De novo synthesis of glutathione is required for both entry into and progression through the cell cycle

To study the putative role of de novo synthesis of glutathione (GSH) in the regulation of the cell cycle, we exposed NIH-3T3 cells to buthionine sulfoximine (BSO) and analysed cell cycle kinetics with continuous bromodeoxyuridine (BrdU) labeling and bivariate Hoechst 33258/ethidium bromide flow cytometry. Treating quiescent cells, which themselves had a low GSH content, with BSO did not affect subsequent entry into and progression through the cell cycle. Adding BSO during serum stimulation, however, provoked a dose-dependent inhibition of cell growth and a delayed increase in GSH level. The cell kinetic mechanism underlying BSO-induced growth inhibition is a diminished entry into the cell cycle and a permanent arrest in the S and G2 phase of the cell cycle. Our results are consistent with the hypothesis that GSH de novo synthesis is required for cell activation and proper S and G2 phase transit. © 1995 Wiley-Liss, Inc.     

Women's understanding of abnormal cervical smear test results: a qualitative interview study.

OBJECTIVE: To describe how women interpret their experiences of diagnosis and treatment of a cervical abnormality and how healthcare services for such women can be improved. DESIGN: Qualitative study using detailed individual interviews. SETTING: Australian gynaecology clinics. SUBJECTS: 29 Women who had a cervical cytological abnormality and who attended a gynaecologist. MAIN OUTCOME MEASURES: Women''s views on their diagnosis and their information needs. RESULTS: Most women wanted to participate in decisions about their care but found it difficult to get the information they required from doctors because they were confused by what their doctors told them and felt unable to ask questions in the consultation. Medical terms such as wart virus and precancer were difficult to understand. Not being able to see their cervix also made it hard for women to understand what their abnormality meant and what treatment entailed. Most women tried to make sense of their abnormality in the context of their everyday lives. For some women their gynaecological care was not consistent with the way they understood their abnormality. CONCLUSIONS: The inherent power structure of medical practice combined with time pressures often make it difficult for doctors to give the detailed information and reassurance patients need when a diagnosis is distressing or when investigation and treatment are strange and upsetting.     

Bioavailability of arsenic in soil and mine wastes of the Tamar valley,SW England

ABSTRACT

The southern part of the Tamar valley area in SW England is highly mineralised and mines in the region were the world's principal producers of tin, copper and arsenic during the mid nineteenth century. The Devon Great Consols Mine, covering 67.6 ha (167 acres) is situated in this area. Residues from the mining activity resulted in unvegetated spoil tips and local soils highly contaminated with As (range 120–52600 μg/g As). Sequential chemical extraction procedures were conducted on eight surface samples (0–15 cm) taken from a 2.0 km long transect from within the mine site to agricultural grassland. The proportion of water extractable As in agricultural top soils was lower (0.05–0.3%) than the values obtained for mine wastes (0.02–1.2%). Arsenic was found to be concentrated in the Fe-organic and residual fractions, which accounted for up 93 % of the total As in mine spoil and nearby soils.     

Proof-of-concept human laboratory study for protracted abstinence in alcohol dependence: effects of gabapentin

There is a need for safe medications that can effectively support recovery by treating symptoms of protracted abstinence that may precipitate relapse in alcoholics, e.g. craving and disturbances in sleep and mood. This proof-of-concept study reports on the effectiveness of gabapentin 1200 mg for attenuating these symptoms in a non-treatment-seeking sample of cue-reactive, alcohol-dependent individuals. Subjects were 33 paid volunteers with current Diagnostic and Statistical Manual of Mental Disorders-IV alcohol dependence and a strength of craving rating 1 SD or greater for alcohol than water cues. Subjects were randomly assigned to gabapentin or placebo for 1 week and then participated in a within-subjects trial where each was exposed to standardized sets of pleasant, neutral and unpleasant visual stimuli followed by alcohol or water cues. Gabapentin was associated with significantly greater reductions than placebo on several measures of subjective craving for alcohol as well as for affectively evoked craving. Gabapentin was also associated with significant improvement on several measures of sleep quality. Side effects were minimal, and gabapentin effects were not found to resemble any major classes of abused drugs. Results suggest that gabapentin may be effective for treating the protracted abstinence phase in alcohol dependence and that a randomized clinical trial would be an appropriate next step. The study also suggests the value of cue-reactivity studies as proof-of-concept screens for potential antirelapse drugs.     

SEPALLATA3: the 'glue' for MADS box transcription factor complex formation

Background  

Plant MADS box proteins play important roles in a plethora of developmental processes. In order to regulate specific sets of target genes, MADS box proteins dimerize and are thought to assemble into multimeric complexes. In this study a large-scale yeast three-hybrid screen is utilized to provide insight into the higher-order complex formation capacity of the Arabidopsis MADS box family. SEPALLATA3 (SEP3) has been shown to mediate complex formation and, therefore, special attention is paid to this factor in this study.     

Use of Galleria mellonella larvae to evaluate the in vivo anti-fungal activity of [Ag2(mal)(phen)3]

Larvae of the insect Galleria mellonella were employed to assess the in vivo antifungal efficacy of ([Ag₂(mal)(phen)₃]), AgNO₃ and 1,10-phenanthroline. Larvae pre-inoculated with these compounds were protected from a subsequent lethal infection by the yeast Candida albicans while larvae inoculated 1 and 4 h post-infection showed significantly increased survival (P < 0.01) compared to control larvae. Administration of these compounds resulted in an increase over 48 h in the density of insect haemocytes (immune cells) but there was no widespread activation of genes for antimicrobial peptides. This work demonstrates that G. mellonella larvae may be employed to ascertain the antifungal efficacy of silver(I) compounds and offers a rapid and effective means of assessing the in vivo activity of inorganic antimicrobial compounds.