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1.  Non-linear association of serum 25-hydroxyvitamin D with urinary albumin excretion rate in normoalbuminuric subjects 
BMC Nephrology  2014;15:97.
Vitamin D deficiencies and increases in urinary albumin excretion (UAE) are both important and potentially related health problems; however, the nature of their relationship has not been established in normoalbuminuric subjects.
We obtained data from 14,594 normoalbuminuric Korean adults who underwent voluntary health screenings. We used a generalized additive model to examine the threshold level for relationship between serum 25-hydroxyvitamin D [25(OH)D] and urinary-albumin creatinine ratio (UACR) levels. We conducted multivariate logistic regression for high-normal UAE (UACR, 10–29 mg/g), according to various categories of vitamin D status.
The generalized additive model confirmed a non-linear relationship between serum 25(OH)D and UACR levels, and the threshold concentration of 25(OH)D was 8.0 ng/mL after multivariate adjustment. Comparing subjects who fell into the lowest category of serum 25(OH)D levels with subjects who were in the reference range (the highest category), we observed that the multivariate adjusted odds ratio (OR) for high-normal UAE was significantly increased, regardless of the criteria used to categorize vitamin D levels: OR of the 1st quartile over the 4th quartile, 1.20 (95% CI, 1.04-1.39); OR of the 1.0-4.9th percentile over the 50-100th percentile, 1.56 (95% CI, 1.25-1.93); and OR of vitamin D deficiency group over vitamin D sufficiency group, 1.28 (95% CI, 1.08-1.52).
We demonstrated that there was an inverse relationship between serum 25(OH)D less than 8.0 ng/mL and UACR in normoalbuminuric subjects, suggesting that severe vitamin D deficiency could cause an increase in UAE in subjects with normoalbuminuria.
PMCID: PMC4079922  PMID: 24957097
Epidemiology; Low-grade albuminuria; Threshold; Vitamin D deficiency
2.  Non-Linear Relationship between Serum 25-Hydroxyvitamin D and Hemoglobin in Korean Females: The Korean National Health and Nutrition Examination Survey 2010–2011 
PLoS ONE  2013;8(8):e72605.
Anemia and vitamin D deficiency are both important health issues; however, the nature of the association between vitamin D and either hemoglobin or anemia remains unresolved in the general population.
Data on 11,206 adults were obtained from the fifth Korean National Health and Nutritional Examination Survey. A generalized additive model was used to examine the threshold level for relationship between serum 25-hydroxyvitamin D [25(OH)D] and hemoglobin levels. A multivariate logistic regression for anemia was conducted according to 25(OH)D quintiles. All analyses were stratified according to sex and menstrual status.
The generalized additive model confirmed a threshold 25(OH)D level of 26.4 ng/mL (male, 27.4 ng/mL; premenopausal females, 11.8 ng/mL; postmenopausal females, 13.4 ng/mL). The threshold level affected the pattern of association between 25(OH)D and anemia risk: the odds ratio of the 1st quintile but not the 2nd, 3rd, and 4th quintiles were significantly different from the 5th quintile in both premenopausal and postmenopausal females, however there was no obvious trend in males.
This population-based study demonstrated a non-linear relationship with a threshold effect between serum 25(OH)D and hemoglobin levels in females. Further interventional studies are warranted to determine whether the appropriate level of hemoglobin can be achieved by the correction of vitamin D deficiency.
PMCID: PMC3755993  PMID: 24015265
3.  Altered expression of adrenocorticotropic hormone in the epileptic gerbil hippocampus following spontaneous seizure 
BMB Reports  2013;46(2):80-85.
