[Show abstract][Hide abstract] ABSTRACT: Beta-blockers such as propranolol and labetalol is known to induce toxic myopathy because of their partial beta-2 adrenoceptor agonistic effect. Nebivolol has the highest beta-1 receptor affinity among beta-blockers and it has never been reported to induce rhabdomyolysis until now. We report a patient who developed rhabdomyolysis after changing medication to nebivolol. A 75-year old woman was admitted to our hospital because of generalized weakness originating 2 weeks before visiting. Approximately 1 month prior to her admission, her medication was changed from carvedilol 12.5 mg to nebivolol 5 mg. Over this time span she had no other life style changes causing rhabdomyolysis. Her blood chemistry and whole body bone scan indicated rhabdomyolysis. We considered newly prescribed nebivolol as a causal agent. She was prescribed carvedilol 12.5mg, which she was previous taken, instead of nebivolol. She was treated with hydration and urine alkalization. She was fully recovered and discharged.
[Show abstract][Hide abstract] ABSTRACT: Recently, a new glomerular filtration rate (GFR) equation for the Japanese population was proposed using measured inulin clearance. To expand its applicability to other Asian populations, we performed a comparative study in the Korean population. Inulin clearance was measured in 166 patients from seven participating medical centers in Korea. Patient's sera and urine were collected, and baseline clinical characteristics were measured to provide an estimated GFR (eGFR) by the Japanese GFR equation using inulin clearance (Japanese-GFR equation), the Modification of Diet in Renal Disease (MDRD) study equation, and the Chronic Kidney Disease - Epidemiology Collaboration (CKD-EPI) equation. We compared the results to determine which equation best estimated the measured GFR (mGFR). Accuracy (95% CI) within 30% of mGFR by the Japanese-GFR equation, the CKD-EPI equation and the MDRD study equation were 66 (58 - 72), 51 (43 - 58), and 55 (47 - 62)%, respectively. Bias (mGFR minus eGFR) were 3.4 ± 22.4, -12.0 ± 22.1, and -9.7 ± 23.8 mL/min/1.73 m2, respectively. The accuracy of the Japanese-GFR equation was significantly better than MDRD study equation in subjects with mGFR < 60 mL/min/1.73 m2 and in total subjects. The bias of the Japanese-GFR equation was significantly smaller compared with other two equations in total subjects. The Japanese-GFR equation has a higher accuracy with less bias than the other equations in estimating GFR in Korean populations. Further studies are required to determine if the current Japanese-GFR equation could represent the standard eGFR for other Asian populations.
No preview · Article · Nov 2015 · Clinical nephrology
[Show abstract][Hide abstract] ABSTRACT: Background:
Bioimpedance analysis (BIA) helps measuring the constituents of the body noninvasively. Prior studies suggest that BIA-guided fluid assessment helps to predict survival in dialysis patients. We aimed to evaluate the clinical usefulness of BIA for predicting the survival rate of hemodialysis patients in Korea.
We conducted a single-center retrospective study. All patients were diagnosed with end-stage renal disorder and started maintenance hemodialysis between June 2009 and April 2014. BIA was performed within the 1(st) week from the start of hemodialysis. The patients were classified into 2 groups based on volume status measured by the body composition monitor (BCM; Fresenius): an overhydrated group [OG; overhydration/extracellular water (OH/ECW) >15%] and a nonoverhydrated group (NOG; OH/ECW ≤15%).
A total of 344 patients met the inclusion criteria. Of these, 252 patients (73.3%) were categorized into the OG and 92 patients (26.7%) into the NOG. Age- and sex-matching patients were selected with a rate of 2:1. Finally, 160 overhydrated patients and 80 nonoverhydrated patients were analyzed. Initial levels of hemoglobin and serum albumin were significantly lower in the OG. During follow-up, 43 patients from the OG and 7 patients from the NOG died (median follow-up duration, 24.0 months). The multivariate-adjusted all-cause mortality was significantly increased in the OG (odds ratio, 2.569; P = 0.033) and older patients (odds ratio, 1.072/y; P < 0.001). No significant difference of all-cause or disease-specific admission rate was observed between the 2 groups.
