<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>

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>

VP2 capsid domain of the H-1 parvovirus determines susceptibility of human cancer cells to H-1 viral infection

Cho, I-R,Kaowinn, S,Song, J,Kim, S,Koh, S S,Kang, H-Y,Ha, N-C,Lee, K H,Jun, H-S,Chung, Y-H Nature America, Inc. 2015 Cancer gene therapy Vol.22 No.5

Although H-1 parvovirus is used as an antitumor agent, not much is known about the relationship between its specific tropism and oncolytic activity. We hypothesize that VP2, a major capsid protein of H-1 virus, determines H-1-specific tropism. To assess this, we constructed chimeric H-1 viruses expressing Kilham rat virus (KRV) capsid proteins, in their complete or partial forms. Chimeric H-1 viruses (CH1, CH2 and CH3) containing the whole KRV VP2 domain could not induce cytolysis in HeLa, A549 and Panc-1 cells. However, the other chimeric H-1 viruses (CH4 and CH5) expressing a partial KRV VP2 domain induced cytolysis. Additionally, the significant cytopathic effect caused by CH4 and CH5 infection in HeLa cells resulted from preferential viral amplification via DNA replication, RNA transcription and protein synthesis. Modeling of VP2 capsid protein showed that two variable regions (VRs) (VR0 and VR2) of H-1 VP2 protein protrude outward, because of the insertion of extra amino-acid residues, as compared with those of KRV VP2 protein. This might explain the precedence of H-1 VP2 protein over KRV in determining oncolytic activity in human cancer cells. Taking these results together, we propose that the VP2 protein of oncolytic H-1 parvovirus determines its specific tropism in human cancer cells.

Two NF-κB inhibitor-alpha (IκBα) genes from rock bream (Oplegnathus fasciatus): Molecular characterization, genomic organization and mRNA expression analysis after immune stimulation

Lee, Y.,Umasuthan, N.,Whang, I.,Revathy, K.S.,Lee, S.,De Zoysa, M.,Oh, C.,Kang, D.H.,Noh, J.K.,Lee, J. Academic Press 2014 FISH AND SHELLFISH IMMUNOLOGY Vol.41 No.2

IκBα is a member of IκB family, which sequesters NF-κB in an inactivate form in the cytoplasm and blocks the translocation of NF-κB to nucleus. The IκBα paralogs of rock bream (OfIκBα-A and OfIκBα-B) encoded IκBα proteins with typical features including, highly conserved IκB degradation motif, six ankyrin repeats and a PEST sequence. However, their amino acid identity and similarity were only 55.6 and 69.7%, respectively suggesting that these two genes could be the two different isoforms of IκBα. The number and size of the exons of OfIκBα-A and OfIκBα-B were conserved well with all the compared vertebrate species, although they have significantly different genomic sizes. Phylogenetic analysis revealed that OfIκBα-A and OfIκBα-B proteins cluster with IκBα family members; however, they were grouped with different subclades in IκBα family. Tissue specific expression of OfIκBα mRNA was constitutively detected in all the tested tissues, and they showed the higher transcription level in heart, liver, gill and peripheral blood cells, respectively. The injection of flagellin stimulated the mRNA expression of OfIκBα paralogs in head kidney and intestine. Moreover, the OfIκBα mRNA expression in gill and liver was significantly up-regulated by LPS, poly I:C and Edwardsiella tarda challenges. The transcription of OfIκBα was up-regulated in early-phase of injection and then rapidly restored. These results suggest that the OfIκBα paralogs might be involved in rapid immune responsive reactions in rock bream against bacterial and viral pathogens.

Experimental infection of mandarin duck with highly pathogenic avian influenza A (H5N8 and H5N1) viruses

Kang, H.M.,Lee, E.K.,Song, B.M.,Heo, G.B.,Jung, J.,Jang, I.,Bae, Y.C.,Jung, S.C.,Lee, Y.J. Elsevier Scientific Pub. Co 2017 Veterinary microbiology Vol.198 No.-

<P>A highly pathogenic avian influenza (HPAI) H5N8 virus was first detected in poultry and wild birds in South Korea in January 2014. Here, we determined the pathogenicity and transmissibility of three different clades of 1-15 viruses in mandarin ducks to examine the potential for wild bird infection. H5N8 (Glade 2.3.4.4) replicated more efficiently in the upper and lower respiratory tract of mandarin ducks than two previously identified H5N1 virus clades (clades 2.2 and 2.3.2.1). However, none of the mandarin ducks infected with H5N8 and H5N1 viruses showed severe clinical signs or mortality, and gross lesions were only observed in a few tissues. Viral replication and shedding were greater in H5N8-infected ducks than in H5N1-infected ducks. Recovery of all viruses from control duck in contact with infected ducks indicated that the highly pathogenic H5 viruses spread horizontally through contact. Taken together, these results suggest that H5N8 viruses spread efficiently in mandarin ducks. Further studies of pathogenicity in wild birds are required to examine possible long-distance dissemination via migration routes. (C) 2016 Elsevier B.V. All rights reserved.</P>

Gibberellin secreting rhizobacterium, Pseudomonas putida H-2-3 modulates the hormonal and stress physiology of soybean to improve the plant growth under saline and drought conditions

Kang, S.M.,Radhakrishnan, R.,Khan, A.L.,Kim, M.J.,Park, J.M.,Kim, B.R.,Shin, D.H.,Lee, I.J. Gauthier-Villars ; Elsevier Science Ltd 2014 Vol. No.

