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HBeAg seroconversion is an important treatment endpoint. We aimed to identify predictors of seroconversion using serum HBsAg and hepatitis B core-related antigen (HBcrAg) in HBeAg-positive patients treated with nucleos(t)ide analogs (NAs). Data and samples from 70 HBeAg-positive patients treated with entecavir or tenofovir between January 2007 and December 2017 were retrospectively analysed. The mean follow-up period was 11 years. The predictive power for HBeAg seroconversion of HBcrAg levels at baseline and 2 years after antiviral therapy was determined using receiver operating curve analysis. Twenty-one patients (30%) achieved HBeAg seroconversion at a mean of 28 (range, 12-84) months after antiviral treatment. The median baseline HBcrAg and HBsAg levels were 6.9(5.7-7.0) vs. 5.8(5.5-6.5) log

Purpose: This study aimed to investigate the effects of exposure to endocrine disruptors, burnout, and social support from peers on premenstrual syndrome (PMS) in nurses. Methods: This descriptive correlational study was conducted among 122 nurses under the age of 49 working at a university hospital. The participants answered self-report questionnaires. The data were analyzed using the t-test, analysis of variance, Pearson or Spearman correlation coefficients, and hierarchical multiple regression in IBM SPSS version 23.0. Results: The mean age of the nurses was 28.9 years. Of these nurses, 49.2% were working in a general ward, 24.6% in the intensive care unit, 14.8% in the emergency room, and 11.4% in an outpatient department. The explanatory power of the model was 38.3%, and it was statistically significant (F=11.74, p≤.001). Exposure to endocrine disruptors (β=0.32, p

Receiving sincere comments from experts in the field on technology that shows new direction and possibility can be a great foundation for further development. Three (1-3) editorials expressed their curiosities and concerns for our study (4) as follows.

// Jung-Hwan Yu 1, * , Joon Mee Kim 2, * , Ja Kyung Kim 1 , Suk Jin Choi 2 , Kwan Sik Lee 1 , Jin-Woo Lee 3 , Hye Young Chang 4 and Jung Il Lee 1 1 Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea 2 Department of Pathology, Inha University School of Medicine, Incheon, Republic of Korea 3 Department of Internal Medicine, Inha University School of Medicine, Incheon, Republic of Korea 4 Medical Research Center, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea * These authors have contributed equally and share the first authorship Correspondence to: Jung Il Lee, email: mdflorence@yuhs.ac Keywords: platelet-derived growth factor receptor α, liver fibrosis, liver cirrhosis, hepatic stellate cell, hepatocellular carcinoma Received: October 07, 2016 Accepted: February 22, 2017 Published: April 17, 2017 ABSTRACT Background and Aims: Platelet-derived growth factor receptor alpha (PDGFRα) is suggested as a prognosis marker for hepatocellular carcinoma (HCC). Since PDGFRα is also known as a marker for activated hepatic stellate cells (HSCs), this study aimed to investigate whether PDGFRα expression in HCC was dependent on the background liver fibrous condition. Results: Strong PDGFRα expression in the tumor lesions was associated with decreased survival after curative HCC resection. Expression of PDGFRα in the tumor correlated with increased collagen α1(I) , lecithin retinol acyltransferase , and smooth muscle α-actin suggesting increased HSCs in tumor sites. The expression of PDGFRα in the tumor sites was associated neither with underlying liver fibrosis/cirrhosis nor with the expression of PDGFRα in adjacent non-tumor sites of the liver. Materials and Methods: Patients with HCC who underwent liver resection as curative treatment were included in this study. Using liver samples of 95 patients, tissue microarray was constructed and immunohistochemical study of PDGFRα was conducted in both tumor and non-tumor sites. PDGFRα expression in tumor and matching non-tumor sites was compared. Freshly frozen liver tissue specimens of 16 HCC patients were used for gene expression analysis of PDGFRα and fibrosis related genes. Conclusions: Our results suggest that PDGFRα overexpression in HCC is a prognostic marker independent of adjacent non-tumor site liver fibrosis status.

Background: Prolonged air leak is the most common complication after pulmonary resection surgery. Water submersion test (WST) has been used to check for air leak. However, it is cumbersome under the circumstances of video-assisted thoracic surgery (VATS). This study aimed to devise a new air leak detection method that is suitable for the VATS. Methods: We decided to utilize the properties of the surfactants to overcome the disadvantages of WST. To find the optimal surfactant, ex-vivo porcine lung experiments were prepared with a custom-made large glass vessel mimicking a human thoracic cavity. A fresh lung was put inside the glass vessel and connected with the ventilator. We made a needle injury on the lung surface and dropped various kinds of liquid surfactants to create air bubbles during the lung ventilation. The appearances of bubbles were recorded through 5mm thoracoscope. Results: Considering the bubble forming ability, Pluronic F-127 solution (PF127), a well-known non-toxic and non-ionic colorless surfactant, was chosen as candidate substance. To find the optimal condition, various concentrations of PF127 (30%, 25%, 20%, 15%, 10%) were tested. Greater than 20% concentration of PF127 were not feasible due to its high viscosity; the bubbles kept increasing in size without popping and blocked the thoracoscopic vision. The 10% PF127 did not form any bubbles. On the contrary, the 15% PF127 formed bubbles that are 1–2 cm in size with dynamic movement allowing for clear visibility of the air leak point. We finally made a green colored 15% PF127 by mixing an indocyanine green to increase its visibility. All of the components in the solution are FDA approved and permissible to be used in the human body. Conclusions: Our bubble solution can easily detect the air leak even in small quantities and is expected to be useful in VATS with limited vision. However, in order for its full-scale clinical use, its safety in the human body must be verified.

