European journal of clinical investigation
-
Acute intermittent porphyria (AIP) is an inherited disorder of haem synthesis wherein a partial deficiency of porphobilinogen (PBG) deaminase (PBGD) with other factors may give rise to biochemical and clinical manifestations of disease. The biochemical hallmarks of active AIP are relative hepatic haem deficiency and uncontrolled up-regulation of hepatic 5-aminolevulinic acid (ALA) synthase-1 (ALAS1) with over-production of ALA and PBG. The treatment of choice is intravenous haem, which restores the deficient regulatory haem pool of the liver and represses ALAS1. Recently, haem has been shown to influence circadian rhythms by controlling their negative feedback loops. We evaluated whether subjects with AIP exhibited an altered circadian profile. ⋯ This pilot study provides evidence for disturbances of circadian markers in women with active AIP that may trigger or sustain some common clinical features of AIP.
-
Vascular injury is the initial manifestation of inflammation resulting in the recruitment and activation of various cell types. The integrity of the vascular wall is monitored by platelets that become activated in the presence of exposed subendothelium. Besides their well-established role in haemostasis, ample data are now emerging on the many immunoregulatory functions of platelets. ⋯ Overall, platelets have multiple functions in both innate and adaptive immunity. Further insight into the multifaceted role of platelets could therefore provide important clues into how we could implement current platelet therapy to reduce both platelet-induced thrombosis and inflammation. In this review, we discuss the current perceptions of platelet involvement in various autoimmune diseases like rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis and multiple sclerosis.
-
Eur. J. Clin. Invest. · Jul 2013
Financial, nonfinancial and editors' conflicts of interest in high-impact biomedical journals.
To assess financial, nonfinancial and editors' conflicts of interest (COI) disclosure policies among the most influential biomedical journals publishing original research. ⋯ Authors' financial COI disclosures were required by about 90% of high-impact clinical and basic journals publishing original research. Unlike recent studies showing a significantly lower prevalence of nonfinancial compared with financial disclosures, the former were required by about 70% of journals, suggesting that editors are increasingly concerned about nonfinancial competing interests. Only 40% of journals required disclosure of editors' COI, in conflict with the recommendations of the most influential editors' associations.
-
Eur. J. Clin. Invest. · Jul 2013
Preserved thrombin-inducible platelet activation in thienopyridine-treated patients.
Abundant thrombin generation may be a major reason for subsequent thromboembolic events in patients with cardiovascular disease receiving dual antiplatelet therapy. We therefore investigated the susceptibility of thienopyridine responders and nonresponders to thrombin receptor-activating peptide (TRAP)-6- and adenosine diphosphate (ADP)-inducible platelet activation. ⋯ Thienopyridine nonresponders are more susceptible to thrombin- and ADP-inducible platelet activation than patients with good platelet inhibition. However, even patients with adequate thienopyridine-mediated platelet inhibition often show a preserved responsiveness to thrombin. These patients may benefit from additional thrombin receptor blockage or inhibition of thrombin generation.