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Biomedical subjects

T J Blake

Publications and source records attributed to T J Blake.

27 records · Page 2Linked to original sources
PubMed1988

The metabolism of 5-(4-acetamidophenyl)pyrazin-2(1H)-one in rat, dog and cynomolgus monkey.

1. The metabolism and disposition of 14C-acetamidophenyl pyrazinone has been studied in rat, dog and cynomolgus monkey. The compound was well absorbed and rapidly excreted in urine and faeces by all three species. 2. Distribution of 14C-pyrazinone was rapid and extensive with the exception of the central nervous system where concentrations were at, or below, the limit of detection. 3. Whereas, in in vitro studies, metabolites (but not the parent compound) weakly inhibited some activities of the cytochrome P-450 system, there was evidence from in vivo studies in the rat that the compound and/or its metabolite(s) are weak selective inducers of cytochrome P-450. 4. Metabolite patterns were similar in all three species. The major route of metabolism was glucuronidation at the oxygen of the pyrazinone ring. Other metabolites originated from metabolism by gut microflora with subsequent hepatic metabolism.

Animals↗
PubMed1987

Structure elucidation of drug metabolites using thermospray liquid chromatography-mass spectrometry.

Thermospray liquid chromatography-mass spectrometry (LC-MS) has been used to provide structural information both from in vitro and in vivo experiments. This paper will describe the more salient aspects of the technique that have emerged. The ability of the interface to handle gradients was essential for its successful application to metabolism studies, owing to the wide range of compound polarity involved. The examples discussed in this paper include the use of LC-MS in the analysis of in vitro incubations of drugs with hepatocyte cell cultures and the direct analysis of plasma samples from in vivo studies in the dog.

Animals↗
PubMed1987

Inhibition of delayed hypersensitivity reactions by cinnamyl 1-thioglycosides.

Cinnamyl 1-thio-alpha-D-manno(and L-rhamno)pyranosides have good inhibitory effects in an antigen-specific T cell proliferation assay. The beta anomers are slightly less effective than the alpha anomers. The 6-substituted analogues of cinnamyl 1-thio-alpha-D-mannopyranoside such as 6-deoxy and 6-O-methyl derivatives also block macrophages in presenting the antigen to T cells. D-Mannose and L-rhamnose, when tested by themselves with no modifications, did not block at concentrations up to 1 mM. These cinnamyl 1-thioglycosides when given ip or po at 3-30 mg/kg to mice significantly inhibited the delayed type hypersensitivity reaction as measured by footpad swelling.

Animals↗
PubMed1987

Variation in water relations of black spruce stock types planted in Ontario.

Upland, intermediate and lowland sites in northeastern Ontario were planted between May 28 and June 8 with three types of black spruce (Picea mariana (Mill.) BSP) nursery stock: (1) spring-lifted, 1.5 + 1.5 bareroot plants (BR); (2) 24-week-old, winter-sown, container stock (CWS); and (3) spring-sown, overwintered, container stock (CO). At the beginning of the growing season, the BR stock had the lowest xylem pressure potentials (Psi(x)), stomatal conductances (g(wv)), and net photosynthetic (P(n)) rates. By the end of the growing season, the BR stock still had lower g(wv)s than the container stock types, but had higher shoot Psi(x) values. In August, the turgor loss points for the BR, CO and CWS stock types were -2.8, -1.93 and -1.6 MPa, respectively, while the minimum observed shoot Psi(x) values were -1.4, -1.7 and -1.9 MPa, respectively. The BR stock produced the greatest dry weight of new shoots and unsuberized roots. No new shoots were produced by the CWS stock, but they produced a greater dry weight of unsuberized roots than the CO stock. As a percent of the dry weight of suberized roots, the greatest production of unsuberized roots was by the CWS stock, the least by the BR trees.

Journal Article↗
PubMed1984

The metabolism in animals and man of oxmetidine--a new histamine H2-receptor antagonist.

