The molecular basis of copper-transport diseases

Copper (Cu) is a potentially toxic yet essential element. Menkes disease, a copper deficiency disorder, and Wilson disease, a copper toxicosis condition, are two human genetic disorders, caused by mutations of two closely related Cu-transporting ATPases. Both molecules efflux copper from cells. Quite diverse clinical phenotypes are produced by different mutations of these two Cu-transporting proteins. The understanding of copper homeostasis has become increasingly important in clinical medicine as the metal could be involved in the pathogenesis of some important neurological disorders such as Alzheimer's disease, motor neurone diseases and prion diseases.

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.

Antitropicality of Pacific fishes : molecular insights

Twenty-one molecular genetic studies of thirteen antitropical Pacific fishes are herein reviewed. High dispersal potentials and Plio-Pleistocene transequatorial divergence are suggested for approximately half of the taxa studied, consistent with movement across the tropics during glacial periods. Divergences within two fish groups were mid-Miocene in age, corresponding to a period suggested for vicariant isolation associated with equatorial warming, but high dispersal potentials complicate the interpretation of biogeographic history. Only one study suggested transequatorial divergence older than 20 million years. There is a greater proportion of Pleistocene transequatorial divergences in the East Pacific than the West Pacific, consistent with the suggestion that conditions in the East Pacific are more amenable to the formation of antitropical distributions. Multiple transequatorial divergences have been observed within at least two groups, and instances of cryptic speciation have been identified twice. Areas for future research concern taxa that differ from the majority studied to date with respect to latitudinal distribution, bathymetry, evolutionary age, and dispersal potential. Molecular characters have demonstrated utility for the study of antitropical fishes, but with limitations.

Miraculous draught of fishes

This print hung in Alfred Deakin's study in 'Llanarth', South Yarra. It is a print of Raphael's original cartoon for the Sistine Chapel tapestries, drawn by him and his workshop in 1515. The original cartoona are in the Victoria and Albert Museum.

Diet, nutrition and the prevention of chronic diseases : report of a Joint WHO/FAO Expert Consultation

This report examines the science base of the relationship between diet and physical activity patterns and the major nutrition-related chronic diseases. Recommendations are made to help prevent death and disability from major nutrition-related chronic diseases.

Purchase commitments : Big business bias or solution to the 'neglected diseases' dilemma?

Miniscule research resources are allocated to researching the diseases of developing countries such as malaria, tuberculosis (TB), dengue fever, river blindness, Chagas disease and leishmaniasis, and the strains of HIV prevalent in Africa. Plainly, the patent system and the commercial model of drug research fail to respond to the needs of the poor for the simple reason that the poor exercise little purchasing power. But pressures are mounting on governments and corporations to tackle the ‘neglected diseases’ calamity. An important argument in an intense global debate is that corporations would respond to the needs of developing countries if the diseases of the poor could be made profitable. This is the idea developed by Kremer and Glennerster in a crisply written book, Strong Medicine: Creating Incentives for Pharmaceutical Research on Neglected Diseases.

Natriuretic peptide signalling in the gills of freshwater and seawater fishes

The gills are considered major targets for cardiac natriuretic peptides with studies confirming natriuretic peptide receptor presence on vascular and sometimes epithelial tissues. Natriuretic peptide intracellular signalling is via guanylyl cyclase receptors and the cGMP pathway, and via inhibitory G-proteins linked to cyclic AMP pathways. Natriuretic peptides in the gills alter branchial blood flow and may also alter ion transport in various salinities. We present an overview of natriuretic peptide cGMP and cAMP signalling in fishes and consider the implications of the recent discovery of several CNPs and BNP in bony fishes on natriuretic peptide receptor studies.

A critical look at the role of self-management for people with arthritis and other chronic diseases

Most patients with chronic conditions, such as osteoarthritis, only have contact with healthcare professionals for a few hours over the course of a year. Good self-management programs are, therefore, critical for patients to cope with their conditions on a daily basis. Drs Osborne, Jordan and Rogers discuss the importance of engaging patients, clinicians and policymakers in the development and implementation of self-management programs.

Effectiveness of prevention programmes for obesity and chronic diseases amongst immigrants to developed countries - a systematic review

Objective: To determine whether interventions tailored specifically to  particular immigrant groups from developing to developed countries  decrease the risk of obesity and obesity-related diseases.

Design: Databases searched were MEDLINE (1966–September 2008), CINAHL (1982–September 2008) and PsychINFO (1960–September 2008), as well as Sociological Abstracts, PsychARTICLES, Science Direct, Web of Knowledge and Google Scholar. Studies were included if they were randomised control trials, ‘quasi-randomised’ trials or controlled before-and-after studies. Due to the heterogeneity of study characteristics only a narrative synthesis was undertaken, describing the target population, type and reported impact of the intervention and the effect size.

Results: Thirteen studies met the inclusion criteria. Ten out of thirteen (77 %) studies focused on diabetes, seven (70 %) of which showed significant improvement in addressing diabetes-related behaviours and glycaemic control. The effect on diabetes was greater in culturally tailored and facilitated interventions that encompassed multiple strategies. Six out of the thirteen studies (46 %) incorporated anthropometric data, physical activity and healthy eating as ways to minimise weight gain and diabetes-related outcomes. Of the six interventions that included anthropometric data, only two (33 %) reported improvement in BMI Z-scores, total skinfold thickness or proportion of body fat. Only one in three (33 %) of the studies that included cardiovascular risk factors reported improvement in diastolic blood pressure after adjusting for baseline characteristics. All studies, except four, were of poor quality (small sample size, poor internal consistency of scale, not controlling for baseline characteristics).

Conclusions: Due to the small number of studies included in the present review, the findings that culturally tailored and facilitated interventions produce better outcomes than generalised interventions, and that intervention content is more important than the duration or venue, require further investigation.

Quantification of urbanization in relation to chronic diseases in developing countries : a systematic review

During and beyond the twentieth century, urbanization has represented a major demographic shift particularly in the developed world. The rapid urbanization experienced in the developing world brings increased mortality from lifestyle diseases such as cancer and cardiovascular disease. We set out to understand how urbanization has been measured in studies which examined chronic disease as an outcome. Following a pilot search of PUBMED, a full search strategy was developed to identify papers reporting the effect of urbanization in relation to chronic disease in the developing world. Full searches were conducted in MEDLINE, EMBASE, CINAHL, and GLOBAL HEALTH. Of the 868 titles identified in the initial search, nine studies met the final inclusion criteria. Five of these studies used demographic measures (such as population density) at an area level to measure urbanization. Four studies used more complicated summary measures of individual and area level data (such as distance from a city, occupation, home and land ownership) to define urbanization. The papers reviewed were limited by using simple area level summary measures (e.g., urban rural dichotomy) or having to rely on preexisting data at the individual level. Further work is needed to develop a measure of urbanization that treats urbanization as a process and which is sensitive enough to track changes in “urbanicity” and subsequent emergence of chronic disease risk factors and mortality.