<i>CYP2C19</i> haplotypes in Koreans as a marker of enzyme activity evaluated with omeprazole

Jin, S. K.,Kang, T. S.,Eom, S. O.,Kim, J.-I.,Lee, H. J.,Roh, J. Blackwell Publishing Ltd 2009 Journal of clinical pharmacy and therapeutics Vol.34 No.4

<P>Summary</P><P>Background and objective: </P><P>CYP2C19 is clinically important in Korea because of the relatively high incidence of poor metabolizers in the population. To fully understand the genetic mechanism of the <I>CYP2C19</I> defect in poor metabolizers, all variants need to be studied simultaneously. The aim of this study was to investigate the usefulness of <I>CYP2C19</I> haplotypes as a marker of CYP2C19 enzyme activity in Koreans.</P><P>Methods: </P><P>We analysed the single nucleotide polymorphisms and haplotypes of the <I>CYP2C19</I> gene in 150 healthy Koreans and found three major (frequency > 0·1) haplotypes (H1, H2 and H3). One oral dose of 40 mg omeprazole (Losec<SUP>®</SUP>) was administered to 30 subjects grouped as H1/H1, H2/H2, H1/H2, H1/H3 and H2/H3. The pharmacokinetics of omeprazole and its metabolites, 5-hydroxyomeprazole and omeprazole sulphone, in those groups was analysed.</P><P>Results and discussion: </P><P>The area under the plasma concentration–time curve (AUC<SUB>0→∞</SUB>) and elimination half-life (<I>T</I><SUB>1/2</SUB>) of omeprazole were significantly greater in the H2/H2 and H2/H3 groups than in the H1/H1 group (<I>P </I><<I> </I>0·05), whereas the metabolic ratios of omeprazole to 5-hydroxyomeprazole were also markedly higher.</P><P>Conclusion: </P><P>Although a specific SNP of <I>CYP2C19</I> may be predictive of enzyme activity, haplotyping is more reliable for identifying poor metabolizers in populations with variant alleles other than <I>CYP2C19*2</I> and <I>*3</I> alleles.</P>

Urinary concentration of transforming growth factor-&bgr;-inducible gene-h3(&bgr;ig-h3) in patients with Type 2 diabetes mellitus

Cha, D. R.,Kim, I. S.,Kang, Y. S.,Han, S. Y.,Han, K. H.,Shin, C.,Ji, Y. H.,Kim, N. H. Blackwell Science Ltd 2005 Diabetic medicine Vol.22 No.1

<P>Abstract</P><P>Aims </P><P>The expression of TGF&bgr;-inducible gene h3(&bgr;ig-h3) has been used to assess the biological activity of TGF&bgr; in the kidney. In this study, we investigated whether the urinary concentration of &bgr;ig-h3 is associated with diabetic nephropathy in patients with Type 2 diabetes mellitus. We also evaluated the relationship between the urinary concentration of &bgr;ig-3 and proteinuria and microalbuminuria (AER) in a normal healthy population and in Type 2 diabetes patients.</P><P>Methods </P><P>Four hundred and seventy-nine Type 2 diabetic patients without non-diabetic kidney diseases and 528 healthy control subjects were enrolled. The study subjects were divided into five groups: a non-diabetic healthy control group with normal ACR (<I>n</I> = 443), a non-diabetic healthy control group with microalbuminuria (<I>n</I> = 85), a normoalbuminuric diabetic group (<I>n</I> = 198), a microalbuminuric diabetic group (<I>n</I> = 155) and an overt proteinuria group (<I>n</I> = 126). Urinary levels of &bgr;ig-h3 were measured by enzyme-linked immunosorbent assay.</P><P>Results </P><P>(i) Urinary excretion of &bgr;ig-h3 was significantly higher in the diabetic groups than in the controls, even in the normoalbuminuric stage (25.02 ± 8.84 vs. 18.67 ± 6.56, <I>P</I> = 0.03). In diabetic patients, urinary &bgr;ig-h3 levels increased significantly as diabetic nephropathy advanced (25.02 ± 8.84 vs. 34.06 ± 24.55 vs. 169.63 ± 57.33, <I>P</I> < 0.001). (ii) Proteinuria was found to be significantly correlated with urinary &bgr;ig-h3 (healthy control; <I>r</I> = 0.137, <I>P</I> = 0.019, diabetic patients; <I>r</I> = 0.604, <I>P</I> < 0.001). ACR was also found to be significantly related with urinary &bgr;ig-h3 in diabetic patients (<I>r =</I> 0.383, <I>P</I> = 0.006). (iii) In diabetic patients, urinary &bgr;ig-h3 was significantly related with systolic and diastolic blood pressure (systolic blood pressure: <I>r</I> = 0.436, <I>P</I> = 0.024; diastolic blood pressure, <I>r</I> = 0.365, <I>P</I> = 0.042), total cholesterol and HbA<SUB>1c</SUB> (cholesterol: <I>r</I> = 0.169, <I>P</I> = 0.03, HbA<SUB>1c</SUB>; <I>r</I> = 0.387, <I>P</I> = 0.044). Logistic regression analyses showed that urinary &bgr;ig-h3 was associated with a significant increase in the risk of microalbuminuria and proteinuria in diabetic patients.</P><P>Conclusions </P><P>Longitudinal monitoring of urinary &bgr;ig-h3 may improve the likelihood of detecting diabetic nephropathy at an earlier stage and &bgr;ig-h3 could be a sensitive marker of diabetic kidney disease progression.</P>