We investigated the temporal alterations of adrenocorticotropic hormone (ACTH) immunoreactivity in the hippocampus after seizure onset. Expression of ACTH was observed within interneurons in the pre-seizure group of seizure sensitive gerbils, whereas its immunoreactivities were rarely detected in seizure resistant gerbil. Three hr after the seizure, ACTH immunoreactivity was significantly increased in interneurons within all hippocampal regions. On the basis of their localization and morphology through immunofluorescence staining, these cells were identified as GABAA α1-containing interneurons. At the 12 hr postictal period, ACTH expression in these regions was down-regulated, in a similar manner to the pre-seizure group of gerbils. These findings support the increase in ACTH synthesis that contributes to a reduction of corticotrophin-releasing factor via the negative feedback system which in turn provides an opportunity to enhance the excitability of GABAergic interneurons. Therefore, ACTH may play an important role in the reduction of excitotoxicity in all hippocampal regions. [BMB Reports 2013; 46(2): 80-85]
PMCID: PMC4133853  PMID: 23433109
Adrenocorticotropic hormone; Epilepsy; Gerbil; Hippocampus; Immunohistochemistry
4.  Alterations in hyperpolarization-activated cyclic nucleotidegated cation channel (HCN) expression in the hippocampus following pilocarpine-induced status epilepticus 
BMB Reports  2012;45(11):635-640.
To understand the effects of HCN as potential mediators in the pathogenesis of epilepsy that evoke long-term impaired excitability; the present study was designed to elucidate whether the alterations of HCN expression induced by status epilepticus (SE) is responsible for epileptogenesis. Although HCN1 immunoreactivity was observed in the hippocampus, its immunoreactivities were enhanced at 12 hrs following SE. Although, HCN1 immunoreactivities were reduced in all the hippocampi at 2 weeks, a re-increase in the expression at 2-3 months following SE was observed. In contrast to HCN1, HCN 4 expressions were un-changed, although HCN2 immunoreactive neurons exhibited some changes following SE. Taken together, our findings suggest that altered expressions of HCN1 following SE may be mainly involved in the imbalances of neurotransmissions to hippocampal circuits; thus, it is proposed that HCN1 may play an important role in the epileptogenic period as a compensatory response. [BMB Reports 2012; 45(11): 635-640]
PMCID: PMC4133809  PMID: 23187002
Epilepsy; HCN channels; Hippocampus; Immunohistochemistry; Status epilepticus
5.  Soluble Epoxide Hydrolase Activity Determines the Severity of Ischemia-Reperfusion Injury in Kidney 
PLoS ONE  2012;7(5):e37075.
Soluble epoxide hydrolase (sEH) in endothelial cells determines the plasma concentrations of epoxyeicosatrienoic acids (EETs), which may act as vasoactive agents to control vascular tone. We hypothesized that the regulation of sEH activity may have a therapeutic value in preventing acute kidney injury by controlling the concentration of EETs. In this study, we therefore induced ischemia-reperfusion injury (IRI) in C57BL/6 mice and controlled sEH activity by intraperitoneal administration of the sEH inhibitor 12-(3-adamantan-1-ylureido)-dodecanoic acid (AUDA). The deterioration of kidney function induced by IRI was partially moderated and prevented by AUDA treatment. In addition, AUDA treatment significantly attenuated tubular necrosis induced by IRI. Ischemic injury induced the down-regulation of sEH, and AUDA administration had no effect on the expression pattern of sEH induced by IRI. In vivo sEH activity was assessed by measuring the substrate epoxyoctadecenoic acid (EpOME) and its metabolite dihydroxyoctadec-12-enoic acid (DHOME). Ischemic injury had no effects on the plasma concentrations of EpOME and DHOME, but inhibition of sEH by AUDA significantly increased plasma EpOME and the EpOME/DHOME ratio. The protective effect of the sEH inhibitor was achieved by suppression of proinflammatory cytokines and up-regulation of regulatory cytokines. AUDA treatment prevented the intrarenal infiltration of inflammatory cells, but promoted endothelial cell migration and neovascularization. The results of this study suggest that treatment with sEH inhibitors can reduce acute kidney injury.
PMCID: PMC3349654  PMID: 22590647
6.  The association of moderate renal dysfunction with impaired preference-based health-related quality of life: 3rd Korean national health and nutritional examination survey 
BMC Nephrology  2012;13:19.
Only a few large-scale studies have investigated the association between health-related quality of life (HRQOL) and renal function. Moreover, the HRQOL of patients with moderate renal dysfunction is frequently underestimated by healthcare providers. This study assessed the impact of renal function on preference-based HRQOL in Korean adult population.
