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.

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.

Femoral sulcus angle and increased patella facet cartilage volume in an osteoarthritic population

Objective
The patellofemoral joint is an example of an incongruent articulation commonly affected by osteoarthritis (OA). The relationship between femoral sulcus angle and the development and progression of patellofemoral OA is unclear. The aim of this study was to examine the relationship between the femoral sulcus angle at baseline and patella cartilage volume at baseline and at 2-year follow-up among community based adults with established knee OA.

Methods
One hundred subjects had magnetic resonance imaging of their symptomatic knee at baseline and at 2-year follow-up. From these images, patella cartilage volume was determined. Radiographic skyline views of the patellofemoral joint were taken at baseline to measure the femoral sulcus angle.

Results
For every 1° increase in the femoral sulcus angle (i.e., as the sulcus angle became more shallow) there was an associated 9.1 mm3 (95% CI 3.1, 15.0) increase in medial patella cartilage volume at baseline (P = 0.003). There was a similar trend that approached statistical significance between the femoral sulcus angle and the lateral patella facet cartilage volume at baseline (P = 0.09). There was no association between the femoral sulcus angle at baseline and the change in patella cartilage volume over 2 years in either patellofemoral compartment.

Conclusion
These results infer that the femoral sulcus angle is a cross-sectional determinant of the amount of patella cartilage, but is not a major determinant of the annual change of patella cartilage volume among people with knee OA. These data suggest that a shallower sulcus in the context of established OA may be an advantageous anatomical variant. Further longitudinal studies are required to determine the role of the femoral sulcus angle in OA.

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.