Lack of MEF2A Δ7aa mutation in Irish families with early onset ischaemic heart disease, a family based study

Background: Ischaemic heart disease (IHD) is a complex disease due to the combination of environmental and genetic factors. Mutations in the MEF2A gene have recently been reported in patients with IHD. In particular, a 21 base pair deletion (Δ7aa) in the MEF2A gene was identified in a family with an autosomal dominant pattern of inheritance of IHD. We investigated this region of the MEF2A gene using an Irish family-based study, where affected individuals had early-onset IHD. Methods: A total of 1494 individuals from 580 families were included (800 discordant sib-pairs and 64 parent-child trios). The Δ7aa region of the MEF2A gene was investigated based on amplicon size. Results: The Δ7aa mutation was not detected in any individual. Variation in the number of CAG (glutamate) and CCG (proline) residues was detected in a nearby region. However, this was not found to be associated with IHD. Conclusion: The Δ7aa mutation was not detected in any individual within the study population and is unlikely to play a significant role in the development of IHD in Ireland. Using family-based tests of association the number of tri-nucleotide repeats in a nearby region of the MEF2A gene was not associated with IHD in our study group. © 2006 Horan et al; licensee BioMed Central Ltd.

Internal mammary artery smooth muscle cells resist migration and possess high antioxidant capacity

Objective: This study investigated whether differences exist in atherogen-induced migratory behaviors and basal antioxidant enzyme capacity of vascular smooth muscle cells (VSMC) from human coronary (CA) and internal mammary (IMA) arteries. Methods: Migration experiments were performed using the Dunn chemotaxis chamber. The prooxidant [NAD(P)H oxidase] and antioxidant [NOS, superoxide dismutase, catalase and glutathione peroxidase] enzyme activities were determined by specific assays. Results: Chemotaxis experiments revealed that while both sets of VSMC migrated towards platelet-derived growth factor-BB (1-50 ng/ml) and angiotensin II (1-50 nM), neither oxidized-LDL (ox-LDL, 25-100 ng/ml) nor native LDL (100 ng/ml) affected chemotaxis in IMA VSMC. However, high dose ox-LDL produced significant chemotaxis in CAVSMC that was inhibited by pravastatin (100 nM), mevastatin (10 nM), losartan (10 nM), enalapril (1 micro.M), and MnTBAP (a free radical scavenger, 50 micro.M). Microinjection experiments with isoprenoids i.e. geranylgeranylpyrophosphate (GGPP) and farnesylpyrophosphate (FPP) showed distinct involvement of small GTPases in atherogeninduced VSMC migration. Significant increases in antioxidant enzyme activities and nitrite production along with marked decreases in NAD(P)H oxidase activity and superoxide levels were determined in IMA versus CA VSMC. Conclusions: Enhanced intrinsic antioxidant capacity may confer on IMAVSMC resistance to migration against atherogenic agents. Drugs that regulate ox-LDL or angiotensin II levels also exert antimigratory effects.

Challenging assumptions of future coastal habitat development around the UK

One habitat management requirement forced by 21st century relative sea-level rise (RSLR), will be the need to re-comprehend the dimensions of long-term transgressive behaviour of coastal systems being forced by such RSLR. Fresh approaches to the conceptual modelling and subsequent implementation of new coastal and peri-marine habitats will be required. There is concern that existing approaches to forecasting coastal systems development (and by implication their associated scarce coastal habitats) over the next century depend on a certain premise of orderly spatial succession of habitats. This assumption is shown to be questionable given the possible future rates of RSLR, magnitude of shoreline retreat and the lack of coastal sediment to maintain the protective morphologies to low-energy coastal habitats. Of these issues, sediment deficiency is regarded as one of the major problem for future habitat development. Examples of contemporary behaviour of UK coasts show evidence of coastal sediment starvation resulting from relatively stable RSLR, anthropogenic sealing of coastal sources, and intercepted coastal sediment pathways, which together force segmentation of coastal systems. From these examples key principles are deduced which may prejudice the existence of future habitats: accelerated future sediment demand due to RSLR may not be met by supply and, if short- to medium-term hold-the-line policies predominate, long-term strategies for managed realignment and habitat enhancement may prove impossible goals. Methods of contemporary sediment husbandry may help sustain some habitats in place but otherwise, instead of integrated coastal organization, managers may need to consider coastal breakdown, segmentation and habitat reduction as the basis of 21st century coastal evolution and planning.

Reduction in gingival overgrowth associated with conversion from cyclosporin A to tacrolimus

Background: Unsightly gingival overgrowth affects many individuals immunosuppressed with cyclosporin A (CsA), Current management involves repeated periodontal surgery and intensive hygienist support. Tacrolimus is an effective alternative immunosuppressive agent for renal transplantation which does not appear to produce gingival enlargement.

The calcium channel blocker used with cyclosporin has an effect on gingival overgrowth

Background/aims, To investigate whether the choice of calcium channel blocker, used in conjunction with cyclosporin A, affected the prevalence of gingival overgrowth.