PURPOSE The Korean society has moved rapidly toward becoming a multicultural society. This study aimed to estimate the seroprevalence of hepatitis viruses and investigate hepatitis B virus (HBV) genotypic diversity in female marriage immigrants. MATERIALS AND METHODS Screening program was conducted at support centers for multicultural families in 21 administrative districts in Korea between July 2011 and January 2017. A total of 963 female marriage immigrants were included in this study. Blood samples were tested for hepatitis viral markers and HBV genotype. RESULTS Subjects' median age was 33 years (20-40 years), and they originated from nine countries including Vietnam (n=422, 43.8%), China (n=311, 32.3%), the Philippines (n=85, 8.8%), Cambodia (n=58, 6.0%), and Japan (n=39, 4.0%). About 30% (n=288) of subjects required hepatitis A vaccination. HBsAg positive rate was 5.4% (n=52). Positive HBsAg results were the highest in subjects from Southeast Asia (6.6%, n=38). Anti-HBs positive rate was 60.4% (n=582). About 34% (n=329) of subjects who were negative for anti-HBs and HBsAg required HBV vaccinations. Genotypes B and C were found in 54.6% (n=12) and 45.4% (n=10) of the 22 subjects with HBV, in whom genotypes were tested. Eight (0.8%) subjects were positive for anti-HCV. Positive anti-HCV results were the highest in subjects from Central Asia (7.9%, n=3). CONCLUSION Testing for hepatitis viral marker (hepatitis A virus IgG and HBsAg/anti-HBs) is needed for female marriage immigrants. Especially, HBV genotype B is different from genotype C of Koreans. Therefore, interest and attention to vaccination programs for female marriage immigrants are necessary for both clinicians and public health institutes.

Deoxycytidine kinase (dCK) is a critical enzyme involved in intracellular phosphorylation of lamivudine (LAM) to its active triphosphates. We conducted this study to determine dCK polymorphisms in Koreans and to evaluate whether the discovered single nucleotide polymorphisms (SNPs) were associated with treatment outcomes in chronic hepatitis B (CHB) patients treated with LAM. The full-length dCK gene was sequenced from 24 healthy volunteers and 24 patients with CHB. One hundred twenty-seven patients with CHB who were followed-up for at least 24 months after LAM treatment were enrolled. Virological response as determined by undetectable HBV DNA was defined as a good drug response. Primary non-response at 6 months and virological breakthrough within 12 months were defined as a poor drug response. Six novel dCK SNPs were found (-2052C/A, IVS3 - 46G/del, IVS4 + 40G/T, IVS5 + 39T/C, IVS5 - 72A/T, and 966-975T10/T11). In particular, two promoter SNPs, namely -360C/G and -201C/T, were in full linkage disequilibrium. These two SNPs had a higher allele frequency than previously reported in Caucasian, Japanese, and Chinese (26% vs. 2%, 13.1%, and 15.6%, respectively). There was no significant difference between treatment response groups in terms of the distributions of SNP genotypes or allele frequencies. However, there was significant difference in the allele frequency of -360G/-201T between HBeAg seroclearance group and HBeAg non-seroclearance group (P = 0.045). In conclusion, six novel dCK SNPs were discovered. Two promoter SNPs, namely -360C/G and -201C/T, were more frequent in Koreans than other populations. In particular, HBeAg-positive patients with the -360G/-201T haplotype may help HBeAg seroclearance in response to LAM therapy.

A 54-year-old man diagnosed with HBeAg-positive chronic hepatitis B (CHB) was treated with entecavir (ETV) 1mg/day following an initial unsuccessful lamivudine (LAM) treatment (rtL180M, rtM204V/I). Subsequently, virological breakthrough with ETV mutation (rtT184A/L) developed. The LAM and adefovir combination therapy was followed by virological breakthrough. The therapy had been switched to TDF monotherapy. However, this patient experienced virological breakthrough under TDF with a HBV strain bearing rtL80M, rtL180M, rtM204V/I, rtA200V, rtF221Y, rtS223A, rtT184A/L, rtR153Q, and rtV191I combined mutations without rtA194T mutation. TDF resistance may emerge due to multi-site polymerase mutations rather than single-site polymerase mutation.

Background and Aim Hepatitis B virus (HBV) replication detected before the resection of hepatocellular carcinoma (HCC) is to be controlled by antiviral agents. However, management strategy for patients with preoperatively undetectable HBV DNA without antiviral therapy is not clearly delineated. This study investigated viral reactivation after the liver resection in non-replicating HBV DNA-related HCC patients and its impact on the surgical outcome. Methods From 198 patients that underwent liver resection due to HBV-related HCC, 101 patients who had serially checked serum HBV DNA were analyzed. Results From 101 patients, 33 patients had baseline undetectable HBV DNA. Eleven patients (11/33, 33.3%) had viral replication after the liver resection. The postoperative viral reactivation (HR: 2.144; 95% CI: 1.122–4.097; P = 0.021), along with the existence of satellite nodules (HR: 3.034; 95% CI: 1.1.376–6.689; P = 0.006), existence of microvascular invasion (HR: 2.479; 95% CI: 1.303–4.718; P = 0.006), and HBeAg positivity (HR: 2.059; 95% CI: 1.155–3.670; P = 0.014) predicted recurrence after the surgery. Quantification of intrahepatic total and covalently closed circular DNA (cccDNA) was done in 14 patients whose baseline serum HBV DNA was undetectable without the use of antiviral agent. Amount of intrahepatic cccDNA expressed as copies/hepatocyte in patients with postoperative viral reactivation showed significantly higher than those in patients with sustained negative serum HBV DNA (P = 0.010). Conclusions This study shows that naturally suppressed preoperative HBV without application of antiviral agent does not ensure undetectable serum HBV after the surgery, and postoperative viral reactivation might be associated with HCC recurrence.

