Copper in disorders with neurological symptoms: Alzheimer`s, Menkes, and Wilson Diseases

Copper is an essential element for the activity of a number of physiologically important enzymes. Enzyme-related malfunctions may contribute to severe neurological symptoms and neurological diseases: copper is a component of cytochrome c oxidase, which catalyzes the reduction of oxygen to water, the essential step in cellular respiration. Copper is a cofactor of Cu/Zn-superoxide-dismutase which plays a key role in the cellular response to oxidative stress by scavenging reactive oxygen species. Furthermore, copper is a constituent of dopamine-β-hydroxylase, a critical enzyme in the catecholamine biosynthetic pathway. A detailed exploration of the biological importance and functional properties of proteins associated with neurological symptoms will have an important impact on understanding disease mechanisms and may accelerate development and testing of new therapeutic approaches. Copper binding proteins play important roles in the establishment and maintenance of metal-ion homeostasis, in deficiency disorders with neurological symptoms (Menkes disease, Wilson disease) and in neurodegenerative diseases (Alzheimer’s disease). The Menkes and Wilson proteins have been characterized as copper transporters and the amyloid precursor protein (APP) of Alzheimer’s disease has been proposed to work as a Cu(II) and/or Zn(II) transporter. Experimental, clinical and epidemiological observations in neurodegenerative disorders like Alzheimer’s disease and in the genetically inherited copper-dependent disorders Menkes and Wilson disease are summarized. This could provide a rationale for a link between severely dysregulated metal-ion homeostasis and the selective neuronal pathology.

The molecular basis of copper homeostasis and copper-related disorders

Copper is an essential trace element that can be extremely toxic in excess due to the pro-oxidant activity of copper ions. Inherited disorders of copper transport, Menkes disease (copper deficiency), and Wilson disease (copper toxicosis) are caused by mutations of two closely related Cu transporting-ATPases, and demonstrate the essentiality and potential toxicity of copper. Other copper toxicosis conditions in humans and animals have been described, but are not well understood at a molecular level. Copper homeostatic mechanisms are being discovered. One such mechanism is copper-induced trafficking of the Cu-ATPases, which allows cells to provide copper to secreted cupro-proteins but also to efflux excess copper. Oxidative damage induced by copper may be involved in the pathogenesis of neurodegenerative conditions such as Alzheimer's disease, familial amyotrophic lateral sclerosis, and prion diseases.

Zinc deficiency and its inherited disorders - A review

Zinc is an essential trace element required by all living organisms because of its critical roles both as a structural component of proteins and as a cofactor in enzyme catalysis. The importance of zinc in human metabolism is illustrated by the effects of zinc deficiency, which include a diminished immune response, reduced healing and neurological disorders. Furthermore, nutritional zinc deficiency can be fatal in newborn or growing animals. While zinc deficiency is commonly caused by dietary factors, several inherited defects of zinc deficiency have been identified. Acrodermatitis enteropathica is the most commonly described inherited condition found in humans. In several of the few cases that have been reported, this disorder is associated with mutations in the hZIP4 gene, a member of the SLC39 family, whose members encode membranebound putative zinc transporters. Mutations in other members of this family or in different genes may account for other cases of acrodermatitis in which defects in hZIP4 have not been detected. Another inherited form of zinc deficiency occurs in the lethal milk mouse, where a mutation in ZnT4 gene, a member of the SLC30 family of transmembrane proteins results in impaired secretion of zinc into milk from the mammary gland. A similar disorder to the lethal milk mouse occurs in humans. In the few cases studied, no changes in ZnT4 orthologue, hZnT4, were detected. This, and the presence of several minor phenotypic differences between the zinc deficiency in humans and mice, suggests that the human condition is caused by defects in genes that are yet to be identified. Taking into account the fact that there are no definitive tests for zinc deficiency and that this disorder can go undiagnosed, plus the recent identification of multiple members of the SCL30 and SLC39, it is likely that mutations in other genes may underlie additional inherited disorders of zinc deficiency.

Australian gp's preferences for education about depression and related disorders

OBJECTIVE: To Investigate Australian general practitioners' experiences of accessing education about depression and their preferences for future education on depression and related disorders.
METHOD: Six hundred and eight anonymous surveys were distributed to GPs through 52 rural and urban divisions of general practice; 420 were retumed.
RESULTS: Educational formats involving direct contact with people having mental health expertise were highly valued. Distance education and web based technologies were least used. In the previous year, women and older GPs had spent more time on education about depression. Most intended to undertake more such education in the future and said that education in psychosocial strategies would be very useful. General practitioners' attitudes to further education about depression were influenced by their gender, practice location, and their previous mental health training.
DISCUSSION: More face-to-face training may be desirable to take advantage of GPs' willingness to spend more time on education about depression and related disorders.

