Natural history of markers of collagen turnover in patients with early diastolic dysfunction and impact of eplerenone

<p>OBJECTIVES: This study was designed to evaluate the impact of eplerenone on collagen turnover in preserved systolic function heart failure (HFPSF).</p><p>BACKGROUND: Despite growing interest in abnormal collagen metabolism as a feature of HFPSF with diastolic dysfunction, the natural history of markers of collagen turnover and the impact of selective aldosterone antagonism on this natural history remains unknown.</p><p>METHODS: We evaluated 44 patients with HFPSF, randomly assigned to control (n = 20) or eplerenone 25 mg daily (n = 24) for 6 months, increased to 50 mg daily from 6 to 12 months. Serum markers of collagen turnover and inflammation were analyzed at baseline and at 6 and 12 months and included pro-collagen type-I and -III aminoterminal peptides, matrix metalloproteinase type-2, interleukin-6 and -8, and tumor necrosis factor-alpha. Doppler-echocardiographic assessment of diastolic filling indexes and tissue Doppler analyses were also obtained.</p><p>RESULTS: The mean age of the patients was 80 +/- 7.8 years; 46% were male; 64% were receiving an angiotensin-converting enzyme inhibitor, 34% an angiotensin-II receptor blocker, and 68% were receiving beta-blocker therapy. Pro-collagen type-III and -I aminoterminal peptides, matrix metalloproteinase type-2, interleukin-6 and -8, and tumor necrosis factor-alpha increased with time in the control group. Eplerenone treatment had no significant impact on any biomarker at 6 months but attenuated the increase in pro-collagen type-III aminoterminal peptide at 12 months (p = 0.006). Eplerenone therapy was associated with modest effects on diastolic function without any impact on clinical variables or brain natriuretic peptide.</p><p>CONCLUSIONS: This study demonstrates progressive increases in markers of collagen turnover and inflammation in HFPSF with diastolic dysfunction. Despite high background utilization of renin-angiotensin-aldosterone modulators, eplerenone therapy prevents a progressive increase in pro-collagen type-III aminoterminal peptide and may have a role in management of this disease. (The Effect of Eplerenone and Atorvastatin on Markers of Collagen Turnover in Diastolic Heart Failure; NCT00505336).</p>

���It is through others that we become ourselves.��� A study of Vygotskian play in Russian and Irish schools.

50 years after publishing his seminal work on play and its role in child development, Vygotskian theory is still highly influential in education, and particularly in early years. This paper presents two examples of full integration of Vygotskian principles into schools in two very different settings. Both report improvements in learning and in well-being, and exemplify the theory-practice-theory cycle, highlighting the development of new theoretical constructs arising out of putting theory firmly into practice. In both settings, the positive results have come from years of effort, in which school personnel who may have been skeptical at first, have been inspired by the impact of adopting Vygotskian play on the children they teach. The Northern Ireland study shows that at least some of the Golden Key principles (mixed-age play and enhanced home-school links) translate perfectly into very different cultural-historical contexts.