Background and Aims Previous studies have found that serum level of IL-6 was increased in HBV-infected patients. Here we evaluate the impact of IL-6 levels according to the natural history of chronic hepatitis B(CHB) infection. Method Patients(n=71) with hepatitis B virus(HBV) were enrolled between September 2016 and Feb. 2018. Treatment-naïve chronic HBV carries were recruited. IFN-γ, TNF-α, IL-2, IL-6, and IL-17A were measured by a cytometric bead assay according to manufacturer’s instructions. Soluble PD-1 and soluble CD14 were made by the enzyme linked immunosorbent assay (ELISA) technique. The assay procedures were followed according to the manufacturer’s instructions. We studied patients with immune inactive phase (HBV DNA< 1,000 copies/ml, anti-HBe + and normal ALT, n=22), immune tolerant phase (HBV DNA > 10,000 copies/ml, HBeAg + and normal ALT, n=36), and immune active phase (elevated ALT and HBV DNA>10,000 copies/ml, n=13). Results Serum IL-6 levels in patients with immune inactive phase were significantly lower than patients with immune tolerant and immune active phases (267.3±245.6 pg/mL vs. 620.2±207.8 pg/mL and 1,815±803.2) (p Conclusion These results demonstrate the potential to apply serum IL-6 as a biomarker for differentiating immune inactive phase from other phases in patients with chronic HBV infection.

Few studies have reported on the clinical characteristics of hepatocellular carcinoma (HCC) at the time of diagnosis with regard to pre-S and basal core promoter (BCP) mutations. In this study, the clinical features and prognosis of 126 Korean HCC patients were examined with respect to pre-S deletion and BCP mutations of hepatitis B virus. The proportion of HCC patients according to tumor-node-metastasis stage are as follows: 8.7% in stage I, 31% in stage II, 30.2% in stage III, 21.4% in stage IV-A, and 8.7% in stage IV-B. Overall, 40.5% of HCC patients were treated by surgery or ablation, 59.5% by other methods. Patients were divided according to pre-S deletion and BCP mutations (103 without pre-S deletion, 23 with pre-S deletion; 44 without BCP mutation, 82 with BCP mutation). The tumor characteristics and prognosis were evaluated between the groups, including size, number, type, vessel invasion, portal vein thrombosis, and metastasis. No significant difference in tumor characteristics between the HCC patients with pre-S deletion was observed, compared with the HCC patients without pre-S deletion. In contrast, the survival rate was lower in those with pre-S deletion than in those without it (P = 0.024). No difference in tumor characteristics was found in non-BCP and BCP mutation patients. Unlike the pre-S deletion group, no difference was observed in survival rate between the non-BCP and BCP patients. In conclusion, pre-S deletion and BCP mutations did not affect the initial tumor features. However, pre-S deletion was an independent risk factor affecting HCC survival.

Quantitative hepatitis B surface antigen (qHBsAg) and quantitative hepatitis B e antigen (qHBeAg) titers are emerging as useful tools for measuring viral loads and for predicting the virological response (VR) and serological response (SR) to pegylated interferon therapy. However, the clinical utility of these assays in patients taking entecavir (ETV) is largely unknown. Treatment-naive patients with chronic hepatitis B (CHB) who were taking ETV for 2 years were enrolled. The qHBsAg and qHBeAg levels were serially measured with the Architect assay. From 95 patients, 60.0% of whom were hepatitis B e antigen–positive [HBeAg(+)], 475 samples were analyzed. The median baseline log hepatitis B virus (HBV) DNA, log qHBsAg, and log qHBeAg values were 6.73 copies/mL (4.04-9.11 copies/mL), 3.58 IU/mL (1.17-5.10 IU/mL), and 1.71 Paul Ehrlich (PE) IU/mL (−0.64 to 2.63 PE IU/mL), respectively. For the prediction of VR (HBV DNA < 60 copies/mL at 24 months) in HBeAg(+) patients, baseline alanine aminotransferase (P = 0.013), HBV DNA (P = 0.040), and qHBsAg levels (P = 0.033) were significant. For the prediction of VR, the area under the curve for the baseline log qHBsAg level was 0.823 (P < 0.001); a cutoff level of 3.98 IU/mL (9550 IU/mL on a nonlogarithmic scale) yielded the highest predictive value with a sensitivity of 86.8% and a specificity of 78.9%. As for SR (HBeAg loss at 24 months), the reduction of qHBeAg was significantly greater in the SR(+) group versus the SR(−) group. The sensitivity and specificity were 75.0% and 89.8%, respectively, with a decline of 1.00 PE IU/mL at 6 months. With ETV therapy, the correlation between HBV DNA and qHBsAg peaked at 6 months in HBeAg(+) patients. Conclusion: Both qHBsAg and qHBeAg decreased significantly with ETV therapy. The baseline qHBsAg levels and the on-treatment decline of qHBeAg in HBeAg(+) patients were proven to be highly useful in predicting VR and SR, respectively. The determination of qHBsAg and qHBeAg can help us to select the appropriate strategy for the management of patients with CHB. However, the dynamic interplay between qHBsAg, qHBeAg, and HBV DNA during antiviral therapy remains to be elucidated. (Hepatology 2011;)

Aspergillus sojae isolated from a traditional Korean fermented soybean product exhibited strong naringinase activity. The naringinase enzyme was purified and had a molecular weight of 70 kDa. The α- l -rhamnosidase activity of this enzyme was optimal at pH 6.0 and stable in the pH range of 5.5–8.0. The purified enzyme also had β- d -glucosidase activity, but the activity was relatively weak compared to the activity of the naringinase from Penicillium decumbens . The enzymatic bioconversion by A. sojae naringinase of naringin to prunin was efficiently performed with a 91% yield and a negligible amount of naringenin. The bioconversion was achieved by repetitive batch reactions with enzyme recycling. Prunin exhibited a markedly enhanced solubility compared to naringenin and naringin while maintaining the in vitro inhibition of HMG-CoA reductase. The results reported in this paper show that the naringinase produced by A. sojae will be useful in enhancing the potential bioavailability of naringin by efficiently converting it to prunin as a food component in citrus.