Developmental language disorders and adolescent risk: a public-health advocacy role for speech pathologists?

Within the multi-disciplinary team concerned with child and adolescent development, speech pathologists are uniquely positioned to understand the nature and overall developmental significance of language acquisition in childhood and adolescence. Other disciplines contribute valuable insights about psychosocial development during the childhood and adolescent years. The field of developmental psychology, for example provides a large and convincing body of evidence about the role of academic success as a protective factor against a range of psychosocial harms, in particular substance misuse, truancy, early school leaving, and juvenile offending. In this paper, we argue that juvenile offending embodies the notion of "adolescent risk", but in Australia in particular, has been under-investigated with respect to possible associations with developmental language disorders and subsequent academic failure. We present findings pertaining to a sample of 30 male juvenile offenders completing community based orders. Performance on a range of oral language processing and production skills was poorer than that of a demographically similar comparison group. Our results confirm the need to conceptualize language within a broader risk and protective framework. We therefore emphasize the public health importance of early language competence, by virtue of the psychosocial protection it confers on young people with respect to the development of prosocial skills, transition to literacy and overall academic achievement. We argue that speech pathologists are best positioned to advocate at a policy level about the broader public health importance of oral language competence.

Dietary assimilation and the digestive strategy of the omnivorous anomuran land crab Birgus latro (Coenobitidae).

On Christmas Island, Indian Ocean, the diet of robber crabs, Birgus latro (Linnaeus) was generally high in fat, storage polysaccharides or protein and largely comprised fruits, seeds, nuts and animal material. The plant items also contained significant amounts of hemicellulose and cellulose. In laboratory feeding trials, crabs had similar intakes of dry matter when fed artificial diets high in either fat or storage polysaccharide, but intake was lower on a high protein diet. Assimilation coefficients of dry matter (69–74%), carbon (72–81%), nitrogen (76–100%), lipid (71–96%) and storage polysaccharide (89–99%) were high on all three diets. B. latro also assimilated significant amounts of the chitin ingested in the high protein diet ( 93%) and hemicellulose (49.6–65%) and cellulose (16–53%) from the high carbohydrate and high fat diets. This is consistent with the presence of chitinase, hemicellulase and cellulase enzymes in the digestive tract of B. latro. The mean retention time (27.2 h) for a dietary particle marker (⁵⁷Co-labelled microspheres) was longer than measured in leaf-eating land crabs. The feeding strategy of B. latro involves the selection of highly digestible and nutrient-rich plant and animal material and retention of the digesta for a period long enough to allow extensive exploitation of storage carbohydrates, lipids, protein and significant amounts of structural carbohydrates (hemicellulose, cellulose and chitin).

Preventing the onset of depressive disorders : a meta-analytic review of psychological interventions

OBJECTIVE: A growing number of studies have tested the efficacy of preventive interventions in reducing the incidence of depressive disorders. Until now, no meta-analysis has integrated the results of these studies. METHOD: The authors conducted a meta-analysis. After a comprehensive literature search, 19 studies were identified that met inclusion criteria. The studies had to be randomized controlled studies in which the incidence of depressive disorders (based on diagnostic criteria) in an experimental group could be compared with that of a control group. RESULTS: The mean incidence rate ratio was 0.78, indicating a reduction of the incidence of depressive disorders by 22% in experimental compared with control groups. Heterogeneity was low to moderate (I²=33%). The number needed to treat to prevent one case of depressive disorder was 22. Moderator analyses revealed no systematic differences between target populations or types of prevention (universal, selective, or indicated). The data included indications that prevention based on interpersonal psychotherapy may be more effective than prevention based on cognitive-behavioral therapy. CONCLUSIONS: Prevention of new cases of depressive disorders does seem to be possible. Prevention may become an important way, in addition to treatment, to reduce the enormous public health burden of depression in the coming years.

