Contribution of Cystine-Glutamate Antiporters to the Psychotomimetic Effects of Phencyclidine

Altered glutamate signaling contributes to a myriad of neural disorders, including schizophrenia. While synaptic levels are intensely studied, nonvesicular release mechanisms, including cystine–glutamate exchange, maintain high steady-state glutamate levels in the extrasynaptic space. The existence of extrasynaptic receptors, including metabotropic group II glutamate receptors (mGluR), pose nonvesicular release mechanisms as unrecognized targets capable of contributing to pathological glutamate signaling. We tested the hypothesis that activation of cystine–glutamate antiporters using the cysteine prodrug N-acetylcysteine would blunt psychotomimetic effects in the rodent phencyclidine (PCP) model of schizophrenia. First, we demonstrate that PCP elevates extracellular glutamate in the prefrontal cortex, an effect that is blocked by N-acetylcysteine pretreatment. To determine the relevance of the above finding, we assessed social interaction and found that N-acetylcysteine reverses social withdrawal produced by repeated PCP. In a separate paradigm, acute PCP resulted in working memory deficits assessed using a discrete trial t-maze task, and this effect was also reversed by N-acetylcysteine pretreatment. The capacity of N-acetylcysteine to restore working memory was blocked by infusion of the cystine–glutamate antiporter inhibitor (S)-4-carboxyphenylglycine into the prefrontal cortex or systemic administration of the group II mGluR antagonist LY341495 indicating that the effects of N-acetylcysteine requires cystine–glutamate exchange and group II mGluR activation. Finally, protein levels from postmortem tissue obtained from schizophrenic patients revealed significant changes in the level of xCT, the active subunit for cystine–glutamate exchange, in the dorsolateral prefrontal cortex. These data advance cystine–glutamate antiporters as novel targets capable of reversing the psychotomimetic effects of PCP

Studies on dental erosion: An in vivo-in vitro model of endogenous dental erosion - its application to testing protection by fluoride gel application

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Background: The objective in this study was to develop an in vivo-in vitro model of endogenous erosion, with a view to exploring the potential for some degree of its control by the use of topical fluoride gel application to teeth. Methods: Six volunteers each wore a small clasp retained palatal acrylic appliance to which six sterilized enamel tiles were bonded. Three tiles on each appliance were coated extra-orally with either 1.23 per cent acidulated phosphate fluoride (APF) or 2.2 per cent sodium fluoride (NaF) neutral gel for four minutes prior to multiple periods of exposure to the simulated gastric acid, cumulating in 16, 36, 80 and 150 minutes of exposure. Impressions of the enamel tiles prior to and following acid exposure permitted dies to be prepared. These were sectioned through the exposed areas and examined under a stereomicroscope to assess maximum depths of erosion. Results: The depth of erosive demineralization of enamel was found to be greatly reduced with increased frequency of APF gel application. The reduction in enamel loss was less following topical application of NaF gel. Conclusions: It was concluded that fluoride gels significantly reduced enamel erosion using this in vivo-in vitro model and therefore, if prescribed appropriately, should help reduce tooth tissue loss from endogenous erosion.L Jones, D Lekkas, D Hunt, J McIntyre and W Rafi

Who wants to join preventive trials? – Experience from the Estonian Postmenopausal Hormone Therapy Trial [ISRCTN35338757]

BACKGROUND: The interest of patients in participating in randomized clinical trials involving treatments has been widely studied, but there has been much less research on interest in preventive trials. The objective of this study was to find out how many women would be interested in a trial involving postmenopausal hormone therapy (PHT) and how the women's background characteristics and opinions correlated to their interest. METHODS: The data come from recruitment questionnaires (n = 2000) sent to women in Estonia in 1998. A random sample of women aged 45 to 64 was drawn from the Population Registry. The trial is a two-group randomized trial comparing estrogen-progestogen therapy with placebo or no drugs. A brief description of the study was attached to the questionnaires. Women were not told at this stage of the recruitment which group they would be assigned to, however, they were told of the chance to receive either hormone, placebo or no treatment. RESULTS: After two reminders, 1312 women (66%) responded. Eleven percent of the women approached (17% of the respondents) were interested in joining the trial, and 8% wanted more information before deciding. When the 225 women who stated clearly that they were interested in joining and the 553 women who said they were not interested were compared, it was found that interested women were younger and, adjusting for age, that more had given birth; in other respects, the sociodemographic characteristics and health habits of the interested women were similar to those of the non-interested women. The interested women had made more use of more health services, calcium preparations and PHT, they were more often overweight, and more had chronic diseases and reported symptoms. Interested women's opinions on the menopause were more negative, and they favoured PHT more than the non-interested women. CONCLUSION: Unlike the situation described in previous reports on preventive trials, in this case Estonian women interested in participating in a PHT trial were not healthier than other women. This suggests that trials involving PHT are more similar to treatment trials than to preventive trials. In a randomized controlled trial, more information should be obtained from those women who decline to participate