Diagnostic usefulness of a T cell-based assay for latent tuberculosis infection in kidney transplant candidates before transplantation

Kim, S.-H.,Lee, S.-O.,Park, I.-A.,Park, S.J.,Choi, S.-H.,Kim, Y.S.,Woo, J.H.,Park, S.-K.,Park, J.S.,Kim, S.C.,Han, D.J. Blackwell Publishing Inc 2010 Transplant infectious disease Vol.12 No.2

<P>S.-H. Kim, S.-O. Lee, I.-A. Park, S.J. Park, S.-H. Choi, Y.S. Kim, J.H. Woo, S.-K. Park, J.S. Park, S.C. Kim, D.J. Han. Diagnostic usefulness of a T cell-based assay for latent tuberculosis infection in kidney transplant candidates before transplantation.Transpl Infect Dis 2010: <B>12:</B> 113–119. All rights reserved</P><P>Background</P><P>The presence of latent tuberculosis (TB) infection (LTBI) should be evaluated before kidney transplantation. Although a new T cell-based assay for diagnosing LTBI gave promising results, this assay has not yet been compared with the tuberculin skin test (TST) for diagnosing LTBI in renal transplant candidates before transplantation.</P><P>Patients and methods</P><P>All adult patients admitted to a single institute for renal transplantation over a 1-year period were prospectively enrolled. A clinically predictive risk of LTBI was defined as: (i) recent close contact with a person with pulmonary TB; (ii) abnormal chest radiography; (iii) a history of untreated or inadequately treated TB; or (iv) a new infection (i.e., a recent conversion of TST).</P><P>Results</P><P>Of 209 renal recipients, 47 (22%) had a positive TST≥5 mm, 21 (10%) had a positive TST≥10 mm, 65 (30%) had a positive T-SPOT.<I>TB</I> test, and 25 (12%) had an indeterminate T-SPOT.<I>TB</I> test. The induration size of TST was significantly associated with a high positivity rate on T-SPOT.<I>TB</I> (<I>P</I><0.001). Agreement between T-SPOT.<I>TB</I> test and TST≥10 mm was fair (<I>k</I>=0.24, 95% confidence interval 0.11–0.36). However, neither univariate nor multivariate analysis showed any association between the clinical risk for LTBI and positivity on T-SPOT.<I>TB</I> or TST.</P><P>Conclusion</P><P>T-SPOT.<I>TB</I> test was more frequently positive than TST in renal transplant candidates. However, further longitudinal studies are awaited to determine whether the ability of T-SPOT.<I>TB</I> assay to detect LTBI in renal transplant recipients can better predict the development of TB than can TST after transplantation.</P>

Influence of <i>CYP2D6*10</i> on the pharmacokinetics of metoprolol in healthy Korean volunteers

Jin, S. K.,Chung, H. J.,Chung, M. W.,Kim, J.-I.,Kang, J.-H.,Woo, S. W.,Bang, S.,Lee, S. H.,Lee, H. J.,Roh, J. Blackwell Publishing Ltd 2008 Journal of clinical pharmacy and therapeutics Vol.33 No.5