The role of omega-3 fatty acids in mood disorders

Research has established that docosahexaenoic acid (DHA), a long-chain omega-3 polyunsaturated fatty acid (PUFA), plays a fundamental role in brain structure and function. Epidemiological and cross-sectional studies have also identified a role for long-chain omega-3 PUFA, which includes DHA, eicosapentaenoic acid, and docosapentaenoic acid, in the etiology of depression. In the past ten years, there have been 12 intervention studies conducted using various preparations of longchain omega-3 PUFA in unipolar and bipolar depression. The majority of these studies administered long-chain omega-3 PUFA as an adjunct therapy. The studies have been conducted over 4 to 16 weeks of intervention and have often included small cohorts. In four out of the seven studies conducted in depressed individuals and in two out of the five studies in bipolar patients, individuals have reported a positive outcome following supplementation with ethyl-eicosapentaenoic acid or fish oil containing long-chain omega-3 PUFA. In the three trials that researched the influence of DHA-rich preparations, no significant effects were reported. The mechanisms that have been invoked to account for the benefits of long-chain omega-3 PUFA in depression include reductions in prostaglandins derived from arachidonic acid, which lead to decreased brain-derived neurotrophic factor levels and/or alterations in blood flow to the brain.

Protein kinase C isozymes as potential therapeutic targets in immune disorders

Background: Members of the protein kinase C (PKC) family are key signalling mediators in immune responses, and pharmacological inhibition of PKCs may be useful for treating immune-mediated diseases. Objective: To review and discuss the insights gained so far into various PKC isozymes and the therapeutic potential and challenges of developing PKC inhibitors for immune disorder therapy. Methods: A literature review of the role of PKCs in immune cell signalling and recent studies describing immune functions associated with PKC isozyme deficiency in relevant mouse disease models, followed by specific case studies of current and potential therapeutic strategies targeting PKCs. Results/conclusion: There is vast amount of data supporting PKC isozymes as attractive drug targets for certain immune disorders. Although the development of specific PKC isozyme inhibitors has been challenging, some progress has been made. It remains to be seen if broad-scale or isozyme-selective inhibition of PKC will have clinical efficacy.

Food utilisation and digestive ability of aquatic and semi-terrestrial crayfishes, Cherax destructor and Engaeus sericatus (Astacidae, Parastacidae)

Both Engaeus sericatus and Cherax destructor are omnivorous crayfishes consuming a variety of food items. Materials identified in the faeces of both E. sericatus and C. destructor consisted of mainly plant material with minor amounts of arthropod animals, algae and fungi. The morphology of the gastric mill of C. destructor suggests that it is mainly involved in crushing of food material while the gastric mill of E. sericatus appears to be better suited to cutting of food material. Given this, the gastric mill of E. sericatus may be better able to cut the cellulose and hemicellulose fibres associated with fibrous plant material. In contrast, the gastric mill of C. destructor appears to be more efficient in grinding soft materials such as animal protein and algae. Both species accumulated high amounts of lipids in their midgut glands (about 60% of the dry mass) which were dominated by triacylglycerols (81–82% of total lipids). The dominating fatty acids were 16:0, 16:1(n-7), 18:1(n-9), 18:2(n-6), and 18:3(n-3). The two latter fatty acids can only be synthesised by plants, and are thus indicative of the consumption of terrestrial plants by the crayfishes. The similarity analysis of the fatty acid patterns showed three distinct clusters of plants and each of the crayfish species. The complement of digestive enzymes, proteinases, total cellulase, endo-β-1,4-glucanase, β-glucosidase, laminarinase and xylanase within midgut gland suggests that both C. destructor and E. sericatus are capable of hydrolysing a variety of substrates associated with an omnivorous diet. Higher activities of total cellulase, endo-β-1,4-glucanase and β-glucosidase indicate that E. sericatus is better able to hydrolyse cellulose within plant material than C. destructor. In contrast to E. sericatus, higher total protease and N-acetyl-β-d-glucosaminidase activity in the midgut gland of C. destructor suggests that this species is better able to digest animal materials in the form of arthropods. Differences in total cellulase and gastric mill morphology suggest that E. sericatus is more efficient at digesting plant material than C. destructor. However, the contents of faecal pellets and the fatty acid compositions seem to indicate that both species opportunistically feed on the most abundant and easily accessible food items.

Towards co-design with users who have autism spectrum disorders

People with cognitive disorders, such as autism or Asperger’s syndrome, face many barriers when being involved in the co-design of information and communications technologies (ICT). Cognitive disorders may require that co-design techniques be modified to fit with individual abilities. Up until recently, with technology design, purpose and use being in the hands of ‘experts’ there was little opportunity for customisation. However, ICT bring together various threads that make open many new possibilities. Not only are technologies cheaper, more powerful and more available than ever, but now parents, support agencies and people with autism spectrum disorders expect information technologies to be part of their worlds, and they have the capacity to participate in co-design for customisation. However, co-design techniques have not evolved to the extent that they capture this potential democratisation of the ICT. This paper reports on an investigation of the potential to develop a set of guidelines for co-design techniques to enable people with autism spectrum disorders to participate in ICT design.