Recombinant uteroglobin prevents the experimental crescentic glomerulonephritis

Recombinant uteroglobin prevents the experimental crescentic glomerulonephritis.BackgroundAlthough uteroglobin is known to have an immunomodulatory property and prevents the deposition of immune-complexes on the glomeruli of mice, the therapeutic potential of uteroglobin is uncertain in glomerulonephritis. To test the hypothesis that uteroglobin can prevent glomerulonephritis, we have studied the effects of recombinant uteroglobin on the development of experimental crescentic glomerulonephritis that is induced by anti-glomerular basement membrane (anti-GBM) antibodies.Methods and ResultsGlomerulonephritis was induced by the intravenous injection of rabbit anti-GBM globulin antibodies into mice (C57BL/6), and renal injury was evaluated 7, 14, and 21 days afterward. Recombinant uteroglobin or phosphate-buffered saline (PBS) were given intravenously to mice for 3 days after anti-GBM antibody injection. Proteinuria was significantly reduced in mice treated with recombinant uteroglobin compared with disease-control mice at 7 and 14 days after an anti-GBM antibody injection, although the serum creatinine concentration was similar in both groups. The amount of proteinuria was similar in recombinant uteroglobin-treated and normal control mice. By histologic analysis, mesangial matrix expansion, mesangial proliferation, and cellular crescents representing crescentic glomerulonephritis were markedly attenuated by injection of recombinant uteroglobin. The in vitro proliferative responses of mesangial cells to lipopolysaccharide (LPS) were blunted by the addition of recombinant uteroglobin in a dose-dependent manner. The preventive effects exerted by recombinant uteroglobin treatment were based on the inhibition of antibodies and complement-3 deposition on the glomeruli.ConclusionThis study demonstrates the preventive effects of recombinant uteroglobin in an experimental model of crescentic glomerulonephritis, and suggests the therapeutic implications of uteroglobin for human chronic glomerulonephritis

The Bilirubin Level is Negatively Correlated with the Incidence of Hypertension in Normotensive Korean Population

Reactive oxygen species have been known to be an important factor in the pathogenesis of hypertension. Bilirubin, one of the metabolites of heme degraded by heme oxygenase, is a potent anti-oxidant. We verified the effect of serum bilirubin level on the incidence of hypertension in normotensive subjects. We grouped 1,208 normotensive subjects by the criterion of the highest quintile value of serum bilirubin, 1.1 mg/dL. The incidence of hypertension was higher in group 1 with bilirubin less than 1.1 mg/dL than in group 2 with bilirubin 1.1 mg/dL or more (186/908 vs. 43/300, p=0.018). The relative risk for hypertension was 0.71 (95% confidence interval, 0.51-0.99), p=0.048 in group 2 compared to group 1 by Cox's proportional hazard model. Among the groups stratified by gender, smoking, and liver function status, the group 2 showed a lower risk of hypertension in females and in non-smokers. In conclusion, a mild increase within the physiological range of serum bilirubin concentration was negatively correlated with the incidence of hypertension. The effect of bilirubin on the development of hypertension was more evident in females and in non-smokers

Duration of acute kidney injury and mortality in critically ill patients: a retrospective observational study

Background : The addition of relevant parameters to acute kidney injury (AKI) criteria might allow better prediction of patient mortality than AKI criteria alone. Here, we evaluated whether inclusion of AKI duration could address this issue. Methods : AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines in 2,143 critically ill patients, within 15 days of patient admission. AKI cases were categorized according to tertiles of AKI duration: 1st tertile, 1–2 days; 2nd tertile, 3–5 days; and 3rd tertile, ≥6 days. The hazard ratios (HRs) for overall survival rates in three groups were calculated after adjustment for multiple covariates compared with ICU patients without AKI as the reference group. The predictive ability for mortality was assessed by calculating the area under the curve (AUC) of the receiver operating characteristic curve. Results : AKI increased the HRs for overall mortality, and the mortality rate increased with AKI duration: the adjusted HRs were 1.99 (1st tertile), 2.67 (2nd tertile), and 2.85 (3rd tertile) compared with the non-AKI group (all Ps < 0.001). The AUC of the ROC curve for overall mortality based on the AKI duration groups (0.716) was higher than the AUC of AKI staging using the KDIGO guidelines (0.696) (P = 0.001). When considering KDIGO stage and AKI duration together, the AUC (0.717) was also significantly higher than that using the KDIGO stage alone (P < 0.001). Conclusions : AKI duration is an additional parameter for the prediction of mortality in critically ill patients. The inclusion of AKI duration could be considered as a refinement of the AKI criteria.This work was supported by a grant from the Seoul National University Bundang Hospital Research Fund (No. 03-2012-020).Peer Reviewe