<P>Summary</P><P>Background and objective: </P><P>Genetic polymorphism of <I>CYP2D6</I> leads to differences in pharmacokinetics of CYP2D6 substrates. The <I>CYP2D6*10</I> allele is clinically important in Koreans because of its high frequency in Asians. We investigated whether the pharmacokinetics of metoprolol was altered by the presence of the <I>CYP2D6*10</I> allele in Korean subjects.</P><P>Methods: </P><P>One hundred and seven volunteers were recruited and grouped as <I>CYP2D6*1/*1</I>, <I>CYP2D6*1/*10</I> and <I>CYP2D6*10/*10</I> according to their genotypes. Metoprolol tartrate 100 mg (Betaloc<SUP>®</SUP>) was administered orally once to each subject in these three groups (<I>n</I> = 6, 7 and 5, respectively). The pharmacokinetic parameters of metoprolol and its metabolite, &agr;-hydroxymetoprolol, and the metabolic ratio for the three groups were estimated and compared.</P><P>Results and discussion: </P><P>The area under the plasma concentration–time curve (AUC<SUB>0→∞</SUB>), the maximum plasma concentration (<I>C</I><SUB>max</SUB>) and the elimination half-life (<I>T</I><SUB>1/2</SUB>) of metoprolol and &agr;-hydroxymetoprolol for the <I>CYP2D6*10/*10</I> group were all significantly different from those of the <I>CYP2D6*1/*1</I> group (<I>P</I> < 0·05). The AUC<SUB>0→∞</SUB>s of metoprolol were 443·7 ± 168·1, 995·6 ± 321·4 and 2545·3 ± 632·0 ng·h/mL, and the AUC<SUB>0→∞</SUB>s of &agr;-hydroxymetoprolol were 1232·0 ± 311·2, 1344·0 ± 288·1 and 877·4 ± 103·4 ng·h/mL for groups <I>CYP2D6*1/*1</I>, <I>*1/*10</I> and <I>*10/*10</I>, respectively. The corresponding <I>T</I><SUB>1/2</SUB> values of metoprolol were 2·7 ± 0·5, 3·2 ± 1·3 and 5·0 ± 1·1 h, while those of &agr;-hydroxymetoprolol were 5·4±1·5, 6·0 ± 1·4 and 10·5 ± 4·2 h, respectively. The metabolic ratios of the three groups were significantly different (<I>P</I> < 0·05).</P><P>Conclusion: </P><P>The <I>CYP2D6*10</I> allele altered the pharmacokinetics of metoprolol in Korean subjects and is likely to affect other drugs metabolized by the CYP2D6 enzyme, similarly.</P>

Genetic diversity and pathogenic potential of low pathogenic H7 avian influenza viruses isolated from wild migratory birds in Korea

Kim, Y.I.,Kim, S.W.,Si, Y.J.,Kwon, H.I.,Park, S.J.,Kim, E.H.,Kim, S.m.,Lee, I.W.,Song, M.S.,Choi, Y.K. Elsevier Science 2016 Infection, genetics and evolution Vol.45 No.-

To detect the circulation of H7 avian influenza viruses, we characterized H7 viruses found in migratory birds and live poultry markets of South Korea from 2005 to 2014. Phylogenic analysis revealed that while all viruses clustered into the Eurasian-lineage of H7 avian viruses, at least 12 distinct genotypes were represented. Most H7 viruses contained at least one gene segment from the highly-pathogenic A/Sck/Hong Kong/YU100/02(H5N1)-like avian virus, and they could be separated into at least two antigenic groups. Although we did not detect genetically identical strains, HI assay demonstrated close cross-reactivity of some isolates with the H7N9 viruses from China. Animal studies revealed that most of the genotypes could replicate in the lungs of mice and chickens without prior adaptation and some, particularly H7N4 and H7N7 subtypes, induced mortality in mice. These results reinforce growing pandemic concerns regarding recent H7 viruses and emphasize the importance of continued surveillance of avian influenza viruses in the wild.

Effect of the Length of Feed Withdrawal on Weight Loss, Yield and Meat Color of Broiler

Kim, D.H.,Yoo, Y.M.,Kim, S.H.,Jang, B.G.,Park, B.Y.,Cho, S.H.,Seong, P.N.,Hah, K.H.,Lee, J.M.,Kim, Y.K.,Hwang, I.H. Asian Australasian Association of Animal Productio 2007 Animal Bioscience Vol.20 No.1

