The effects of two new antagonists of secretory PLA2 on TNF, iNOS, and COX-2 expression in activated macrophages

Phospholipase A2 (PLA2) regulates eicosanoid and platelet-activating factor production. It also plays an important role in the regulation of critical mediators in inflammatory diseases in which PLA2 activity is significantly enhanced during sepsis and multiple organ failure. Therefore, inhibitors of PLA2 activity offer themselves as target substances in the development of anti-inflammatory drugs. We identified 2 biflavonoids, bilobetin and ginkgetin, that can inhibit PLA2 activity. In experiments using 2-linol-[1-14C]PE as substrate both substances potently inhibited several kinds of type II 14-kDa PLA2 while inhibiting type I 14-kDa PLA2 to a lesser extent. We tested these PLA2 inhibitors for their ability to inhibit the production of tumor necrosis factor alpha (TNFalpha) and 2 enzymes, inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (COX-2) in an assay system using lipopolysaccharide (LPS)-stimulated Raw264.7 macrophages. In Raw264.7cells, bacterial LPS induced the production of COX-2 and iNOS proteins as well as TNFalpha. The inhibitors consistently inhibited the production of TNFalpha in a dose-dependent manner. Moreover, treatment of the macrophages with bilobetin and ginkgetin shut down the production of nitrite, one of the stable end products of NO released into the culture supernatant. The decrease in NO products was accompanied by a decrease in iNOS protein level as assessed by Western blot probed with specific anti-iNOS antibody. Both inhibitors also reduced the expression of COX-2 protein in the LPS-stimulated cells, which coincided with the reduction in iNOS protein. These results, therefore, suggest that these two sPLA2 inhibitors may be useful for inhibiting the production of inflammatory cytokine and NO production in inflammatory diseases.     

Health-related quality of life and mental health in older women with urinary incontinence

Objectives: The purpose of this cross-sectional study was to compare health-related quality of life (QOL) and mental health between older women with and without urinary incontinence.

Method: This study is a secondary data analysis using raw data from 1874 women aged 65 years or older who participated in the Korea National Health and Nutrition Examination Survey (KNHANES) IV (2008–2009), a nationally representative sample.

Results: In the pain/discomfort dimension of the EuroQol-5, 25.4% of the participants experienced urinary incontinence and 14.7% did not (p = .001). In the anxiety/depression dimension, urinary incontinence was present in 8.3% of the participants and absent in 3.6% (p = 0.012). In addition, the results of an ANCOVA showed that scores in both the EuroQol visual analogue scale and the EQ-5D index were significantly lower in participants with urinary incontinence relative to those without. The risk of stress and depression in older women with urinary incontinence was approximately 2 and 1.5 times higher, respectively, than that of participants without urinary incontinence.

Conclusion: Health-related QOL in older women with urinary incontinence was relatively low, while levels of stress and depression were high. Therefore, in order to improve QOL and mental health in older women, the understanding and management of urinary incontinence interventions is required.     

Association between RELN Gene Polymorphisms and Attention Deficit Hyperactivity Disorder in Korean Children

Objective

Attention deficit hyperactivity disorder (ADHD) is common disorder of the school-age population. ADHD is familial and genetic studies estimate heritability at 80–90%. The aim of the present study was to investigate the association between the genetic type and alleles for RELNgene (rs736707, rs2229864, rs362746, rs362726, rs362691, rs1062831, rs607755, and rs2072403) in Korean children with ADHD.

Methods

The sample consisted of 180 ADHD children and 159 control children. We diagnosed ADHD according to DSM-IV. ADHD symptoms were evaluated with Conners'' Parent Rating Scales and Dupaul Parent ADHD Rating Scales. Blood samples were taken from the 339 subjects, DNA was extracted from blood lymphocytes, and PCR was performed for RELN Polymorphism. Alleles and genotype frequencies were compared using the chi-square test. We compared the allele and genotype frequencies of RELN gene polymorphism in the ADHD and control groups.

Results

This study showed that there was a significant correlation among the frequencies of the rs736707 (OR=1.40, 95% CI=1.03–1.90, p=0.031) of alleles of RELN, but the final conclusions are not definite.

Conclusion

Follow up studies with larger patient or pure subgroups are expected. These results suggested that RELN might be related to ADHD symptoms.     