The absorption, distribution, metabolism and excretion of [14C]oxmetidine in rat, dog and man has been studied following both i.v. and oral administration. Excretion is rapid and essentially complete in all three species. The biliary route is predominant. Distribution of radioactivity is widespread although none is seen in the brain. Metabolite patterns in urine from rat, dog and man have been compared by thin-layer chromatography. Metabolite patterns in urine and bile from rat and dog have been compared by high pressure liquid chromatography. Six major metabolites have been isolated and identified including two O-glucuronides and one N-glucuronide.

Absorption↗
PubMed1983

Gibberellins and Heterosis in Maize : II. Response to Gibberellic Acid and Metabolism of [H]Gibberellin A(20).

Two maize inbreds, CM7 and CM49, and CM7 x CM49, their F(1) hybrid (which displayed significant heterosis), were examined with regard to response to exogenous gibberellin A(3) (GA(3)), and in their ability to metabolize GA(20), a native GA of maize. The leaf sheath elongation response to GA(3) was far greater for the imbreds than for their hybrid. The inbreds also displayed significant elongation of the leaf blades in response to GA(3), whereas the hybrid was unaffected. Promotion of cell division in the leaf sheath of CM7 and the hybrid was effected by GA(3), but no promotion of cell elongation was observed in CM49, even though significant leaf sheath elongation occurred. Shoot dry weight of both inbreds was significantly increased by GA(3), but response by the hybrid in this parameter was slight and variable. Root dry weight of CM7 was significantly increased by GA(3), but was unchanged in CM49 and the hybrid. Thus, inbred shoot dry weight increases effected by GA(3) were not at the expense of the root system. Rapid metabolism of [2,3-(3)H]GA(20) occurred in all genotypes, although genotypic differences were observed. The hybrid had the highest rates of metabolism to GA glucosyl conjugate-like substances. Oxidative metabolism was also fastest in the hybrid, followed by CM7, and slowest in CM49, the slowest-growing inbred. Thus, rate of GA(20) metabolism is under genetic control in normal (i.e. not dwarfed) maize genotypes. These results, taken together with previous reports that the hybrid has significantly enhanced levels of endogenous GA-like substances, suggest that GA play a role in the expression of heterosis in maize.

Journal Article↗
PubMed1981

Mass spectrometric sequence studies of a superoxide dismutase from Bacillus stearothermophilus.

A partial sequence of the manganese-containing superoxide dismutase from Bacillus stearothermophilus has been determined by mass spectrometry. A new fragmentation reaction at N-terminal proline is described and an 'in-chain' fragmentation, also occurring at proline, has been observed. There is some evidence that the latter cleavage may also occur at other residues. Some differences from the classically determined sequence are reported, and the validity of these observations is discussed.

Amino Acid Sequence↗
PubMedDate not supplied

Metabolism of temelastine (SK&F 93944) in hepatocytes from rat, dog, cynomolgus monkey and man.

A species comparison of the metabolic pathways of temelastine has been made using hepatocyte preparations from rat, dog, cynomolgus monkey, and man. Metabolites and unchanged temelastine were separated by HPLC and were compared with authentic standards by retention. The characteristic UV spectra of SK&F 93944 and its metabolites aided in the preliminary identification of metabolites in hepatocyte incubates, subsequently confirmed by liquid chromatography/mass spectrometry (LC/MS). The metabolic profile of temelastine is complex, both in vivo and in vitro, but all of the metabolites identified unambiguously from in vivo studies have also been demonstrated in vitro. Moreover, the time-dependent nature of the metabolic profile has been investigated in rat hepatocytes. Marked differences in the rate of production, extent of accumulation, and distribution between cells and culture medium have been observed for specific metabolites. Species differences in the metabolism of temelastine by rat, dog, cynomolgus monkey, and human hepatocytes have been observed. In particular, SK&F 94224 (a hydroxylated metabolite of temelastine) was not detected in human hepatocyte incubations at appreciable concentrations, but was present in varying amounts in the other species and especially in incubations from dog hepatocytes. Temelastine N-glucuronide was not detected in the rat hepatocyte system but was present to a modest or significant extent in hepatocyte incubations from dog, cynomolgus monkey, and man.

Animals↗