The current study was conducted to determine the optimum length of feed withdrawal for pre-harvest broilers. A total of three hundred broilers were sampled from an industrial population, and 30 chicks for each weight group (e.g., 1.5 and 2.5 kg) were randomly assigned to feed withdrawal treatments for 0, 3, 6, 9 and 12 h. Weight loss, yield, muscle pH, objective meat color and weights of gastro intestinal contents, crop, gizzard, provenriculus, small intestine, caecum, and rectum were determined. Live weight loss was significantly (p<0.05) increased as length of feed withdrawal extended. A significant (p<0.05) carcass yield for both 1.5 and 2.5 kg groups coincided after 9 and 6 h feed withdrawal, respectively. Net weights of intestinal contents for crop and gizzard were significantly (p<0.05) reduced by 6 h, and the reduction for proventriculus and small intestine occurred from 3 h. A noticeable effect of feed withdrawal on pH for breast muscle at 3 h postmortem occurred only when chicks were fasted for 3 h of which pH (6.05) was significantly (p<0.05) higher than that for other groups including the control (5.74). There was a linear tendency of higher lightness (Hunter L* value) numerically for chicks fasted for longer periods. The highest coefficient of determinations of regression models to estimate weight loss as a function of fasting period and body weights were achieved, when the models included both linear and quadratic terms for fasting period, and linear term for both 1.5 ($R^2=0.76$) and 2.5 kg ($R^2=0.78$) body weight groups. Given the practical aspect, approximately 1.5 kg of body weight is dominant, weight loss could be predicted by the following function; live weight $loss=26.6-0.28{\times}(fasting period)^2+12.34{\times}pasting\;period-0.012{\times}body\;weight$, $R^2=0.76$. Current data implied that the optimum fasting time for pre-slaughter chicks varied depending on slaughter weight; 6 and 9-h fasting were recommendable for 2.5 and 1.5 kg chicks, with little effect on objective meat color.

Genetic and phylogenetic characterizations of a novel genotype of highly pathogenic avian influenza (HPAI) H5N8 viruses in 2016/2017 in South Korea

Kim, Y.I.,Park, S.J.,Kwon, H.I.,Kim, E.H.,Si, Y.J.,Jeong, J.H.,Lee, I.W.,Nguyen, H.D.,Kwon, J.J.,Choi, W.S.,Song, M.S.,Kim, C.J.,Choi, Y.K. Elsevier Science 2017 INFECTION GENETICS AND EVOLUTION Vol.53 No.-

<P>During the outbreaks of highly pathogenic avian influenza (HPAI) H5N6 viruses in 2016 in South Korea, novel H5N8 viruses were also isolated from migratory birds. Phylogenetic analysis revealed that the HA gene of these H5N8 viruses belonged to clade 2.3.4.4, similarly to recent H5Nx viruses, and originated from A/Brk/Korea/Gochang1/14(H5N8), a minor lineage of H5N8 that appeared in 2014 and then disappeared. At least four reassortment events occurred with different subtypes (H5N8, H7N7, H3N8 and H10N7) and a chicken challenge study revealed that they were classified as HPAI viruses according to OIE criteria. (C) 2017 Elsevier B.V. All rights reserved.</P>

5,7-dihydroxy-3,4,6-trimethoxyflavone inhibits the inflammatory effects induced by <i>Bacteroides fragilis</i> enterotoxin via dissociating the complex of heat shock protein 90 and I&kgr;B&agr; and I&kgr;B kinase-&ggr; in intestinal epithelial cell cultu

Kim, J. M.,Lee, D. H.,Kim, J. S.,Lee, J. Y.,Park, H.-G.,Kim, Y.-J.,Oh, Y.-K.,Jung, H. C.,Kim, S. I. Blackwell Publishing Ltd 2009 Clinical and experimental immunology Vol.155 No.3

<P>Summary</P><P>Enterotoxin produced by enterotoxigenic <I>Bacteroides fragilis</I> (BFT) has been associated with mucosal inflammation and diarrhoeal diseases. In this study, the anti-inflammatory molecular mechanism of 5,7-dihydroxy-3,4,6-trimethoxyflavone (eupatilin) was characterized in an HT-29 intestinal epithelial cell line stimulated with BFT. Pre-treatment of HT-29 cells with eupatilin decreased the production significantly of both interleukin (IL)-8 and prostaglandin E<SUB>2</SUB> induced by BFT in a dose-dependent manner. BFT-activated nuclear factor-kappaB (NF-&kgr;B) signals in HT-29 cells and pretreatment with eupatilin suppressed NF-&kgr;B activation that resulted in the significant inhibition of IL-8 and cyclo-oxygenase-2 expression. BFT-induced phosphorylation of both I&kgr;B&agr; and I&kgr;B kinase (IKK) signals was prevented in eupatilin-pretreated HT-29 cells. Transfection of siRNA for IKK-&agr; and IKK-&bgr; decreased the production of IL-8 and prostaglandin E<SUB>2</SUB>; however, the transfection of IKK-&bgr; siRNA showed a more significant reduction of BFT-induced I&kgr;B&agr; phosphorylation compared with that of IKK-&agr; siRNA. In addition, herbimycin A, a specific inhibitor of heat shock protein 90 (Hsp90), decreased the BFT-induced activation of IKK and NF-&kgr;B, suggesting that Hsp90 is associated with a pathway of IKK-NF-&kgr;B-IL-8/cyclo-oxygenase-2 gene signalling. Furthermore, eupatilin dissociated the complex between Hsp90 and IKK-&ggr; in BFT-stimulated HT-29 cells. These results suggest that eupatilin can suppress the NF-&kgr;B signalling pathway by targeting the Hsp90-IKK-&ggr; complex in intestinal epithelial cells and may attenuate BFT-induced inflammatory responses.</P>

