Plasma levels of intermedin (adrenomedullin-2) in healthy human volunteers and patients with heart failure

Intermedin/adrenomedullin-2 (IMD) is a member of the adrenomedullin/CGRP peptide family. Less is known about the distribution of IMD than for other family members within the mammalian cardiovascular system, particularly in humans. The aim was to evaluate plasma IMD levels in healthy subjects and patients with chronic heart failure. IMD and its precursor fragments, preproIMD25–56 and preproIMD57–92, were measured by radioimmunoassay in 75 healthy subjects and levels of IMD were also compared to those of adrenomedullin (AM) and mid-region proadrenomedullin45–92 (MRproAM45–92) in 19 patients with systolic heart failure (LVEF < 45%). In healthy subjects, plasma levels (mean + SE) of IMD (6.3 + 0.6 pg ml−1) were lower than, but correlated with those of AM (25.8 + 1.8 pg ml−1; r = 0.49, p < 0.001). Plasma preproIMD25–56 (39.6 + 3.1 pg ml−1), preproIMD57–92 (25.9 + 3.8 pg ml−1) and MRproAM45–92 (200.2 + 6.7 pg ml−1) were greater than their respective bioactive peptides. IMD levels correlated positively with BMI but not age, and were elevated in heart failure (9.8 + 1.3 pg ml−1, p < 0.05), similarly to MRproAM45–92 (329.5 + 41.9 pg ml−1, p < 0.001) and AM (56.8 + 10.9 pg ml−1, p < 0.01). IMD levels were greater in heart failure patients with concomitant renal impairment (11.3 + 1.8 pg ml−1) than those without (6.5 + 1.0 pg ml−1; p < 0.05). IMD and AM were greater in patients receiving submaximal compared with maximal heart failure drug therapy and were decreased after 6 months of cardiac resynchronization therapy. In conclusion, IMD is present in the plasma of healthy subjects less abundantly than AM, but is similarly correlated weakly with BMI. IMD levels are elevated in heart failure, especially with concomitant renal impairment, and tend to be reduced by high intensity drug or pacing therapy.

Retinal pigment epithelial cell multinucleation in the aging eye - a mechanism to repair damage and maintain homoeostasis

Retinal pigment epithelial (RPE) cells are central to retinal health and homoeostasis. Dysfunction or death of RPE cells underlies many age-related retinal degenerative disorders particularly age-related macular degeneration. During aging RPE cells decline in number, suggesting an age-dependent cell loss. RPE cells are considered to be postmitotic, and how they repair damage during aging remains poorly defined. We show that RPE cells increase in size and become multinucleate during aging in C57BL/6J mice. Multinucleation appeared not to be due to cell fusion, but to incomplete cell division, that is failure of cytokinesis. Interestingly, the phagocytic activity of multinucleate RPE cells was not different from that of mononuclear RPE cells. Furthermore, exposure of RPE cells in vitro to photoreceptor outer segment (POS), particularly oxidized POS, dose-dependently promoted multinucleation and suppressed cell proliferation. Both failure of cytokinesis and suppression of proliferation required contact with POS. Exposure to POS also induced reactive oxygen species and DNA oxidation in RPE cells. We propose that RPE cells have the potential to proliferate in vivo and to repair defects in the monolayer. We further propose that the conventionally accepted 'postmitotic' status of RPE cells is due to a modified form of contact inhibition mediated by POS and that RPE cells are released from this state when contact with POS is lost. This is seen in long-standing rhegmatogenous retinal detachment as overtly proliferating RPE cells (proliferative vitreoretinopathy) and more subtly as multinucleation during normal aging. Age-related oxidative stress may promote failure of cytokinesis and multinucleation in RPE cells.

Promoting healthy dietary behaviour through personalised nutrition: technology push or technology pull?