The ratio of OH/ECW volume measured with body composition monitor is related to the overall survival of end-stage renal disorder patients who started maintenance hemodialysis.
[Show abstract][Hide abstract] ABSTRACT: Idiopathic membranous glomerulonephritis (IMGN) is commonly diagnosed in adults with proteinuria. Rapid deterioration of renal function is a rare complication of IMGN, except when accompanied by renal vein thrombosis, malignant hypertension, or other underlying disease, including lupus nephritis. Here, we present a case of rapid deterioration of renal function in a patient with MGN superimposed with anti-neutrophil cytoplasmic antibody (ANCA)-associated rapidly progressive crescentic glomerulonephritis (RPGN). Overall, about 20 cases of MGN with ANCA-associated RPGN have been reported. This case of biopsy-proven MGN with ANCA-associated RPGN is the first to be reported in Korea.
[Show abstract][Hide abstract] ABSTRACT: Fibrinolytic enzyme genes (aprE2, aprE176, and aprE179) were introduced into the Bacillus subtilis 168 chromosome without any antibiotic resistance gene. An integration vector, pDG1662, was used to deliver the genes into the amyE site of B. subtilis 168. Integrants, SJ3-5nc, SJ176nc, and SJ179nc, were obtained after two successive homologous recombinations. The integration of each fibrinolytic gene into the middle of amyE site was confirmed by phenotypes (Amy(-), Spec(S)) and colony PCR results for these strains. The fibrinolytic activities of integrants were higher than that of B. subtilis 168 by at least 3.2 fold when grown in LB broth. Cheonggukjang was prepared by inoculating each strain of B. subtilis 168, SJ3-5nc, SJ176nc, and SJ179nc, and the fibrinolytic activity of Cheonggukjang was 4.6±0.7, 10.8±0.9, 7.0±0.6, and 8.0±0.2 (U/g of Cheonggukjang), respectively at 72 h. These results showed that construction of B. subtilis strains with enhanced fibrinolytic activities is possible by integration of a strong fibrinolytic gene via marker-free manner.
No preview · Article · Jul 2015 · Journal of Microbiology and Biotechnology
[Show abstract][Hide abstract] ABSTRACT: In hemodialysis patients, vascular access infection remains a significant cause of morbidity and mortality. It has various complications, including bacterial endocarditis, spinal epidural abscess, osteomyelitis, septic arthritis, and septic pulmonary emboli. However, aortitis with infected pseudoaneurysm formation is very rare. Here, we report a case of necrotizing aortitis in a hemodialysis patient with an arteriovenous graft infection.
No preview · Article · Jun 2015 · Clinical nephrology
[Show abstract][Hide abstract] ABSTRACT: A gamma-aminobutyric acid (GABA) producing microorganism was isolated from jeot-gal (anchovy), a Korean fermented seafood. The isolate, A156, produced GABA profusely when incubated in MRS broth with monosodium glutamate (MSG, 3%, w/v) at 37degrees C for 48 h. A156 was identified as Lactobacillus sakei by 16S rRNA gene sequencing. GABA conversion yield was 86% as determined by GABase enzyme assay. gadB gene encoding glutamate decarboxylase (GAD) was cloned by PCR. gadC encoding a glutamate/GABA antiporter is present in the 5' of gadB, forming an operon structure of gadCB. gadB was overexpressed in Escherichia coli BL21(DE3) and GAD was purified. Purified GAD was 54.4 kDa in size by SDS-PAGE. Maximum GAD activity was observed at pH 5.0 and 55°C and the activity was dependent on pyridoxal 5'-phosphate (PLP). Km and Vmax of GAD were 0.045 mM and 0.011 mM/min, respectively, when glutamate was used as the substrate.
