The purpose of this clinical study is to comparatively investigate the interleukin-33 (IL-33) levels in gingival crevicular fluid (GCF), saliva and plasma of patients with periodontal disease as well as periodontally healthy subjects and the association between these levels and clinical parameters. GCF, saliva and plasma samples were collected from systemically healthy, non-smoker chronic periodontitis patients (CP group, n = 20), gingivitis patients (G group, n = 20) and periodontally healthy control groups (H group, n = 20). Full-mouth clinical periodontal parameters were also recorded. IL-33 levels were determined by ELISA. The total amount of GCF IL-33 was greater in the G and CP groups compared to the H group (p < 0.05). The GCF IL-33 concentration was significantly lower in the CP group than in the H and G groups (p < 0.001). Salivary or plasma IL-33 levels were similar in the study groups. The total amount of GCF IL-33 was positively correlated with the GI, PI and BOP (%) (p < 0.05). Considering the present findings, the increase in total amounts of GCF IL-33 may have a role in the pathogenesis of periodontal disease.

Background This study compared long-term outcomes of biological and mechanical mitral valve replacement (MVR) in patients requiring replacement of the mitral valve where repair was not feasible. Methods A single-centre registry of patients receiving MVR between 2005 and 2015 was established. Thirty-day mortality and long-term outcomes were analysed and compared. Results Three hundred twenty four patients underwent MVR (265 biological; 59 mechanical valves). Patients receiving biological valves were older ( p < 0.001), had a higher log EuroSCORE ( p < 0.001) and received less minimally invasive surgery ( p < 0.001). Immediate procedural mortality was 1.9%, which only occurred in the biological valve group. At 30 days, 9.0% of patients had died, 4.0% experienced stroke, 8.0% received a pacemaker and 10.5% suffered an acute renal failure. The rate of re-thoracotomy (14.2%) was lower in the biological (12.5%) than in the mechanical valve group (22.0%; adjOR 0.45 [0.20–1.00]; p = 0.050). Frequent long-term complications were stroke (9.2%) and bleeding (4.8%), with bleeding complications being higher in the mechanical valve group ( p = 0.009). During the follow-up period biological valves showed a numerically higher survival rate during the first years, which shifted after 3 years in favour of mechanical valves. At 10 years, survival rates were 62.4% vs. 77.1% in the biological and mechanical valve groups ( p = 0.769). Hazard ratio after adjustment was 0.833 (95% CI 0.430–1.615). Conclusion These data confirm that mechanical valve implantation is associated with an increased risk of bleeding. While there was a potential survival benefit during the first years after surgery for patients receiving a biological valves the difference became insignificant after a follow-up of 10 years. Electronic supplementary material The online version of this article (10.1186/s13019-019-0943-6) contains supplementary material, which is available to authorized users.

Background. Pediatric patients show an impressive capacity of cardiac regeneration. In contrast, severely deteriorated adult hearts do usually not recover. Since cardiac remodeling—involving the expression of fetal genes—is regarded as an adaptation to stress, we compared hearts of adult patients suffering from dilated cardiomyopathy (DCM) with remodeling of cultured neonatal (NRC) as well as adult (ARC) rat cardiomyocytes and the developing postnatal myocardium. Methods. NRC and ARC were stimulated with serum and cardiac morphogens derived from DCM hearts. Protein synthesis (PS) as well as protein accumulation (PA) was measured, and cell survival was determined under ischemic conditions. Fetal markers were investigated by Western blot. Biomarkers of remodeling were analyzed in controls, DCM, and 2- to 6-month-old children with tetralogy of Fallot as well as in neonatal and adult rats by immunofluorescence. Results. In NRC, serum and morphogens strongly stimulated PS and PA and the reestablishment of cell-cell contacts (CCC). In ARC, both stimulants increased PS and CCC, but PA was only elevated after serum stimulation. In contrast to serum, morphogen treatment resulted in the expression of fetal genes in ARC as determined by nonmuscle α-actinin-1 and α-actinin-4 expression (NM-actinins) and was associated with increased survival under ischemia. NM-actinins were present in cardiomyocytes of DCM in a cross-striated pattern reminiscent of sarcomeres as well as in extensions of the area of the intercalated disc (ID). NM-actinins are expressed in NRC and in the developing heart. Radixin staining revealed remodeling of the area of the ID in DCM almost identical to stimulated cultured ARC. Conclusions. Remodeling was similar in ARC and in cardiomyocytes of DCM suggesting evolutionary conserved mechanisms of regeneration. Despite activation of fetal genes, the atrophy of ARC indicates differences in their regenerative capacity from NRC. Cardiac-derived factors induced NM-actinin expression and increased survival of ischemic ARC while circulating molecules were less effective. Identification of these cardiac-derived factors and determination of their individual capacity to heal or damage are of particular importance for a biomarker-guided therapy in adult patients.

Fetal and hypertrophic remodeling are hallmarks of cardiac restructuring leading chronically to heart failure. Since the Ras/Raf/MEK/ERK cascade (MAPK) is involved in the development of heart failure, we hypothesized, first, that fetal remodeling is different from hypertrophy and, second, that remodeling of the MAPK occurs. To test our hypothesis, we analyzed models of cultured adult rat cardiomyocytes as well as investigated myocytes in the failing human myocardium by western blot and confocal microscopy. Fetal remodeling was induced through endothelial morphogens and monitored by the reexpression of Acta2, Actn1, and Actb. Serum-induced hypertrophy was determined by increased surface size and protein content of cardiomyocytes. Serum and morphogens caused reprogramming of Ras/Raf/MEK/ERK. In both models H-Ras, N-Ras, Rap2, B- and C-Raf, MEK1/2 as well as ERK1/2 increased while K-Ras was downregulated. Atrophy, MAPK-dependent ischemic resistance, loss of A-Raf, and reexpression of Rap1 and Erk3 highlighted fetal remodeling, while A-Raf accumulation marked hypertrophy. The knock-down of B-Raf by siRNA reduced MAPK activation and fetal reprogramming. In conclusion, we demonstrate that fetal and hypertrophic remodeling are independent processes and involve reprogramming of the MAPK.