The physiological changes in tolerant soybean plants under salt and drought stress conditions with Pseudomonas putida H-2-3 were investigated. A bacterial isolate H-2-3 was isolated from soil and identified as Pseudomonas putida H-2-3 by 16S rDNA sequences. The treatment of P. putida H-2-3 significantly increased the length, fresh and dry weight of shoot and chlorophyll content in gibberellins (GAs) deficient mutant Waito-c rice seedlings over the control, it might be the presence of GA<SUB>1</SUB>, GA<SUB>4,</SUB> GA<SUB>9</SUB> and GA<SUB>20.</SUB> The soybean plant growth was retarded in salt (120 mM sodium chloride) and drought (15% polyethylene glycol) stress conditions at 10 days treatments, while P. putida H-2-3 effectively enhanced the shoot length and fresh weight of plants suffered at salt and drought stress. The chlorophyll content was lower in abiotic stress conditions and bacterial inoculant P. putida H-2-3 mitigated the stress effects by an evidence of higher quantity of chlorophyll content in plants exposed to salt and drought. The stress hormonal analysis revealed that individual treatment of P. putida H-2-3, salt and drought significantly enhanced the abscisic acid and salicylic acid content than their control. P. putida H-2-3 applied to salt and drought stressed plants showed a lower level of abscisic acid and salicylic acid and a higher level of jasmonic acid content. Under stress condition induced by salt and drought in plants expressed higher level of total polyphenol, superoxide dismutase and radical scavenging activity and no significant changes in flavonoids. The bio-inoculant, P. putida H-2-3 modulated those antioxidants by declining superoxide dismutase, flavonoids and radical scavenging activity. P. putida H-2-3 induced tolerance against abiotic stress was confirmed by a reduction of Na content in abiotic stressed plants. The results suggest that P. putida H-2-3 application reprograms the chlorophyll, stress hormones and antioxidants expression in abiotic stress affected soybean plant and improves their growth under stress environment.

A novel canine influenza H3N2 virus isolated from cats in an animal shelter

Jeoung, H.Y.,Lim, S.I.,Shin, B.H.,Lim, J.A.,Song, J.Y.,Song, D.S.,Kang, B.K.,Moon, H.J.,An, D.J. Elsevier Scientific Pub. Co 2013 Veterinary microbiology Vol.165 No.3

The interspecies transmission of avian-origin H3N2 canine influenza virus (CIV) to dogs was first reported in 2007. The present study characterized a novel CIV H3N2 isolated from cats in an animal shelter. A comparative analysis of the deduced amino acid sequences of the A/Canine/Korea/CY009/2010(H3N2) (CY009) and A/Feline/Korea/FY028/2010 (H3N2) (FY028) strains isolated from dogs and cats, respectively, in the animal shelter identified point mutations in 18 amino acid positions within eight viral genes. Interestingly, CY009 and FY028 replicated well in specific pathogen-free embryonated chicken eggs and in mice, respectively. Mice infected with the FY028 strain exhibited significant over expression of IL-10, TNF-α, and IFN-γ (p<0.001) at 3 days postinfection. Thus, an emergency monitoring system should be developed to identify influenza mutations that occur during interspecies transmission in companion animals and for continuous public health surveillance.

자외선의 상이한 선량이 브로일러 병아리의 중족골 광물질 함량에 미치는 영향

조인호,장윤환,여영수,강훈석,김강수,배은경 한국축산학회 1994 한국축산학회지 Vol.36 No.2

This study was carried out to investigate the concentrations of Ca, P and ash in the metatarsus of broiler chicks exposed to 0.204 mJ/㎠ 30 min) or 0.409 mJ/㎠(60 min) of medium wave ultraviolet(UVB) fight. Eighty two Hubbard dayold broiler chicks(2 doses × 9 elapsed times × 4 replicate + 10 negative controls) were fed vitamin D(VD)deficient diets for 31 days in a windowless subdued light room. The metatarsus were collected at 0, 6, 12, 18, 30, 42, 66, 90, or 138 h after UVB irradiation. The metatarsus bones were separated from adhering tissue, ether extracted, dried and ashed(A.O.A.C., 1984). The Ca content in non-fat dry metatarsus was measured by atomic absorption spectrophotometry and P by urnmonium metavanadate colorimetry. The mean Ca concentration in metatarsus of negative control birds was 21 %, and those of chicks exposed to UVB light for 30 and 60 min were 30 and 38%, respectively with the maximum values at 42 h after irradiation. Thereafter, the Ca contents decreased throughout the l38 h period of this research. The mean P level of control chicks was 8.5%, and the level peaked at 15% (30 min treatment) and 11%(60 min) at 66 h after exposure. The decreasing trend continued later than 66 h. This mean ash content of the control group was 43% with the ash contents of the 0.204 mJ/㎠(30 min) and 0.409 mJ/㎠(60 min) groups decreasing slightly until 42 h, but increasing to 46%(30 min) and 47%(60 min) at l38 h after irradiation. This verified that Ca and P contents increased first and ash amount increased later in metatarsal bones of broiler chicks when they were exposed to 0.204 and 0.409 mJ/㎠ UVB light. Since there was not a big difference between minerals in metatarsal bones of chicks exposed to 0.204 or 0.409 mJ/㎠ UVB light, it was thought that further experiments would be necessary to elucidate the optimum dose of UVB light less than 0.204 mJ/㎠.

공정육묘 온실의 표준모델 및 자동화 시스템 개발과 활용기술연구 8 : 제4장 공정묘 생산기술 개발:제5절 Chaper4 Development of Plug Seedling Production Technology

박중춘,민영봉,정병룡,설인준,이영만,윤용철,강호종,김태규,김광용,장사문,정한택,오태한,김평태,김진일,손영걸,박봉식,김시론,이형정,오상석,김명승,조정호,하종규,임동희,이은주,변정희,이정한,최우진,강환규 경상대학교 시설원예연구소 1997 施設園藝硏究 Vol.4 No.-