Induction chemotherapy in head and neck squamous cell carcinoma of the paranasal sinus and nasal cavity: A role in organ preservation

Background/Aims: The role of induction chemotherapy (IC) for eyeball preservation has not been established in head and neck squamous cell carcinoma (HNSCC) of the paranasal sinus and nasal cavity (PNSNC). Periorbital involvement frequently leads to eyeball exenteration with a margin of safety. We evaluated the treatment outcomes, including survival and eyeball preservation, of patients who received IC for HNSCC of the PNSNC. Methods: We reviewed 21 patients diagnosed with HNSCC of the PNSNC who were treated with IC. We analyzed response, eyeball preservation rate, and overall survival. Results: Tumors were located in the paranasal sinus (n = 14) or nasal cavity (n = 7). Most patients had stage T4a (n = 10) or T4b (n = 7) disease. More than half of the patients received a chemotherapy regimen of docetaxel, fluorouracil, and cisplatin (n = 11). Thirteen patients (61.9%) achieved a partial response after IC and 15 patients (71.4%) achieved T down-staging. Among 17 patients with stage T4 disease, which confers a high risk of orbital exenteration, 14 (82.4%) achieved preservation of the involved eye. The 3-year overall survival (OS) rate of patients who achieved a partial response to IC was 84.6%. The 3-year OS rate of patients with stable disease or disease progression after IC was 25.0% (p = 0.038). Conclusions: IC could be considered for down-staging patients with advanced T-stage disease. It could also be a reasonable option for eyeball preservation in locally advanced HNSCC of the PNSNC.

Preparation and In Vitro

Magnesium ion substituted biphasic calcium phosphate (Mg-BCP) bioceramic microscaffolds with spherical and porous morphology were successfully prepared using in situ coprecipitation and rotary spray drying atomization process for application of tissue engineering combined with human adipose tissue-derived mesenchymal stem cells (hAT-MSCs). After 4 weeks of immersion in Hanks’ balanced salt solution (HBSS), Mg-BCP micro-scaffolds showed the enhanced biodegradation and bioactivity due to the substituted Mg2+ ion present in the BCP structure. In this study, it was observed that hAT-MSCs have clearly attached on the surface of Mg-BCP micro-scaffolds. In addition, Mg-BCP micro-scaffolds exhibited the improved biocompatibility and osteoconductivity via in vitro and in vivo biological tests with hAT-MSCs. Therefore, these bioceramic micro-scaffolds had potential to be used as hAT-MSCs microcarriers for biomedical applications

Proteinuria and hematuria are associated with acute kidney injury and mortality in critically ill patients: a retrospective observational study

Background: Proteinuria and hematuria are both important health issues; however, the nature of the association between these findings and acute kidney injury (AKI) or mortality remains unresolved in critically ill patients. Methods: Proteinuria and hematuria were measured by a dipstick test and scored using a scale ranging from a negative result to 3+ in 1883 patients admitted to the intensive care unit. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. The odds ratios (ORs) for AKI and 3-year mortality were calculated after adjustment for multiple covariates according to the degree of proteinuria or hematuria. For evaluating the synergistic effect on mortality among proteinuria, hematuria, and AKI, the relative excess risk due to interaction (RERI) was used. Results: Proteinuria and hematuria increased the ORs for AKI: the ORs of proteinuria were 1.66 (+/−), 1.86 (1+), 2.18 (2+), and 4.74 (3+) compared with non-proteinuria; the ORs of hematuria were 1.31 (+/−), 1.58 (1+), 2.63 (2+), and 2.52 (3+) compared with non-hematuria. The correlations between the mortality risk and proteinuria or hematuria were all significant and graded (Ptrend < 0.001). There was a relative excess risk of mortality when both AKI and proteinuria or hematuria were considered together: the synergy indexes were 1.30 and 1.23 for proteinuria and hematuria, respectively. Conclusions: Proteinuria and hematuria are associated with the risks of AKI and mortality in critically ill patients. Additionally, these findings had a synergistic effect with AKI on mortality.Peer Reviewe