N-acetylcysteine in psychiatry - current therapeutic evidence and potential mechanisms of action

There is an expanding field of research investigating the benefits of alternatives to current pharmacological therapies in psychiatry. N-acetylcysteine (NAC) is emerging as a useful agent in the treatment of psychiatric disorders. Like many therapies, the clinical origins of NAC are far removed from its current use in psychiatry. Whereas the mechanisms of NAC are only beginning to be understood, it is likely that NAC is exerting benefits beyond being a precursor to the antioxidant, glutathione, modulating glutamatergic, neurotropic and inflammatory pathways. This review outlines the current literature regarding the use of NAC in disorders including addiction, compulsive and grooming disorders, schizophrenia and bipolar disorder. N-acetylcysteine has shown promising results in populations with these disorders, including those in whom treatment efficacy has previously been limited. The therapeutic potential of this acetylated amino acid is beginning to emerge in the field of psychiatric research.

Mechanisms of action in the relationship between mindfulness and problem gambling behaviour

Previous studies have found an inverse relationship between mindfulness and problem gambling severity. This paper presents the findings from two studies of treatment seeking problem gamblers designed to explore the role of mindfulness in problem gambling. Treatment-seeking problem gamblers displayed significantly lower mindfulness scores than adult community members and university students. Mindfulness was significantly related to most indices of gambling, and psychological distress was an important mechanism in these relationships. Rumination, emotion dysregulation and thought suppression were also implicated as mediators in the inverse relationship between mindfulness and psychological distress. Taken together, the findings provide theoretical support for existing models of mindfulness which suggest that mindfulness operates by reducing psychological distress through these cognitive mechanisms. They also suggest that mindfulness training may be a new and innovative avenue for therapy to improve treatment effectiveness for problem

Diet and bipolar disorder: a review of its relationship and potential therapeutic mechanisms of action

OBJECTIVES: It is well accepted that diet quality has an important role in the prevention and treatment of several physical diseases. However, its influence on mental health has received far less attention, although there is increasing evidence to support a relationship with depression. In this narrative review, investigations into the relationship between diet and bipolar disorder are examined and the potential implications in the management and treatment of bipolar disorder are reviewed. METHODS: The authors provide a narrative review of the relevant information. RESULTS: Research is limited, although there are preliminary findings to suggest a relationship between diet and bipolar disorder. Findings from cross-sectional research suggest that people with bipolar disorder consume an unhealthier dietary pattern. This has significant treatment implications as bipolar disorder has a high comorbidity with several physical diseases. In addition, diet also influences several biological processes that are dysregulated in bipolar disorder, namely monoaminergic activity, immune/inflammatory processes, oxidative stress, mitochondrial activity, and neuroprogression. CONCLUSIONS: The role of diet in bipolar disorder requires further attention in research as it presents as a factor that may contribute to the worsening course of this condition and may potentially enhance current treatment outcomes.

Exercise, muscle glycogen and insulin action

The aim of this thesis was to investigate the influence of muscle glycogen concentration on whole body insulin stimulated glucose uptake in humans and to examine the potential signalling mechanisms responsible for enhanced insulin action in the post exercise period. Untrained male subjects were conditioned to achieve a range of muscle glycogen concentrations via acute exercise or a combination of exercise and diet. The influence of muscle glycogen content on whole body insulin stimulated glucose uptake was determined via hyperinsulinaemic / euglycaemic clamps conducted at rest, 30 min after exercise or 24 hours after exercise. Muscle glycogen content did not influence insulin mediated glucose disposal either 30 min or 24 hrs after exercise when compared with basal. Conventional insulin signalling to muscle glucose uptake and signalling through the p38 MAPK cascade was also largely unaltered by glycogen concentration. Muscle glycogen synthesis was significantly increased in heavily but not moderately glycogen depleted muscle 30 min after exercise. Enhanced muscle glycogen synthesis occurred in line with a significant increase in insulin stimulated GSK-3 serine phosphorylation. This finding suggests that enhanced insulin sensitivity of muscle glycogen synthesis following glycogen depleting exercise may be mediated via a pathway involving alterations in insulin stimulated GSK-3 phosphorylation. In summary, whilst glycogen influences insulin mediated GSK-3 phosphorylation and glycogen synthesis, the findings of the present series of investigations suggest that the role of muscle glycogen in the process of insulin stimulated glucose uptake may not be as important as previously theorised.

Surface forces and their action in ceramic materials

A descriptive account is given of the surface forces acting between two solids. Different contributions to the force are outlined, with particular attention paid to the underlying mechanisms, and how they are affected by the nature of the medium between the surfaces. This is followed by a discussion of the areas of ceramic science and engineering in which surface forces play a role.