Korea is an endemic area of hepatitis B virus (HBV) infection but very little is known about the molecular characteristics of HBV isolates from Korean patients or the association with disease progression. The complete HBV genome sequences from 53 Korean patients with chronic hepatitis B, advanced cirrhosis, or hepatocellular carcinoma (HCC) were analyzed to identify (i) subgenotype distribution and genetic diversity and (ii) signature mutations associated with liver disease progression. With the exception of 1 patient infected with HBV/B, all 52 patients (98.1%) were infected with HBV/C, subgenotype C2. These strains were 98.4% identical and the frequency of amino acid substitutions occurring within key immunological epitopes increased with disease severity. A number of amino acid/nucleotide substitutions were associated with HCC, namely sR24K (HBsAg), SI126T (HBsAg), and pcA1846T (precore gene) mutations (P = 0.029, 0.001, and 0.008, respectively). HBV harboring deletions in the pre-S region were also associated with increased liver disease severity (chronic hepatitis B vs. cirrhosis, P = 0.040; chronic hepatitis B vs. HCC, P = 0.040). Despite the high degree of sequence conservation, several key HBV mutations were associated with disease progression. Prospective studies with larger cohorts of patients are required to evaluate further the clinical manifestation of HBV/C2 in Korea. J. Med. Virol. 82: 1126–1134, 2010. © 2010 Wiley-Liss, Inc.

TNF-alpha promoter polymorphism is known to play an important role in the immunopathogenesis of infection of hepatitis B virus.We investigated whether polymorphisms of TNF-alpha promoter at position -308 or -238 had associations with the response to lamivudine treatment.A total of 89 healthy subjects (control group) and 225 patients with chronic hepatitis B treated with lamivudine were included in this study. Polymorphisms of TNF-alpha promoter at position -308 and -238 were analyzed by polymerase chain reaction. Recruited patients were classified according to the outcome of lamivudine treatment into the responder (103 patients) or non-responder (122 patients) group.The numbers of A allelic polymorphism of TNF-alpha promoter at position -238 were four (2.2%) in the control, five (2.4%) in the responder and 19 (7.8%) in the non-responder group. The A allele was noted significantly more frequently in the responder than non-responder group (P = 0.012). At position -308, a significant difference was observed between the control group (14; 7.9%) and total chronic hepatitis B patients (15; 3.3%) (P = 0.015).Our study demonstrated that the non-response to lamivudine treatment in patients with chronic hepatitis B might be related to the A allelic polymorphism of TNF-alpha promoter at position -238.

Recently, hepatitis B virus (HBV) genotypes and mutations have been reported to be related to hepatocellular carcinoma (HCC). This cross-sectional case-control study examined the relationship between HCC and mutations in the enhancer II/core promoter and precore regions of HBV by comparing 135 Korean HCC patients infected with HBV genotype C2 (HBV/C2; HCC group) with 135 age-, sex-, and hepatitis B e antigen (HBeAg) status-matched patients without HCC (non- HCC group). Age and sex were also matched between HBeAg-positive and -negative patients. The prevalence of T1653, A1689, V1753, T1762/A1764, T1846, A1850, C1858, and A1896 mutations was evaluated in this population. The prevalence of the T1653 mutation in the box alpha region, the T1689 [corrected] mutation in between the box alpha and beta regions, and the T1762/A1764 mutations in the basal core promoter region was significantly higher in the HCC group compared to the non-HCC group (8.9% vs. 2.2%, P = 0.017; 19.3% vs. 4.4%, P < 0.001; and 60.7% vs. 22.2%; P < 0.001). Among HBeAg-negative patients, the frequency of the T1653 mutation was higher in the HCC group. Regardless of HBeAg status, the prevalence of the T1689, [corrected] and T1762/A1764 mutations was higher in the HCC group than in the non-HCC group. However, no association was observed between mutations in the precore region and HCC. Upon multivariate analysis, the presence of the T1653, T1689, [corrected] and T1762/A1764 mutations was an independent predictive factor for HCC. The addition of the T1653 or T1689 [corrected] mutation to T1762/A1764 increased the risk of HCC. In conclusion, the T1653, T1689, [corrected] and/or T1762/A1764 mutations were associated with the development of HCC in Korean patients infected with HBV/C2.

Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, South KoreaMostpatientswithhepatitisBeantigen(HBeAg)-negative chronic hepatitis B have variants of thehepatitis B virus (HBV) that include mutations inthe precore or core promoter regions of the HBVgenome. The aim of this study was to investigatethe patterns of precore and core promotermutations and their relationship to HBeAgexpression in Korean patients. Four hundredseventy-five Korean patients with chronic HBVinfection between February 1995 and December2003 were enrolled in this study. There were236 HBeAg-positive and 239 HBeAg-negativepatients. Blood samples were tested for HBsAg,anti-HBs, HBeAg, hepatitis B e antibody (anti-HBe), liver function tests, and serum HBV DNA.Mutations in the precore and core promoterregions were determined by direct sequencing.In the core promoter region, the C1740, C1753,T1762/A1764, and T1766 mutations were associ-ated with HBeAg escape (all; P

A glassy carbon (GC) electrode was modified with electropolymerized macrocyclic Ni(II) complex, at which dopamine (DA) and ascorbic acid (AA) were clearly resolved below pH 6.0 by cyclic voltammetry. Their charge transfer reaction was examined to elucidate their resolution and the oxidation reaction. DA had two charge transfer reactions below pH 6.0, allowing resolution of DA and AA. DA increased the peak separation between DA and AA, and the GC surface exposed to DA was involved in the DA oxidation that occurred at the Ni(II) complex-modified electrode. DA was determined selectively using the Ni(II) complex-modified electrode and the selective DA accumulation improved the DA response. The linear range was 0.5–50 μM ( R = 0.9989) and the limit of detection (S/N = 3) was 0.15 μM. A Ni(II) complex-modified electrode can be used for selective DA detection in an acidic sample, such as urinary DA.

As a new practical model of Korean Library statistics, It suggests 6 parts, fifty-four items for 4 types of libraries. In comparison with last version, `library use and users`, `electronic services` parts are increased which are occupied as more than hair of the whole statistical items. Budget parts are increased also. The new model which is developed based on the international standards like ISO2789 and NISO/ANSI Z39.7 is advised by professionals in the fields.