No preview · Article · Mar 2015 · Journal of Microbiology and Biotechnology
[Show abstract][Hide abstract] ABSTRACT: Bacillus subtilis HK176 with high fibrinolytic activity was isolated from cheonggukjang, a Korean fermented soyfood. A gene, aprE176, encoding the major fibrinolytic enzyme was cloned from B. subtilis HK176 and overexpressed in E. coli BL21(DE3) using plasmid pET26b(+). The specific activity of purified AprE176 was 216.8 +/- 5.4 plasmin unit/mg protein and the optimum pH and temperature were pH 8.0 and 40 degrees C, respectively. Error-prone PCR was performed for aprE176, and the PCR products were introduced into E. coli BL21(DE3) after ligation with pET26b(+). Mutants showing enhanced fibrinolytic activities were screened first using skim-milk plates and then fibrin plates. Among the mutants, M179 showed the highest activity on a fibrin plate and it had one amino acid substitution (A176T). The specific activity of M179 was 2.2-fold higher than that of the wild-type enzyme, but the catalytic efficiency (k(cat)/K-m) of M179 was not different from the wild-type enzyme owing to reduced substrate affinity. Interestingly, M179 showed increased thermostability. M179 retained 36% of activity after 5 h at 45 degrees C, whereas AprE176 retained only 11%. Molecular modeling analysis suggested that the 176th residue of M179, threonine, was located near the cation-binding site compared with the wild type. This probably caused tight binding of M179 with Ca2+, which increased the thermostability of M179.
Preview · Article · Jan 2015 · Journal of Microbiology and Biotechnology
[Show abstract][Hide abstract] ABSTRACT: Three Pediococcus pentosaceus strains were isolated from jeotgals, salted and fermented Korean sea-foods, and their probiotic potentials were examined. After 2 h exposure to pH 3.0, P. pentosaceus F66 survived with the survival ratio of 32.6% followed by P. pentosaceus D56 (17.2%) and P. pentosaceus A24 (7.5%). P. pentosaceus F66 also survived better (26.6%) than P. pentosaceus A24 (13.7%) and P. pentosaceus D56 (5.8%) after 2 h exposure to 0.3% bile salts. Three strains grew slowly on MRS broth with 15% NaCl (w/v), reaching the OD600 values of 0.4-0.8 in 36 h. They adhered to Caco-2 cells (10.9 - 13.9 CFU/cell) with similar degree of adherence of a positive control, Lb. rhamnosus GG (12.8 ± 0.5 CFU/cell). Three strains possess some desirable enzyme activities such as β-galactosidase, α-glucosidase, β-glucosidase, and N-acetyl-β-glucosidase. From these results, P. pentosaceus F66 seems qualified as a probiotic and can be utilized for fermented foods including jeotgals.
[Show abstract][Hide abstract] ABSTRACT: Introduction and Aims: Acute interstitial nephritis (AIN) is a common cause of acute kidney injury (AKI). In severe cases, AIN may progress to chronic
kidney disease or end-stage renal disease. We previously reported that WNT10A is a novel angio/stromagenic factor in wound
healing and organ fibrosis. In this study, we investigated the role of WNT10A in fibrotic progression of AIN.
Methods: Kidney biopsy specimens from 25 AKI patients (all men, ≥60 years) treated in our hospital between 2007 and 2013 were examined
for WNT proteins, α-SMA, and fibronectin expression by immunohistochemistry. The relationship between each WNT proteins expression
level and estimated glomerular filtration rate (eGFR) was evaluated by the Mann-Whitney U test. COS1 cells (kidney fibroblasts
from African green monkey) were transfected with a WNT10A expression plasmid or a siRNA targeting peroxiredoxin 5 (PRDX5).
The effects of WNT10A overexpression and PRDX5 knockdown on proliferation and hydrogen peroxide induced cytotoxicity were
measured by WST-8 assay.
Results: The 10 patients exhibiting WNT10A expression in biopsy tissue had significantly lower eGFR values (median, 11.12 mL/min per
1.73 m2; range, 7.16−28.15 mL/min per 1.73 m2) than the 15 patients exhibiting no detectable WNT10A expression (34.70, 8.37−134.58; p = 0.0033). There was no significant
relationship between eGFR and the expression level of any other WNT protein examined (WNT-1, -3, and -4). Overexpression of
WNT10A in COS1 cells enhanced proliferation, fibronectin expression, PRDX5 expression, and resistance to hydrogen peroxide,
while PRDX5 downregulation sensitized COS1 cells to hydrogen peroxide.
