Myeloid-related protein 8/14 complex describes microcirculatory alterations in patients with type 2 diabetes and nephropathy

<p>Abstract</p> <p>Background</p> <p>Inflammation contributes to cardiovascular complications in type 2 diabetes, which are often characterized by microvascular alterations. We investigated whether myeloid-related protein 8/14 complex (MRP8/14) secreted by transmigrating monocytes and granulocytes may represent a biomarker for microvascular alterations in patients with type 2 diabetes and nephropathy.</p> <p>Methods</p> <p>MRP8/14 was measured in 43 patients with type 2 diabetes and nephropathy. Additionally, the inflammatory markers Interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) were quantified. To detect microvascular alterations proteinuria and retinal vessel caliber were used as classical and novel marker, respectively. Proteinuria was quantified by protein-creatinine ratio (PCR); retinal vessel caliber was quantified after retina photography on digitalized retina pictures.</p> <p>Results</p> <p>MRP8/14 was positively associated with inflammation (<it>r </it>= 0.57), proteinuria (<it>r </it>= 0.40) and retinal arterial caliber (<it>r </it>= 0.48). Type 2 diabetic patients with MRP8/14 values above the median of 5.8 μg/ml demonstrated higher proteinuria and larger retinal artery caliber than patients with MRP8/14 values below the median (logPCR: -0.51 ± 0.52 versus -0.96 ± 0.46, <it>P </it>< 0.01; retinal artery lumen (μm): 178.3 ± 14.1 versus 162.7 ± 14.9 <it>P </it>< 0.01). Both groups did not differ with regard to metabolic factors and blood pressure. MRP8/14 was an independent predictor of retinal artery caliber in multivariate stepwise regression analysis (<it>β </it>= 0.607) and was positively associated with IL-6 (<it>r </it>= 0.57, <it>P </it>< 0.001) and TNF-α (<it>r </it>= 0.36, <it>P </it>< 0.05).</p> <p>Conclusion</p> <p>MRP8/14 – a marker for transendothelial migration – describes not only the state of inflammation in diabetic nephropathy, but additionally the degree of microvascular alterations in the glomerular and retinal bed. Therefore, MRP8/14 may be a potentially selective novel biomarker for microcirculatory defects in diabetic nephropathy.</p

Elevated Levels of Lipopolysaccharide-Binding Protein and Soluble CD14 in Plasma in Neonatal Early-Onset Sepsis

No data on lipopolysaccharide-binding protein (LBP) in newborns with sepsis have been available up to now. We therefore determined levels of LBP and soluble CD14 (sCD14) in plasma of healthy and septic neonates in order to evaluate their potential diagnostic role. The study included prospectively collected patient samples of two recently published studies on cytokine expression in neonatal sepsis. Twenty-nine septic patients were enrolled in the present analysis. Samples—either cord blood or peripheral blood—from patients admitted within the first 24 h of life for suspicion of sepsis and cord blood samples of a control group of 40 healthy mature infants delivered spontaneously were analyzed. For seven patients of the septic group, a second sample collected between 24 and 48 h of life was available. Levels of sCD14 and LBP in plasma were determined by an enzyme immunoassay using recombinant CD14 and LBP as standards. LBP and sCD14 were correlated to cytokine plasma levels. In septic neonates, LBP (median, 36.6 versus 7.8 μg/ml; P < 0.001) and sCD14 (median, 0.42 versus 0.28 μg/ml; P < 0.001) levels were highly elevated when compared to those of healthy neonates and strongly correlated to granulocyte colony-stimulating factor (G-CSF), interleukin-1β (IL-1β), IL-6, and IL-8 levels. LBP levels in septic neonates analyzed between 24 and 48 h of life even increased when compared to samples obtained at or shortly after delivery (median, 36.6 versus 60 μg/ml; P = 0.038). In summary, levels of LBP in plasma of neonates with early-onset sepsis are significantly elevated; the elevated plasma levels seem to persist for more than 24 h, which could provide the clinician with a prolonged time period to identify the newborn with bacterial sepsis

Associations between Bone Mineral Density and Longitudinal Changes of Vertebral Bone Marrow and Paraspinal Muscle Composition Assessed Using MR-Based Proton Density Fat Fraction and T2* Maps in Patients with and without Osteoporosis

Background: Proton-density fat fraction (PDFF) and T2* of the vertebrae, as well as the cross-sectional area (CSA) of the paraspinal musculature (PSM), have been suggested as biomarkers for bone fragility. The aim of this study was to longitudinally assess changes in PDFF, T2* and CSA of the PSM over 6 months in patients with and without osteoporosis. Methods: Opportunistic bone mineral density (BMD) measurements (BMD &lt; 120 mg/cm3) were obtained from a CT acquired during the clinical routine work up in osteoporotic/osteopenic patients (n = 29, mean age 72.37 &plusmn; 10.12 years, 16 women). These patients were frequency-matched for age and sex to subjects with normal BMD values (n = 29). All study patients underwent 3T MR imaging at baseline and 6-month follow up, including spoiled gradient echo sequences for chemical shift encoding-based water-fat separation, from which T2* and PDFF values of the lumbar spine and the PSM were obtained. Moreover, the CSA of the PSM was assessed longitudinally. Changes in T2*, PDFF and CSA over 6 months were calculated for the vertebrae and PSM and associations with baseline BMD values were assessed. Results: The change in CSA of the PSM over 6 months was significantly lower in the osteoporotic/osteopenic group (&minus;91.5 &plusmn; 311.7 mm2), compared to the non-osteoporotic group, in which the CSA increased (29.9 &plusmn; 164.0 mm2, p = 0.03). In a further analysis, patients with higher vertebral PDFF at baseline showed a significantly stronger increase in vertebral T2*, compared to those patients with lower vertebral PDFF at baseline (0.9 &plusmn; 1.6 ms vs. 0.0 &plusmn; 1.8 ms, p = 0.04). Moreover, patients with higher PSM PDFF at baseline showed a significantly stronger increase in vertebral T2*, compared to those patients with lower PSM PDFF at baseline (0.9 &plusmn; 2.0 ms vs. 0.0 &plusmn; 1.3 ms, p = 0.03). Conclusion: The PSM CSA decreased significantly longitudinally in patients with osteoporosis/osteopenia, compared to those without. Additionally, higher vertebral and PSM PDFF at baseline were associated with stronger changes in vertebral bone marrow T2*. Therefore, longitudinal PDFF and T2* mapping may be useful quantitative radiation-free tools for the assessment and prediction of muscle and bone health in patients with suspected osteoporosis/osteopenia