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Biomedical subjects

S J Foster

Publications and source records attributed to S J Foster.

At least 109 records · Page 6Linked to original sources
PubMed1986

The metabolism of selenomethionine, Se-methylselenocysteine, their selenonium derivatives, and trimethylselenonium in the rat.

The formation of dimethylselenide (respiratory) and trimethylselenonium (urinary) metabolites from [75Se]selenomethionine, [75Se]methylselenomethionineselenonium, [75Se]methylselenocysteine, [75Se]dimethylselenocysteineselenonium, and [75Se]trimethylselenonium was determined using single sc doses of 2 or 0.064 mg Se/kg in male and female rats. The 75Se content of liver, kidney, pancreas, testis, spleen, blood, heart, brain, and skeletal muscle was determined at 0.5 and 24 h. Respiratory 75Se after 24 h was greatest from Se-dimethylselenocysteineselenonium (38 and 17% for the high and low doses, respectively). Respiratory 75Se was about 8% for the high dose of Se-methylselenocysteine and was less for all other compounds. Total 75Se excretion in the urine was highest from rats given trimethylselenonium (about 90%, both doses) and was lowest from rats given selenomethionine (4%, low dose). Urine samples were chromatographed on SP-Sephadex cation-exchange columns and 75Se was eluted with ammonium formate; trimethylselenonium was precipitated with ammonium Reineckete solution and trimethylsulfonium carrier. Urinary trimethylselenonium excretion was greatest from rats given trimethylselenonium, but rats given Se-dimethylselenocysteineselenonium (low dose) excreted 35-45% of the dose as trimethylselenonium ion. The lowest quantity of trimethylselenonium was excreted by rats given the low dose of selenomethionine (0-3%). Pancreas, kidney, and liver showed the highest uptake (% of dose/g) of the selenium compounds. Trimethylselenonium was highly concentrated by the kidney and also showed high myocardial uptake (heart/blood ratio = 5) 0.5 h after injection; the selective uptake of trimethylselenonium in heart was not observed for the other selenonium compounds.

Animals↗
PubMed1986

The use of inhibitors to identify early events during Bacillus megaterium KM spore germination.

The germination response of spores of Bacillus megaterium KM, as measured by loss of A600, is more than 95% inhibited by 1 mM-HgCl2. Two Hg2+-sensitive sites (referred to as 'sites I and II') have been identified during germination. Site I represents a pre-commitment event and can be protected from HgCl2 by 50 mM-D-alanine, whereas site II represents a post-commitment event and is not D-alanine-protectable. At 1 mM-HgCl2, 25% of the spore population becomes committed to germinate, but an A600 loss of less than 5% occurs. In this system, loss of heat resistance was associated with commitment, whereas selective cortex hydrolysis, release of pyridine-2,6-dicarboxylic acid, Zn2+ and soluble peptidoglycan, as well as loss of refractility, were identified as post-commitment events. The commitment event was reversibly inhibited by several proteinase inhibitors and a membrane bulking agent. A model of spore germination based on these results is presented.

Alanine↗
PubMed1986

Formation of dimethyl selenide and trimethylselenonium from selenobetaine in the rat.

The 24-h respiratory excretion of dimethyl selenide (DMSe) and urinary excretion of trimethylselenonium (TMSe) were studied in adult male rats injected with 2 mg Se/kg as selenobetaine [(CH3)2Se+CH2COOH] or its methyl ester, labeled with 75Se and 14C. The DMSe was trapped by means of 20% benzyl chloride in xylene. TMSe was measured by cation exchange high performance liquid chromatography. There was extensive respiratory excretion of DMSe from selenobetaine methyl ester (about 50% of the dose) and from selenobetaine (about 25%). About 12% of the dose was converted to TMSe for both compounds. When the Se-methyl carbons were labeled with 14C and the selenium with 75Se, doubly labeled DMSe and TMSe were formed; the 14C/75Se ratio in DMSe formed from selenobetaine methyl ester was almost unchanged from that administered, and the ratio in TMSe was only slightly lower than in DMSe. In contrast to its ester, doubly labeled selenobetaine yielded DMSe having a lower 14C/75Se ratio (approximately one-half of that administered) and a further decrease was observed between DMSe and TMSe. These data indicate that the (CH3)2Se moiety in selenobetaine methyl ester undergoes facile release to form DMSe, which is directly methylated to form TMSe. Selenobetaine, however, appears to lose a methyl group prior to scission of the Se-CH2COOH bond. The results with selenobetaine also suggest that TMSe generated metabolically is not inert, and can undergo demethylation followed by remethylation; confirmatory evidence for this metabolic instability is provided by the exhalation of [75Se]DMSe after the direct administration of [75Se]TMSe. When [75Se]selenobetaine or its ester was given with the methylene carbon in the acetic acid moiety labeled with 14C, only 75Se was present in the DMSe and TMSe, indicating that TMSe did not arise by decarboxylation of selenobetaine. It is concluded that both selenobetaine and its methyl ester are readily converted to DMSe and TMSe by pathways that do not involve decarboxylation or the formation of hydrogen selenide as an intermediate, and DMSe is a direct precursor of TMSe.