Conclusions: WNT10A expression may promote fibrotic progression and kidney dysfunction in AIN. Blockade of WNT10A expression may be a
feasible therapeutic strategy against kidney fibrosis.
Full-text · Article · May 2014 · Nephrology Dialysis Transplantation
[Show abstract][Hide abstract] ABSTRACT: Severe hypernatremia is an important electrolyte disorder that has serious effects. The patient had no medical history. A. 20-year-old ingested bamboo salt for digestion and weight reduction according to the folk remedies posted on an internet website. She presented with vomiting and diarrhea over ten times per day. Her initial serum sodium concentration was 174mEq/L. Her symptoms improved rapidly with hypotonic saline infusion. She recovered completely without any sequelae in three days. Severe hypernatremia in a normal young adult with clear consciousness and normal renal function has not been reported in Korea yet. So we report a case of severe hypernatremia by excessive bamboo salt ingestion in healthy young woman.
Preview · Article · Dec 2013 · Electrolyte & blood pressure: E & BP
[Show abstract][Hide abstract] ABSTRACT: Unlabelled:
Ischemia/reperfusion (I/R) is the most common cause of acute renal injury. I/R-induced reactive oxygen species (ROS) are thought to be a major factor in the development of acute renal injury by promoting the initial tubular damage.
quinone oxidoreductase 1 (NQO1) is a well-known antioxidant protein that regulates ROS generation. The purpose of this study was to investigate whether NQO1 modulates the renal I/R injury (IRI) associated with NADPH oxidase (NOX)-derived ROS production in an animal model. We analyzed renal function, oxidative stress, and tubular apoptosis after IRI. NQO1(-/-) mice showed increased blood urea nitrogen and creatinine levels, tubular damage, oxidative stress, and apoptosis. In the kidneys of NQO1(-/-) mice, the cellular NADPH/NADP(+) ratio was significantly higher and NOX activity was markedly higher than in those of NQO1(+/+) mice. The activation of NQO1 by β-lapachone (βL) significantly improved renal dysfunction and reduced tubular cell damage, oxidative stress, and apoptosis by renal I/R. Moreover, the βL treatment significantly lowered the cellular NADPH/NADP(+) ratio and dramatically reduced NOX activity in the kidneys after IRI. From these results, it was concluded that NQO1 has a protective role against renal injury induced by I/R and that this effect appears to be mediated by decreased NOX activity via cellular NADPH/NADP(+) modulation. These results provide convincing evidence that NQO1 activation might be beneficial for ameliorating renal injury induced by I/R.
No preview · Article · Nov 2013 · Free Radical Biology and Medicine
[Show abstract][Hide abstract] ABSTRACT: Background
The aim of this study was to evaluate the clinical characteristics of nondiabetic nephropathy in type 2 diabetes mellitus patients and to find a clinical significance of renal biopsy and immunosuppressive treatment in such a patient.
Renal biopsy results, clinical parameters, and renal outcomes were analyzed in 75 diabetic patients who underwent kidney biopsy at Chungnam National University Hospital from January 1994 to December 2010.
The three most common reasons for renal biopsy were nephrotic range proteinuria (44%), proteinuria without diabetic retinopathy (20%), and unexplained decline in renal function (20.0%). Ten patients (13.3%) had only diabetic nephropathy (Group I); 11 patients (14.7%) had diabetic nephropathy with superimposed nondiabetic nephropathy (Group II); and 54 patients (72%) had only nondiabetic nephropathy (Group III). Membranous nephropathy (23.1%), IgA nephropathy (21.5%), and acute tubulointerstitial nephritis (15.4%) were the three most common nondiabetic nephropathies. Group III had shorter duration of diabetes and lesser diabetic retinopathy than Groups I and II (P=0.008). Group II had the lowest baseline estimated glomerular filtration rate (P=0.002), with the greatest proportion of renal deterioration during follow-up (median 38.0 months, P<0.0001). The patients who were treated with intensive method showed better renal outcomes (odds ratio 4.931; P=0.01). Absence of diabetic retinopathy was associated with favorable renal outcome in intensive treatment group (odds ratio 0.114; P=0.032).
