Clinical implication of plasma and urine YKL-40, as a proinflammatory biomarker, on early stage of nephropathy in type 2 diabetic patients

ObjectiveChronic inflammation has emerged as being a key pathophysiology in the early stages of diabetic nephropathy. YKL-40 has been established as an inflammatory marker in chronic inflammation. The aim of this study was to evaluate the association of plasma and urine YKL-40 with albuminuria in the early stage of type 2 diabetic nephropathy.Design and methodsA total of 75 type 2 diabetic patients and 22 nondiabetic controls with estimated glomerular filtration (eGFR) ≥ 60 ml/min/1.73 m² were enrolled. Plasma and urine concentrations of YKL-40 were analyzed by ELISA kit.ResultsThe plasma levels of YKL-40 were significantly higher in the normoalbuminuric group with diabetes than in the control group, and increased with increasing severity of albuminuria among diabetes. However, urine YKL-40 was only increased in macroalbuminuric state. Plasma YKL-40 was positively correlated with urine YKL-40 (r = 0.291, P = 0.011). Urinary albumin significantly correlated with both plasma and urine YKL-40 in a univariate analysis. After adjusting for several confounding factors, plasma YKL-40 was significantly correlated with albuminuria (r = 0.359; P = 0.001), whereas urine YKL-40 did not show significant correlation with albuminuria (r = 0.128, P = 0.241).ConclusionsAlthough urine YKL-40 has a limited role, plasma YKL-40, as an proinflammatory marker, was an independent factor associated with albuminuria in early stage of nephropathy in type 2 diabetes and might have an useful role as a noninvasive marker for the early diabetic nephropathy detection.     

Efficient gene delivery by urocanic acid-modified chitosan.

Nonviral delivery systems for gene therapy have been increasingly proposed as safer alternatives to viral vectors. Chitosan is considered to be a good candidate for the gene delivery system since it is already known as a biocompatible, biodegradable, and low toxic material with high cationic charge potential. However, the use of chitosan for gene delivery is limited due to low transfection efficiency. To enhance the transfection efficiency, water-soluble chitosan (WSC) was coupled with urocanic acid (UA) bearing imidazole ring which can play the crucial role in endosomal rupture through proton sponge mechanism. The urocanic acid-modified chitosan (UAC) was complexed with DNA, and UAC/DNA complexes were characterized. The sizes of UAC/DNA complexes under physiological condition (109-342 nm) were almost same as those of chitosan-DNA complexes. UAC also showed good DNA binding ability, high protection of DNA from nuclease attack, and low cytotoxicity. The transfection efficiency of chitosan into 293T cells was much enhanced after coupling with UA and increased with an increase of UA contents in the UAC.     

Studies on autoimmunity for initiation of beta-cell destruction. VII. Evidence for antigenic changes on beta-cells leading to autoimmune destruction of beta-cells in BB rats.

The diabetic syndrome in BioBreeding (BB) rats is believed to result from the destruction of beta-cells by autoimmune responses. However, the initial events that cause the autoimmune destruction of beta-cells remain largely unknown. This investigation was initiated to see whether there are any antigenic changes on the beta-cells from neonatal to adult BB rats that may lead to the autoimmune destruction of beta-cells. Pancreatic grafts from neonatal BB rats remained largely intact without insulitis when transplanted into the renal subcapsular space of acutely diabetic BB rats. Similarly transplanted islet grafts from neonatal BB rats were also not subject to autoimmune destruction. In contrast, islet grafts obtained from adult BB rats, which had been treated with silica to prevent insulitis, were rapidly destroyed in diabetic recipients. These results indicate that beta-cells from neonatal BB rats are different from beta-cells from adult BB rats, at least regarding their recognition by immunologic effectors. Considering our observations and previous information on the initial role of macrophages/dendritic cells in the development of insulitis in BB rats, we suggest that beta-cell-specific antigenic changes that precede insulitis may result in the autoimmune destruction of beta-cells in BB rats.     

ADENOSINE DEAMINASE IN HUMAN SKIN

Adenosine deaminase (adenosine aminohydrolase, ADA), which catalyzes the deamination of adenosine to yield inosine and ammonia, was assayed in human penile foreskin. The skin tissue was separated into two layers; epidermis and dermis. ADA was found to be present in both layers (epidermis, 0.24 ΔoD/mg protein; dermis, 0.19 ΔOD/mg protein) with slightly higher activity in the epidermis. As in earlier reports, it was found that ADA in the skin showed nearly even activity throughout the pH range of 5.0–8.0. Considering the significance of ADA in immunological function, the presence of ADA in the skin suggests that the tissue may participate in the immune function.     