Liver fibrosis is characterized by an excess accumulation and repressed degradation of extracellular matrix. Although methods of alleviating already established liver fibrosis have scarcely been reported, continuous relaxin (RLX) infusion has demonstrated some promising results. In the present study, we investigated whether a single adenoviral delivery of RLX would attenuate established liver fibrosis in rats.Rats were given thioacetamide (TAA) for 8 weeks and infected once with either RLX-expressing adenovirus (TAA + RLX) or control virus (TAA + Vector) via the tail vein. They were sacrificed either 3 days or 3 weeks after adenovirus infection.Morphometric analysis of picrosirius red stained area demonstrated that the TAA + RLX group had significantly decreased fibrosis at week 3 when liver fibrosis of the TAA + Vector group remained unchanged. Although the liver and serum RLX levels were elevated on day 3 and reversed by week 3, expression of RLX receptor (Rxfp1; relaxin-like family peptide receptor-1) in TAA + RLX rats was sustained and elevated. The production of tissue cyclic adenosine monophosphate, which is a second messenger of activated Rxfp1, was still enhanced in the TAA + RLX group by week 3. Expression of lysyl oxidase homolog 2, which contributes to collagen cross-linking and is up-regulated by TAA treatment, was significantly decreased by week 3 in the TAA + RLX group. Expression of tissue inhibitor of metalloprotiase-2 was alleviated in the TAA + RLX group at week 3, whereas that of TAA + Vector rats was still elevated.A single adenoviral delivery of RLX in the liver attenuated established hepatic fibrosis by suppressing collagen cross-linking and enhancing collagen degradation.

Deoxycytidine kinase (dCK) is a critical enzyme involved in intracellular phosphorylation of lamivudine (LAM) to its active triphosphates. We conducted this study to determine dCK polymorphisms in Koreans and to evaluate whether the discovered single nucleotide polymorphisms (SNPs) were associated with treatment outcomes in chronic hepatitis B (CHB) patients treated with LAM. The full-length dCK gene was sequenced from 24 healthy volunteers and 24 patients with CHB. One hundred twenty-seven patients with CHB who were followed-up for at least 24 months after LAM treatment were enrolled. Virological response as determined by undetectable HBV DNA was defined as a good drug response. Primary non-response at 6 months and virological breakthrough within 12 months were defined as a poor drug response. Six novel dCK SNPs were found (-2052C/A, IVS3 - 46G/del, IVS4 + 40G/T, IVS5 + 39T/C, IVS5 - 72A/T, and 966-975T10/T11). In particular, two promoter SNPs, namely -360C/G and -201C/T, were in full linkage disequilibrium. These two SNPs had a higher allele frequency than previously reported in Caucasian, Japanese, and Chinese (26% vs. 2%, 13.1%, and 15.6%, respectively). There was no significant difference between treatment response groups in terms of the distributions of SNP genotypes or allele frequencies. However, there was significant difference in the allele frequency of -360G/-201T between HBeAg seroclearance group and HBeAg non-seroclearance group (P = 0.045). In conclusion, six novel dCK SNPs were discovered. Two promoter SNPs, namely -360C/G and -201C/T, were more frequent in Koreans than other populations. In particular, HBeAg-positive patients with the -360G/-201T haplotype may help HBeAg seroclearance in response to LAM therapy.

The aims of this study were to investigate the efficacy of prolonged entecavir (ETV) therapy in treatment-naive chronic hepatitis B (CHB) patients and to determine whether continuous ETV therapy is feasible to achieve HBeAg seroconversion, particularly in patients with partial virological response (PVR). A total of 142 treatment-naive patients with CHB were enrolled. The mean duration of treatment was 65 (range, 26 to 90) months, and 86 patients (60.6%) were HBeAg positive. PVR was defined as detectable hepatitis B virus (HBV) DNA (>116 copies/ml) at year 1. The cumulative incidence of virological response (VR) increased from 54.9% at year 1 to 98.2% at year 7. HBeAg positivity (odds ratio [OR], 4.146; P = 0.001) and initial alanine aminotransferase (ALT) (OR, 0.997; P = 0.004) were independent risk factors for PVR. Among the 64 patients with PVR, 47 patients (73.4%) achieved VR within 4 years after prolonged ETV therapy without treatment adaptation. Three patients (2.1%) experienced virological breakthrough and HBV variants with genotypic resistance. The cumulative rate of HBeAg seroconversion was significantly higher in the patients with VR than in the patients with PVR ( P = 0.018). None of the PVR patients with HBV DNA at ≥5,000 copies/ml at year 1 ever experienced HBeAg seroconversion. Multivariate analysis identified VR at year 1 as the only determinant of HBeAg seroconversion (hazard ratio [HR], 3.009; P = 0.010). In conclusion, although there were patients with PVR, prolonged ETV therapy showed excellent VR, with only 2.1% emergence of viral resistance during a 7-year follow-up. However, to achieve HBeAg seroconversion, drug modification is needed for HBeAg-positive patients with PVR (especially those with HBV DNA at ≥5,000 copies/ml at year 1).

Homocysteine is an intermediate formed during the metabolism of methionine to cysteine, and high levels of blood plasma homocysteine are considered to be a risk factor for heart attack and stroke. It exists in either its reduced (homocysteine, RSH) or oxidized form (homocystine, RSSR), and the oxidized form the major one in human blood plasma. Since it contains sulfur in its structure, it was also used to modify the electrode surface for the electrocatalytic detection of another compound, such as catecholamine. Homocysteine is usually determined by using fluorescence, UV/Vis and electrochemical detection methods. Spectroscopic detection requires derivatization of homocysteine, and electrochemical detection needs electrodes that enable continuous measurements. However, electrochemical detection has a representative advantage, which is to be able to detect homocysteine without any additional derivatization, if electrodes are free from adsorption. Modified electrodes can solve the problem caused by adsorption and then have high reproducibility for repetitive measurements. A self-assembly technique for electrode modification is simple and has diverse materials for modification. A number of organic compounds containing the thiol group can readily adsorb on the electrode surface, such as gold, and form a self-assembled monolayer (SAM). Macrocyclic complexes with an electrocatalytic effect can be used to determine homocysteine for higher sensitivity and reproducibility, if they can form a SAM on the electrode surface. Previous studies have shown that compounds with sulfur, such as thiophene and its derivatives, and disulfide compounds of 6-mercaptopurine and mercaptobenzimidazole, formed a stable SAM. Although it may be difficult to synthesize macrocyclic complexes containing sulfur, using these materials can extend the fields for the determination of homocysteine. In this work, Ni(II)-macrocyclic complex with thiophene groups (NiMCT) was synthesized and used to form a SAM on a gold electrode surface. A gold electrode modified with the SAM of NiMCT (NiMCT SAM) was characterized spectroscopically and electrochemically. It was used to determine homocysteine by differential pulse voltammetry and its reproducibility was examined for repetitive measurements. The oxidation process of homocysteine at the NiMCT-SAM modified electrode is discussed. Experimental Section

