Hypoxia Modulates Platelet Purinergic Signalling Pathways.

BACKGROUND: Hypoxia resulting from ascent to high-altitude or pathological states at sea level is known to increase platelet reactivity. Previous work from our group has suggested that this may be adenosine diphosphate (ADP)-specific. Given the clinical importance of drugs targeting ADP pathways, research into the impact of hypoxia on platelet ADP pathways is highly important. METHODS: Optimul aggregometry was performed on plasma from 29 lowland residents ascending to 4,700 m, allowing systematic assessment of platelet reactivity in response to several platelet agonists. Aggregometry was also performed in response to ADP in the presence of inhibitors of the two main ADP receptors, P2Y1 and P2Y12 (MRS2500 and cangrelor, respectively). Phosphorylation of vasodilator-stimulated phosphoprotein (VASP), a key determinant of platelet aggregation, was analysed using the VASPFix assay. RESULTS: Hypobaric hypoxia significantly reduced the ability of a fixed concentration of cangrelor to inhibit ADP-induced aggregation and increased basal VASP phosphorylation. However, in the absence of P2Y receptor inhibitors, we did not find evidence of increased platelet sensitivity to any of the agonists tested and found reduced sensitivity to thrombin receptor-activating peptide-6 amide. CONCLUSION: Our results provide evidence of increased P2Y1 receptor activity at high altitude and suggest down-regulation of the P2Y12 pathway through increased VASP phosphorylation. These changes in ADP pathway activity are of potential therapeutic significance to high-altitude sojourners and hypoxic sea level patients prescribed platelet inhibitors and warrant further investigation.

Web-based interventions for prevention and treatment of perinatal mood disorders: a systematic review.

BACKGROUND: Perinatal depression is strikingly common with a prevalence of 10-15%. The adverse effects of perinatal depression on maternal and child health are profound with considerable costs. Despite this, few women seek medical attention. E-health, providing healthcare via the Internet is an accessible and effective solution for the treatment of depression in the general population. We aimed to conduct a systematic review of web-based interventions for the prevention and treatment of mood disorders in the perinatal period, defined as the start of pregnancy to 1 year post-partum. METHODS: Six databases were searched until 26(th) March 2015. Two researchers independently screened articles for eligibility. Of the 547 screened articles, four met the inclusion criteria. These included three randomised-controlled trials and one feasibility trial, with total data from 1274 participants. MOOSE and PRISMA guidelines were adhered to for the conduct and reporting of the systematic review. RESULTS: All studies were conducted in the post-partum period. All reported an improvement in maternal mood following intervention. A significant improvement in depressive symptoms was measured using validated rating scales, such as the Edinburgh Postnatal Depression Scale (EPDS), either at post-treatment or follow-up which ranged from 3 to 12 months post study completion. For the two RCTs utilising the EPDS, the EPDS score reductions were (mean ± SEM) 8.52 ± 0.22 (Range 19.46 to10.94) and 9.19 ± 0.63 (Range, 20.24 to 11.05) for treatment groups and 5.16 ± 0.25 (Range 19.44 to 14.28) and 6.81 ± 0.71 (Range 21.07 to 14.26) for comparator groups. However attrition within studies ranged from 13 to 61%. One study was rated as 'good' quality. CONCLUSIONS: Preliminary data suggests web-based therapies for perinatal depression delivered in the post-partum period may play a role in improving maternalmood but more studies are needed, particularly with interventions delivered antenatally. Further research is needed to address the limitations of the existing evidence base.