Induction of bone formation by <i>Escherichia coli</i>‐expressed recombinant human bone morphogenetic protein‐2 using block‐type macroporous biphasic calcium phosphate in orthotopic and ectopic rat models

Park, J‐,C.,So, S‐,S.,Jung, I‐,H.,Yun, J‐,H.,Choi, S‐,H.,Cho, K‐,S.,Kim, C‐,S. Blackwell Publishing Ltd 2011 Journal of periodontal research Vol.46 No.6

<P><I>Park J‐C, So S‐S, Jung I‐H, Yun J‐H, Choi S‐H, Cho K‐S, Kim C‐S. Induction of bone formation by</I> Escherichia coli<I>‐expressed recombinant human bone morphogenetic protein‐2 using block‐type macroporous biphasic calcium phosphate in orthotopic and ectopic rat models. J Periodont Res 2011; 46: 682–690. © 2011 John Wiley & Sons A/S</I></P><P><B>Background and Objective: </B> The potential of the <I>Escherichia coli</I>‐expressed recombinant human bone morphogenetic protein‐2 (ErhBMP‐2) to support new bone formation/maturation using a block‐type of macroporous biphasic calcium phosphate (bMBCP) carrier was evaluated in an orthotopic and ectopic rat model.</P><P><B>Material and Methods: </B> Critical‐size (Φ 8 mm) calvarial defects and subcutaneous pockets in 32 Sprague–Dawley rats received implants of rhBMP‐2 (2.5 μg) in a bMBCP carrier or bMBCP alone (control). Implant sites were evaluated using histological and histometric analysis following 2‐ and 8‐wk healing intervals (eight animals/group/interval).</P><P><B>Results: </B> ErhBMP‐2/bMBCP supported significantly greater bone formation at 2 and 8 wk (10.8% and 25.4%, respectively) than the control at 2 and 8 wk (5.3% and 14.0%, respectively) in calvarial defects (<I>p</I> < 0.01). Bone formation was only observed for the ErhBMP‐2/bMBCP ectopic sites and was significantly greater at 8 wk (7.5%) than at 2 wk (4.5%) (<I>p</I> < 0.01). Appositional and endochondral bone formation was usually associated with a significant increase in fatty marrow at 8 wk. The bMBCP carrier showed no evidence of bioresorption.</P><P><B>Conclusion: </B> ErhBMP‐2/bMBCP induced significant bone formation in both calvarial and ectopic sites. Further study appears to be required to evaluate the relevance of the bMBCP carrier.</P>

Application of fluoride iontophoresis to improve remineralization

KIM, H. E.,KWON, H. K.,KIM, B. I. Blackwell Publishing Ltd 2009 Journal of oral rehabilitation Vol.36 No.10

<P>Summary </P><P>Iontophoresis is generally used to maximize the therapeutic action of drugs in medicine. This technique can be used to improve the remineralization effect of topical fluoride applications in dentistry. The aim of this study was to compare the remineralization effect of fluoride iontophoresis (FI) with the conventional fluoride application (CFA) method <I>in vitro</I>. Sixty bovine enamel specimens were divided into three groups: no fluoride treatment, CFA and FI. Fluoride was applied to the demineralized specimens for 4 min in each experimental group. The types of fluoride system used for application were 1·23% acidulated phosphate fluoride gel (12 300 p.p.m. F, pH 3·5) and 2% sodium fluoride solution (9050 p.p.m. F, pH 7) in the experimental groups. All the specimens were then placed in a remineralizing solution for 24 h. This cycle was repeated five times. An iontophoresis device (0·4 mA, 12 V) was used in the FI groups. The efficacy of this technique was evaluated by measuring changes in the surface microhardness and lesion depth of the specimens using confocal laser scanning microscope (CLSM). Data were analysed using <SMALL>ANOVA</SMALL> and Tukey’s <I>post hoc</I> test (<I>P </I><<I> </I>0·05). Although the FI groups showed higher &Dgr;VHN than the CFA groups, there were no significant differences between these fluoride application methods (<I>P </I>><I> </I>0·05). When the lesion depth was measured using CLSM imaging, there was also no significant difference between the FI and CFA groups (<I>P </I>><I> </I>0·05). In conclusion, FI was not significantly superior to CFA in terms of the remineralization effect.</P>