A dopamine (DA) polymer was deposited electrochemically on to a glassy carbon (GC) surface until the electrode surface was passivated. The DA film on the GC surface was re-formed for high sensitivity and reproducibility by electrochemical degradation. The re-formed electrode was sensitive and selective in the determination of DA in the presence of ascorbic acid. The linear range obtained by square-wave voltammetry was between 0.1 and 2.1 μM (R=0.996, n=6) with a sensitivity of 1.2 μA μM−1 and a detection limit (S/N=3) of 0.04 μM. The electropolymerized DA film was stable and the re-formed electrode was reproducible for DA determination.

Immunogenetic factors may play a role in determining the susceptibility of an individual to viral infection. The aim of current study was to investigate the association of clearance of hepatitis B virus (HBV) with promoter polymorphisms within the CC chemokine receptor 5 (CCR5) and its major ligand, regulated upon activation, normal T cells expressed and secreted (RANTES) genes. Five chemokine system polymorphisms (CCR5 Delta32, CCR5 promoter 59029G/A, 59353C/T, RANTES -403G/A, and -28C/G) were studied in a total of 698 subjects. The carriage of each genetic variant was compared among "spontaneously recovered" group (n = 243), "chronic carrier" group (n = 349), and "unexposed" group (n = 106). CCR5 59029G promoter variant was associated with clearance of HBV infection in an acute phase (OR = 1.71, P = 0.006, dominant model; OR = 2.17, P < 0.001, recessive model) and amelioration of hepatic inflammation (P = 0.003) with the control of HBV replication (P = 0.04) in chronic carriers. Interestingly, CCR5 59029 was linked completely to CCR5 59353, and CCR5 Delta32 homozygosity or heterozygosity was not found in any Korean patient. No association was seen with RANTES polymorphisms at position -403 and -28. The CCR5 59029G/CCR5 59353T polymorphism may play a role in the clearance of HBV infection.

Macrocyclic Ni(II) complex and hydrophilic polyurethane (PU) were used to modify activated glassy carbon (GC) electrodes for the electrocatalytic oxidation and selective detection of norepinephrine (NE). The Ni(II) complex was electropolymerized using cycling potentials, and the Ni(II) complex-modified electrode had a negatively shifted oxidation potential and increased current in phosphate buffer at pH 7.4. The linear range and detection limit were from 0.10 to 10 μM (390 nA μM −1 , R =0.999) and 7.7 nM (signal-to-noise ratio, S/ N =3) by amperometry with flow injection, respectively. The Ni(II) complex-modified electrodes were coated with hydrophilic PU for higher selectivity. Hydrophilic anionic PU was produced by the hydrolysis of PU containing γ-benzyl l -glutamate (PUBLG) segments. The hydrophilic PU-coated electrodes increased the selectivity for NE over ascorbic acid (AA) and uric acid (UA). Moreover, NE in a human urine sample was detected with higher sensitivity, reproducibility, and stability than by using Nafion-coated electrodes. Therefore, hydrophilic PU and Ni(II) complex can be used as new electrode materials for the electrocatalysis and selective electroanalysis of NE. In particular, hydrophilic PU can be used as an alternative anionic material to Nafion for better urine compatibility.

occurs with relatively higher concentrations of ascorbic acid (AA). When DA is oxidized to DA quinone, AA is oxidized at a similar potential to DA at ordinary solid electrodes, which decreases the electrodes' selectivity for DA. To increase the selectivity for DA, electrodes can be modified with materials that can separate DA and AA electrochemically. Most of these materials are cationic or anionic polymers, 3-6 because cationic DA and anionic AA at the physiological pH of 7.4 can be separated by the exclusion effect of polymer films of the same charge. In addition to ionic polymers, self-assembled monolayers 7 and carbon nanotubes 8 also increase the selectivity for DA. Anionic polymer-modified electrodes are useful for increasing the selectivity toward cationic DA over anionic AA. The desirable anionic polymer material should be well suited to biological samples. The macrocyclic Ni(II) complex is readily electropolymerized by oxidation or cycling the potential, and the stable polymer film has a catalytic effect on substances such as AA. 9 To obtain an anionic polymermodified electrode, the macrocyclic Ni(II) complex can be used with an anionic polymer or a macrocyclic Ni(II) complex with an introduced carboxylic acid group. The anionic macrocyclic Ni(II) complex also readily forms a negatively charged electropolymerized film on an electrode surface. Polyurethane (PU) containing γ-benzyl L-glutamate segments (PUBLG) is a new polymer, 10 which is a segmented PU. Segmented PUs are used in devices that contact blood, such as catheters and artificial hearts, because of their good mechanical properties and tolerance of blood. 11,12 A hydrophobic PUBLG film can be converted into an anionic hydrophilic PU film on introducing carboxylate groups by hydrolysis. We applied an anionic PU film to the selective determination of DA for the first time. This study examined the selectivity of anionic polymermodified electrodes for DA over AA and their suitability for use with human urine. Their sensitivity and reproducibility were evaluated using amperometry with flow injection. These anionic polymers were compared with Nafion, a perfluorosulfonated ion-exchange material.