Renal biopsy should be recommended for type 2 diabetic patients with atypical nephropathy because a considerable number of these patients may have nondiabetic nephropathies. And intensive treatment including corticosteroid or immunosuppressants could be recommended for type 2 diabetic patients with nondiabetic nephropathy, especially if the patients do not have diabetic retinopathy.
[Show abstract][Hide abstract] ABSTRACT: Background:
The purpose of this study is to identify whether hemoglobin (Hb) concentrations can be maintained, and to investigate changes in biomarkers, when switching from erythropoietin stimulating agents (ESA) with shorter half-life to once-monthly subcutaneous methoxy polyethylene glycol-epoetin β (CERA) in pre-dialysis chronic kidney disease (CKD) patients.
Pre-dialysis CKD patients (n=191) aged ≥18 years who maintained their Hb level 10-12 g/dL through use of epoetin-α, epoetin-β, or darbepoetin-α were enrolled. Hb levels and CERA dose was assessed prospectively for 24 weeks. Serum biomarkers related to coagulation, endothelial function, and iron metabolism were measured at weeks 0 and 24.
Baseline Hb concentration was 10.8±0.6 g/dL Twelve and 24 weeks after conversion, mean Hb levels were 11.9±0.9 and 11.2±0.9 g/dL, respectively. The mean monthly CERA dose required to maintain Hb levels was gradually reduced. Of total 387 dose adjustments, dose increases and decreases occurred in 35 (9.0%) and 352 (91.0%) episodes, respectively. Hb overshoot occurred in 14 (9.7%) patients. P-selectin was significantly decreased, whereas VCAM was significantly increased 24 weeks after conversion (P < 0.05). Serum soluble transferrin receptor E-selectin and prohepcidin levels were similar before and after switching to CERA (P=N-S).
Conversion from ESA with shorter half-life to subcutaneous once-monthly CERA in pre-dialysis CKD patients can efficaciously maintain Hb. The CERA dose requirement decreased significantly. The conversion ratio may need to be reduced when switching from ESA with shorter half-life to CERA. CERA may change biomarkers associated with platelet reactivity and endothelial microenvironment.
No preview · Article · Jul 2013 · Kidney and Blood Pressure Research
[Show abstract][Hide abstract] ABSTRACT: Three-dimensional (3D) LSIs using TSVs are indispensable to achieve high performance and low power LSIs with smaller form factor. A wafer-to-wafer (WtW) technology is suitable for stacking chips with high production yield such as DRAM since the overall yield after stacking rapidly decreases as the number of stacking layers increases. The chip-to-wafer (CtW) is suitable for stacking known good dies (KGDs). In addition, chips with different size which are fabricated using different process technologies can be stacked in the CtW technology. The inherent problem in the CtW technology, however, is low production throughput. To solve these problems, we have proposed a new 3D heterogeneous integration technology called a super-chip technology using self-assembly and electrostatic (SAE) bonding method.
[Show abstract][Hide abstract] ABSTRACT: A three-dimensional LSI (3D-LSI) that vertically stacks Si chips with a number of through-silicon vias (TSVs) and metal microbumps has attracted much attention recently. However, there are some issues to be resolved in the fabrication of 3D-LSI. In this study, we investigated impacts of local bending stress on the performance of a complementary metal-oxide-semiconductor (CMOS) circuit fabricated in a thinned Si chip. First, we proposed a novel method and a test structure to easily induce the local bending stress in the thinned Si chip. Then, we evaluated the distribution of the local bending stress and its effects on the electrical characteristics of metal-oxide-semiconductor field-effect transistor (MOSFETs). As a result, we observed the degradations of the MOSFET currents and CMOS inverter switching behaviors in accordance with the chip local bending. Our experimental results obviously indicate that the local bending stress caused large fluctuations in the performance of the circuit fabricated in the thinned Si chip. (C) 2013 The Japan Society of Applied Physics
Full-text · Article · Apr 2013 · Japanese Journal of Applied Physics
[Show abstract][Hide abstract] ABSTRACT: This study evaluated the clinical characteristics of patients who underwent kidney biopsies, and the relative changes in pathological diagnosis, according to time periods over the last 30 years (1981-2010).