Engaging fathers: : acknowledging the barriers

Engaging fathers has the potential to benefit the entire family through 1. promoting fathers’ wellbeing directly, 2. building on fathers’ vital capacity to support mothers’ psychological wellbeing, 3. maternal health behaviours, and 4. promoting children’s mental health and development. Benefits to a child’s development include positive impacts on cognitive development, educational attainment, social competence, positive self-esteem and reduced incidence of emotional and behavioural problems. However, the barriers to father-inclusive practice are real and numerous and include personal, organisational, strategic and societal factors. This article reviews the need to work more closely and fruitfully with fathers, and acknowledges some of the barriers

The Management of Disclosure in Children’s Accounts of Domestic Violence: Practices of Telling and Not Telling

Children and young people who experience domestic violence are often represented as passive witnesses, too vulnerable to tell the stories of their own lives. This article reports on findings from a 2 year European research project (Understanding Agency and Resistance Strategies, UNARS) with children and young people in Greece, Italy, Spain and the UK, who had experienced domestic violence. It explores children and young people’s understandings of their own capacity to reflect on and disclose their experiences Extracts from individual interviews with 107 children and young people (age 8–18) were analysed. Three themes are presented, that illustrate children and young people’s strategies for managing disclosure: (1) “Being silenced or choosing silence?”, explores children and young people’s practices of self-silencing; (2) “Managing disclosures: Finding ways to tell” outlines how children and young people value self-expression, and the strategies they use to disclose safely; and in (3) “Speaking with many voices” considers how children and young people’s accounts of their experiences are constituted relationally, and are often polyvocal. The article concludes that children and young people can be articulate, strategic and reflexive communicators, and that good support for families struggling with domestic violence must enable space for children and young people’s voice to be heard. This is possible only in an integrated framework able to encompass multiple layers and perspectives, rather than privileging the adult point of view. Practitioners who work with families affected by domestic violence need to recognize that children and young people are able to reflect on and speak about their experiences. This requires that attention is paid to the complexity of children and young people’s communication practices, and the relational context of those communications

Development and validation of makeup and sexualized clothing questionnaires

Abstract Background Body acceptance programs on college campuses indicated that collegiate women often report feeling pressure to dress in a sexualized manner, and use makeup to enhance beauty. Currently, no quantitative measures exist to assess attitudes and daily behaviors that may arise in response to perceived pressure to wear makeup or dress in a provocative manner. The goal of the current studies was to develop brief self-report questionnaires aimed at assessing makeup and sexualized clothing use and attitudes in young women. Methods An exploratory factor analysis in a sample of 403 undergraduate women was used in Study 1 to create items to measure the pressure women feel to wear makeup and sexualized clothing. A confirmatory factor analysis (N = 153) was used in Study 2 to confirm the factor structure found in Study 1. An incremental validity analysis was also conducted in Study 2. Across both studies, participants completed online questionnaires. Results In Study 1, items were developed for two questionnaires to assess perceived pressure to wear makeup and discomfort when not wearing makeup, and perceived pressure to wear sexualized clothing, and body image concerns with regards to sexualized clothing. The exploratory factor analyses revealed Unconfident and Unease scales for the Makeup Questionnaire (MUQ) and Body Dissatisfaction and Pressure scales for the Sexualized Clothing Questionnaire (SCQ). In Study 2, the confirmatory factor analyses confirmed the factor structure for the MUQ and SCQ. The incremental validity analysis revealed that these measures can be used to predict self-objectification and shape and weight concern in women. Conclusion These studies provide preliminary support for the factor structure of two novel questionnaires aimed at assessing perceived pressure to wear makeup and sexualized clothing