The main purpose of this research is to look into not only how users evaluate two major databases(BIST and SATURN) of the scientific and technical literature in Korea, but also what users expect from scientific and technical information services in general. The result of the user evaluation shows that there is a very little difference between two databases in database quality. It was found that BIST is better than SATURN in terms of accuracy, customer support, searching capability, and currency, whereas SATURN is preferred to BIST for completeness and the average number of retrieved items. User expectation for scientific and technical information is also investigated by surveying its user community. Among three user groups, there is notable disagreement in language uses to search non-korean literature. Each group also shows different demands for translation of original literature. This study attempted to evaluate the quality of the scientific and technical information (BIST and SATURN) and simultaneously to investigate users demands in general. By doing so, the specificity implied in quality evaluation of specific information services as well as the generalization of the users behaviors in scientific and technical community were accommodated in this study.

Background Kruppel-like-factor (KLF) 10 is identified as transforming growth factor (TGF) β inducible early gene and is reported to suppress lipogenic genes. Although previous studies report that TGFβ plays an important role in progression of nonalcoholic steatohepatitis (NASH) by regulating liver fibrosis, the association of KLF10 and NASH has never been explored. Thus we evaluated expressions and changes of KLF10 in diet induced NASH and in NASH which was alleviated by ursodeoxycholic acid (UDCA). We also assessed KLF10 in quiescent and activated hepatic stellate cells (HSCs). Methods C57BL/6 mice were given high fat, sucrose diet (HFSD) at least for 12 weeks up to 48 weeks and sacrificed at 12, 24 and 48 weeks thereafter. In other groups, either standard diet (SD) or HFSD was given for 24 weeks at which point mice fed with HFSD were divided into two groups, and were given either UDCA in combination with HFSD or vehicle with HFSD. Mice under SD were given vehicle. HSCs were isolated from C57BL/6 mice in order to evaluated KLF10 expression in activated HSCs. Results The mice were found to acquire liver steatosis and inflammation starting from week 12 of HFSD feeding, although significant liver fibrosis was noticed by week 24. Increased TGFβ and collagen α1(I) (Col1α(I)) expression was also apparent from week 24. However, expression of KLF10 mRNA started to increase from week 12, earlier than TGFβ gene. Up-regulation of KLF10 was accompanied by suppressed carbohydrate response element-binding protein (ChREBP) that is known to be protective against insulin resistance. The mice fed with HFSD and UDCA had decreased Colα(I) mRNA that was coincided with reduced TGFβ and KLF10 expression. Expression of ChREBP was also recovered by UDCA administration. Enhanced KLF10 was noticed in activated HSCs when quiescent cell showed minimal expression. Conclusions Our study demonstrated that KLF10 expression was significantly increased in diet induced NASH and collagen producing activated HSCs. We also noticed that this up-regulation of KLF10 was accompanied by increased TGFβ signaling genes and suppressed ChREBP expression. These observations suggest possible association of KLF10 and NASH progression.

1,5,8,12-Tetraaza-2,4,9,11-tetramethylcyclotetradecinatonickel(II) was synthesized for a new Ni(II) complex of the asymmetric tetraaza macrocycle and this complex was electropolymerized on a glassy carbon electrode in acetonitrile by cyclic voltammetric and constant potential methods. The modified electrodes were characterized by cyclic voltammetry and hydrodynamic voltammetry. They showed electrocatalytic effects on the oxidation of l -ascorbic acid and the peak potential shifted to the negative by 200 mV compared with that for the bare electrode in the cyclic voltammograms. In the flow injection analysis the oxidation potential of l -ascorbic acid at the modified dual glassy carbon electrode also shifted to a lower potential and the sensitivity was enhanced greatly. The amperometric determination of l -ascorbic acid by the flow injection method was performed at 0.5 V versus Ag ∣ AgCl ∣ NaCl(sat.) and the calibration curve was linear in the range of 5.0×10−7 to 1.0×10−3 M (R=0.9989). The detection limit was 4.7×10−7 M. The modified electrode was highly stable under the hydrodynamic conditions, which could be used for 45 repeated injections within a relative standard deviation of 5%. A GCE electropolymerized with the Ni(II) complex of the tetraaza macrocycle was used for the determination of l -ascorbic acid in commercial beverage samples and the results were in good agreement with the labeled values and those obtained by the reference method. The analysis with the polymer modified electrodes was selective for l -ascorbic acid from the various additives in the real samples.

Adenosine-modified glassy carbon electrodes were prepared for the determination of glucose without using an immobilized redox mediator. Glucose oxidase (GOD) was immobilized with Nafion film onto an adenosine-modified electrode, which could electrochemically oxidize the immobilized GOD by differential pulse voltammetry at a peak potential of -470 mV vs. SCE. The peak can be used in the analysis of the substrate, although from the response of the GOD electrode it is not clear whether the redox centers from the GOD are dissociated completely or partially. The increase of the peak current with the concentration of glucose shows that the adenosine-modified electrode can be used for the determination of glucose. The enzymatic activity of GOD immobilized on the adenosine-modified electrode was greatly influenced by the length of electrode surface oxidation. The apparent Michaelis constant, K m' and the current maximum, I max, obtained from Lineweaver-Burk plot of the calibration curve were 33 mM and 1....

Hepatitis B virus (HBV) replication detected before the resection of hepatocellular carcinoma (HCC) is to be controlled by antiviral agents. However, management strategy for patients with preoperatively undetectable HBV DNA without antiviral therapy is not clearly delineated. This study investigated viral reactivation after the liver resection in non-replicating HBV DNA-related HCC patients and its impact on the surgical outcome.From 198 patients that underwent liver resection due to HBV-related HCC, 101 patients who had serially checked serum HBV DNA were analyzed.From 101 patients, 33 patients had baseline undetectable HBV DNA. Eleven patients (11/33, 33.3%) had viral replication after the liver resection. The postoperative viral reactivation (HR: 2.144; 95% CI: 1.122-4.097; P = 0.021), along with the existence of satellite nodules (HR: 3.034; 95% CI: 1.1.376-6.689; P = 0.006), existence of microvascular invasion (HR: 2.479; 95% CI: 1.303-4.718; P = 0.006), and HBeAg positivity (HR: 2.059; 95% CI: 1.155-3.670; P = 0.014) predicted recurrence after the surgery. Quantification of intrahepatic total and covalently closed circular DNA (cccDNA) was done in 14 patients whose baseline serum HBV DNA was undetectable without the use of antiviral agent. Amount of intrahepatic cccDNA expressed as copies/hepatocyte in patients with postoperative viral reactivation showed significantly higher than those in patients with sustained negative serum HBV DNA (P = 0.010).This study shows that naturally suppressed preoperative HBV without application of antiviral agent does not ensure undetectable serum HBV after the surgery, and postoperative viral reactivation might be associated with HCC recurrence.