The notion of educating the public through generic healthy eating messages has pervaded dietary health promotion efforts over the years and continues to do so through various media, despite little evidence for any enduring impact upon eating behaviour. There is growing evidence, however, that tailored interventions such as those that could be delivered online can be effective in bringing about healthy dietary behaviour change. The present paper brings together evidence from qualitative and quantitative studies that have considered the public perspective of genomics, nutrigenomics and personalised nutrition, including those conducted as part of the EU-funded Food4Me project. Such studies have consistently indicated that although the public hold positive views about nutrigenomics and personalised nutrition, they have reservations about the service providers' ability to ensure the secure handling of health data. Technological innovation has driven the concept of personalised nutrition forward and now a further technological leap is required to ensure the privacy of online service delivery systems and to protect data gathered in the process of designing personalised nutrition therapies.

Biomarker responses to folic acid intervention in healthy adults: a meta-analysis of randomized controlled trials

BACKGROUND: The task of revising dietary folate recommendations for optimal health is complicated by a lack of data quantifying the biomarker response that reliably reflects a given folate intake.

OBJECTIVE: We conducted a dose-response meta-analysis in healthy adults to quantify the typical response of recognized folate biomarkers to a change in folic acid intake.

DESIGN: Electronic and bibliographic searches identified 19 randomized controlled trials that supplemented with folic acid and measured folate biomarkers before and after the intervention in apparently healthy adults aged ≥18 y. For each biomarker response, the regression coefficient (β) for individual studies and the overall pooled β were calculated by using random-effects meta-analysis.

RESULTS: Folate biomarkers (serum/plasma and red blood cell folate) increased in response to folic acid in a dose-response manner only up to an intake of 400 μg/d. Calculation of the overall pooled β for studies in the range of 50 to 400 μg/d indicated that a doubling of folic acid intake resulted in an increase in serum/plasma folate by 63% (71% for microbiological assay; 61% for nonmicrobiological assay) and red blood cell folate by 31% (irrespective of whether microbiological or other assay was used). Studies that used the microbiological assay indicated lower heterogeneity compared with studies using nonmicrobiological assays for determining serum/plasma (I(2) = 13.5% compared with I(2) = 77.2%) and red blood cell (I(2) = 45.9% compared with I(2) = 70.2%) folate.

CONCLUSIONS: Studies administering >400 μg folic acid/d show no dose-response relation and thus will not yield meaningful results for consideration when generating dietary folate recommendations. The calculated folate biomarker response to a given folic acid intake may be more robust with the use of a microbiological assay rather than alternative methods for blood folate measurement.

Community dynamics and the lower airway microbiota in stable chronic obstructive pulmonary disease, smokers and healthy non-smokers

RATIONALE: The role bacteria play in the progression of COPD has increasingly been highlighted in recent years. However, the microbial community complexity in the lower airways of patients with COPD is poorly characterised.

OBJECTIVES: To compare the lower airway microbiota in patients with COPD, smokers and non-smokers.

METHODS: Bronchial wash samples from adults with COPD (n=18), smokers with no airways disease (n=8) and healthy individuals (n=11) were analysed by extended-culture and culture-independent Illumina MiSeq sequencing. We determined aerobic and anaerobic microbiota load and evaluated differences in bacteria associated with the three cohorts. Culture-independent analysis was used to determine differences in microbiota between comparison groups including taxonomic richness, diversity, relative abundance, 'core' microbiota and co-occurrence.

MEASUREMENT AND MAIN RESULTS: Extended-culture showed no difference in total load of aerobic and anaerobic bacteria between the three cohorts. Culture-independent analysis revealed that the prevalence of members of Pseudomonas spp. was greater in the lower airways of patients with COPD; however, the majority of the sequence reads for this taxa were attributed to three patients. Furthermore, members of Bacteroidetes, such as Prevotella spp., were observed to be greater in the 'healthy' comparison groups. Community diversity (α and β) was significantly less in COPD compared with healthy groups. Co-occurrence of bacterial taxa and the observation of a putative 'core' community within the lower airways were also observed.

CONCLUSIONS: Microbial community composition in the lower airways of patients with COPD is significantly different to that found in smokers and non-smokers, indicating that a component of the disease is associated with changes in microbiological status.