The bacterial colonization in tunneled cuffed dialysis catheter and its effects on residual renal function in incident hemodialysis patients

Background

The bacterial colonization of hemodialysis catheter occurs frequently and reaches to the catheter-related bloodstream infections (CRBSIs). We hypothesized bacterial colonization promotes inflammation and that might be associated with renal outcome. The aim of this study was to investigate the colonization status for tunneled cuffed dialysis catheter (TCC) and the factors for contributing to the catheter colonization and explore whether bacterial colonization would be related with declining of residual renal function (RRF).

Methods

115 patients who received TCC removal operation and underwent catheter tip culture from January 2005 to June 2014 were enrolled. The follow-up data such as urine output (UO), time to anuria and patients’ survival were collected from the patients or their family members by telephone in June, 2014.

Results

There were nineteen patients (16.5 %, 19/115) with positive tip culture (colonization group). In the analysis of demographic and biochemical parameters, there were no significant differences between both groups. Fifty of all the subjects responded to the telephone survey and ten patients (20.0 %, 10/50) belonged to colonization group. The monthly decreasing rate of UO was significantly more rapid in colonization group (p = 0.001). The survival analysis showed that colonization group had worse estimated anuria-free survival than non-colonization group (p < 0.001). In multivariate cox regression, bacterial colonization of TCC was an independent factor influencing the loss of RRF (HR 4.29, 95 % CI: 1.905–9.683, p ≤ 0.001).

Conclusions

Bacterial colonization of TCC was associated with rapid loss of RRF.

     

Up-regulation of p21-activated kinase 1 by in vitro treatment with interleukin 1-beta and its increased expression in ovarian endometriotic cysts

We evaluated whether the proinflammatory cytokines can regulate p21-activated kinase (Pak1) expression in endometrial cells as well as whether its expression is increased in endometriotic cysts. We found that interleukin-1β up-regulates Pak1 expression in endometrial stromal cells (ESC) and that the immunoreactivity of Pak1 is increased in the endometriotic cysts.     

Bowenoid epidermotropic metastatic squamous cell carcinoma

Epidermotropic metastatic squamous cell carcinoma produced full-thickness cellular atypia of bowenoid carcinoma in situ or vulvar intraepithelial neoplasia, grade 3 (VIN 3), in a 73-year-old woman who had past history of uterine cervical carcinoma. The presence of intravascular tumor cell nests and areas showing smooth continuity of the malignant squamous cell nodules with the adjoining benign epidermis supported the possibility of the epidermotropic metastasis. To our knowledge, metastatic epidermotropic squamous carcinoma clinicopathologically simulating primary Bowen's disease has not been reported.     

Effect of dialysis on cerebral blood flow in depressive end-stage renal disease patients

Objective

The aim of this study was to investigate regional cerebral blood flow (rCBF) changes of end-stage renal disease (ESRD) patients with depressive symptoms during dialysis.

Methods

Fourteen patients with ESRD underwent Tc-99m ethylcysteinate dimer (Tc-99m ECD) brain single photon emission computed tomography (SPECT) and were evaluated the severity of depressive mood at pre-dialytic period and at least 6 months after dialysis initiation. rCBF was analyzed using statistical parametric mapping (SPM) in brain SPECT image. The responder was defined as a decrease of ≥25% in Hamilton Depression Rating Scale (HDRS) score from baseline HDRS score.

Results

Pre-dialysis brain SPECT did not show any rCBF differences between responders and non-responders. The follow-up brain SPECT revealed a significant higher perfusion in left middle temporal gyrus of responder group when compared with non-responder (hemisphere coordinate X, Y, Z; ?58, ?2, ?16, peak Z = 3.36, p = 0.046). In responder, a significant increase in rCBF was found in right parahippocampal gyrus (hemisphere coordinate X, Y, Z; 30, ?40, ?14, peak Z = 3.51, p = 0.043). In non-responder, there were significant decreases in rCBF in left superior frontal gyrus (hemisphere coordinate X, Y, Z; ?22, 30, 42, peak Z = 3.86, p = 0.032) and right orbitofrontal cortex (hemisphere coordinate X, Y, Z; 10, 58, ?6, peak Z = 3.81, p = 0.046).

Conclusion

The present findings showed the characteristic patterns of rCBF changes in depressive ESRD patients having maintenance dialysis. Further investigations in brain blood flow and glucose metabolism are needed to elucidate the effect of dialysis itself and the difference of according to dialysis modality in patients having depression and ESRD.