Brief Episodes of Newly Developed Intraoperative Atrial Fibrillation Predicts Worse Outcomes in Adult Liver Transplantation

Background

Although patients undergoing liver transplantation (LT) are frequently exposed to predisposing factors of atrial fibrillation (AF) such as autonomic imbalance, surgical stress, and elevated catecholamine levels, the occurrence of intraoperative AF (IOAF) has not been fully examined in LT candidates.

The blind pushing technique for peripherally inserted central catheter placement through brachial vein puncture

Objective

The objective of this study was to conduct a prospective clinical trial evaluating the technical feasibility and short-term clinical outcome of the blind pushing technique for placement of pretrimmed peripherally inserted central catheters (PICCs) through brachial vein access.

Backleak,tight junctions,and cell- cell adhesion in postischemic injury to the renal allograft.

Postischemic injury in recipients of 3-7-d-old renal allografts was classified into sustained (n = 19) or recovering (n = 20) acute renal failure (ARF) according to the prevailing inulin clearance. Recipients of optimally functioning, long-standing allografts and living donors undergoing nephrectomy served as functional (n = 14) and structural controls (n = 10), respectively. Marked elevation above control of fractional clearance of dextrans of graded size was consistent with transtubular backleak of 57% of filtrate (inulin) in sustained ARF. No backleak was detected in recovering ARF. To explore a structural basis for backleak, allograft biopsies were taken intraoperatively, 1 h after reperfusion in all recipients, and again on day 7 after transplant in a subset (n = 10). Electron microscopy revealed disruption of both apical and basolateral membranes of proximal tubule cells in both sustained and recovering ARF, but cell exfoliation and tubule basement membrane denudation were negligible. Histochemical analysis of membrane-associated adhesion complexes confirmed an abnormality of proximal but not distal tubule cells, marked in sustained ARF but not in recovering ARF. Staining for the zonula occludens complex (ZO-1) and adherens complex (alpha, beta, and gamma catenins) revealed diminished intensity and redistribution of each cytoskeletal protein from the apico-lateral membrane boundary. We conclude that impaired integrity of tight junctions and cell-cell adhesion in the proximal tubule provides a paracellular pathway through which filtrate leaks back in sustained allograft ARF.     

Baseline FGF23 is Associated with Cardiovascular Outcome in Incident PD Patients

♦ Background:

Fibroblast growth factor 23 (FGF23) is a phosphate regulating protein. Several studies demonstrated that elevated FGF23 is independently associated with mortality for early-stage chronic kidney disease and incident hemodialysis (HD) patients. However, little is known about the significance of elevated FGF23 in peritoneal dialysis (PD) patients. Here, we analyzed the association of FGF23 with cardiovascular (CV) events, all-cause mortality, residual renal function (RRF), and CV parameters in PD patients.

♦ Methods:

The present study is a single-center, retrospective study. Patients who started PD at Seoul National University Hospital between January 2005 and July 2011 and whose baseline serum samples were available were enrolled. C-terminal FGF23 was measured. Subjects were divided into 2 groups; lower 2 tertiles (FGF23 ≤ 119.0 RU/mL) and top tertile (FGF23 > 119.0 RU/mL). The primary outcome was time to fatal or non-fatal CV events. In the subgroup analysis, the associations of FGF23 with aortic stiffness or with vascular calcification were analyzed.

♦ Results:

A total of 205 incident PD patients were analyzed. Mean duration of follow-up was 41.6 ± 20.0 months. The baseline median FGF23 level was 78.6 RU/mL (inter-quartile range [IQR], 34.1 – 155.0). At baseline, subjects in the higher FGF23 group were younger, and had a lower RRF, lower prevalence of diabetes mellitus (DM), and cerebrovascular disease. During follow-up, 22 of the 205 patients (10.7%) reached primary outcome. After adjustment for age, DM, pre-existing coronary artery disease, cerebrovascular disease, congestive heart failure, and left ventricular mass index, the higher FGF23 group exhibited significantly higher risk of primary outcome, compared with the lower group (hazard ratio [HR], 2.54; 95% confidence interval [CI], 1.05 – 6.12; p = 0.045). There were no significant differences in all-cause mortality and development of anuria between the 2 FGF23 groups. In the subgroup analysis, FGF23 groups were not associated with pulse wave velocity and abdominal aortic calcification score.

♦ Conclusion:

Elevated FGF23 is associated with higher risk of adverse CV outcome for incident PD patients.