Plasma myeloperoxidase-conjugated DNA level predicts outcomes and organ dysfunction in patients with septic shock

Abstract Background Recent studies have suggested that excessive formation of neutrophil extracellular traps (NETs) plays a critical role in the pathogenesis of sepsis. Although elevation of the plasma level of cell-free DNA (cf-DNA) has been reported in sepsis patients, there has been little direct measurement of circulating free NETs such as myeloperoxidase-conjugated DNA (MPO-DNA). The objectives of this study were to detect NETs in the bloodstream of patients with septic shock, and to assess the correlations of circulating NET levels with organ dysfunction, disease severity, and mortality. Methods Fifty-five patients with septic shock admitted to the intensive care units (ICUs) of 35 Japanese hospitals were studied. Septic shock was diagnosed according to the 1997 definition of the American College of Chest Physicians/Society of Critical Care Medicine. To detect circulating NETs, plasma levels of MPO-DNA and cf-DNA were measured by sandwich enzyme-linked immunosorbent assay and by fluorometric assay on days 1, 3, and 7 after the onset of septic shock. Physiological and mortality data were collected from the clinical database. Results On days 1, 3, and 7, the patients showed a marked increase in plasma MPO-DNA levels compared with healthy volunteers, whereas the plasma cf-DNA level was only increased significantly on day 1 and then decreased rapidly. A high MPO-DNA level on days 3 and 7 were associated with 28-day mortality. On days 3 and 7, the MPO-DNA levels were inversely correlated with both the mean arterial pressure and the PaO2/FIO2 ratio, whereas the cf-DNA level was not correlated with either parameter. There was a positive correlation between the plasma MPO-DNA level and the sepsis-related organ failure assessment score on days 3 and 7. Neither cf-DNA nor MPO-DNA levels were correlated with the disseminated intravascular coagulation (DIC) score or the platelet count. Conclusion The increase in circulating MPO-DNA in patients with septic shock indicates acceleration of NET formation in the early stages of sepsis. High MPO-DNA levels are associated with the severity of organ dysfunction and 28-day mortality due to septic shock, but not with the DIC score. These results suggest that excessive NET formation contributes to the pathogenesis of septic shock

Additional file 3: of Plasma myeloperoxidase-conjugated DNA level predicts outcomes and organ dysfunction in patients with septic shock

Figure S3. Correlations of MPO-DNA and cf-DNA levels with the platelet count and the DIC score. Correlations of MPO-DNA and cf-DNA levels with the platelet count (A) and the DIC score (B) on day 3 after the diagnosis of septic shock. (PPTX 76 kb

Additional file 2: of Plasma myeloperoxidase-conjugated DNA level predicts outcomes and organ dysfunction in patients with septic shock

Figure S2. Correlations of MPO-DNA and cf-DNA levels with organ failure parameters. Correlations of MPO-DNA and cf-DNA levels with the MAP (A), the P/F ratio (B), and the SOFA score (C) on day 1 after the diagnosis of septic shock. (PPTX 114 kb

Additional file 1: of Plasma myeloperoxidase-conjugated DNA level predicts outcomes and organ dysfunction in patients with septic shock

Figure S1. Determination of linearity of the MPO-DNA assay. The linear range of optical density (OD) in the MPO-DNA assay was determined with various sample volumes: A) 0, 6.25, 12.5, 25, 50, 75, and 100 μl; B) 0, 6.25, 12.5, 25, and 50 μl (n = 4 for each sample volume). (PPTX 64 kb

A double patella-like condition secondary to synovial osteochondromatosis

<p>Abstract</p> <p>To our knowledge, this is the first case of synovial osteochondromatosis in a patient presenting with a double patella-like condition. The true duplication of the patella, which is called double patella, is extremely rare. In our case, the operative and histopathological findings showed that the double patella-like condition was secondarily induced by synovial osteochondromatosis. Synovial osteochondromatosis should be considered as a differential diagnosis for congenital double patella.</p

Junctophilin-mediated channel crosstalk essential for cerebellar synaptic plasticity

Functional crosstalk between cell-surface and intracellular ion channels plays important roles in excitable cells and is structurally supported by junctophilins (JPs) in muscle cells. Here, we report a novel form of channel crosstalk in cerebellar Purkinje cells (PCs). The generation of slow afterhyperpolarization (sAHP) following complex spikes in PCs required ryanodine receptor (RyR)-mediated Ca(2+)-induced Ca(2+) release and the subsequent opening of small-conductance Ca(2+)-activated K(+) (SK) channels in somatodendritic regions. Despite the normal expression levels of these channels, sAHP was abolished in PCs from mutant mice lacking neural JP subtypes (JP-DKO), and this defect was restored by exogenously expressing JPs or enhancing SK channel activation. The stimulation paradigm for inducing long-term depression (LTD) at parallel fiber–PC synapses adversely established long-term potentiation in the JP-DKO cerebellum, primarily due to the sAHP deficiency. Furthermore, JP-DKO mice exhibited impairments of motor coordination and learning, although normal cerebellar histology was retained. Therefore, JPs support the Ca(2+)-mediated communication between voltage-gated Ca(2+) channels, RyRs and SK channels, which modulates the excitability of PCs and is fundamental to cerebellar LTD and motor functions