by shaking with NaOH, re-extracted into H2SO4 and again extracted into n-heptane by addition of NaOH. Finally, the organic phase is separated, concentrated under N2 and PM determined by N-FID. However, a rapid, single-step method requiring only NaOH extraction into n-heptane may be used whenever GC background permits. Imipramine is used as an internal standard for calibration by peak height ratios in the overall range 5--1500 ng PM per sample. Recovery of both methods is high (97--99%) but precision of the single-step method is lower (relative S.D. 10% versus 3--4%). Use of sample volumes up to 1 ml allows accurate determination of concentrations as low as 10 ng/g. Examples of applications to commonly used animal models employing PM are given and simple adaptation for clinical samples suggested.

Animals↗
PubMed1980

Thioproline.

Explore the source record for details and available documents.

Animals↗
PubMed1979

Nucleotide metabolism by microsomal UDP-glucuronyltransferase and nucleoside diphosphatase as determine by 31P nuclear-magnetic-resonance spectroscopy.

31P n.m.r. spectroscopy was used to study the nucleotide kinetics of UDP-glucuronyltransferase and associated reactions in the liver microsomal fraction. The effects of Mg2+ and EDTA on these reactions were investigated qualitatively. It was found that the rabbit microsomal fraction has no nucleoside pyrophosphatase activity, that UDP was immediately hydrolysed and that it was released from the microsomal surface. Reverse glucuronyltransferase could be demonstrated. The results are discussed with reference to functional coupling of UDP-glucuronyltransferase to other enzymes and the effects of Mg2+ and EDTA on the system.

Acid Anhydride Hydrolases↗
PubMed1979

Effects of carbon tetrachloride on isolated rat hepatocytes. Inhibition of protein and lipoprotein secretion.

The effects of carbon tetrachloride on protein and lipoprotein secretion, and on lipid peroxidation, have been investigated in isolated rat hepatocytes. It was found that although the free-radical scavenger promethazine completely suppressed the increased peroxidation produced by carbon tetrachloride, it had no effect on the inhibitory action of carbon tetrachloride on lipoprotein secretion. In consequence, the latter effect of carbon tetrachloride does not appear to be mediated through a peroxidative stage.

Animals↗
PubMed1978

Biochemical studies of transient intermediates in relation to chemical carcinogenesis.

Many chemical carcinogens must be metabolized to chemically reactive transient species before they can exert their full toxic action on mammalian cells. In general, this metabolic activation is performed by NADPH-dependent enzymes in the endoplasmic reticulum; the NADPH-cytochrome P-450 electron-transport chain is very important in this respect. Biochemical studies on the chemical reactivities of such transient intermediates require the application of various fast-reaction and free-radical techniques: the use of such techniques is illustrated by reference to the metabolism of carbon tetrachloride. CCl4 is metabolized by liver endoplasmic reticulum in the presence of NADPH to a highly reactive product, probably CCl3; this activation of CCl4 results in covalent binding of CCl3 and lipid peroxidation. The steady-state concentration of CCl3 is too low to be measured directly by e.s.r. spectroscopy but radical species can be accumulated with spin-trap techniques. The CCl3 radical can be generated by pulse radiolysis and the ensuing reactions with biologically important neighbouring species can be followed in the microsecond range by kinetic spectroscopy. The results point to the high reactivity of CCl3 and its restriction to a microenvironment within the endoplasmic reticulum. Highly reactive electrophilic radicals (e.g. CCl3) can initiate lipid peroxidation in biomembranes and this is associated with changes in polyunsaturated fatty acids and in membrane fluidity. The results are discussed in relation to carcinogen activation, to free-radical-mediated reactions in biomembranes, and to the general thesis that the production of reactive aldehydes by lipid peroxidation may act as a 'coarse control' of cell division.

Animals↗
PubMed1978

Studies on the reduction of nitroblue tetrazolium chloride mediated through the action of NADH and phenazine methosulphate.

The general features of the reduction of nitroblue tetrazolium chloride (NBT) by NADH and phenazine methosulphate (PMS) have been studied under aerobic and anaerobic conditions. Under aerobic condition the reduction appears to be mediated through the intermediate formation of the superoxide anion radical O2-.; this reaction is strongly inhibited by superoxide dismutase and by a number of O2-. scavengers such as propyl gallate, (+)-catechin, manganous ions, reduced glutathione and benzoquinone. Cupric ions inhibited the overall reaction by reoxidising reduced PMS. Under anaerobic conditions, superoxide dismutase had only a small inhibitory action and, with the exception of cupric ions, the other substances mentioned above were ineffective as inhibitors. The data presented show that the use of NBT to detect the presence of O2-. is fraught with difficulties due to an equally rapid reduction of NBT by NADH and PMS under anaerobic conditions.

Free Radicals↗
PubMed1978

Cytochrome P-450 distribution in rat liver and the effect of sodium phenobarbitone administration.

A microspectrophotometric method for assaying cytochrome P-450 in fresh 24 micrometer unfixed cryostat sections of rat liver has been developed. When used to assay this cytochrome in sections of microsomal preparations it has yielded results equivalent to those obtained by the conventional spectrophotometric assay of the same preparations. Random measurements made throughout sections of liver have given mean values for cytochrome P-450 concentrations which are twice those measured in microsomes prepared from the livers of the same animals (not corrected for the yield in the homogenate). Measurements of the cytochrome P-450 content of liver cells by the microspectrophotometric method show that in liver from male Wistar rats, cells nearer to the central veins contain up to twice as much cytochrome P-450 as those nearer to the portal tract (mean cell concentrations of 26.4 (+/-4.4) mumol/l and 17.5 (+/-3.0) mumol/l respectively). In the livers from similar rats, killed at the same time, but which has received 1 mg/ml sodium phenobarbitone in their drinking water for one week, the cells near the central vein contained up to five times as much cytochrome P-450 as those near the portal tract (mean cell concentrations of 77.3 (+/-25.0) mumol/l and 28.3 (+/-9.6) mumol/l respectively). The results show a selective increase in cytochrome P-450 content by the cells in the centrilobular region after treatment with sodium phenobarbitone and a smaller increase by some of the cells in the periportal region.

Animals↗
PubMed1978

Modification by metals, sulphydryl reagents and cyanide of the particle stimulated enhancement of oxygen consumption in bovine granulocytes.

A simple, rapid method for the isolation of neutrophil-enriched leucocyte suspensions from bovine blood is described. The capacity of these cells to produce a particle stimulated increase in oxygen consumption deteriorated during a period of storage of the cells whilst the viability of the cells remained unchanged. Potassium cyanide inhibited the basal oxygen consumption but enhanced the stimulated respiratory burst. Zinc ions also enhanced this respiratory burst but ferric and manganous ions did not. The lipid-soluble non-haem iron chelator, 4,4,4-trifluoro-1-(2 thienyl)-1,3-butanedione, preferentially inhibited the particle stimulated type of oxygen consumption, as did the sulphydryl reagents, N-ethyl maleimide and diazine dicarboxylic acid bis-dimethyl amide. These data allow us to consider that zinc ions may play a role in the respiratory burst associated with phagocytosis and that iron-sulphur interactions may be important in oxygen consuming reactions.

Animals↗