Animals↗
PubMed1986

Leukocyte recruitment in the subcutaneous sponge implant model of acute inflammation in the rat is not mediated by leukotriene B1.

The subcutaneous sponge implant model of acute inflammation in the rat has been evaluated as a suitable test system for evaluating the potential anti-inflammatory efficacy of 5-lipoxygenase inhibitors. The inflammatory parameters measured were exudate volume and leukocyte recruitment. Specific radioimmunoassays were used to measure (1) 5-lipoxygenase (LPO) and cyclo-oxygenase (CO) activity in exudate leukocytes stimulated ex vivo with A23187, and (2) the LTB4 and PGE2 content of inflammatory exudate. The NSAIDs flurbiprofen and indomethacin inhibited cell recruitment, exudate volume and CO activity with ED50S of approximately 1 mg per kg p.o. but failed to inhibit LPO activity at 10 mg per kg p.o. Nafazatrom (Bayer 6575), quercetin and NDGA, which inhibit LPO activity in vitro, were inactive against all parameters when dosed at 100 mg per kg p.o. The "mixed inhibitors" BW755C and phenidone were approximately equipotent inhibitors of LPO activity but BW755C was 10 times more potent than phenidone against CO activity. BW755C was also greater than 10 times more potent at inhibiting cell recruitment and exudate volume than phenidone suggesting that the anti-inflammatory efficacy of the mixed inhibitors reflect their potency against CO rather than LPO activity. Time course studies demonstrated that the inhibitor effects of BW755C and phenidone on leukocyte recruitment reflected a reduction in the PGE2 but not the LTB4 content of the inflammatory exudate. Polyester sponges soaked in high concentrations of LTB4 caused only a modest (2-fold) increase in leukocyte recruitment whilst physiological levels were inactive. The results taken together suggest that CO products make a major contribution to leukocyte recruitment in this model whilst the LPO product LTB4 has little role. This model therefore is of little value for evaluating the anti-inflammatory efficacy of 5-lipoxygenase inhibitors. Moreover, the rat would appear to be unsuitable for evaluating the role of LTB4 in acute inflammation.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1986

The inflammatory response of rabbit skin to topical arachidonic acid and its pharmacological modulation.

The inflammatory reaction induced by the intradermal injection of arachidonic acid into the rabbit dermis has been investigated. Plasma extravasation was measured by the leakage of 125I-albumin into the tissues and polymorphonuclear leukocyte (PMNL) accumulation was assessed histologically. Arachidonic, 5,8,11,14,17-eicosapentaenoic and 8,11,14-eicosatrienoic acids, but not oleic, linoleic or linolenic acids, caused a concentration-related plasma extravasation following their intra-dermal injection. The plasma extravasation induced by arachidonic acid was dependent on PMNLs. PMNL infiltration and plasma extravasation into arachidonic acid-injected skin sites was inhibited by the mixed cyclo-oxygenase-lipoxygenase inhibitor, BW755C. Arachidonic acid-induced plasma extravasation was inhibited by cyclo-oxygenase and 5-lipoxygenase inhibitors but not by the Paf antagonist, kadsurenone. The inflammation induced by arachidonic acid in the rabbit dermis may be a useful model for evaluating 5-lipoxygenase inhibitors which could be potentially useful anti-inflammatory agents for the treatment of psoriasis and other inflammatory diseases.

Administration, Topical↗
PubMed1985

Analysis of trimethylselenonium ion in urine by high-performance liquid chromatography.