The mechanisms of Chansu in inducing efficient apoptosis in colon cancer cells

Chansu is one of the most widely used traditional Chinese medicines in China, Japan, and other Southeast Asian countries primarily for antipain, anti-inflammation, and recently anticancer. Over 10 recipes and remedies contained Chansu, which are easily available in pharmacies and hospitals, but the mechanisms of action were not clearly articulated. In the present study, Cinobufagin (CBF), the major compound of Chansu, was employed as a surrogate marker to determine its ability in inducing cancer cell death. As expected, CBF has significant cancer-killing capacity for a range of cancers, but such ability differs markedly. Colon and prostate cancers are more sensitive than skin and lung cancers. Interestingly, cancer cells die through apoptotic pathway either being biphasic caspase- 3-dependent (HCT116) or independent (HT29). Multipathway analysis reveals that CBF-induced apoptosis is likely modulated by the hypoxia-inducing factor-1 alpha subunit (HIF-1

Salt reduction in Australia: from advocacy to action

BACKGROUND: As part of its endorsement of the World Health Organization's Global Action Plan to prevent non-communicable diseases, the Federal Government of Australia has committed to a 30% reduction in average population salt intake by 2025. Currently, mean daily salt intake levels are 8-9 g, varying by sex, region and population group. A number of salt reduction initiatives have been established over the last decade, but key elements for a co-ordinated population-level strategy are still missing. The objective of this review is to provide a comprehensive overview of existing population-level salt reduction activities in Australia and identify opportunities for further action.

METHODS: A review of the published literature and stakeholder activities was undertaken to identify and document current activities. The activities were then assessed against a pre-defined framework for salt reduction strategies.

RESULTS: A range of initiatives were identified from the review. The Australian Division of World Action on Salt and Health (AWASH) was established in 2005 and in 2007 launched its Drop the Salt! Campaign. This united non-governmental organisations (NGOs), health and medical and food industry organisations in a co-ordinated advocacy effort to encourage government to develop a national strategy to reduce salt. Subsequently, in 2010 the Federal Government launched its Food and Health Dialogue (FHD) with a remit to improve the health of the food supply in Australia through voluntary partnerships with food industry, government and non-government public health organisations. The focus of the FHD to date has been on voluntary reformulation of foods, primarily through salt reduction targets. More recently, in December 2014, the government's Health Star Rating system was launched. This front of pack labelling scheme uses stars to highlight the nutritional profile of packaged foods. Both government initiatives have clear targets or criteria for industry to meet, however, both are voluntary and the extent of industry uptake is not yet clear. There is also no parallel public awareness campaign to try and influence consumer behaviour relating to salt and no agreed mechanism for monitoring national changes in salt intake. The Victorian Health Promotion Foundation (VicHealth) has recently instigated a State-level partnership to advance action and will launch its strategy in 2015.

CONCLUSIONS: In conclusion, salt reduction activities are currently being implemented through a variety of different programs but additional efforts and more robust national monitoring mechanisms are required to ensure that Australia is on track to achieve the proposed 30% reduction in salt intake within the next decade.

Site and mechanism of the colokinetic action of the ghrelin receptor agonist, HM01

Background It has been recently demonstrated that the ghrelin receptor agonist, HM01, caused defecation in rats that were treated to provide a model for the constipation of Parkinson's disease. HM01 significantly increased fecal output and increased Fos activity in neurons of the hypothalamus and hindbrain, but not in the spinal defecation center. Other ghrelin agonists act on the defecation center. Methods Receptor pharmacology was examined in ghrelin receptor (GHSR1a) transfected cells. Anesthetized rats were used to investigate sites and mechanisms of action. Key Results HM01 activated rat GHSR1a at nanomolar concentrations and was antagonized by the GHSR1a antagonist, YIL781. HM01, intravenous, was potent to activate propulsive colorectal contractions. This was prevented by pelvic nerve section and by intravenous YIL781, but not by spinal cord section rostral to the defecation centers. Direct intrathecal application of HM01 to the defecation center at spinal level L6-S1 initiated propulsive contractions of the colorectum. Conclusions & Inferences HM01 stimulates GHSR1a receptors on neurons in the lumbosacral defecation centers to cause propulsive contractions and emptying of the colorectum. It has greater potency when given systemically, compared with other GHSR1a agonists.

Bacterial modes of action for enhancing of plant growth

The greatest issue affecting the sustainability of broad acre cropping both environmentally and economically is the requirement of fertilizers. These are based on mined phosphorous or other mineral ores, ammonia produced through the Harbour-Bosch process and industrially manufactured potash. As global demand for fertilizers increases, the costs associated with the production for each of these major nutrients increases. Biofertilizers such as plant growth promoting bacteria (PGPB) are a possible biotechnology that could alleviate the need for addition of increasing amounts of fertilizers. These bacteria naturally occur in soils and aggressively colonize around plant roots and have been shown to have plant growth promoting effects. PGPB are known to influence plant growth by various direct and indirect mechanisms; while some can affect plant physiology directly by mimicking synthesis of plant hormones,others increase mineral availability and nitrogen content in soil. Here we review the previously characterized modes of action for enhancement of plant growth by PGPB such as nitrogen fixation, nutrient solubilization and production of auxins and enzymes, as well as discussing more recent proposed modes of action such as secondary metabolites.