Search PubMed⌕ Search

Biomedical subjects

S Groves

Publications and source records attributed to S Groves.

7 recordsLinked to original sources

Increased levels of superoxide in brains from old female rats.

Hypertension, aging and a range of neurodegenerative diseases are associated with increased oxidative damage. The present study examined whether superoxide (O2*-) levels in brain are increased during aging in female rats, and the role of superoxide dismutase (SOD) and oestrogen in regulating O2*- levels. Young adult (3 month) and old (11 month) female spontaneously hypertensive stroke prone rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY) were studied. O2*- levels were measured in brain homogenates by lucigenin chemiluminescence and SOD expression by Western blotting. Ageing significantly increased brain O2*- levels in WKY (cortex +216%, hippocampus +320%, striatum +225%) and to a greater extent in SHRSP (cortex +540%, hippocampus +580%, striatum +533%). Older SHRSP showed a decline in cortical Cu/Zn SOD expression compared to young adult SHRSP. Oestrogen did not attenuate O2*- levels. The results show a significant age-dependent increase in brain O2*- levels which is exaggerated in SHRSP. The excess cortical O2*- levels in the SHRSP may be associated with a down-regulation of Cu/Zn SOD but are not related to a decrease in oestrogen.

Aging↗

RRR-alpha-tocopheryl succinate inhibits proliferation and enhances secretion of transforming growth factor-beta (TGF-beta) by human breast cancer cells.

The RRR-alpha-tocopheryl succinate form of vitamin E inhibits the proliferation of estrogen receptor-positive and estrogen receptor-negative human breast cancer cell lines in a dose-dependent manner in vitro. Analyses of cell-conditioned medium from RRR-alpha-tocopheryl succinate growth-inhibited cells revealed the presence of a potent antiproliferative activity. Characterization of the antiproliferative activity as transforming growth factor-beta (TGF-beta) was established by 1) growth inhibition of the TGF-beta-responsive Mv1Lu-CCL-64 mink lung and murine CTLL-2 cell lines, 2) combination of physical characteristics including heat stability, acid stability, and Bio-Gel P-60 column chromatography elution profile, and 3) neutralization of the antiproliferative activity in the conditioned media by antibodies specific for TGF-beta.

Antioxidants↗

Flumazenil in alcohol withdrawal.

This is a preliminary study to explore the theory that there may be abnormalities of the benzodiazepine receptor, or a possible endogenous inverse agonist ligand in alcohol withdrawal. The benzodiazepine antagonist flumazenil was administered to 8 alcoholics in early withdrawal in a double blind placebo controlled design. Self ratings of mood and physical symptoms, and observer ratings of withdrawal symptoms revealed differences in the effects of flumazenil and placebo. Flumazenil had an immediate slight anxiogenic action which was short-lived. It then appeared to ameliorate withdrawal symptoms, quite markedly in 2 patients.

Adult↗

Isolation, purification, and properties of Penicillium charlesii alkaline protease.

A serine protease with a pH optimum from 7 to 9 and activity over the range of pH 3 to 10 was isolated and purified from culture filtrates of Penicillium charlesii 16 days after inoculation. The enzyme was purified by the following sequence of procedures: (i) gel permeation chromatography through Sephacryl S-200, (ii) DEAE-Sepharose anion-exchange chromatography, and (iii) fast protein liquid chromatography (FPLC) over Superose 12. Anion-exchange chromatography separated the protease activity into a major activity (protease PII, 82%) and two minor activities (proteases PI and PIII, 10 and 8%, respectively, of the total activity). Protease PII has a molecular mass of 44 kilodaltons. Purified preparations of this enzyme are susceptible to autodegradation. FPLC of heat-treated PII gave one major species (PIIa), whereas untreated enzyme resulted in three species (PIIb, PIIc, and PIId). PIIb and PIIc also catalyzed the hydrolysis of protein (hide powder azure). PIIb and PIIc were in the molecular mass range of 10 to 20 kilodaltons. Protease PII is completely inhibited by phenylmethylsulfonyl fluoride (PMSF). The protease has primary substrate specificity for phenylalanyl or arginyl amino acyl residues attached to amines. The enzyme has amidase, but no esterase activity toward similar synthetic substrates such as occurs with trypsinlike microbial serine proteases. The addition of PMSF (final concentration, 10(-4) M) to 1- and 2-day-old cultures of P. charlesii inhibited the production of extracellular peptidophosphogalactomannan (pPGM) by 41 and 34%, respectively, and inhibited the alkaline protease activity by 85%. These results suggest that the production and release of pPGM may be affected by alkaline protease.

Chromatography, High Pressure Liquid↗

Flumazenil in alcohol withdrawal: a double-blind placebo-controlled study.

The purpose of the present study was to study gamma-aminobutyric acid (GABA)-A receptor function in alcohol-dependent subjects during withdrawal, using the benzodiazepine antagonist flumazenil. In particular, we wanted to examine the hypotheses that an endogenous inverse agonist ligand at the GABA-A benzodiazepine receptor (GBzR) is active during withdrawal (in which case flumazenil should be anxiolytic), or whether chronic alcohol intake results in a shift in sensitivity of the receptor in the inverse agonist direction (in which case flumazenil should be anxiogenic). Results from 15 alcohol-dependent subjects in a double-blind placebo-controlled cross-over study showed that flumazenil was neither anxiolytic nor anxiogenic, although withdrawal scores were reduced during the course of the study. The fact that flumazenil was not anxiogenic, as it is in panic disorder, suggests that the GBzR is functioning differently in these two clinically similar conditions.

Adult↗