A rapid and simple method for the separation of trimethylselenonium ion and other cationic forms of selenium in urine by HPLC on a strong cation exchanger is described. Most of the inorganic salts in urine are removed prior to chromatography by means of ethanolic precipitation, thus minimizing interferences. Following sample loading and elution with 0.003 M ammonium phosphate (pH 4), a linear gradient to 0.33 M ammonium phosphate (pH 4) is employed. Complete separation of the trimethylselenonium ion from four other selenonium compounds was achieved, and good recovery of the compounds was obtained for the desalting and chromatographic procedures. The procedure was successfully employed to demonstrate that dimethylselenocysteineselenonium iodide and Se-methylselenomethionineselenonium iodide are extensively metabolized when administered to rats, and that trimethylselenonium ion is a major urinary metabolite of both compounds.

Animals↗
PubMed1985

Corneal stromal fibroblasts from adult rabbits retain the capacity to deposit an orthogonal matrix.

Stromal fibroblasts from the adult rabbit cornea were propagated in vitro, then injected into the vitreous compartment of normal rabbit eyes. In this environment the stromal cells deposited a matrix of imperfect orthogonal collagenous lamellae resembling normal corneal stroma. Extracellular matrices were also secreted by other ocular and nonocular cell types intravitreally, but no orthogonal regions were observed. The vitreous appears to provide some of the physical and humoral factors required to permit adult corneal fibroblasts to secrete a stroma-like matrix in the absence of embryonic tissue influences.

Animals↗
PubMed1985

Induction of DNA synthesis by co-culture of retinal glia and pigment epithelium.

Retinal glia (RG) and retinal pigment epithelial cells (RPE) have been previously identified in intravitreal cellular membranes of patients with proliferative vitreoretinopathy (PVR). This study was undertaken to determine if the co-presence of both cell types might lead to increased membrane growth due to some heterotypic cell interactions that enhance cell proliferation. Cell proliferation in co-cultures of RPE plus RG, RPE plus dermal fibroblasts (DF), or RG plus DF was evaluated by quantitation of labeled nuclei in radioautographs prepared from monolayer co-cultures exposed to 3H-thymidine. In each co-culture, one cell type was premarked by phagocytosis of latex particles so that the cells could be identified and the labeling rates in each cell type could be assessed. In co-cultures of RPE and RG, both cell types exhibited a higher labeling rate. In RG-DF co-cultures, DF-labeling was increased, but RG-labeling was unaffected or suppressed. Co-culture of RPE and DF did not affect labeling in either cell type. Studies of conditioned media suggested that RG stimulate RPE and DF by means of a product secreted into the culture medium by the RG. Further, cell-cell contact might modulate the growth response at least for RG. The interaction of RPE and RG in co-culture differed from the interaction of either cell type with DF in that the co-culture of RPE and RG resulted in a higher apparent proliferation rate for both cell types. If similar interactions occur in vivo, the presence of both types of retinal cells in intravitreal membranes of PVR might result in greater growth than in lesions derived from a single retinal cell population.

Animals↗
PubMed1984

Synthesis of [75Se]trimethylselenonium iodide from [75Se]selenocystine.

The synthesis of [75Se]trimethylselenonium iodide from [75Se]selenocystine is described. The starting compound is reduced to [75Se]selenocysteine with borohydride and reacted with methyl iodide to form [75Se]Se-methyl-selenocysteine, then treated with methyl iodide in formic acid solution to form Se-dimethyl-selenocysteine selenonium iodide. Over a period of days, the selenonium intermediate undergoes spontaneous elimination to form alanine and dimethyl selenide, which reacts with methyl iodide to give the trimethylselenonium product in over 90% yield.

Borohydrides↗
PubMed1984

Culture of adult rabbit retinal glial cells: methods and cellular origin of explant outgrowth.

Culture methods to propagate glial cells from the avascular adult rabbit neural retina are described. To determine the site(s) in the retina from which the cells originated, retina fragments were retrieved from culture at intervals after explanation and processed for light microscopy to localize surviving cells. Tritiated-thymidine radioautography was used to determine the time of onset and the localization of proliferating cells in the isolated retina and in the early culture outgrowth. Although some glial cells located just subjacent to the inner limiting membrane and at the interface between the ganglion cell and inner plexiform layers were activated to DNA synthesis in three to five days after explanation of the retina, the dominant cell type in the cultures derived from the retina appeared to be the Muller cell. Regionally, in isolated retina fragments, Muller cells became hyperplastic and formed tissue masses of proliferating cells surrounding photoreceptor remnants. These proliferating clusters could be retrieved from the culture medium after about 10 days in vitro and replated whereupon they attached to the culture substrate and gave rise to cellular outgrowths. The cells in the early explant outgrowth were heteromorphic, but passaged cultures contained a relatively homogeneous population of cells that exhibited a low maximal growth rate and senesced quickly in vitro.