We analyzed data for 5,555 adults from the 3rd Korean National Health and Nutritional Examination Survey 2005. The EuroQol-5D (EQ-5D) utility score was used to evaluate HRQOL. The study subjects were stratified into three groups based on their estimated glomerular filtration rates (eGFRs): ≥ 90.0, 60.0-89.9 and 30.0-59.9 mL/min/1.73 m2. Individuals with advanced renal dysfunction were excluded from the analysis.
The proportions of participants who reported problems in each of the five EQ-5D dimensions increased significantly with decreasing eGFR. However, a significant decrease in the EQ-5D utility score was observed among participants with an eGFR of 30.0-59.9 mL/min/1.73 m2. Participants with an eGFR of 30.0-59.9 mL/min/1.73 m2 had an almost 1.5-fold higher risk of impaired health utility (the lowest quartile of EQ-5D utility score) compared with those participants with eGFRs ≥ 90.0 mL/min/1.73 m2, after adjustment for age, gender, health-related behaviors, socioeconomic and psychological variables, and other comorbidities. Among the five dimensions of the EQ-5D, an eGFR of 30.0-59.9 mL/min/1.73 m2 was an independent determinant of self-reported problems in the mobility and pain/discomfort dimensions.
Although age affects the association between renal dysfunction and the EQ-5D, moderate renal dysfunction seems to be an important determinant of impaired health utility in a general population and may affect the mobility and pain/discomfort dimensions of health utility.
PMCID: PMC3404912  PMID: 22530944
Chronic kidney disease; EuroQol-5D; Preference-based health utility
7.  A YIDD Mutation in a Case of Recurrent Hepatitis B after Liver Transplantation Induced by an S-escape Mutant 
Gut and Liver  2010;4(2):253-257.
A 47-year-old woman underwent orthotopic liver transplantation (OLT) for hepatitis B virus (HBV)-related end-stage liver cirrhosis. The patient received hepatitis B immunoglobulin prophylaxis after OLT. Despite the protective level of the serum anti-hepatitis-B surface antibody, HBV recurred at 22 months post-OLT and induced subacute hepatic failure. The pre-OLT HBV genome contained a complex mutation pattern in overlapping frame regions of the surface (S) and polymerase (P) genes, which is the same mutation pattern as seen in post-OLT HBV DNA. G145R and K141R mutations in the "a" determinant were detected only in the post-OLT sample. Clevudine (30 mg once daily) was administered for recurrent hepatitis B. Hepatitis B was reactivated with a flare-up, and a M204I mutation (YIDD mutant type) appeared with a higher viral load at 9 months after clevudine treatment. We report here a case of a YIDD mutation that developed in recurrent hepatitis B after OLT induced by an S-escape mutant.
PMCID: PMC2886939  PMID: 20559531
G145R; G1896A; Recurrent hepatitis B; Liver transplantation; rtM204I
8.  A Case of Hepatocellular Carcinoma with Pulmonary Metastases Treated Successfully with a Combination of Repeated Hepatic Arterial Infusion Epirubicin and Cisplatin Chemotherapy and Systemic Low-Dose Infusion of 5-Fluorouracil 
Gut and Liver  2009;3(4):343-348.
We report a case of hepatocellular carcinoma (HCC) with pulmonary metastases treated with repeated hepatic arterial infusion chemotherapy (HAIC) comprising epirubicin and cisplatin, and systemic infusion of 5-fluorouracil (a modified EC/F protocol), which led to complete remission. A 49-year-old man with compensated liver cirrhosis experienced intrahepatic recurrence of HCC with extensive lung metastases. The modified EC/F therapeutic protocol, which was applied at the tenth cycle every 4-5 weeks, resulted in disappearance of the pulmonary metastases and normalization of serum α-fetoprotein levels. A single small HCC lesion was found in the left lobe of the liver 13 months after the final chemotherapy session. HAIC with the same regimen was conducted again, followed by percutaneous intratumoral chemoinjection therapy with 5-fluorouracil and interferon-γ. Thereafter, there was no evidence of recurrence in either the liver or the lung, as evidenced by image analysis and expression of tumor markers. The disease-free intervals for the liver and lung were 41 and 54 months, respectively.
PMCID: PMC2852739  PMID: 20431774
Carcinoma, Hepatocellular; Lung metastasis; Hepatic arterial infusion chemotherapy; Drug therapy

Results 1-8 (8)