European journal of clinical investigation
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Eur. J. Clin. Invest. · Mar 2015
ReviewBiological embedding of early-life exposures and disease risk in humans: a role for DNA methylation.
Following wider acceptance of 'the thrifty phenotype' hypothesis and the convincing evidence that early-life exposures can influence adult health even decades after the exposure, much interest has been placed on the mechanisms through which early-life exposures become biologically embedded. ⋯ Based on these results, we hypothesize that epigenetics, in particular DNA methylation, is a plausible mechanism through which early-life exposures are biologically embedded. This review describes the current status of the field and acts as a stepping stone for future, better designed investigations on how early-life exposures might become biologically embedded through epigenetic effects.
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Eur. J. Clin. Invest. · Mar 2015
ReviewFrequency, risk factors and prophylaxis of infection in ANCA-associated vasculitis.
Antineutrophil cytoplasm antibody (ANCA)-associated vasculitides are potentially life-threatening disorders. ⋯ We suggest to routinely prescribe trimethoprim-sulfamethoxazole or antimicrobial agents such as pentamidine in case of intolerance or contraindication in the early phase of induction therapy irrespective of the immunosuppressive strategy used and to continue therapy, together with other targeted measures (antiviral, antimycotic or antibiotic) in the presence of risk factors for a prolonged period of time. Finally, there is an urgent need to standardize the reporting of infectious complications in clinical trials to enable comparing the adverse event spectrum of distinct treatment approaches more appropriately.
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Eur. J. Clin. Invest. · Mar 2015
Low serum tryptophan predicts higher mortality in cardiovascular disease.
The essential amino acid tryptophan is required for protein synthesis and formation of the neurotransmitter serotonin and may exert immunoregulatory functions. An accelerated tryptophan breakdown rate is associated with inflammation and immune activation. ⋯ Low serum tryptophan in patients with CAD is associated with immune activation and indicates reduced life expectancy.
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Renal hypoxia is known to play an important role in the pathophysiology of acute renal injury as well as in chronic kidney diseases. The mediators of hypoxia are the transcription factors HIF (hypoxia-inducible factors), that are highly regulated. Under normoxic conditions constitutively expressed HIF-α subunits are hydroxylated by prolyl hydroxylases (PHD1, PHD2, and PHD3) and subsequently degraded by proteasomes. ⋯ This review summarizes the current knowledge regarding the role of hypoxia, HIF signalling, and Morg1 in acute and chronic renal injury.
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Eur. J. Clin. Invest. · Mar 2015
ReviewUpdate on the role of angiotensin in the pathophysiology of coronary atherothrombosis.
Coronary atherothrombosis due to atherosclerotic plaque rupture or erosion is frequently associated with acute coronary syndromes (ACS). Significant efforts have been made to elucidate the pathophysiological mechanisms underlying acute coronary events. ⋯ Treatments selectively targeting angiotensins (including Mas and AT2 agonists, ACE2 recombinant, or Ang-(1-7) and almandine in oral formulations) have been tested in animal studies or in small human subgroups, expanding the perspective in the ACS prevention. These novel strategies, especially in the counter-regulatory axis ACE2/Ang-(1-7)/Mas, might be promising to reduce plaque vulnerability and inflammation.