Animals↗
PubMed1984

Stainable glomerular basement membrane polyanions and renal hemodynamics during hexadimethrine-induced proteinuria.

To clarify the mechanism of hexadimethrine-induced proteinuria, we studied the changes in stainable glomerular basement membrane anions and renal hemodynamics during hexadimethrine (HDM) infusion. To determine whether glomerular anions were neutralized in vivo, animals infused with HDM received cationized ferritin intravenously, or their kidneys were perfused in situ with lysozyme. During its infusion, HDM bound heavily within the glomerular basement membrane, and binding of the cationic probes was virtually abolished. During recovery after HDM infusion, HDM deposits diminished and the binding of the cationic probes recovered to normal. The inverse correlation between HDM binding and binding of the cationic probes confirms that the glomerular binding of HDM is associated with neutralization or shielding of the glomerular basement membrane anions in vivo. Renal hemodynamic parameters and urinary protein excretion rate were measured before, during, and after infusion of HDM. Heavy proteinuria appeared during HDM infusion and persisted for 1 hour after its discontinuation. Although glomerular filtration rate, renal plasma flow, and urine flow rate decreased transiently at the onset of proteinuria, they returned to baseline levels before resolution of proteinuria. Filtration fraction never changed significantly. Thus, proteinuria cannot be attributed solely to renal hemodynamic factors. These results strengthen our hypothesis that HDM induces proteinuria as a consequence of its binding to and neutralization of glomerular basement membrane fixed anions.

Animals↗
PubMed1983

Identification of selenocysteine in glutathione peroxidase by mass spectroscopy.

A convenient procedure was developed for identifying selenocysteine in selenoproteins by mass spectroscopy, based on formation of the 2,4-dinitrophenyl (DNP) derivative. Pure ovine erythrocyte glutathione peroxidase was reduced with sodium borohydride and reacted with 1-fluoro-2,4-dinitrobenzene at neutral pH under anaerobic conditions in 4 M guanidine. The inactivated enzyme was hydrolyzed with 6 N HCl for 20 h at 110 degrees C under anaerobic conditions. Following extraction of the hydrolysate with benzene, Se-(2,4-dinitrophenyl)selenocysteine in the aqueous phase was separated from non-DNP-amino acids by gel-filtration chromatography and then separated from other water-soluble DNP-amino acids by reversed-phase high-performance liquid chromatography. The Se-(2,4-dinitrophenyl)selenocysteine was converted to Se-methyl-N-(2,4-dinitrophenyl)selenocysteine by the addition of sodium barbital to induce an intramolecular Se leads to N shift (Smiles rearrangement) under anaerobic conditions, in the presence of methyl iodide to trap the liberated selenol group. Following esterification of the product's carboxyl group with methanol and hydrochloric acid, it was subjected to direct probe mass spectroscopy and identified as the methyl ester of Se-methyl-N-(2,4-dinitrophenyl)selenocysteine. This procedure allows selenocysteine to be isolated quite easily as a readily identifiable derivative and has permitted the first identification of a seleno amino acid in a protein by mass spectroscopy.

2,4-Dinitrophenol↗
PubMed1983

Anti-proliferative properties of Clozic, a disease-modifying anti-arthritic agent.

Cytostatic drugs have been used in the treatment of rheumatoid arthritis but are of limited clinical application due to their severe toxic side-effects. We have discovered that 'Clozic' (ICI 55897), an agent with disease-modifying properties in rheumatoid arthritis patients, inhibits the growth of a variety of mammalian cell types including a matrix-secreting cell culture derived from neonatal rat hearts. The inhibition of growth was reversible and no loss of cell viability occurred when measured by lactate dehydrogenase released into the medium or by vital staining, suggesting a cytostatic rather than a cytotoxic mechanism. Cytostatic activity was observed at ICI 55897 concentrations within the reported therapeutic plasma concentration range and was related to the concentration of unbound compound, since the effect could be reduced by increasing the albumin concentration in the medium. Other oxyalkanoic acids inhibited cell growth. Their inhibitory potency correlated with lipophilicity. The anti-proliferative potencies of R and S enantiomers of two oxyalkanoic acids containing asymmetric centres were similar. These observations suggest that the anti-proliferative effect of the oxyalkanoic acids is due to their interaction with lipophilic cell target sites.

Animals↗