Background/Aims To investigate pre-existing hepatitis B virus (HBV) quasispecies and the genotypic evolution of several variants. Methods From six patients with lamivudine (LAM) failure, serum samples at pretreatment, 6 months of LAM therapy, and virologic breakthrough were obtained. One hundred clones with HBV inserts in each patient were sequenced at each time point. Pretreatment serum samples were also analyzed from six patients who achieved good responses to LAM therapy. Results Among the six patients with LAM failure, the analysis of 100 clones from patient 1 revealed the substitutions L180M in 1% of clones and V173L in 2% of clones. Patient 2 had substitutions of L80V, W153Q, and L180M. In patient 3, mutations conferring resistance to adefovir at V84I (5%), I169L (1%), and N236H (7%) and entecavir at S202G (2%) were detected. Patient 4 had mutations at T128N (1%), I169L (1%), V173L (2%), A181V (1%), and Q215H (1%). In patient 5, M204V/I was detected in 1% and 2% of clones, respectively. L80I and V173L were also identified in patient 6. In the six patients who responded to LAM, the degree of overall quasispecies was less than those with LAM failure. Conclusions Various HBV quasispecies associated with drug resistance existed before treatment, and the quasispecies dynamically changed through LAM therapy.

Background: Entecavir (ETV) has potent antiviral activity against hepatitis B virus (HBV), and the emergence of drug resistance is rare in nucleoside-naive patients. Resistance requires simultaneous appearance of three mutations which account for the very low resistance profile of ETV. We experienced one case of genotypic ETV resistance with viral rebound during ETV treatment of nucleoside-naive patients with chronic hepatitis B (CHB). Case: A 50-year-old HBV e antigen-positive man received ETV 0.5 mg/day for 120 weeks. The level of HBV DNA was 9.0 log10 copies/ml at baseline, declined to a nadir of 2.7 at week 60 and then rebounded to 6.0 at week 108 and 7.5 at week 120. The serum alanine aminotransferase level did not increase during ETV treatment. The ETV resistance-related substitution (T184A) and lamivudine resistance-related substitutions (L180M and M204V) were detected by sequence analysis at week 96. Conclusions: The three substitutions associated with ETV and lamivudine resistance developed simultaneously without complete suppression in a nucleoside-naive CHB patient after extended therapy. In spite of the extremely rare chance of viral mutation during ETV treatment, treatment-naive patients with high pretreatment viral loads and detectable HBV DNA during treatment should be carefully monitored or undergo targeted surveillance for resistance.

Hepatitis B virus (HBV) induces inflammatory signaling leading to progressive liver damage. Polymorphisms of the toll-like receptor (TLR) 2 (Arg677Trp, Arg753Gln) and TLR4 (Asp299Gly, Thr399Ile) genes, which are important components of innate immunity against viral infection, have recently been described. We evaluated the association between TLR2 and TLR4 polymorphisms and the development of liver cirrhosis in Koreans with chronic HBV infection.This study enrolled 456 Koreans with chronic HBV infection between December 2004 and October 2007; 242 with chronic hepatitis B (group I) and 214 with liver cirrhosis (group II). TLR2 and TLR4 polymorphisms were determined using direct sequencing.Mean age differed significantly between groups (group I, 34.8 +/- 11.4 years; group II 51.0 +/- 8.9 years; p0.001), whereas the proportion of males (80.2% vs. 73.4%, respectively; p = 0.085) and hepatitis B e antigen-positive patients (40.7% vs. 43.6%, respectively; p = 0.575) did not. The serum alanine aminotransferase level was significantly higher in group I (87.9 +/- 138.5 IU/L) than in group II (56.6 +/- 70.7 IU/L, p = 0.003). However, the TLR2 Arg677Trp and Arg753Gln and TLR4 Asp299Gly and Thr399Ile mutant alleles were not detected in any patients.The TLR2 Arg677Trp, Arg753Gln and TLR4 Asp299Gly, Thr399Ile mutant alleles were not detected in any patient, suggesting that they are very rare in the Korean population. Our results do not permit any conclusion regarding their role in the development of liver cirrhosis.

The interactions among hepatitis B virus (HBV) mutations in developing hepatocellular carcinoma (HCC) remain unclear and thus we investigated the risk of HCC related with single or multiple HBV mutations in Korean patients infected with HBV subgenotype C2.From January 2003 to December 2008, HBV isolates from 135 patients with HCC were compared with those from 135 patients without HCC, matching for age, gender, and HBeAg status. The prevalence of preS deletions and G1896A and A1762T/G1764A mutations was evaluated.The frequency of preS deletions significantly differed between the non-HCC and HCC groups, with 6 (4.4%) versus 25 (18.5%) patients, respectively (p0.001). Additionally, the frequency of A1762T/G1764A mutations was higher in the HCC than the non-HCC group [82 (60.7%) versus 30 (22.2%), p0.001]. For combined mutations, the odds ratio (OR) was highest in patients with both preS deletions and the A1762T/G1764A mutation, with 1 (0.7%) versus 11 (8.1%) patients (p = 0.005; OR 11.887).HCC was associated with preS deletions and A1762T/G1764A mutations, and the combination of both mutations had a stronger association with HCC in Korean patients infected with HBV subgenotype C2.